Gynecology

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

A version of this article first appeared on Medscape.com.

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

A version of this article first appeared on Medscape.com.

Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.

Jupiterimages/ThinkStock

Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.

Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.

The drug was also “generally well tolerated” and had a safety profile that was “consistent” with what has been seen previously with the drug, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.

“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”

The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
 

High placebo response

However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.

Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.

Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.

Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.

The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.

The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.

The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).

Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).

At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.

A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.

Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.

On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).

Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.

The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.

From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”

Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.

“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.

“What impact did that have? The placebo is not really placebo” in this case.

More effective than results suggest?

Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.

Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said

“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.

Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.

Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.

Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”

Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”

The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.

A version of this article first appeared on Medscape.com.

Barnhart K, Hansen KR, Stephenson MD, et al; Reproductive Medicine Network. Effect of an active vs expectant management strategy on successful resolution of pregnancy among patients with a persisting pregnancy of unknown location: the ACT or NOT randomized clinical trial. JAMA. 2021;326:390-400.

EXPERT COMMENTARY

Among patients with persistent PUL, it can be difficult to distinguish between ectopic pregnancy and an early nonviable intrauterine pregnancy.¹ If untreated, ectopic pregnancy can lead to serious morbidity and mortality.² Management options for persistent PUL include expectant management, empirical methotrexate, or diagnostic uterine evacuation with methotrexate as needed. Data on the potential for these options to achieve pregnancy resolution is valuable for patients and clinicians choosing a treatment plan.

Details of the study

Barnhart and colleagues conducted a multicenter, randomized controlled trial that enrolled 225 women with persistent PUL (defined by transvaginal ultrasound imaging without a definitive intrauterine or extrauterine gestation and at least 2 consecutive human chorionic gonadotropin [hCG] values with less than a 15% rise per day). Participants were randomly assigned to 1 of 3 treatment groups: expectant management, empirical methotrexate, or uterine evacuation followed by methotrexate if needed.

The primary outcome was pregnancy resolution without a change in management strategy. A secondary outcome was noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed in achieving pregnancy resolution.

Results. The active management groups were significantly more likely to achieve pregnancy resolution without changing strategies than the expectant management group (51.5% vs 36.0%; difference, 15.4%). However, 39% of enrolled participants declined their randomized allocation and crossed over into a different management strategy.

Empirical methotrexate was found to be noninferior to uterine evacuation followed by methotrexate as needed in achieving pregnancy resolution (54.9% vs 48.3%; difference, 6.6%).

Study strengths and limitations

Prior studies of hemodynamically stable patients with persistent PUL or stable tubal ectopic pregnancy and low initial hCG values (<2,000 IU/L) failed to demonstrate that active management with methotrexate or uterine evacuation leads to more successful or faster pregnancy resolution.^3-5 Barnhart and colleagues’ study results, however, found that active management with 2-dose empirical methotrexate or uterine evacuation was more likely to lead to pregnancy resolution without requiring a change in management plan than was expectant management. The authors performed both an intention-to-treat and an as-treated analysis to confirm results.

The 39% crossover rate between the treatment groups likely reflected both patient preference and clinical presentation, potentially biasing the results. The low overall rate of adverse events confirms the safety and acceptability of a patient-centered approach to persistent PUL management. ●

Barnhart K, Hansen KR, Stephenson MD, et al; Reproductive Medicine Network. Effect of an active vs expectant management strategy on successful resolution of pregnancy among patients with a persisting pregnancy of unknown location: the ACT or NOT randomized clinical trial. JAMA. 2021;326:390-400.

EXPERT COMMENTARY

Among patients with persistent PUL, it can be difficult to distinguish between ectopic pregnancy and an early nonviable intrauterine pregnancy.¹ If untreated, ectopic pregnancy can lead to serious morbidity and mortality.² Management options for persistent PUL include expectant management, empirical methotrexate, or diagnostic uterine evacuation with methotrexate as needed. Data on the potential for these options to achieve pregnancy resolution is valuable for patients and clinicians choosing a treatment plan.

Details of the study

Barnhart and colleagues conducted a multicenter, randomized controlled trial that enrolled 225 women with persistent PUL (defined by transvaginal ultrasound imaging without a definitive intrauterine or extrauterine gestation and at least 2 consecutive human chorionic gonadotropin [hCG] values with less than a 15% rise per day). Participants were randomly assigned to 1 of 3 treatment groups: expectant management, empirical methotrexate, or uterine evacuation followed by methotrexate if needed.

The primary outcome was pregnancy resolution without a change in management strategy. A secondary outcome was noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed in achieving pregnancy resolution.

Results. The active management groups were significantly more likely to achieve pregnancy resolution without changing strategies than the expectant management group (51.5% vs 36.0%; difference, 15.4%). However, 39% of enrolled participants declined their randomized allocation and crossed over into a different management strategy.

Empirical methotrexate was found to be noninferior to uterine evacuation followed by methotrexate as needed in achieving pregnancy resolution (54.9% vs 48.3%; difference, 6.6%).

Study strengths and limitations

Prior studies of hemodynamically stable patients with persistent PUL or stable tubal ectopic pregnancy and low initial hCG values (<2,000 IU/L) failed to demonstrate that active management with methotrexate or uterine evacuation leads to more successful or faster pregnancy resolution.^3-5 Barnhart and colleagues’ study results, however, found that active management with 2-dose empirical methotrexate or uterine evacuation was more likely to lead to pregnancy resolution without requiring a change in management plan than was expectant management. The authors performed both an intention-to-treat and an as-treated analysis to confirm results.

The 39% crossover rate between the treatment groups likely reflected both patient preference and clinical presentation, potentially biasing the results. The low overall rate of adverse events confirms the safety and acceptability of a patient-centered approach to persistent PUL management. ●

Barnhart K, Hansen KR, Stephenson MD, et al; Reproductive Medicine Network. Effect of an active vs expectant management strategy on successful resolution of pregnancy among patients with a persisting pregnancy of unknown location: the ACT or NOT randomized clinical trial. JAMA. 2021;326:390-400.

EXPERT COMMENTARY

Among patients with persistent PUL, it can be difficult to distinguish between ectopic pregnancy and an early nonviable intrauterine pregnancy.¹ If untreated, ectopic pregnancy can lead to serious morbidity and mortality.² Management options for persistent PUL include expectant management, empirical methotrexate, or diagnostic uterine evacuation with methotrexate as needed. Data on the potential for these options to achieve pregnancy resolution is valuable for patients and clinicians choosing a treatment plan.

Details of the study

Barnhart and colleagues conducted a multicenter, randomized controlled trial that enrolled 225 women with persistent PUL (defined by transvaginal ultrasound imaging without a definitive intrauterine or extrauterine gestation and at least 2 consecutive human chorionic gonadotropin [hCG] values with less than a 15% rise per day). Participants were randomly assigned to 1 of 3 treatment groups: expectant management, empirical methotrexate, or uterine evacuation followed by methotrexate if needed.

The primary outcome was pregnancy resolution without a change in management strategy. A secondary outcome was noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed in achieving pregnancy resolution.

Results. The active management groups were significantly more likely to achieve pregnancy resolution without changing strategies than the expectant management group (51.5% vs 36.0%; difference, 15.4%). However, 39% of enrolled participants declined their randomized allocation and crossed over into a different management strategy.

Empirical methotrexate was found to be noninferior to uterine evacuation followed by methotrexate as needed in achieving pregnancy resolution (54.9% vs 48.3%; difference, 6.6%).

Study strengths and limitations

Prior studies of hemodynamically stable patients with persistent PUL or stable tubal ectopic pregnancy and low initial hCG values (<2,000 IU/L) failed to demonstrate that active management with methotrexate or uterine evacuation leads to more successful or faster pregnancy resolution.^3-5 Barnhart and colleagues’ study results, however, found that active management with 2-dose empirical methotrexate or uterine evacuation was more likely to lead to pregnancy resolution without requiring a change in management plan than was expectant management. The authors performed both an intention-to-treat and an as-treated analysis to confirm results.

The 39% crossover rate between the treatment groups likely reflected both patient preference and clinical presentation, potentially biasing the results. The low overall rate of adverse events confirms the safety and acceptability of a patient-centered approach to persistent PUL management. ●

Prior to 1980, medical record notes were generally hand-written, short, and to the point. Senior physicians often wrote their 3-line notes using a fountain pen in an elegant cursive. With the transition to electronic medical records, notes have become bloated with irrelevant information and frequently lack a focus on the critical clinical insights that optimize patient care. The use of smart phrases to pull vast amounts of raw data into the note is a major contributor to note bloat. The unrestrained use of the copy and paste functionality generates a sequence of cloned notes that grow in length as new information is added and little information from prior notes removed. With each subsequent clone the note often becomes less accurate, lengthier, and more difficult for a reader to understand. In one survey of 253 physicians who wrote electronic notes, 90% reported that they used the copy and paste function, with 71% reporting that use of this function caused inconsistencies within and among notes and increased the repetitive presentation of outdated information in the note.¹ Although the surveyed clinicians recognized that the copy and paste function caused problems, 80% reported that they planned to continue to use the copy and paste function.¹

The SOAP note

The problem-oriented SOAP note is written in the classic structure of subjective and objective information, followed by an assessment and plan.² The structure of the SOAP note emphasizes the logical and sequential collection of data followed by data analysis, resulting in a focused assessment and plan. When notes were hand-written and short, the entire SOAP note could be viewed on one page. Like a dashboard, the eye could quickly scan each key component of the note, facilitating the simultaneous integration of all 4 components of the note, facilitating understanding of the patient’s clinical situation. When the SOAP note structure is used to create a multipage electronic note, the result is a note that often confuses rather than enlightens the reader. A 5- to 10-page SOAP note is often useless for patient care but demonstrates the ability of computer-savvy clinicians to quickly generate a note thousands of words in length.

The APSO note, a response to note bloat

When a medical record note becomes a multipage document, clinicians should consider switching from the SOAP note structure to the APSO note, where the assessment and plan are at the top of the note, and the subjective and objective information is below the assessment and plan. The APSO format permits the reader to more quickly grasp the critical thinking of the author and facilitates a focus on key points relevant to the patient’s condition. The note can be written in the SOAP format, but then the assessment and plan are brought to the top of the note. In my clinical experience fewer than 10% of clinicians are using an APSO note structure. I believe that, with a multipage note, the APSO structure improves the experience of the reader and should be more widely utilized, especially by clinicians who are prone to crafting a bloated note. In a survey of more than 3,000 clinicians, approximately two-thirds of the respondents reported that, compared with SOAP notes, APSO notes were easier and faster to read, and APSO notes made it easier to follow the clinical reasoning of the author.³

Continue to: New evaluation and management billing guidelines—An opportunity to reduce note bloat...

New evaluation and management billing guidelines—An opportunity to reduce note bloat

Previous evaluation and management federal billing guidelines emphasized documentation of a myriad of clinically irrelevant details contributing to note bloat. The new federal evaluation and management billing guidelines pivot the focus of the note to the quality and complexity of medical decision making as demonstrated in the assessment and plan.⁴ Prioritizing the assessment and plan as the key feature of the medical record note should help reduce the length of notes. The American College of Physicians recently recommended deleting the complete review of systems and prior histories from most notes unless relevant to medical decision making and the assessment and plan.⁵

The open note

The open note mandate was contained in federal regulations developed to implement the 21st Century Cures Act, which required patients to have access to the information in their medical record. In order to comply with the regulation, health systems are sending most notes and test results to the patient through the health system’s patient gateway. The open note process entered my practice through a stealthy progression, from an initial step of permitting a clinician to easily share their note with a patient to a top-down edict that all notes, except some notes that have a high risk of causing patient harm, must be sent immediately to the patient. Obviously, an open note supports “transparency,” but I am unaware of high quality evidence that open notes improve the health of a population or reduce morbidity or mortality from health problems.

The federal mandate that clinicians share their notes or risk fiscal penalties is coercive and undermines the independence of health professionals. Open notes may have many benefits, including:

• improving a patient’s comprehension and sense of control over their health issues
• increasing patient trust in their health system
• increasing the number of questions patients ask their clinician.⁶

Open notes may also cause unintended adverse emotional trauma to patients, especially when the note communicates “bad news.” In one study of 100 oncology patients, approximately 25% of respondents reported that reading clinical notes was emotionally difficult, and they sometimes regretted having read the note.⁶ One patient reported, “I think MyChart is great but in this whole cancer thing MyChart has not been a good thing.” Another patient reported, “Reading serious stuff like that is just too taxing for me to be honest with you.”⁶ An additional finding of the study was that patients reported their notes were written with too much medical jargon and repetition of information.

Open laboratory, pathology, and imaging data—Helpful or harmful?

A component of the open note mandate is that laboratory, pathology, and imaging data must be shared timely with patients. Some health systems incorporate a 3-day pause prior to sharing such data, in order to provide the clinical team with time to communicate with the patient before the test results are shared. Some health systems, including my health system, have engineered the open note data-sharing system to immediately share the results of most completed laboratory, pathology, and imaging studies with the patient. Immediate sharing of data may result in the patient first learning that they have a serious, life-threatening health problem, such as cancer, from their patient portal rather than from a clinician. As an example, a patient may first learn that they have metastatic cancer from a CT scan that was ordered for a benign indication.

Another example is that a patient may first learn that they have an HIV infection from their patient portal. This can be a shocking and emotionally damaging experience for the patient. For many test results, it would be best if a clinician were able to communicate the result to the patient, providing support and context to the meaning of the result, rather than sending sensitive, life-altering information directly from the laboratory or imaging department to the patient. Leaders in medical education have spent decades teaching clinicians how to communicate “bad news” in a sensitive, supportive, and effective manner. The open sharing of laboratory, pathology, and imaging data short-circuits the superior process of relying on a highly capable clinician to communicate bad news.

Continue to: Crafting the open medical record note...

Building on the advice that “when life gives you lemons, make lemonade,” I have begun to pivot the purpose of my medical notes from a product useful to myself and other clinicians to a product whose primary purpose is to be helpful for the patient. The open note can facilitate building a trusting relationship with the patient. My notes are becoming a series of written conversations with the patient, emphasizing compassion and empathy. I am increasing significantly the amount of educational information in the note to help the patient understand their situation. In addition, I am replacing traditional medical terms with verbiage more appropriate in the context of a conversation with the patient, reducing the use of medical jargon. For example, I have stopped using “chief complaint” and replaced it with “health issues.” I am diligently avoiding the use of medical terms that have negative connotations, including “obese,” “psychosomatic,” “alcoholic,” and “drug addiction.” I include encouragement and positive comments in many of my notes. For example, “Ms. X is successfully managing her health issues and experiencing improved health. It is a pleasure collaborating with her on achieving optimal health.”

Can we bring sanity back to medical note writing?

The primary role of a clinician is to spend as much time as possible listening to patients, understanding their needs, and helping them achieve optimal health. There are many benefits to an electronic medical record, including legibility, accessibility, interoperability, and efficiency. However, in current practice “note bloat” undermines the potential of the electronic medical record and makes many notes ineffective to the process of advancing the patient’s health. We are competent and highly trained clinicians. We can craft notes that are simple, specific, story-driven, compassionate, and empathetic. If we return to the ABCs of note writing, focusing on accuracy, brevity, and clarity, we will make note writing and reading more rewarding and improve patient care. ●

Prior to 1980, medical record notes were generally hand-written, short, and to the point. Senior physicians often wrote their 3-line notes using a fountain pen in an elegant cursive. With the transition to electronic medical records, notes have become bloated with irrelevant information and frequently lack a focus on the critical clinical insights that optimize patient care. The use of smart phrases to pull vast amounts of raw data into the note is a major contributor to note bloat. The unrestrained use of the copy and paste functionality generates a sequence of cloned notes that grow in length as new information is added and little information from prior notes removed. With each subsequent clone the note often becomes less accurate, lengthier, and more difficult for a reader to understand. In one survey of 253 physicians who wrote electronic notes, 90% reported that they used the copy and paste function, with 71% reporting that use of this function caused inconsistencies within and among notes and increased the repetitive presentation of outdated information in the note.¹ Although the surveyed clinicians recognized that the copy and paste function caused problems, 80% reported that they planned to continue to use the copy and paste function.¹

The SOAP note

The problem-oriented SOAP note is written in the classic structure of subjective and objective information, followed by an assessment and plan.² The structure of the SOAP note emphasizes the logical and sequential collection of data followed by data analysis, resulting in a focused assessment and plan. When notes were hand-written and short, the entire SOAP note could be viewed on one page. Like a dashboard, the eye could quickly scan each key component of the note, facilitating the simultaneous integration of all 4 components of the note, facilitating understanding of the patient’s clinical situation. When the SOAP note structure is used to create a multipage electronic note, the result is a note that often confuses rather than enlightens the reader. A 5- to 10-page SOAP note is often useless for patient care but demonstrates the ability of computer-savvy clinicians to quickly generate a note thousands of words in length.

The APSO note, a response to note bloat

When a medical record note becomes a multipage document, clinicians should consider switching from the SOAP note structure to the APSO note, where the assessment and plan are at the top of the note, and the subjective and objective information is below the assessment and plan. The APSO format permits the reader to more quickly grasp the critical thinking of the author and facilitates a focus on key points relevant to the patient’s condition. The note can be written in the SOAP format, but then the assessment and plan are brought to the top of the note. In my clinical experience fewer than 10% of clinicians are using an APSO note structure. I believe that, with a multipage note, the APSO structure improves the experience of the reader and should be more widely utilized, especially by clinicians who are prone to crafting a bloated note. In a survey of more than 3,000 clinicians, approximately two-thirds of the respondents reported that, compared with SOAP notes, APSO notes were easier and faster to read, and APSO notes made it easier to follow the clinical reasoning of the author.³

Continue to: New evaluation and management billing guidelines—An opportunity to reduce note bloat...

New evaluation and management billing guidelines—An opportunity to reduce note bloat

Previous evaluation and management federal billing guidelines emphasized documentation of a myriad of clinically irrelevant details contributing to note bloat. The new federal evaluation and management billing guidelines pivot the focus of the note to the quality and complexity of medical decision making as demonstrated in the assessment and plan.⁴ Prioritizing the assessment and plan as the key feature of the medical record note should help reduce the length of notes. The American College of Physicians recently recommended deleting the complete review of systems and prior histories from most notes unless relevant to medical decision making and the assessment and plan.⁵

The open note

The open note mandate was contained in federal regulations developed to implement the 21st Century Cures Act, which required patients to have access to the information in their medical record. In order to comply with the regulation, health systems are sending most notes and test results to the patient through the health system’s patient gateway. The open note process entered my practice through a stealthy progression, from an initial step of permitting a clinician to easily share their note with a patient to a top-down edict that all notes, except some notes that have a high risk of causing patient harm, must be sent immediately to the patient. Obviously, an open note supports “transparency,” but I am unaware of high quality evidence that open notes improve the health of a population or reduce morbidity or mortality from health problems.

The federal mandate that clinicians share their notes or risk fiscal penalties is coercive and undermines the independence of health professionals. Open notes may have many benefits, including:

• improving a patient’s comprehension and sense of control over their health issues
• increasing patient trust in their health system
• increasing the number of questions patients ask their clinician.⁶

Open notes may also cause unintended adverse emotional trauma to patients, especially when the note communicates “bad news.” In one study of 100 oncology patients, approximately 25% of respondents reported that reading clinical notes was emotionally difficult, and they sometimes regretted having read the note.⁶ One patient reported, “I think MyChart is great but in this whole cancer thing MyChart has not been a good thing.” Another patient reported, “Reading serious stuff like that is just too taxing for me to be honest with you.”⁶ An additional finding of the study was that patients reported their notes were written with too much medical jargon and repetition of information.

Open laboratory, pathology, and imaging data—Helpful or harmful?

A component of the open note mandate is that laboratory, pathology, and imaging data must be shared timely with patients. Some health systems incorporate a 3-day pause prior to sharing such data, in order to provide the clinical team with time to communicate with the patient before the test results are shared. Some health systems, including my health system, have engineered the open note data-sharing system to immediately share the results of most completed laboratory, pathology, and imaging studies with the patient. Immediate sharing of data may result in the patient first learning that they have a serious, life-threatening health problem, such as cancer, from their patient portal rather than from a clinician. As an example, a patient may first learn that they have metastatic cancer from a CT scan that was ordered for a benign indication.

Another example is that a patient may first learn that they have an HIV infection from their patient portal. This can be a shocking and emotionally damaging experience for the patient. For many test results, it would be best if a clinician were able to communicate the result to the patient, providing support and context to the meaning of the result, rather than sending sensitive, life-altering information directly from the laboratory or imaging department to the patient. Leaders in medical education have spent decades teaching clinicians how to communicate “bad news” in a sensitive, supportive, and effective manner. The open sharing of laboratory, pathology, and imaging data short-circuits the superior process of relying on a highly capable clinician to communicate bad news.

Continue to: Crafting the open medical record note...

Building on the advice that “when life gives you lemons, make lemonade,” I have begun to pivot the purpose of my medical notes from a product useful to myself and other clinicians to a product whose primary purpose is to be helpful for the patient. The open note can facilitate building a trusting relationship with the patient. My notes are becoming a series of written conversations with the patient, emphasizing compassion and empathy. I am increasing significantly the amount of educational information in the note to help the patient understand their situation. In addition, I am replacing traditional medical terms with verbiage more appropriate in the context of a conversation with the patient, reducing the use of medical jargon. For example, I have stopped using “chief complaint” and replaced it with “health issues.” I am diligently avoiding the use of medical terms that have negative connotations, including “obese,” “psychosomatic,” “alcoholic,” and “drug addiction.” I include encouragement and positive comments in many of my notes. For example, “Ms. X is successfully managing her health issues and experiencing improved health. It is a pleasure collaborating with her on achieving optimal health.”

Can we bring sanity back to medical note writing?

The primary role of a clinician is to spend as much time as possible listening to patients, understanding their needs, and helping them achieve optimal health. There are many benefits to an electronic medical record, including legibility, accessibility, interoperability, and efficiency. However, in current practice “note bloat” undermines the potential of the electronic medical record and makes many notes ineffective to the process of advancing the patient’s health. We are competent and highly trained clinicians. We can craft notes that are simple, specific, story-driven, compassionate, and empathetic. If we return to the ABCs of note writing, focusing on accuracy, brevity, and clarity, we will make note writing and reading more rewarding and improve patient care. ●

Prior to 1980, medical record notes were generally hand-written, short, and to the point. Senior physicians often wrote their 3-line notes using a fountain pen in an elegant cursive. With the transition to electronic medical records, notes have become bloated with irrelevant information and frequently lack a focus on the critical clinical insights that optimize patient care. The use of smart phrases to pull vast amounts of raw data into the note is a major contributor to note bloat. The unrestrained use of the copy and paste functionality generates a sequence of cloned notes that grow in length as new information is added and little information from prior notes removed. With each subsequent clone the note often becomes less accurate, lengthier, and more difficult for a reader to understand. In one survey of 253 physicians who wrote electronic notes, 90% reported that they used the copy and paste function, with 71% reporting that use of this function caused inconsistencies within and among notes and increased the repetitive presentation of outdated information in the note.¹ Although the surveyed clinicians recognized that the copy and paste function caused problems, 80% reported that they planned to continue to use the copy and paste function.¹

The SOAP note

The problem-oriented SOAP note is written in the classic structure of subjective and objective information, followed by an assessment and plan.² The structure of the SOAP note emphasizes the logical and sequential collection of data followed by data analysis, resulting in a focused assessment and plan. When notes were hand-written and short, the entire SOAP note could be viewed on one page. Like a dashboard, the eye could quickly scan each key component of the note, facilitating the simultaneous integration of all 4 components of the note, facilitating understanding of the patient’s clinical situation. When the SOAP note structure is used to create a multipage electronic note, the result is a note that often confuses rather than enlightens the reader. A 5- to 10-page SOAP note is often useless for patient care but demonstrates the ability of computer-savvy clinicians to quickly generate a note thousands of words in length.

The APSO note, a response to note bloat

When a medical record note becomes a multipage document, clinicians should consider switching from the SOAP note structure to the APSO note, where the assessment and plan are at the top of the note, and the subjective and objective information is below the assessment and plan. The APSO format permits the reader to more quickly grasp the critical thinking of the author and facilitates a focus on key points relevant to the patient’s condition. The note can be written in the SOAP format, but then the assessment and plan are brought to the top of the note. In my clinical experience fewer than 10% of clinicians are using an APSO note structure. I believe that, with a multipage note, the APSO structure improves the experience of the reader and should be more widely utilized, especially by clinicians who are prone to crafting a bloated note. In a survey of more than 3,000 clinicians, approximately two-thirds of the respondents reported that, compared with SOAP notes, APSO notes were easier and faster to read, and APSO notes made it easier to follow the clinical reasoning of the author.³

Continue to: New evaluation and management billing guidelines—An opportunity to reduce note bloat...

New evaluation and management billing guidelines—An opportunity to reduce note bloat

Previous evaluation and management federal billing guidelines emphasized documentation of a myriad of clinically irrelevant details contributing to note bloat. The new federal evaluation and management billing guidelines pivot the focus of the note to the quality and complexity of medical decision making as demonstrated in the assessment and plan.⁴ Prioritizing the assessment and plan as the key feature of the medical record note should help reduce the length of notes. The American College of Physicians recently recommended deleting the complete review of systems and prior histories from most notes unless relevant to medical decision making and the assessment and plan.⁵

The open note

The open note mandate was contained in federal regulations developed to implement the 21st Century Cures Act, which required patients to have access to the information in their medical record. In order to comply with the regulation, health systems are sending most notes and test results to the patient through the health system’s patient gateway. The open note process entered my practice through a stealthy progression, from an initial step of permitting a clinician to easily share their note with a patient to a top-down edict that all notes, except some notes that have a high risk of causing patient harm, must be sent immediately to the patient. Obviously, an open note supports “transparency,” but I am unaware of high quality evidence that open notes improve the health of a population or reduce morbidity or mortality from health problems.

The federal mandate that clinicians share their notes or risk fiscal penalties is coercive and undermines the independence of health professionals. Open notes may have many benefits, including:

• improving a patient’s comprehension and sense of control over their health issues
• increasing patient trust in their health system
• increasing the number of questions patients ask their clinician.⁶

Open notes may also cause unintended adverse emotional trauma to patients, especially when the note communicates “bad news.” In one study of 100 oncology patients, approximately 25% of respondents reported that reading clinical notes was emotionally difficult, and they sometimes regretted having read the note.⁶ One patient reported, “I think MyChart is great but in this whole cancer thing MyChart has not been a good thing.” Another patient reported, “Reading serious stuff like that is just too taxing for me to be honest with you.”⁶ An additional finding of the study was that patients reported their notes were written with too much medical jargon and repetition of information.

Open laboratory, pathology, and imaging data—Helpful or harmful?

A component of the open note mandate is that laboratory, pathology, and imaging data must be shared timely with patients. Some health systems incorporate a 3-day pause prior to sharing such data, in order to provide the clinical team with time to communicate with the patient before the test results are shared. Some health systems, including my health system, have engineered the open note data-sharing system to immediately share the results of most completed laboratory, pathology, and imaging studies with the patient. Immediate sharing of data may result in the patient first learning that they have a serious, life-threatening health problem, such as cancer, from their patient portal rather than from a clinician. As an example, a patient may first learn that they have metastatic cancer from a CT scan that was ordered for a benign indication.

Another example is that a patient may first learn that they have an HIV infection from their patient portal. This can be a shocking and emotionally damaging experience for the patient. For many test results, it would be best if a clinician were able to communicate the result to the patient, providing support and context to the meaning of the result, rather than sending sensitive, life-altering information directly from the laboratory or imaging department to the patient. Leaders in medical education have spent decades teaching clinicians how to communicate “bad news” in a sensitive, supportive, and effective manner. The open sharing of laboratory, pathology, and imaging data short-circuits the superior process of relying on a highly capable clinician to communicate bad news.

Continue to: Crafting the open medical record note...

Building on the advice that “when life gives you lemons, make lemonade,” I have begun to pivot the purpose of my medical notes from a product useful to myself and other clinicians to a product whose primary purpose is to be helpful for the patient. The open note can facilitate building a trusting relationship with the patient. My notes are becoming a series of written conversations with the patient, emphasizing compassion and empathy. I am increasing significantly the amount of educational information in the note to help the patient understand their situation. In addition, I am replacing traditional medical terms with verbiage more appropriate in the context of a conversation with the patient, reducing the use of medical jargon. For example, I have stopped using “chief complaint” and replaced it with “health issues.” I am diligently avoiding the use of medical terms that have negative connotations, including “obese,” “psychosomatic,” “alcoholic,” and “drug addiction.” I include encouragement and positive comments in many of my notes. For example, “Ms. X is successfully managing her health issues and experiencing improved health. It is a pleasure collaborating with her on achieving optimal health.”

Can we bring sanity back to medical note writing?

The primary role of a clinician is to spend as much time as possible listening to patients, understanding their needs, and helping them achieve optimal health. There are many benefits to an electronic medical record, including legibility, accessibility, interoperability, and efficiency. However, in current practice “note bloat” undermines the potential of the electronic medical record and makes many notes ineffective to the process of advancing the patient’s health. We are competent and highly trained clinicians. We can craft notes that are simple, specific, story-driven, compassionate, and empathetic. If we return to the ABCs of note writing, focusing on accuracy, brevity, and clarity, we will make note writing and reading more rewarding and improve patient care. ●

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sexually transmitted infection rates have not increased as dramatically in older women as they have in women in their teens and 20s, but rates of chlamydia and gonorrhea in women over age 35 have seen a steady incline over the past decade, and syphilis rates have climbed steeply, according to data from the Centers for Disease Control and Prevention.

That makes the STI treatment guidelines released by the CDC in July even timelier for practitioners of menopause medicine, according to Michael S. Policar, MD, MPH, a professor emeritus of ob.gyn. and reproductive sciences at the University of California, San Francisco.

Dr. Policar discussed what clinicians need to know about STIs in midlife women at the hybrid annual meeting of the North American Menopause Society. Even the nomenclature change in the guidelines from “sexually transmitted diseases” to “sexually transmitted infections” is important “because they want to acknowledge the fact that a lot of the sexually transmitted infections that we’re treating are asymptomatic, are colonizations, and are not yet diseases,” Dr. Policar said. “We’re trying to be much more expansive in thinking about finding these infections before they actually start causing morbidity in the form of a disease.”
 

Sexual history

The primary guidelines update for taking sexual history is the recommendation to ask patients about their intentions regarding pregnancy. The “5 Ps” of sexual history are now Partners, Practices, Protection from STIs, Past history of STIs, and Pregnancy intention.

“There should be a sixth P that has to do with pleasure questions,” Policar added. “We ask all the time for patients that we see in the context of perimenopausal and menopausal services, ‘Are you satisfied with your sexual relationship with your partner?’ Hopefully that will make it into the CDC guidelines as the sixth P at some point, but for now, that’s aspirational.”

In asking about partners, instead of asking patients whether they have sex with men, women, or both, clinicians should ask first if the patient is having sex of any kind – oral, vaginal, or anal – with anyone. From there, providers should ask how many sex partners the patient has had, the gender(s) of the partners, and whether they or their partners have other sex partners, using more gender-inclusive language.

When asking about practices, in addition to asking about the type of sexual contact patients have had, additional questions include whether the patient met their partners online or through apps, whether they or any of their partners use drugs, and whether the patient has exchanged sex for any needs, such as money, housing, or drugs. The additional questions can identify those at higher risk for STIs.

After reviewing the CDC’s list of risk factors for gonorrhea and chlamydia screening, Dr. Policar shared the screening list from the California Department of Public Health, which he finds more helpful:

• History of gonorrhea, chlamydia, or pelvic inflammatory disease (PID) in the past 2 years.
• More than 1 sexual partner in the past year.
• New sexual partner within 90 days.
• Reason to believe that a sex partner has had other partners in the past year.
• Exchanging sex for drugs or money within the past year.
• Other factors identified locally, including prevalence of infection in the community.

STI screening guidelines

For those with a positive gonorrhea/chlamydia (GC/CT) screen, a nucleic acid amplification test (NAAT) vaginal swab is the preferred specimen source, and self-collection is fine for women of any age, Dr. Policar said. In addition, cis-women who received anal intercourse in the preceding year should consider undergoing a rectal GC/CT NAAT, and those who performed oral sex should consider a pharyngeal GC/CT NAAT, based on shared clinical decision-making. A rectal swab requires an insertion of 3-4 cm and a 360-degree twirl of the wrist, not the swab, to ensure you get a sample from the entire circumference. Pharyngeal samples require swabbing both tonsillar pillars while taking care for those who may gag.

For contact testing – asymptomatic people who have had a high-risk sexual exposure – providers should test for gonorrhea, chlamydia, HIV, and syphilis but not for herpes, high-risk HPV, hepatitis B, hepatitis C, or bacterial vaginosis. “Maybe we’ll do a screen for trichomoniasis, and maybe we’ll offer herpes type 2 serology or antibody screening,” Dr. Policar said. Providers should also ask patients requesting contact testing if they have been vaccinated for hepatitis B. If not, “the conversation should be how can we get you vaccinated for hepatitis B,” Dr. Policar said.

HIV screening only needs to occur once between the ages of 15 and 65 for low-risk people and then once annually (or more often if necessary) for those who have a sex partner with HIV, use injectable drugs, engage in commercial sex work, have a new sex partner with unknown HIV status, received care at an STD or TB clinic, or were in a correctional facility or homeless shelter.

Those at increased risk for syphilis include men who have sex with men, men under age 29, and anyone living with HIV or who has a history of incarceration or a history of commercial sex work. In addition, African Americans have the greatest risk for syphilis of racial/ethnic groups, followed by Hispanics. Most adults only require hepatitis C screening with anti-hep C antibody testing once in their lifetime. Periodic hepatitis C screening should occur for people who inject drugs. If the screening is positive, providers should conduct an RNA polymerase chain reaction (PCR) test to determine whether a chronic infection is present.

Trichomoniasis screening should occur annually in women living with HIV or in correctional facilities. Others to consider screening include people with new or multiple sex partners, a history of STIs, inconsistent condom use, a history of sex work, and intravenous drug use. Dr. Policar also noted that several new assays, including NAAT, PCR, and a rapid test, are available for trichomoniasis.
 

STI treatment guidelines

For women with mucoprurulent cervicitis, the cause could be chlamydia, gonorrhea, herpes, trichomonas, mycoplasma, or even progesterone from pregnancy or contraception, Dr. Policar said. The new preferred treatment is 100 mg of doxycycline. The alternative, albeit less preferred, treatment is 1 g azithromycin.

The preferred treatment for chlamydia is now 100 mg oral doxycycline twice daily, or doxycycline 200 mg delayed-release once daily, for 7 days. Alternative regimens include 1 g oral azithromycin in a single dose or 500 mg oral levofloxacin once daily for 7 days. The switch to recommending doxycycline over azithromycin is based on recent evidence showing that doxycycline has a slightly higher efficacy for urogenital chlamydia and a substantially higher efficacy for rectal chlamydia. In addition, an increasing proportion of gonorrheal infections have shown resistance to azithromycin, particularly beginning in 2014.

Preferred treatment of new, uncomplicated gonorrhea infections of the cervix, urethra, rectum, and pharynx is one 500-mg dose of ceftriaxone for those weighing under 150 kg and 1 g for those weighing 150 kg or more. If ceftriaxone is unavailable, the new alternative recommended treatment for gonorrhea is 800 mg cefixime. For pharyngeal gonorrhea only, the CDC recommends a test-of-cure 7-14 days after treatment.

For gonorrheal infections, the CDC also recommends treatment with doxycycline if chlamydia has not been excluded, but the agency no longer recommends dual therapy with azithromycin unless it’s used in place of doxycycline for those who are pregnant, have an allergy, or may not be compliant with a 7-day doxycycline regimen.

The preferred treatment for bacterial vaginosis has not changed. The new recommended regimen for trichomoniasis is 500 mg oral metronidazole for 7 days, with the alternative being a single 2-g dose of tinidazole. Male partners should receive 2 g oral metronidazole. The CDC also notes that patients taking metronidazole no longer need to abstain from alcohol during treatment.

”Another area where the guidelines changed is in their description of expedited partner therapy, which means that, when we find an index case who has gonorrhea or chlamydia, we always have a discussion with her about getting her partners treated,” Dr. Policar said. “The CDC was quite clear that the responsibility for discussing partner treatment rests with us as the diagnosing provider” since city and county health departments don’t have the time or resources for contact tracing these STIs.

The two main ways to treat partners are to have the patient bring their partner(s) to the appointment with them or to do patient-delivered partner therapy. Ideally, clinicians who dispense their own medications can give the patient enough drugs to give her partner(s) a complete dose as well. Otherwise, providers can prescribe extra doses in the index patients’ name or write prescriptions in the partner’s name.

“In every state of the union now, it is legal for you to to prescribe antibiotics for partners sight unseen, Dr. Policar said.

Margaret Sullivan, MD, an ob.gyn. from rural western North Carolina, noted during the Q&A that an obstacle to partner therapy at her practice has been cost, particularly since many of the men don’t have insurance.

“I have not heard before of prescribing the extra doses for partners under the patient’s name,” Dr. Sullivan said. “I’ve thought about doing it, but [was worried about] it potentially being fraudulent if that patient has Medicaid and we’re prescribing extra doses under her name, so how do you work around that?”

Dr. Policar acknowledged that barrier and recommended that patients use the website/app Goodrx.com to find discounts for out-of-pocket generic medications. He also noted the occasional obstacle of pharmacists balking at filling a double or triple dose.

“What we’ve been suggesting in that circumstance is to literally copy that part of the CDC guidelines, which explains expedited partner therapy or patient-delivered partner therapy and send that off to the pharmacist so they can see that it’s a national recommendation of the CDC,” Dr. Policar said.

Claudia Rodriguez, MD, an ob.gyn. who works at Sherman Hospital in Elgin, Ill., asked about the CDC recommendations for HPV vaccination in older women. Although the CDC permits women over age 26 to receive the HPV vaccine, the agency does not “make a solid recommendation to have this done, which oftentimes makes a big difference in whether or not health insurance will actually pay for vaccination in that circumstance,” Dr. Policar said.

Patients are welcome to request the vaccine after shared decision-making, but “we should never present this as something which is routine,” he said. For women in their 50s, for example, “there’s virtually no data about any additional degree of protection that you would get” from HPV vaccination, Dr. Policar said in response to a similar question from Tara Allmen, MD, an ob.gyn. in New York City. “If you ask me for my personal clinical opinion about it, I would say it’s not going to be worth it,” he said.

Dr Policar had no disclosures. Disclosures were unavailable for attendees who spoke.

Sexually transmitted infection rates have not increased as dramatically in older women as they have in women in their teens and 20s, but rates of chlamydia and gonorrhea in women over age 35 have seen a steady incline over the past decade, and syphilis rates have climbed steeply, according to data from the Centers for Disease Control and Prevention.

That makes the STI treatment guidelines released by the CDC in July even timelier for practitioners of menopause medicine, according to Michael S. Policar, MD, MPH, a professor emeritus of ob.gyn. and reproductive sciences at the University of California, San Francisco.

Dr. Policar discussed what clinicians need to know about STIs in midlife women at the hybrid annual meeting of the North American Menopause Society. Even the nomenclature change in the guidelines from “sexually transmitted diseases” to “sexually transmitted infections” is important “because they want to acknowledge the fact that a lot of the sexually transmitted infections that we’re treating are asymptomatic, are colonizations, and are not yet diseases,” Dr. Policar said. “We’re trying to be much more expansive in thinking about finding these infections before they actually start causing morbidity in the form of a disease.”
 

Sexual history

The primary guidelines update for taking sexual history is the recommendation to ask patients about their intentions regarding pregnancy. The “5 Ps” of sexual history are now Partners, Practices, Protection from STIs, Past history of STIs, and Pregnancy intention.

“There should be a sixth P that has to do with pleasure questions,” Policar added. “We ask all the time for patients that we see in the context of perimenopausal and menopausal services, ‘Are you satisfied with your sexual relationship with your partner?’ Hopefully that will make it into the CDC guidelines as the sixth P at some point, but for now, that’s aspirational.”

In asking about partners, instead of asking patients whether they have sex with men, women, or both, clinicians should ask first if the patient is having sex of any kind – oral, vaginal, or anal – with anyone. From there, providers should ask how many sex partners the patient has had, the gender(s) of the partners, and whether they or their partners have other sex partners, using more gender-inclusive language.

When asking about practices, in addition to asking about the type of sexual contact patients have had, additional questions include whether the patient met their partners online or through apps, whether they or any of their partners use drugs, and whether the patient has exchanged sex for any needs, such as money, housing, or drugs. The additional questions can identify those at higher risk for STIs.

After reviewing the CDC’s list of risk factors for gonorrhea and chlamydia screening, Dr. Policar shared the screening list from the California Department of Public Health, which he finds more helpful:

• History of gonorrhea, chlamydia, or pelvic inflammatory disease (PID) in the past 2 years.
• More than 1 sexual partner in the past year.
• New sexual partner within 90 days.
• Reason to believe that a sex partner has had other partners in the past year.
• Exchanging sex for drugs or money within the past year.
• Other factors identified locally, including prevalence of infection in the community.

STI screening guidelines

For those with a positive gonorrhea/chlamydia (GC/CT) screen, a nucleic acid amplification test (NAAT) vaginal swab is the preferred specimen source, and self-collection is fine for women of any age, Dr. Policar said. In addition, cis-women who received anal intercourse in the preceding year should consider undergoing a rectal GC/CT NAAT, and those who performed oral sex should consider a pharyngeal GC/CT NAAT, based on shared clinical decision-making. A rectal swab requires an insertion of 3-4 cm and a 360-degree twirl of the wrist, not the swab, to ensure you get a sample from the entire circumference. Pharyngeal samples require swabbing both tonsillar pillars while taking care for those who may gag.

For contact testing – asymptomatic people who have had a high-risk sexual exposure – providers should test for gonorrhea, chlamydia, HIV, and syphilis but not for herpes, high-risk HPV, hepatitis B, hepatitis C, or bacterial vaginosis. “Maybe we’ll do a screen for trichomoniasis, and maybe we’ll offer herpes type 2 serology or antibody screening,” Dr. Policar said. Providers should also ask patients requesting contact testing if they have been vaccinated for hepatitis B. If not, “the conversation should be how can we get you vaccinated for hepatitis B,” Dr. Policar said.

HIV screening only needs to occur once between the ages of 15 and 65 for low-risk people and then once annually (or more often if necessary) for those who have a sex partner with HIV, use injectable drugs, engage in commercial sex work, have a new sex partner with unknown HIV status, received care at an STD or TB clinic, or were in a correctional facility or homeless shelter.

Those at increased risk for syphilis include men who have sex with men, men under age 29, and anyone living with HIV or who has a history of incarceration or a history of commercial sex work. In addition, African Americans have the greatest risk for syphilis of racial/ethnic groups, followed by Hispanics. Most adults only require hepatitis C screening with anti-hep C antibody testing once in their lifetime. Periodic hepatitis C screening should occur for people who inject drugs. If the screening is positive, providers should conduct an RNA polymerase chain reaction (PCR) test to determine whether a chronic infection is present.

Trichomoniasis screening should occur annually in women living with HIV or in correctional facilities. Others to consider screening include people with new or multiple sex partners, a history of STIs, inconsistent condom use, a history of sex work, and intravenous drug use. Dr. Policar also noted that several new assays, including NAAT, PCR, and a rapid test, are available for trichomoniasis.
 

STI treatment guidelines

For women with mucoprurulent cervicitis, the cause could be chlamydia, gonorrhea, herpes, trichomonas, mycoplasma, or even progesterone from pregnancy or contraception, Dr. Policar said. The new preferred treatment is 100 mg of doxycycline. The alternative, albeit less preferred, treatment is 1 g azithromycin.

The preferred treatment for chlamydia is now 100 mg oral doxycycline twice daily, or doxycycline 200 mg delayed-release once daily, for 7 days. Alternative regimens include 1 g oral azithromycin in a single dose or 500 mg oral levofloxacin once daily for 7 days. The switch to recommending doxycycline over azithromycin is based on recent evidence showing that doxycycline has a slightly higher efficacy for urogenital chlamydia and a substantially higher efficacy for rectal chlamydia. In addition, an increasing proportion of gonorrheal infections have shown resistance to azithromycin, particularly beginning in 2014.

Preferred treatment of new, uncomplicated gonorrhea infections of the cervix, urethra, rectum, and pharynx is one 500-mg dose of ceftriaxone for those weighing under 150 kg and 1 g for those weighing 150 kg or more. If ceftriaxone is unavailable, the new alternative recommended treatment for gonorrhea is 800 mg cefixime. For pharyngeal gonorrhea only, the CDC recommends a test-of-cure 7-14 days after treatment.

For gonorrheal infections, the CDC also recommends treatment with doxycycline if chlamydia has not been excluded, but the agency no longer recommends dual therapy with azithromycin unless it’s used in place of doxycycline for those who are pregnant, have an allergy, or may not be compliant with a 7-day doxycycline regimen.

The preferred treatment for bacterial vaginosis has not changed. The new recommended regimen for trichomoniasis is 500 mg oral metronidazole for 7 days, with the alternative being a single 2-g dose of tinidazole. Male partners should receive 2 g oral metronidazole. The CDC also notes that patients taking metronidazole no longer need to abstain from alcohol during treatment.

”Another area where the guidelines changed is in their description of expedited partner therapy, which means that, when we find an index case who has gonorrhea or chlamydia, we always have a discussion with her about getting her partners treated,” Dr. Policar said. “The CDC was quite clear that the responsibility for discussing partner treatment rests with us as the diagnosing provider” since city and county health departments don’t have the time or resources for contact tracing these STIs.

The two main ways to treat partners are to have the patient bring their partner(s) to the appointment with them or to do patient-delivered partner therapy. Ideally, clinicians who dispense their own medications can give the patient enough drugs to give her partner(s) a complete dose as well. Otherwise, providers can prescribe extra doses in the index patients’ name or write prescriptions in the partner’s name.

“In every state of the union now, it is legal for you to to prescribe antibiotics for partners sight unseen, Dr. Policar said.

Margaret Sullivan, MD, an ob.gyn. from rural western North Carolina, noted during the Q&A that an obstacle to partner therapy at her practice has been cost, particularly since many of the men don’t have insurance.

“I have not heard before of prescribing the extra doses for partners under the patient’s name,” Dr. Sullivan said. “I’ve thought about doing it, but [was worried about] it potentially being fraudulent if that patient has Medicaid and we’re prescribing extra doses under her name, so how do you work around that?”

Dr. Policar acknowledged that barrier and recommended that patients use the website/app Goodrx.com to find discounts for out-of-pocket generic medications. He also noted the occasional obstacle of pharmacists balking at filling a double or triple dose.

“What we’ve been suggesting in that circumstance is to literally copy that part of the CDC guidelines, which explains expedited partner therapy or patient-delivered partner therapy and send that off to the pharmacist so they can see that it’s a national recommendation of the CDC,” Dr. Policar said.

Claudia Rodriguez, MD, an ob.gyn. who works at Sherman Hospital in Elgin, Ill., asked about the CDC recommendations for HPV vaccination in older women. Although the CDC permits women over age 26 to receive the HPV vaccine, the agency does not “make a solid recommendation to have this done, which oftentimes makes a big difference in whether or not health insurance will actually pay for vaccination in that circumstance,” Dr. Policar said.

Patients are welcome to request the vaccine after shared decision-making, but “we should never present this as something which is routine,” he said. For women in their 50s, for example, “there’s virtually no data about any additional degree of protection that you would get” from HPV vaccination, Dr. Policar said in response to a similar question from Tara Allmen, MD, an ob.gyn. in New York City. “If you ask me for my personal clinical opinion about it, I would say it’s not going to be worth it,” he said.

Dr Policar had no disclosures. Disclosures were unavailable for attendees who spoke.

Sexually transmitted infection rates have not increased as dramatically in older women as they have in women in their teens and 20s, but rates of chlamydia and gonorrhea in women over age 35 have seen a steady incline over the past decade, and syphilis rates have climbed steeply, according to data from the Centers for Disease Control and Prevention.

That makes the STI treatment guidelines released by the CDC in July even timelier for practitioners of menopause medicine, according to Michael S. Policar, MD, MPH, a professor emeritus of ob.gyn. and reproductive sciences at the University of California, San Francisco.

Dr. Policar discussed what clinicians need to know about STIs in midlife women at the hybrid annual meeting of the North American Menopause Society. Even the nomenclature change in the guidelines from “sexually transmitted diseases” to “sexually transmitted infections” is important “because they want to acknowledge the fact that a lot of the sexually transmitted infections that we’re treating are asymptomatic, are colonizations, and are not yet diseases,” Dr. Policar said. “We’re trying to be much more expansive in thinking about finding these infections before they actually start causing morbidity in the form of a disease.”
 

Sexual history

The primary guidelines update for taking sexual history is the recommendation to ask patients about their intentions regarding pregnancy. The “5 Ps” of sexual history are now Partners, Practices, Protection from STIs, Past history of STIs, and Pregnancy intention.

“There should be a sixth P that has to do with pleasure questions,” Policar added. “We ask all the time for patients that we see in the context of perimenopausal and menopausal services, ‘Are you satisfied with your sexual relationship with your partner?’ Hopefully that will make it into the CDC guidelines as the sixth P at some point, but for now, that’s aspirational.”

In asking about partners, instead of asking patients whether they have sex with men, women, or both, clinicians should ask first if the patient is having sex of any kind – oral, vaginal, or anal – with anyone. From there, providers should ask how many sex partners the patient has had, the gender(s) of the partners, and whether they or their partners have other sex partners, using more gender-inclusive language.

When asking about practices, in addition to asking about the type of sexual contact patients have had, additional questions include whether the patient met their partners online or through apps, whether they or any of their partners use drugs, and whether the patient has exchanged sex for any needs, such as money, housing, or drugs. The additional questions can identify those at higher risk for STIs.

After reviewing the CDC’s list of risk factors for gonorrhea and chlamydia screening, Dr. Policar shared the screening list from the California Department of Public Health, which he finds more helpful:

• History of gonorrhea, chlamydia, or pelvic inflammatory disease (PID) in the past 2 years.
• More than 1 sexual partner in the past year.
• New sexual partner within 90 days.
• Reason to believe that a sex partner has had other partners in the past year.
• Exchanging sex for drugs or money within the past year.
• Other factors identified locally, including prevalence of infection in the community.

STI screening guidelines

For those with a positive gonorrhea/chlamydia (GC/CT) screen, a nucleic acid amplification test (NAAT) vaginal swab is the preferred specimen source, and self-collection is fine for women of any age, Dr. Policar said. In addition, cis-women who received anal intercourse in the preceding year should consider undergoing a rectal GC/CT NAAT, and those who performed oral sex should consider a pharyngeal GC/CT NAAT, based on shared clinical decision-making. A rectal swab requires an insertion of 3-4 cm and a 360-degree twirl of the wrist, not the swab, to ensure you get a sample from the entire circumference. Pharyngeal samples require swabbing both tonsillar pillars while taking care for those who may gag.

For contact testing – asymptomatic people who have had a high-risk sexual exposure – providers should test for gonorrhea, chlamydia, HIV, and syphilis but not for herpes, high-risk HPV, hepatitis B, hepatitis C, or bacterial vaginosis. “Maybe we’ll do a screen for trichomoniasis, and maybe we’ll offer herpes type 2 serology or antibody screening,” Dr. Policar said. Providers should also ask patients requesting contact testing if they have been vaccinated for hepatitis B. If not, “the conversation should be how can we get you vaccinated for hepatitis B,” Dr. Policar said.

HIV screening only needs to occur once between the ages of 15 and 65 for low-risk people and then once annually (or more often if necessary) for those who have a sex partner with HIV, use injectable drugs, engage in commercial sex work, have a new sex partner with unknown HIV status, received care at an STD or TB clinic, or were in a correctional facility or homeless shelter.

Those at increased risk for syphilis include men who have sex with men, men under age 29, and anyone living with HIV or who has a history of incarceration or a history of commercial sex work. In addition, African Americans have the greatest risk for syphilis of racial/ethnic groups, followed by Hispanics. Most adults only require hepatitis C screening with anti-hep C antibody testing once in their lifetime. Periodic hepatitis C screening should occur for people who inject drugs. If the screening is positive, providers should conduct an RNA polymerase chain reaction (PCR) test to determine whether a chronic infection is present.

Trichomoniasis screening should occur annually in women living with HIV or in correctional facilities. Others to consider screening include people with new or multiple sex partners, a history of STIs, inconsistent condom use, a history of sex work, and intravenous drug use. Dr. Policar also noted that several new assays, including NAAT, PCR, and a rapid test, are available for trichomoniasis.
 

STI treatment guidelines

For women with mucoprurulent cervicitis, the cause could be chlamydia, gonorrhea, herpes, trichomonas, mycoplasma, or even progesterone from pregnancy or contraception, Dr. Policar said. The new preferred treatment is 100 mg of doxycycline. The alternative, albeit less preferred, treatment is 1 g azithromycin.

The preferred treatment for chlamydia is now 100 mg oral doxycycline twice daily, or doxycycline 200 mg delayed-release once daily, for 7 days. Alternative regimens include 1 g oral azithromycin in a single dose or 500 mg oral levofloxacin once daily for 7 days. The switch to recommending doxycycline over azithromycin is based on recent evidence showing that doxycycline has a slightly higher efficacy for urogenital chlamydia and a substantially higher efficacy for rectal chlamydia. In addition, an increasing proportion of gonorrheal infections have shown resistance to azithromycin, particularly beginning in 2014.

Preferred treatment of new, uncomplicated gonorrhea infections of the cervix, urethra, rectum, and pharynx is one 500-mg dose of ceftriaxone for those weighing under 150 kg and 1 g for those weighing 150 kg or more. If ceftriaxone is unavailable, the new alternative recommended treatment for gonorrhea is 800 mg cefixime. For pharyngeal gonorrhea only, the CDC recommends a test-of-cure 7-14 days after treatment.

For gonorrheal infections, the CDC also recommends treatment with doxycycline if chlamydia has not been excluded, but the agency no longer recommends dual therapy with azithromycin unless it’s used in place of doxycycline for those who are pregnant, have an allergy, or may not be compliant with a 7-day doxycycline regimen.

The preferred treatment for bacterial vaginosis has not changed. The new recommended regimen for trichomoniasis is 500 mg oral metronidazole for 7 days, with the alternative being a single 2-g dose of tinidazole. Male partners should receive 2 g oral metronidazole. The CDC also notes that patients taking metronidazole no longer need to abstain from alcohol during treatment.

”Another area where the guidelines changed is in their description of expedited partner therapy, which means that, when we find an index case who has gonorrhea or chlamydia, we always have a discussion with her about getting her partners treated,” Dr. Policar said. “The CDC was quite clear that the responsibility for discussing partner treatment rests with us as the diagnosing provider” since city and county health departments don’t have the time or resources for contact tracing these STIs.

The two main ways to treat partners are to have the patient bring their partner(s) to the appointment with them or to do patient-delivered partner therapy. Ideally, clinicians who dispense their own medications can give the patient enough drugs to give her partner(s) a complete dose as well. Otherwise, providers can prescribe extra doses in the index patients’ name or write prescriptions in the partner’s name.

“In every state of the union now, it is legal for you to to prescribe antibiotics for partners sight unseen, Dr. Policar said.

Margaret Sullivan, MD, an ob.gyn. from rural western North Carolina, noted during the Q&A that an obstacle to partner therapy at her practice has been cost, particularly since many of the men don’t have insurance.

“I have not heard before of prescribing the extra doses for partners under the patient’s name,” Dr. Sullivan said. “I’ve thought about doing it, but [was worried about] it potentially being fraudulent if that patient has Medicaid and we’re prescribing extra doses under her name, so how do you work around that?”

Dr. Policar acknowledged that barrier and recommended that patients use the website/app Goodrx.com to find discounts for out-of-pocket generic medications. He also noted the occasional obstacle of pharmacists balking at filling a double or triple dose.

“What we’ve been suggesting in that circumstance is to literally copy that part of the CDC guidelines, which explains expedited partner therapy or patient-delivered partner therapy and send that off to the pharmacist so they can see that it’s a national recommendation of the CDC,” Dr. Policar said.

Claudia Rodriguez, MD, an ob.gyn. who works at Sherman Hospital in Elgin, Ill., asked about the CDC recommendations for HPV vaccination in older women. Although the CDC permits women over age 26 to receive the HPV vaccine, the agency does not “make a solid recommendation to have this done, which oftentimes makes a big difference in whether or not health insurance will actually pay for vaccination in that circumstance,” Dr. Policar said.

Patients are welcome to request the vaccine after shared decision-making, but “we should never present this as something which is routine,” he said. For women in their 50s, for example, “there’s virtually no data about any additional degree of protection that you would get” from HPV vaccination, Dr. Policar said in response to a similar question from Tara Allmen, MD, an ob.gyn. in New York City. “If you ask me for my personal clinical opinion about it, I would say it’s not going to be worth it,” he said.

Dr Policar had no disclosures. Disclosures were unavailable for attendees who spoke.

Remarkable advances in care for early pregnancy loss (EPL) have occurred over the past several years. Misoprostol with mifepristone pretreatment is now the gold standard for medical management after recent research showed that this regimen improves both the efficacy and cost-effectiveness of medical management.¹ Manual vacuum aspiration (MVA)’s portability, effectiveness, and safety ensure that providers can offer procedural EPL management in almost any clinical setting. Medication management and in-office uterine aspiration are two evidence-based options for EPL management that may increase access for the 25% of pregnant women who experience EPL. Unfortunately, many women do not have access to either option. Equitable access to early pregnancy loss management can be achieved by expanding access to mifepristone and office-based MVA.

However, access to mifepristone and initiating office-based MVA is challenging. Mifepristone is one of several medications regulated under the Food and Drug Administration’s Risk Evaluation and Management Strategies (REMS) program.²

The REMS guidelines restrict clinicians in prescribing and dispensing mifepristone, including the key provision that mifepristone may be dispensed only in clinics, medical offices, and hospitals. Clinicians cannot write a prescription for mifepristone for a patient to pick up at the pharmacy. Efforts are underway to roll back the REMS. Barriers to office-based MVA include time, culture shift among staff, gathering equipment, and creating protocols. Clinicians can improve access to EPL management in a variety of ways:

• MVA training: Ob.gyns. who lack training in MVA use can take advantage of several programs designed to teach the skill to clinicians, including programs such as Training, Education, and Advocacy in Miscarriage Management (TEAMM).^3,4 MVA is easy to learn for ob.gyns. and procedural complications are uncommon. In the office setting, complications requiring transfer to a higher level of care are rare.⁵ With adequate training, whether during residency or afterward, ob.gyns. can learn to safely and effectively use MVA for procedural EPL management in the office and in the emergency department.
• Partnerships with pharmacists to reduce barriers to mifepristone: Ob.gyns. working in a variety of clinical settings, including independent clinics, critical access hospitals, community hospitals, and academic medical centers, have worked closely with on-site pharmacists to place mifepristone on their practice sites’ formularies.⁶ These ob.gyn.–pharmacist collaborations often require explanations to institutional Pharmacy and Therapeutics (P&T) committees of the benefits of mifepristone to patients, detailed indications for mifepristone’s use, and methods to secure mifepristone on site.
• Partnerships with emergency department and outpatient nursing and administration to promote MVA: Provision of MVA is ideal for safe, effective, and cost-efficient procedural EPL management in both the emergency department and outpatient setting. However, access to MVA in emergency rooms and outpatient clinical settings is suboptimal. Some clinicians push back against MVA use in the emergency department, citing fears that performing the procedure in the emergency department unnecessarily uses staff and resources reserved for patients with more critical illnesses. Ob.gyns. should also work with emergency medicine physicians and emergency department nursing staff and hospital administrators in explaining that MVA in the emergency room is patient centered and cost effective.

Interdisciplinary collaboration and training are two strategies that can increase access to mifepristone and MVA for EPL management. Use of mifepristone/misoprostol and office/emergency department MVA for treatment of EPL is patient centered, evidence based, feasible, highly effective, and timely. These two health care interventions are practical in almost any setting, including rural and other low-resource settings. By using these strategies to overcome the logistical and institutional challenges, ob.gyns. can help countless women with EPL gain access to the best EPL care.
 

Dr. Espey is chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque. Dr. Jackson is an obstetrician/gynecologist at Michigan State University in Flint. They have no disclosures to report.

References

1. Schreiber CA et al. N Engl J Med. 2018 Jun 7;378(23):2161-70.

2. Food and Drug Administration. Mifeprex (mifepristone) information.

3. The TEAMM (Training, Education, and Advocacy in Miscarriage Management) Project. Training interprofessional teams to manage miscarriage. Accessed March 15, 2021.

4. Quinley KE et al. Ann Emerg Med. 2019 Jul;72(1):86-92.

5. Milingos DS et al. BJOG. 2009 Aug;116(9):1268-71.

6. Calloway D et al. Contraception. 2021 Jul;104(1):24-8.

Remarkable advances in care for early pregnancy loss (EPL) have occurred over the past several years. Misoprostol with mifepristone pretreatment is now the gold standard for medical management after recent research showed that this regimen improves both the efficacy and cost-effectiveness of medical management.¹ Manual vacuum aspiration (MVA)’s portability, effectiveness, and safety ensure that providers can offer procedural EPL management in almost any clinical setting. Medication management and in-office uterine aspiration are two evidence-based options for EPL management that may increase access for the 25% of pregnant women who experience EPL. Unfortunately, many women do not have access to either option. Equitable access to early pregnancy loss management can be achieved by expanding access to mifepristone and office-based MVA.

However, access to mifepristone and initiating office-based MVA is challenging. Mifepristone is one of several medications regulated under the Food and Drug Administration’s Risk Evaluation and Management Strategies (REMS) program.²

The REMS guidelines restrict clinicians in prescribing and dispensing mifepristone, including the key provision that mifepristone may be dispensed only in clinics, medical offices, and hospitals. Clinicians cannot write a prescription for mifepristone for a patient to pick up at the pharmacy. Efforts are underway to roll back the REMS. Barriers to office-based MVA include time, culture shift among staff, gathering equipment, and creating protocols. Clinicians can improve access to EPL management in a variety of ways:

• MVA training: Ob.gyns. who lack training in MVA use can take advantage of several programs designed to teach the skill to clinicians, including programs such as Training, Education, and Advocacy in Miscarriage Management (TEAMM).^3,4 MVA is easy to learn for ob.gyns. and procedural complications are uncommon. In the office setting, complications requiring transfer to a higher level of care are rare.⁵ With adequate training, whether during residency or afterward, ob.gyns. can learn to safely and effectively use MVA for procedural EPL management in the office and in the emergency department.
• Partnerships with pharmacists to reduce barriers to mifepristone: Ob.gyns. working in a variety of clinical settings, including independent clinics, critical access hospitals, community hospitals, and academic medical centers, have worked closely with on-site pharmacists to place mifepristone on their practice sites’ formularies.⁶ These ob.gyn.–pharmacist collaborations often require explanations to institutional Pharmacy and Therapeutics (P&T) committees of the benefits of mifepristone to patients, detailed indications for mifepristone’s use, and methods to secure mifepristone on site.
• Partnerships with emergency department and outpatient nursing and administration to promote MVA: Provision of MVA is ideal for safe, effective, and cost-efficient procedural EPL management in both the emergency department and outpatient setting. However, access to MVA in emergency rooms and outpatient clinical settings is suboptimal. Some clinicians push back against MVA use in the emergency department, citing fears that performing the procedure in the emergency department unnecessarily uses staff and resources reserved for patients with more critical illnesses. Ob.gyns. should also work with emergency medicine physicians and emergency department nursing staff and hospital administrators in explaining that MVA in the emergency room is patient centered and cost effective.

Interdisciplinary collaboration and training are two strategies that can increase access to mifepristone and MVA for EPL management. Use of mifepristone/misoprostol and office/emergency department MVA for treatment of EPL is patient centered, evidence based, feasible, highly effective, and timely. These two health care interventions are practical in almost any setting, including rural and other low-resource settings. By using these strategies to overcome the logistical and institutional challenges, ob.gyns. can help countless women with EPL gain access to the best EPL care.
 

Dr. Espey is chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque. Dr. Jackson is an obstetrician/gynecologist at Michigan State University in Flint. They have no disclosures to report.

References

1. Schreiber CA et al. N Engl J Med. 2018 Jun 7;378(23):2161-70.

2. Food and Drug Administration. Mifeprex (mifepristone) information.

3. The TEAMM (Training, Education, and Advocacy in Miscarriage Management) Project. Training interprofessional teams to manage miscarriage. Accessed March 15, 2021.

4. Quinley KE et al. Ann Emerg Med. 2019 Jul;72(1):86-92.

5. Milingos DS et al. BJOG. 2009 Aug;116(9):1268-71.

6. Calloway D et al. Contraception. 2021 Jul;104(1):24-8.

Remarkable advances in care for early pregnancy loss (EPL) have occurred over the past several years. Misoprostol with mifepristone pretreatment is now the gold standard for medical management after recent research showed that this regimen improves both the efficacy and cost-effectiveness of medical management.¹ Manual vacuum aspiration (MVA)’s portability, effectiveness, and safety ensure that providers can offer procedural EPL management in almost any clinical setting. Medication management and in-office uterine aspiration are two evidence-based options for EPL management that may increase access for the 25% of pregnant women who experience EPL. Unfortunately, many women do not have access to either option. Equitable access to early pregnancy loss management can be achieved by expanding access to mifepristone and office-based MVA.

However, access to mifepristone and initiating office-based MVA is challenging. Mifepristone is one of several medications regulated under the Food and Drug Administration’s Risk Evaluation and Management Strategies (REMS) program.²

The REMS guidelines restrict clinicians in prescribing and dispensing mifepristone, including the key provision that mifepristone may be dispensed only in clinics, medical offices, and hospitals. Clinicians cannot write a prescription for mifepristone for a patient to pick up at the pharmacy. Efforts are underway to roll back the REMS. Barriers to office-based MVA include time, culture shift among staff, gathering equipment, and creating protocols. Clinicians can improve access to EPL management in a variety of ways:

• MVA training: Ob.gyns. who lack training in MVA use can take advantage of several programs designed to teach the skill to clinicians, including programs such as Training, Education, and Advocacy in Miscarriage Management (TEAMM).^3,4 MVA is easy to learn for ob.gyns. and procedural complications are uncommon. In the office setting, complications requiring transfer to a higher level of care are rare.⁵ With adequate training, whether during residency or afterward, ob.gyns. can learn to safely and effectively use MVA for procedural EPL management in the office and in the emergency department.
• Partnerships with pharmacists to reduce barriers to mifepristone: Ob.gyns. working in a variety of clinical settings, including independent clinics, critical access hospitals, community hospitals, and academic medical centers, have worked closely with on-site pharmacists to place mifepristone on their practice sites’ formularies.⁶ These ob.gyn.–pharmacist collaborations often require explanations to institutional Pharmacy and Therapeutics (P&T) committees of the benefits of mifepristone to patients, detailed indications for mifepristone’s use, and methods to secure mifepristone on site.
• Partnerships with emergency department and outpatient nursing and administration to promote MVA: Provision of MVA is ideal for safe, effective, and cost-efficient procedural EPL management in both the emergency department and outpatient setting. However, access to MVA in emergency rooms and outpatient clinical settings is suboptimal. Some clinicians push back against MVA use in the emergency department, citing fears that performing the procedure in the emergency department unnecessarily uses staff and resources reserved for patients with more critical illnesses. Ob.gyns. should also work with emergency medicine physicians and emergency department nursing staff and hospital administrators in explaining that MVA in the emergency room is patient centered and cost effective.

Interdisciplinary collaboration and training are two strategies that can increase access to mifepristone and MVA for EPL management. Use of mifepristone/misoprostol and office/emergency department MVA for treatment of EPL is patient centered, evidence based, feasible, highly effective, and timely. These two health care interventions are practical in almost any setting, including rural and other low-resource settings. By using these strategies to overcome the logistical and institutional challenges, ob.gyns. can help countless women with EPL gain access to the best EPL care.
 

Dr. Espey is chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque. Dr. Jackson is an obstetrician/gynecologist at Michigan State University in Flint. They have no disclosures to report.

References

1. Schreiber CA et al. N Engl J Med. 2018 Jun 7;378(23):2161-70.

2. Food and Drug Administration. Mifeprex (mifepristone) information.

3. The TEAMM (Training, Education, and Advocacy in Miscarriage Management) Project. Training interprofessional teams to manage miscarriage. Accessed March 15, 2021.

4. Quinley KE et al. Ann Emerg Med. 2019 Jul;72(1):86-92.

5. Milingos DS et al. BJOG. 2009 Aug;116(9):1268-71.

6. Calloway D et al. Contraception. 2021 Jul;104(1):24-8.

Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.

In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms. 

WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.

“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.

The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
 

Beyond the usual suspects

As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.

More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).

In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).

The associations persisted after adjusting for depressive or post-traumatic stress symptoms.

“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.

“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
 

‘Burgeoning’ literature

Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”

“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.

“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted. 

The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.

In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms. 

WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.

“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.

The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
 

Beyond the usual suspects

As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.

More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).

In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).

The associations persisted after adjusting for depressive or post-traumatic stress symptoms.

“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.

“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
 

‘Burgeoning’ literature

Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”

“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.

“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted. 

The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.

In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms. 

WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.

“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.

The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
 

Beyond the usual suspects

As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.

More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).

In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).

The associations persisted after adjusting for depressive or post-traumatic stress symptoms.

“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.

“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
 

‘Burgeoning’ literature

Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”

“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.

“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted. 

The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Preventive Services Task Force (USPSTF) announced on Tuesday that it is standing by its 2014 recommendations that sexually active girls and young women be screened for chlamydia and gonorrhea. But the panel is not ready to provide guidance about screening males even amid an outbreak of gonorrhea infections among men who have sex with men (MSM).

“For men in general, there’s not enough evidence to determine whether screening will reduce the risk of complications or spreading infections to others,” said Marti Kubik, PhD, RN, in an interview. Dr. Kubik is a professor at the George Mason University School of Nursing, Fairfax, Va., and is a member of the task force. “We need further research so we will know how to make those recommendations,” she said.

The screening recommendations for chlamydia and gonorrhea were published Sept. 14 in the Journal of the American Medical Association. The guidance is identical to the panel’s 2014 recommendations. The task force recommends screening for chlamydia and gonorrhea in all sexually active females aged 24 years or younger and in sexually active women aged 25 and older if they are at higher risk because of factors such as new or multiple sex partners.

“We continue to see rising rates of these infections in spite of consistent screening recommendations,” Dr. Kubik said. “In 2019, the CDC recorded nearly 2 million cases of chlamydia and a half million cases of gonorrhea. The big clincher is that chlamydia and gonorrhea can occur without symptoms. It’s critical to screen if we’re going to prevent serious health complications.”

The report notes that chlamydia and gonorrhea may lead to pelvic inflammatory disease in women and to multiple complications in infants born to infected mothers. Men can develop urethritis and epididymitis. Both diseases can boost the risk for HIV infection and transmission.

“We want clinicians to review the new recommendation and feel confident about the evidence base that supports a need for us to be screening young women and older women who are at increased risk,” Dr. Kubik said. She noted that almost two-thirds of chlamydia cases and more than half of gonorrhea cases occur in men and women aged 15-24.

Unlike the CDC, which recommends annual chlamydia and gonorrhea screening in appropriate female patients, the task force provides no guidance on screening frequency. “We didn’t have the evidence base to make a recommendation about how often to screen,” Dr. Kubik said. “But recognizing that these often occur without symptoms, it’s reasonable for clinicians to screen patients whose sexual history reveals new or consistent risk factors.”

Philip A. Chan, MD, an associate professor at Brown University, Providence, R.I., who directs a sexually transmitted disease clinic, told this news organization that he found it frustrating that the task force didn’t make recommendations about screening of MSM. According to a commentary accompanying the new recommendations, the rate of gonorrhea in MSM – 5,166 cases per 100,000, or more than 5% – is at a historic high.

In contrast to the task force, the CDC recommends annual or more frequent testing for gonorrhea and chlamydia plus HIV and syphilis in sexually active MSM.

Dr. Chan noted that the task force’s guidance “tends to be the most evidence-based recommendations that exist. If the evidence isn’t there, they usually don’t make a recommendation.” Still, he said, “I would argue that there’s good evidence that in MSM, the risk for HIV acquisition warrants routine screening.”

Jeanne Marrazzo, MD, MPH, director of the division of infectious diseases at the University of Alabama at Birmingham, also noted the limits of the task force’s insistence on certain kinds of evidence. Dr. Marrazzo, who coauthored a commentary that accompanies the recommendations, said in an interview that the panel’s “reliance on randomized-controlled-trial-level evidence tends to limit its ability to evolve their recommendations in a way that could account for evolving epidemiology or advances in our understanding of pathophysiology of these infections.”

Dr. Chan noted that obstacles exist for patients even when screening recommendations are in place. Although insurers typically cover costs of chlamydia and gonorrhea screening tests, he said, the uninsured may have to pay $100 or more each.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Kubik, Dr. Chan, and Dr. Marrazzo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Preventive Services Task Force (USPSTF) announced on Tuesday that it is standing by its 2014 recommendations that sexually active girls and young women be screened for chlamydia and gonorrhea. But the panel is not ready to provide guidance about screening males even amid an outbreak of gonorrhea infections among men who have sex with men (MSM).

“For men in general, there’s not enough evidence to determine whether screening will reduce the risk of complications or spreading infections to others,” said Marti Kubik, PhD, RN, in an interview. Dr. Kubik is a professor at the George Mason University School of Nursing, Fairfax, Va., and is a member of the task force. “We need further research so we will know how to make those recommendations,” she said.

The screening recommendations for chlamydia and gonorrhea were published Sept. 14 in the Journal of the American Medical Association. The guidance is identical to the panel’s 2014 recommendations. The task force recommends screening for chlamydia and gonorrhea in all sexually active females aged 24 years or younger and in sexually active women aged 25 and older if they are at higher risk because of factors such as new or multiple sex partners.

“We continue to see rising rates of these infections in spite of consistent screening recommendations,” Dr. Kubik said. “In 2019, the CDC recorded nearly 2 million cases of chlamydia and a half million cases of gonorrhea. The big clincher is that chlamydia and gonorrhea can occur without symptoms. It’s critical to screen if we’re going to prevent serious health complications.”

The report notes that chlamydia and gonorrhea may lead to pelvic inflammatory disease in women and to multiple complications in infants born to infected mothers. Men can develop urethritis and epididymitis. Both diseases can boost the risk for HIV infection and transmission.

“We want clinicians to review the new recommendation and feel confident about the evidence base that supports a need for us to be screening young women and older women who are at increased risk,” Dr. Kubik said. She noted that almost two-thirds of chlamydia cases and more than half of gonorrhea cases occur in men and women aged 15-24.

Unlike the CDC, which recommends annual chlamydia and gonorrhea screening in appropriate female patients, the task force provides no guidance on screening frequency. “We didn’t have the evidence base to make a recommendation about how often to screen,” Dr. Kubik said. “But recognizing that these often occur without symptoms, it’s reasonable for clinicians to screen patients whose sexual history reveals new or consistent risk factors.”

Philip A. Chan, MD, an associate professor at Brown University, Providence, R.I., who directs a sexually transmitted disease clinic, told this news organization that he found it frustrating that the task force didn’t make recommendations about screening of MSM. According to a commentary accompanying the new recommendations, the rate of gonorrhea in MSM – 5,166 cases per 100,000, or more than 5% – is at a historic high.

In contrast to the task force, the CDC recommends annual or more frequent testing for gonorrhea and chlamydia plus HIV and syphilis in sexually active MSM.

Dr. Chan noted that the task force’s guidance “tends to be the most evidence-based recommendations that exist. If the evidence isn’t there, they usually don’t make a recommendation.” Still, he said, “I would argue that there’s good evidence that in MSM, the risk for HIV acquisition warrants routine screening.”

Jeanne Marrazzo, MD, MPH, director of the division of infectious diseases at the University of Alabama at Birmingham, also noted the limits of the task force’s insistence on certain kinds of evidence. Dr. Marrazzo, who coauthored a commentary that accompanies the recommendations, said in an interview that the panel’s “reliance on randomized-controlled-trial-level evidence tends to limit its ability to evolve their recommendations in a way that could account for evolving epidemiology or advances in our understanding of pathophysiology of these infections.”

Dr. Chan noted that obstacles exist for patients even when screening recommendations are in place. Although insurers typically cover costs of chlamydia and gonorrhea screening tests, he said, the uninsured may have to pay $100 or more each.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Kubik, Dr. Chan, and Dr. Marrazzo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Preventive Services Task Force (USPSTF) announced on Tuesday that it is standing by its 2014 recommendations that sexually active girls and young women be screened for chlamydia and gonorrhea. But the panel is not ready to provide guidance about screening males even amid an outbreak of gonorrhea infections among men who have sex with men (MSM).

“For men in general, there’s not enough evidence to determine whether screening will reduce the risk of complications or spreading infections to others,” said Marti Kubik, PhD, RN, in an interview. Dr. Kubik is a professor at the George Mason University School of Nursing, Fairfax, Va., and is a member of the task force. “We need further research so we will know how to make those recommendations,” she said.

The screening recommendations for chlamydia and gonorrhea were published Sept. 14 in the Journal of the American Medical Association. The guidance is identical to the panel’s 2014 recommendations. The task force recommends screening for chlamydia and gonorrhea in all sexually active females aged 24 years or younger and in sexually active women aged 25 and older if they are at higher risk because of factors such as new or multiple sex partners.

“We continue to see rising rates of these infections in spite of consistent screening recommendations,” Dr. Kubik said. “In 2019, the CDC recorded nearly 2 million cases of chlamydia and a half million cases of gonorrhea. The big clincher is that chlamydia and gonorrhea can occur without symptoms. It’s critical to screen if we’re going to prevent serious health complications.”

The report notes that chlamydia and gonorrhea may lead to pelvic inflammatory disease in women and to multiple complications in infants born to infected mothers. Men can develop urethritis and epididymitis. Both diseases can boost the risk for HIV infection and transmission.

“We want clinicians to review the new recommendation and feel confident about the evidence base that supports a need for us to be screening young women and older women who are at increased risk,” Dr. Kubik said. She noted that almost two-thirds of chlamydia cases and more than half of gonorrhea cases occur in men and women aged 15-24.

Unlike the CDC, which recommends annual chlamydia and gonorrhea screening in appropriate female patients, the task force provides no guidance on screening frequency. “We didn’t have the evidence base to make a recommendation about how often to screen,” Dr. Kubik said. “But recognizing that these often occur without symptoms, it’s reasonable for clinicians to screen patients whose sexual history reveals new or consistent risk factors.”

Philip A. Chan, MD, an associate professor at Brown University, Providence, R.I., who directs a sexually transmitted disease clinic, told this news organization that he found it frustrating that the task force didn’t make recommendations about screening of MSM. According to a commentary accompanying the new recommendations, the rate of gonorrhea in MSM – 5,166 cases per 100,000, or more than 5% – is at a historic high.

In contrast to the task force, the CDC recommends annual or more frequent testing for gonorrhea and chlamydia plus HIV and syphilis in sexually active MSM.

Dr. Chan noted that the task force’s guidance “tends to be the most evidence-based recommendations that exist. If the evidence isn’t there, they usually don’t make a recommendation.” Still, he said, “I would argue that there’s good evidence that in MSM, the risk for HIV acquisition warrants routine screening.”

Jeanne Marrazzo, MD, MPH, director of the division of infectious diseases at the University of Alabama at Birmingham, also noted the limits of the task force’s insistence on certain kinds of evidence. Dr. Marrazzo, who coauthored a commentary that accompanies the recommendations, said in an interview that the panel’s “reliance on randomized-controlled-trial-level evidence tends to limit its ability to evolve their recommendations in a way that could account for evolving epidemiology or advances in our understanding of pathophysiology of these infections.”

Dr. Chan noted that obstacles exist for patients even when screening recommendations are in place. Although insurers typically cover costs of chlamydia and gonorrhea screening tests, he said, the uninsured may have to pay $100 or more each.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Kubik, Dr. Chan, and Dr. Marrazzo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.

Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.

As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.

With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.

In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.

The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.

The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).

While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.

Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).

Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.

“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.

In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”

They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.

“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.

In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.

“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”

In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.

“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.

This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
 

The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.

Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.

As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.

With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.

In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.

The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.

The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).

While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.

Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).

Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.

“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.

In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”

They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.

“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.

In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.

“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”

In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.

“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.

This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
 

The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.

Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.

As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.

With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.

In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.

The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.

The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).

While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.

Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).

Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.

“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.

In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”

They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.

“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.

In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.

“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”

In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.

“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.

This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
 

As more and more gynecologic therapies move to the outpatient setting, keeping up on the latest data regarding emerging options can be challenging. Furthermore, it can be difficult to justify purchasing expensive equipment for the office when a therapy is not covered by medical insurance plans. However, if a therapy is efficacious and patients are willing to pay out of pocket, clinicians may want to have these options available for their patients.

In an effort to work through these complex issues, a panel of experts was convened at the 47th Annual Scientific Meeting of the Society of Gynecologic Surgeons in Palm Springs, California, on June 29, 2021. This article includes the salient points from that panel discussion.

Fractionated CO2 laser therapy

Fractionated CO2 laser therapy is considered second-line therapy for the treatment of genitourinary syndrome of menopause (GSM). In 2018, the US Food and Drug Administration (FDA) issued a safety warning about the use of CO2 laser therapy and warned patients and clinicians that the FDA had not approved the treatment for vaginal rejuvenation or treatment of vaginal symptoms related to menopause, urinary incontinence, or sexual function. Despite this warning, laser treatments are still performed in many practices.

In 2019, the International Continence Society (ICS) and the International Society for the Study of Vulvovaginal Disease (ISSVD) put out a joint practice consensus statement that essentially did not recommend the routine use of laser treatment for GSM, urinary incontinence, or lichen sclerosus.¹ Conversely, the 2020 American Urogynecologic Society (AUGS) published a clinical consensus statement that spoke to the promising results of laser therapy for the treatment of vulvovaginal atrophy, vaginal dryness, and menopausal dyspareunia, with benefits lasting up to 1 year.² This statement also suggested that the short-term safety profile of the CO2 laser device was favorable.

How CO2 lasers work

Fractionated CO2 laser therapy differs from unfractionated treatment (which often is used in the treatment of condyloma) in that it is not ablative. The laser works by using fractionated beams of light to penetrate the affected tissue to create small wounds in the epithelium and underlying lamina propria, which leads to collagen remodeling and regeneration that then results in the restoration of the superficial epithelium, vaginal rugae, and lubrication.³ Most clinicians perform 3 applications of the laser treatment 6 weeks apart, a recommendation that is based on manufacturer-sponsored studies in menopausal women.

Study results of patient outcomes with laser therapy

GSM. Several retrospective^4,5 and prospective studies^6-10 have looked at short- and longer-term outcomes in patients undergoing treatment with the CO2 laser. All of these studies showed improvement in patient symptoms related to GSM.

The VeLVET trial, conducted by Paraiso and colleagues, was a randomized trial that compared CO2 laser treatment with vaginal estrogen in women with GSM.¹¹ While the study was underpowered due to cessation of enrollment once the FDA safety warning was issued, the authors reported that at 6 months, both the fractionated CO2 laser therapy group and the vaginal estrogen group had similar improvements, with 70% to 80% of participants reporting satisfaction with treatment. The authors concluded that laser therapy is likely to be as efficacious as vaginal estrogen and may be a good option for patients who cannot use vaginal estrogen to treat GSM.¹¹

Lichen sclerosus. Some data exist on the efficacy of laser therapy for the treatment of lichen sclerosus. One recently published randomized trial showed that at 6 months, fractionated CO2 laser treatment and prior treatment with high potency topical corticosteroids was associated with higher improvement in subjective symptoms and objective measures compared with clobetasol propionate treatment.¹² Another trial, however, revealed that laser treatment was not an effective monotherapy treatment for lichen sclerosus when compared with placebo.¹³ Fewer studies have examined the effect of laser therapy on urinary incontinence.

More prospective data are emerging, evidenced by trials currently registered in ClinicalTrials.gov. While some studies provide evidence that laser therapy may be efficacious in the treatment of vulvovaginal atrophy, additional data are needed to confirm the favorable outcomes observed with laser therapy for the treatment of lichen sclerosus, and a significant amount of data are needed to evaluate the efficacy of laser treatment for urinary incontinence.

Until such evidence is available, fractionated CO2 vaginal laser therapy will remain a fee-for-service treatment option and will be inaccessible to patients who cannot afford the cost of treatment.

Continue to: Hydrogel urethral bulking...

Urethral bulking agents have been used for 5 decades in the treatment of stress urinary incontinence (SUI) in women. Unlike midurethral slings, in which many medical device companies use the same implant material (microporous, monofilament polypropylene mesh), the material for bulking agents has varied greatly. A 2017 Cochrane review of urethral bulking listed these agents used for this indication: autologous fat, carbon beads, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, glutaraldehyde cross-linked bovine collagen, hyaluronic acid with dextranomer, porcine dermal implant, polytetrafluoroethylene, and silicone particles.¹⁴ These agents can be injected through a transurethral or periurethral technique. The review failed to find superiority of one material or injection technique over another.

New bulking agent available

In January 2020, the FDA approved the premarket application for a new bulking agent. This new agent is a permanently implanted, nonresorbable hydrogel that consists of cross-linked polyacrylamide (2.5%) and water (97.5%). It is intended to be used with a transurethral bulking system that includes a rotatable sheath and two 23-guage needles; a total of 1.5 to 2.0 mL of the hydrogel is injected in 3 locations in the proximal urethra per session. Patients may undergo an additional 2 sessions, if needed, at least 4 weeks after the previous session.

Polyacrylamide hydrogel has been used as a bulking agent in cosmetic and ophthalmic surgery for many years, and it was first approved for medical use in Europe in 2001. The initial European data on its use as a urethral bulking agent was published in 2006.¹⁵ The first North American data came in 2014 from a multicenter, randomized trial that compared polyacrylamide hydrogel with collagen gel.¹⁶ This investigation followed 345 women for 12 months and concluded that the safety and efficacy of polyacrylamide hydrogel was not inferior to collagen, with a little over half of both cohorts demonstrating a 50% or greater decrease in incontinence episodes.

Since these initial studies, 3-year¹⁷ and 7-year safety and efficacy data¹⁸ have been reported, with reassuring findings, but both studies experienced significant attrition of the original group of patients. The most commonly reported adverse events associated with the procedure are pain at the injection site (4%–14%) and urinary tract infection (3%–7%); transient urinary retention rates range in incidence from 1.5% to 15%.¹⁹

Short procedure, long-term results

Given that a urethral bulking procedure can be done in less than 10 minutes in the office under local analgesia, this treatment may lend itself to use in more brittle patient populations. One study of women aged 80 or older showed a greater than 50% decrease in the number of daily pads used for up to 2 years after initial injection.²⁰ Another study found the greatest treatment success in women aged 60 years or older with fewer than 2.5 episodes of SUI per day.²¹

Platelet-rich plasma therapy

Platelet-rich plasma (PRP) therapy has been used in multiple disciplines for more than 2 decades as a treatment to regenerate damaged tissue, particularly in sports medicine for treating tendonitis as well as in plastic surgery, gynecology, urology, and ophthalmology, and good outcomes have been demonstrated with no serious adverse effects. PRP is a natural product in which high levels of platelets are concentrated through centrifugation with bioactive growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin growth factor (IGF).²² The activated platelets are then injected autologously back into the patient’s tissue. This process releases activated growth factors that accelerate tissue healing by stimulating the number of reparative cells to create collagen production, angiogenesis, and neurogenesis while fighting infection and downregulating the autoimmune system.

Continue to: Uses for PRP in gynecology...

In gynecology, dating back to 2007 PRP was shown to facilitate wound healing, when Fanning and colleagues reported PRP applications in gynecologic operative wounds, such as hysterectomies and urogynecologic procedures, to reduce postoperative pain.²³ In the last decade, there has been a dramatic increasing trend in the application of PRP injections as an alternative therapy in gynecology to improve intimate health. PRP has been used to treat lichen sclerosus, atrophic vaginitis, SUI, and female sexual dysfunction; however, there is a dearth of studies that compare PRP with traditional therapies.

Runels and colleagues described the effects of localized injections of autologous PRP for the treatment of sexual dysfunction early in 2014.²⁴ Those authors pioneered PRP use in women with dyspareunia and other symptoms related to sexual dysfunction. Women were offered PRP injections into the periurethral area of the Skene glands and the clitoris. Sexual satisfaction and pain were improved but results did not reach statistical significance. The results of this pilot study of 11 patients suggested that PRP injections could perhaps be an effective method to treat certain types of female sexual dysfunction, including desire, arousal, lubrication, and orgasm.

In another pilot study, Long and colleagues looked at the effectiveness of local injection of PRP for treating women with SUI.²⁵ In that study, younger patients with mild severity of SUI had promising results, with up to 75% cured or improved. Results in the older group, with 50% cured or improved, did not reach statistical significance. Other small, limited studies have been conducted under the hypothesis that PRP as an “O-shot” may be a promising treatment that is a safe, effective, nonsurgical, and nonhormonal option for women with dyspareunia from lack of lubrication and related sexual dysfunction, such as decreased libido or arousal.^26-29 A pilot study by Behnia-Willison and colleagues demonstrated clinical improvement in PRP use as an alternative to topical steroids for lichen sclerosus.³⁰ Several other studies also have shown efficacy for the treatment of lichen sclerosus.^31-34

More evidence of efficacy needed

To date, preliminary studies suggest that PRP holds promise for a host of gynecologic conditions. Since PRP is autologous, there are no significant contraindications, and thus far there have been no known serious adverse effects. However, most health insurers still do not cover this therapy, so for now patients must pay out-of-pocket fees for these treatments.

As we continue to investigate therapies in regenerative medicine, the continued efforts of our discipline are required to conduct well-designed prospective, randomized controlled studies. While initial series suggest that PRP is safe, it is unlikely that this therapy will be embraced widely in the paradigm as an alternative treatment option for many genitourinary symptoms of menopause and vulvar disorders until efficacy is better established.

Radiofrequency therapy

For the past 20 years, radiofrequency (RF) energy has been used through the vagina, urethra, and periurethral tissues for the treatment of genitourinary symptoms, with limited success. More recently, because some patients hesitate to receive mesh implants for treatment of urinary incontinence,³⁵ there has been gravitation to office-based procedures.

In contrast to lasers, which transmit energy through light, RF waves (measured in hertz) transform the kinetic energy of the intracellular atoms, which move and collide, generating thermal energy.^36,37 RF therapy has been shown to increase the proportion of smooth muscle and connective tissue; stimulate proliferation of the epithelium, neovascularization, and collagen formation in the lamina propria; and improve natural lubrication.^36,38 In addition, RF is:

• ablative when the heat is capable of generating ablation and/or necrosis of the epidermis and dermis
• microablative when energy fractionation produces microscopic columns of ablative thermal lesions in the epidermis and upper dermis, resulting in microscopic columns of treated tissue interspersed with areas of untreated skin,³⁹ and
• nonablative when trauma occurs only in the dermis by heating without causing ablation of the epidermis.³⁹

The RF devices discussed below are used with settings for microablation in the treatment of SUI and sexual health/vaginal laxity, and with nonablative settings in the treatment of GSM.

RF for the treatment of urinary incontinence

Studies with RF have shown its benefits in urinary symptoms as secondary outcomes, such as improvement of SUI.^38,40 One theory that favors energy devices as a treatment for SUI is that the treatment strengthens suburethral and pubocervical support, thereby decreasing urethral mobility.⁴¹

In 2016, the Viveve system (Viveve) received FDA 510(k) clearance for “use in general surgical procedures for electrocoagulation and hemostasis.” A single-site, randomized, nonblinded pilot study compared 1 treatment (group 1) versus 2 treatments (group 2) with the Viveve system for SUI in 35 participants.⁴² At 12 months, only for group 2 did mean scores on the Incontinence Impact Questionnaire Short Form (IIQ-7) and the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) decrease by the minimum clinically important difference of 16 and 2.52 points, respectively, compared with baseline.

The ThermiVa device (ThermiGen, LLC) received FDA clearance for “use in dermatological and general surgical procedures for electrocoagulation and hemostasis” in 2017. A single-site, prospective, double-blind, randomized controlled pilot trial evaluated the efficacy of this device for the treatment of SUI in 20 participants randomly assigned in a 1:1 fashion to active and sham groups.⁴³ At 12 weeks, mean scores of the Urogenital Distress Inventory (UDI-6) and the ICIQ-UI-SF decreased by the minimal clinically important difference only in the treatment group arm. Additionally, 70% of treatment group participants had a negative stress test at 12 weeks compared with 0% of control group participants.⁴³ In another study of 48 patients who were followed longitudinally for 5 months, a substantial improvement in genital appearance was observed.⁴⁴ Assessment based on validated instruments demonstrated significant improvements in sexual function and SUI.⁴⁴

A microablative RF device (Wavetronic 6000 Touch Device, Megapulse HF FRAXX system; Loktal Medical Electronics) consists of a vaginal probe with 64 microneedles at the tip, each capable of penetrating to a depth of 1 mm. During activation, delivery of RF energy, which results in vaporization of tissue at 100 °C, occurs in a preset sequence of 8 needles at a time, preventing the overheating of intervening tissue between adjacent needles.

Slongo and colleagues conducted a 3-arm randomized clinical trial that included 117 climacteric women with SUI.⁴⁵ In group 1, treatment consisted of 3 monthly sessions of RF; group 2 received 12 weekly sessions of pelvic floor muscle training (PFMT); and group 3 received RF treatment plus PFMT simultaneously. Assessments were conducted at baseline and 30 days after the end of therapy using validated questionnaires and scales for urinary, vaginal, and sexual functions, and cytology was used to assess vaginal atrophy. The association between RF and PFMT showed significant improvement in the SUI symptoms assessed by questionnaire. The vaginal symptoms and dryness showed more substantial improvement with the RF treatment, and vaginal laxity showed similar improvement in the 3 treatment groups.⁴⁵

Continue to: RF for the treatment of GSM...

RF for the treatment of GSM

For women who are not candidates for localized hormone therapy, as well as others who simply do not wish to use hormones, nonablative RF laser therapy may be an alternative for the management of GSM.

The VIVEVE I trial was one of the largest randomized, sham-controlled trials performed to determine the efficacy of vaginal rejuvenation using surface-cooled RF; 174 women received either RF treatment (90 J/cm²) or sham treatment (1 J/cm²).⁴⁶ Treated participants had a significant improvement in perception of vaginal laxity/looseness and sexual function up to 6 months posttreatment.⁴⁶ Overall, participants were satisfied with the treatment (77.8%–100%) and reported significant improvements in vaginal laxity and symptoms of atrophy. RF was well tolerated with minimal adverse effects, such as procedure-related erythema and edema of treated tissue, and vaginal discharge. One patient discontinued treatment because of procedural pain.^47,48

The ThermiVa system also was evaluated for efficacy in the treatment of GSM in a single-site, double-blind randomized controlled pilot study, the methods of which were previously described above.⁴³ GSM symptoms were evaluated at baseline and 12 weeks using the Vaginal Health Index (VHI) and visual analog scale (VAS). At the 12-week follow-up, compared with baseline scores, VHI scores were unchanged in the control group and improved in the treatment group. Additionally, VAS scores for dyspareunia decreased in the treatment group compared with baseline while VAS for dyspareunia in the sham group did not change from baseline to 12 weeks.

RF treatment for sexual health

The efficacy of the Viveve RF system for female sexual dysfunction was evaluated in an international, randomized, controlled, single-blinded study (n = 154) that compared 6-month outcomes of RF treatment versus sham treatment.⁴⁶ Although there was a statistically significant improvement in patient-reported sexual dysfunction on validated instruments, it is essential to note that the study was powered for the primary outcome of vaginal laxity. In addition, the study was not adequately powered to evaluate safety; however, the adverse events reported were mild, and the most frequently reported adverse event was vaginal discharge.

Microablative monopolar RF treatment for GSM has been evaluated in 2 single-arm clinical trials that included a total of 70 patients.^39,49 Pre- and posttreatment outcomes were analyzed after delivery of 3 treatment sessions 28 to 40 days apart. Although the only significant improvement in quality of life was in the health domain of the World Health Organization Quality of Life Adapted Questionnaire (P = .04), significant improvements in sexual functioning were seen in terms of the desire (P = .002), lubrication (P = .001), satisfaction (P = .003), and pain (P = .007) domains of the Female Sexual Function Index (FSFI) questionnaire except for excitation and orgasm.³⁹ Overall, 100% of participants reported being satisfied or very satisfied with treatments, and 13 of 14 women felt “cured” or “much better.”³⁹ After treatment, significant increases in vaginal Lactobacillus (P<.001), decreases in vaginal pH (P<.001), improvements in maturation of vaginal cellularity (decreased parabasal cells, P<.001; increased superficial cells, P<.001), and increased VHI score (P<.001) alone occurred.⁴⁹ No adverse events beyond self-limited vaginal burning and redness were reported.^39,49 In another study mentioned above, the combination of RF and PFMT in sexual function does not offer benefits superior to those achieved by the therapies alone.⁴⁵

Evidence on RF treatment does not support marketing efforts

Radiofrequency devices have been marketed for a variety of genitourinary problems in women, with limited high-quality, randomized, comparative evidence of efficacy and durability in the literature. It is unfortunate that RF treatment continues to be promoted by practitioners around the world who cite small, short-term studies that lack biostatistical rigor in their reporting of protocols and results. Statements from both AUGS and the International Urogynecological Association have heeded caution on the use of lasers but they could not even evaluate RF devices due to lack of evidence.^2,41

Informed counseling and shared decision making remain the bottom line

By the year 2025, all members of the Baby Boom generation will be aged 60 or older. While in the past there has been a reluctance to discuss women’s sexual health, urinary incontinence, and GSM, the need for open discussion and a variety of treatment options for these conditions has never been more critical.

Many patients prefer office-based therapies over hospital-based procedures, and others are leery of synthetic implants. These concerns are leading toward great interest in the types of treatments covered in this article. However, it is paramount that clinicians are aware of the evidence-based data behind these emerging options so that we can openly and accurately counsel our patients.

As we have shown, the quality of the data behind these officed-based therapies varies significantly. Until a greater body of research data is available, we must carefully balance our desire to meet patient wishes with solid, informed counseling and shared decision making. ●

As more and more gynecologic therapies move to the outpatient setting, keeping up on the latest data regarding emerging options can be challenging. Furthermore, it can be difficult to justify purchasing expensive equipment for the office when a therapy is not covered by medical insurance plans. However, if a therapy is efficacious and patients are willing to pay out of pocket, clinicians may want to have these options available for their patients.

In an effort to work through these complex issues, a panel of experts was convened at the 47th Annual Scientific Meeting of the Society of Gynecologic Surgeons in Palm Springs, California, on June 29, 2021. This article includes the salient points from that panel discussion.

Fractionated CO2 laser therapy

Fractionated CO2 laser therapy is considered second-line therapy for the treatment of genitourinary syndrome of menopause (GSM). In 2018, the US Food and Drug Administration (FDA) issued a safety warning about the use of CO2 laser therapy and warned patients and clinicians that the FDA had not approved the treatment for vaginal rejuvenation or treatment of vaginal symptoms related to menopause, urinary incontinence, or sexual function. Despite this warning, laser treatments are still performed in many practices.

In 2019, the International Continence Society (ICS) and the International Society for the Study of Vulvovaginal Disease (ISSVD) put out a joint practice consensus statement that essentially did not recommend the routine use of laser treatment for GSM, urinary incontinence, or lichen sclerosus.¹ Conversely, the 2020 American Urogynecologic Society (AUGS) published a clinical consensus statement that spoke to the promising results of laser therapy for the treatment of vulvovaginal atrophy, vaginal dryness, and menopausal dyspareunia, with benefits lasting up to 1 year.² This statement also suggested that the short-term safety profile of the CO2 laser device was favorable.

How CO2 lasers work

Fractionated CO2 laser therapy differs from unfractionated treatment (which often is used in the treatment of condyloma) in that it is not ablative. The laser works by using fractionated beams of light to penetrate the affected tissue to create small wounds in the epithelium and underlying lamina propria, which leads to collagen remodeling and regeneration that then results in the restoration of the superficial epithelium, vaginal rugae, and lubrication.³ Most clinicians perform 3 applications of the laser treatment 6 weeks apart, a recommendation that is based on manufacturer-sponsored studies in menopausal women.

Study results of patient outcomes with laser therapy

GSM. Several retrospective^4,5 and prospective studies^6-10 have looked at short- and longer-term outcomes in patients undergoing treatment with the CO2 laser. All of these studies showed improvement in patient symptoms related to GSM.

The VeLVET trial, conducted by Paraiso and colleagues, was a randomized trial that compared CO2 laser treatment with vaginal estrogen in women with GSM.¹¹ While the study was underpowered due to cessation of enrollment once the FDA safety warning was issued, the authors reported that at 6 months, both the fractionated CO2 laser therapy group and the vaginal estrogen group had similar improvements, with 70% to 80% of participants reporting satisfaction with treatment. The authors concluded that laser therapy is likely to be as efficacious as vaginal estrogen and may be a good option for patients who cannot use vaginal estrogen to treat GSM.¹¹

Lichen sclerosus. Some data exist on the efficacy of laser therapy for the treatment of lichen sclerosus. One recently published randomized trial showed that at 6 months, fractionated CO2 laser treatment and prior treatment with high potency topical corticosteroids was associated with higher improvement in subjective symptoms and objective measures compared with clobetasol propionate treatment.¹² Another trial, however, revealed that laser treatment was not an effective monotherapy treatment for lichen sclerosus when compared with placebo.¹³ Fewer studies have examined the effect of laser therapy on urinary incontinence.

More prospective data are emerging, evidenced by trials currently registered in ClinicalTrials.gov. While some studies provide evidence that laser therapy may be efficacious in the treatment of vulvovaginal atrophy, additional data are needed to confirm the favorable outcomes observed with laser therapy for the treatment of lichen sclerosus, and a significant amount of data are needed to evaluate the efficacy of laser treatment for urinary incontinence.

Until such evidence is available, fractionated CO2 vaginal laser therapy will remain a fee-for-service treatment option and will be inaccessible to patients who cannot afford the cost of treatment.

Continue to: Hydrogel urethral bulking...

Urethral bulking agents have been used for 5 decades in the treatment of stress urinary incontinence (SUI) in women. Unlike midurethral slings, in which many medical device companies use the same implant material (microporous, monofilament polypropylene mesh), the material for bulking agents has varied greatly. A 2017 Cochrane review of urethral bulking listed these agents used for this indication: autologous fat, carbon beads, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, glutaraldehyde cross-linked bovine collagen, hyaluronic acid with dextranomer, porcine dermal implant, polytetrafluoroethylene, and silicone particles.¹⁴ These agents can be injected through a transurethral or periurethral technique. The review failed to find superiority of one material or injection technique over another.

New bulking agent available

In January 2020, the FDA approved the premarket application for a new bulking agent. This new agent is a permanently implanted, nonresorbable hydrogel that consists of cross-linked polyacrylamide (2.5%) and water (97.5%). It is intended to be used with a transurethral bulking system that includes a rotatable sheath and two 23-guage needles; a total of 1.5 to 2.0 mL of the hydrogel is injected in 3 locations in the proximal urethra per session. Patients may undergo an additional 2 sessions, if needed, at least 4 weeks after the previous session.

Polyacrylamide hydrogel has been used as a bulking agent in cosmetic and ophthalmic surgery for many years, and it was first approved for medical use in Europe in 2001. The initial European data on its use as a urethral bulking agent was published in 2006.¹⁵ The first North American data came in 2014 from a multicenter, randomized trial that compared polyacrylamide hydrogel with collagen gel.¹⁶ This investigation followed 345 women for 12 months and concluded that the safety and efficacy of polyacrylamide hydrogel was not inferior to collagen, with a little over half of both cohorts demonstrating a 50% or greater decrease in incontinence episodes.

Since these initial studies, 3-year¹⁷ and 7-year safety and efficacy data¹⁸ have been reported, with reassuring findings, but both studies experienced significant attrition of the original group of patients. The most commonly reported adverse events associated with the procedure are pain at the injection site (4%–14%) and urinary tract infection (3%–7%); transient urinary retention rates range in incidence from 1.5% to 15%.¹⁹

Short procedure, long-term results

Given that a urethral bulking procedure can be done in less than 10 minutes in the office under local analgesia, this treatment may lend itself to use in more brittle patient populations. One study of women aged 80 or older showed a greater than 50% decrease in the number of daily pads used for up to 2 years after initial injection.²⁰ Another study found the greatest treatment success in women aged 60 years or older with fewer than 2.5 episodes of SUI per day.²¹

Platelet-rich plasma therapy

Platelet-rich plasma (PRP) therapy has been used in multiple disciplines for more than 2 decades as a treatment to regenerate damaged tissue, particularly in sports medicine for treating tendonitis as well as in plastic surgery, gynecology, urology, and ophthalmology, and good outcomes have been demonstrated with no serious adverse effects. PRP is a natural product in which high levels of platelets are concentrated through centrifugation with bioactive growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin growth factor (IGF).²² The activated platelets are then injected autologously back into the patient’s tissue. This process releases activated growth factors that accelerate tissue healing by stimulating the number of reparative cells to create collagen production, angiogenesis, and neurogenesis while fighting infection and downregulating the autoimmune system.

Continue to: Uses for PRP in gynecology...

In gynecology, dating back to 2007 PRP was shown to facilitate wound healing, when Fanning and colleagues reported PRP applications in gynecologic operative wounds, such as hysterectomies and urogynecologic procedures, to reduce postoperative pain.²³ In the last decade, there has been a dramatic increasing trend in the application of PRP injections as an alternative therapy in gynecology to improve intimate health. PRP has been used to treat lichen sclerosus, atrophic vaginitis, SUI, and female sexual dysfunction; however, there is a dearth of studies that compare PRP with traditional therapies.

Runels and colleagues described the effects of localized injections of autologous PRP for the treatment of sexual dysfunction early in 2014.²⁴ Those authors pioneered PRP use in women with dyspareunia and other symptoms related to sexual dysfunction. Women were offered PRP injections into the periurethral area of the Skene glands and the clitoris. Sexual satisfaction and pain were improved but results did not reach statistical significance. The results of this pilot study of 11 patients suggested that PRP injections could perhaps be an effective method to treat certain types of female sexual dysfunction, including desire, arousal, lubrication, and orgasm.

In another pilot study, Long and colleagues looked at the effectiveness of local injection of PRP for treating women with SUI.²⁵ In that study, younger patients with mild severity of SUI had promising results, with up to 75% cured or improved. Results in the older group, with 50% cured or improved, did not reach statistical significance. Other small, limited studies have been conducted under the hypothesis that PRP as an “O-shot” may be a promising treatment that is a safe, effective, nonsurgical, and nonhormonal option for women with dyspareunia from lack of lubrication and related sexual dysfunction, such as decreased libido or arousal.^26-29 A pilot study by Behnia-Willison and colleagues demonstrated clinical improvement in PRP use as an alternative to topical steroids for lichen sclerosus.³⁰ Several other studies also have shown efficacy for the treatment of lichen sclerosus.^31-34

More evidence of efficacy needed

To date, preliminary studies suggest that PRP holds promise for a host of gynecologic conditions. Since PRP is autologous, there are no significant contraindications, and thus far there have been no known serious adverse effects. However, most health insurers still do not cover this therapy, so for now patients must pay out-of-pocket fees for these treatments.

As we continue to investigate therapies in regenerative medicine, the continued efforts of our discipline are required to conduct well-designed prospective, randomized controlled studies. While initial series suggest that PRP is safe, it is unlikely that this therapy will be embraced widely in the paradigm as an alternative treatment option for many genitourinary symptoms of menopause and vulvar disorders until efficacy is better established.

Radiofrequency therapy

For the past 20 years, radiofrequency (RF) energy has been used through the vagina, urethra, and periurethral tissues for the treatment of genitourinary symptoms, with limited success. More recently, because some patients hesitate to receive mesh implants for treatment of urinary incontinence,³⁵ there has been gravitation to office-based procedures.

In contrast to lasers, which transmit energy through light, RF waves (measured in hertz) transform the kinetic energy of the intracellular atoms, which move and collide, generating thermal energy.^36,37 RF therapy has been shown to increase the proportion of smooth muscle and connective tissue; stimulate proliferation of the epithelium, neovascularization, and collagen formation in the lamina propria; and improve natural lubrication.^36,38 In addition, RF is:

• ablative when the heat is capable of generating ablation and/or necrosis of the epidermis and dermis
• microablative when energy fractionation produces microscopic columns of ablative thermal lesions in the epidermis and upper dermis, resulting in microscopic columns of treated tissue interspersed with areas of untreated skin,³⁹ and
• nonablative when trauma occurs only in the dermis by heating without causing ablation of the epidermis.³⁹

The RF devices discussed below are used with settings for microablation in the treatment of SUI and sexual health/vaginal laxity, and with nonablative settings in the treatment of GSM.

RF for the treatment of urinary incontinence

Studies with RF have shown its benefits in urinary symptoms as secondary outcomes, such as improvement of SUI.^38,40 One theory that favors energy devices as a treatment for SUI is that the treatment strengthens suburethral and pubocervical support, thereby decreasing urethral mobility.⁴¹

In 2016, the Viveve system (Viveve) received FDA 510(k) clearance for “use in general surgical procedures for electrocoagulation and hemostasis.” A single-site, randomized, nonblinded pilot study compared 1 treatment (group 1) versus 2 treatments (group 2) with the Viveve system for SUI in 35 participants.⁴² At 12 months, only for group 2 did mean scores on the Incontinence Impact Questionnaire Short Form (IIQ-7) and the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) decrease by the minimum clinically important difference of 16 and 2.52 points, respectively, compared with baseline.

The ThermiVa device (ThermiGen, LLC) received FDA clearance for “use in dermatological and general surgical procedures for electrocoagulation and hemostasis” in 2017. A single-site, prospective, double-blind, randomized controlled pilot trial evaluated the efficacy of this device for the treatment of SUI in 20 participants randomly assigned in a 1:1 fashion to active and sham groups.⁴³ At 12 weeks, mean scores of the Urogenital Distress Inventory (UDI-6) and the ICIQ-UI-SF decreased by the minimal clinically important difference only in the treatment group arm. Additionally, 70% of treatment group participants had a negative stress test at 12 weeks compared with 0% of control group participants.⁴³ In another study of 48 patients who were followed longitudinally for 5 months, a substantial improvement in genital appearance was observed.⁴⁴ Assessment based on validated instruments demonstrated significant improvements in sexual function and SUI.⁴⁴

A microablative RF device (Wavetronic 6000 Touch Device, Megapulse HF FRAXX system; Loktal Medical Electronics) consists of a vaginal probe with 64 microneedles at the tip, each capable of penetrating to a depth of 1 mm. During activation, delivery of RF energy, which results in vaporization of tissue at 100 °C, occurs in a preset sequence of 8 needles at a time, preventing the overheating of intervening tissue between adjacent needles.

Slongo and colleagues conducted a 3-arm randomized clinical trial that included 117 climacteric women with SUI.⁴⁵ In group 1, treatment consisted of 3 monthly sessions of RF; group 2 received 12 weekly sessions of pelvic floor muscle training (PFMT); and group 3 received RF treatment plus PFMT simultaneously. Assessments were conducted at baseline and 30 days after the end of therapy using validated questionnaires and scales for urinary, vaginal, and sexual functions, and cytology was used to assess vaginal atrophy. The association between RF and PFMT showed significant improvement in the SUI symptoms assessed by questionnaire. The vaginal symptoms and dryness showed more substantial improvement with the RF treatment, and vaginal laxity showed similar improvement in the 3 treatment groups.⁴⁵

Continue to: RF for the treatment of GSM...

RF for the treatment of GSM

For women who are not candidates for localized hormone therapy, as well as others who simply do not wish to use hormones, nonablative RF laser therapy may be an alternative for the management of GSM.

The VIVEVE I trial was one of the largest randomized, sham-controlled trials performed to determine the efficacy of vaginal rejuvenation using surface-cooled RF; 174 women received either RF treatment (90 J/cm²) or sham treatment (1 J/cm²).⁴⁶ Treated participants had a significant improvement in perception of vaginal laxity/looseness and sexual function up to 6 months posttreatment.⁴⁶ Overall, participants were satisfied with the treatment (77.8%–100%) and reported significant improvements in vaginal laxity and symptoms of atrophy. RF was well tolerated with minimal adverse effects, such as procedure-related erythema and edema of treated tissue, and vaginal discharge. One patient discontinued treatment because of procedural pain.^47,48

The ThermiVa system also was evaluated for efficacy in the treatment of GSM in a single-site, double-blind randomized controlled pilot study, the methods of which were previously described above.⁴³ GSM symptoms were evaluated at baseline and 12 weeks using the Vaginal Health Index (VHI) and visual analog scale (VAS). At the 12-week follow-up, compared with baseline scores, VHI scores were unchanged in the control group and improved in the treatment group. Additionally, VAS scores for dyspareunia decreased in the treatment group compared with baseline while VAS for dyspareunia in the sham group did not change from baseline to 12 weeks.

RF treatment for sexual health

The efficacy of the Viveve RF system for female sexual dysfunction was evaluated in an international, randomized, controlled, single-blinded study (n = 154) that compared 6-month outcomes of RF treatment versus sham treatment.⁴⁶ Although there was a statistically significant improvement in patient-reported sexual dysfunction on validated instruments, it is essential to note that the study was powered for the primary outcome of vaginal laxity. In addition, the study was not adequately powered to evaluate safety; however, the adverse events reported were mild, and the most frequently reported adverse event was vaginal discharge.

Microablative monopolar RF treatment for GSM has been evaluated in 2 single-arm clinical trials that included a total of 70 patients.^39,49 Pre- and posttreatment outcomes were analyzed after delivery of 3 treatment sessions 28 to 40 days apart. Although the only significant improvement in quality of life was in the health domain of the World Health Organization Quality of Life Adapted Questionnaire (P = .04), significant improvements in sexual functioning were seen in terms of the desire (P = .002), lubrication (P = .001), satisfaction (P = .003), and pain (P = .007) domains of the Female Sexual Function Index (FSFI) questionnaire except for excitation and orgasm.³⁹ Overall, 100% of participants reported being satisfied or very satisfied with treatments, and 13 of 14 women felt “cured” or “much better.”³⁹ After treatment, significant increases in vaginal Lactobacillus (P<.001), decreases in vaginal pH (P<.001), improvements in maturation of vaginal cellularity (decreased parabasal cells, P<.001; increased superficial cells, P<.001), and increased VHI score (P<.001) alone occurred.⁴⁹ No adverse events beyond self-limited vaginal burning and redness were reported.^39,49 In another study mentioned above, the combination of RF and PFMT in sexual function does not offer benefits superior to those achieved by the therapies alone.⁴⁵

Evidence on RF treatment does not support marketing efforts

Radiofrequency devices have been marketed for a variety of genitourinary problems in women, with limited high-quality, randomized, comparative evidence of efficacy and durability in the literature. It is unfortunate that RF treatment continues to be promoted by practitioners around the world who cite small, short-term studies that lack biostatistical rigor in their reporting of protocols and results. Statements from both AUGS and the International Urogynecological Association have heeded caution on the use of lasers but they could not even evaluate RF devices due to lack of evidence.^2,41

Informed counseling and shared decision making remain the bottom line

By the year 2025, all members of the Baby Boom generation will be aged 60 or older. While in the past there has been a reluctance to discuss women’s sexual health, urinary incontinence, and GSM, the need for open discussion and a variety of treatment options for these conditions has never been more critical.

Many patients prefer office-based therapies over hospital-based procedures, and others are leery of synthetic implants. These concerns are leading toward great interest in the types of treatments covered in this article. However, it is paramount that clinicians are aware of the evidence-based data behind these emerging options so that we can openly and accurately counsel our patients.

As we have shown, the quality of the data behind these officed-based therapies varies significantly. Until a greater body of research data is available, we must carefully balance our desire to meet patient wishes with solid, informed counseling and shared decision making. ●

As more and more gynecologic therapies move to the outpatient setting, keeping up on the latest data regarding emerging options can be challenging. Furthermore, it can be difficult to justify purchasing expensive equipment for the office when a therapy is not covered by medical insurance plans. However, if a therapy is efficacious and patients are willing to pay out of pocket, clinicians may want to have these options available for their patients.

In an effort to work through these complex issues, a panel of experts was convened at the 47th Annual Scientific Meeting of the Society of Gynecologic Surgeons in Palm Springs, California, on June 29, 2021. This article includes the salient points from that panel discussion.

Fractionated CO2 laser therapy

Fractionated CO2 laser therapy is considered second-line therapy for the treatment of genitourinary syndrome of menopause (GSM). In 2018, the US Food and Drug Administration (FDA) issued a safety warning about the use of CO2 laser therapy and warned patients and clinicians that the FDA had not approved the treatment for vaginal rejuvenation or treatment of vaginal symptoms related to menopause, urinary incontinence, or sexual function. Despite this warning, laser treatments are still performed in many practices.

In 2019, the International Continence Society (ICS) and the International Society for the Study of Vulvovaginal Disease (ISSVD) put out a joint practice consensus statement that essentially did not recommend the routine use of laser treatment for GSM, urinary incontinence, or lichen sclerosus.¹ Conversely, the 2020 American Urogynecologic Society (AUGS) published a clinical consensus statement that spoke to the promising results of laser therapy for the treatment of vulvovaginal atrophy, vaginal dryness, and menopausal dyspareunia, with benefits lasting up to 1 year.² This statement also suggested that the short-term safety profile of the CO2 laser device was favorable.

How CO2 lasers work

Fractionated CO2 laser therapy differs from unfractionated treatment (which often is used in the treatment of condyloma) in that it is not ablative. The laser works by using fractionated beams of light to penetrate the affected tissue to create small wounds in the epithelium and underlying lamina propria, which leads to collagen remodeling and regeneration that then results in the restoration of the superficial epithelium, vaginal rugae, and lubrication.³ Most clinicians perform 3 applications of the laser treatment 6 weeks apart, a recommendation that is based on manufacturer-sponsored studies in menopausal women.

Study results of patient outcomes with laser therapy

GSM. Several retrospective^4,5 and prospective studies^6-10 have looked at short- and longer-term outcomes in patients undergoing treatment with the CO2 laser. All of these studies showed improvement in patient symptoms related to GSM.

The VeLVET trial, conducted by Paraiso and colleagues, was a randomized trial that compared CO2 laser treatment with vaginal estrogen in women with GSM.¹¹ While the study was underpowered due to cessation of enrollment once the FDA safety warning was issued, the authors reported that at 6 months, both the fractionated CO2 laser therapy group and the vaginal estrogen group had similar improvements, with 70% to 80% of participants reporting satisfaction with treatment. The authors concluded that laser therapy is likely to be as efficacious as vaginal estrogen and may be a good option for patients who cannot use vaginal estrogen to treat GSM.¹¹

Lichen sclerosus. Some data exist on the efficacy of laser therapy for the treatment of lichen sclerosus. One recently published randomized trial showed that at 6 months, fractionated CO2 laser treatment and prior treatment with high potency topical corticosteroids was associated with higher improvement in subjective symptoms and objective measures compared with clobetasol propionate treatment.¹² Another trial, however, revealed that laser treatment was not an effective monotherapy treatment for lichen sclerosus when compared with placebo.¹³ Fewer studies have examined the effect of laser therapy on urinary incontinence.

More prospective data are emerging, evidenced by trials currently registered in ClinicalTrials.gov. While some studies provide evidence that laser therapy may be efficacious in the treatment of vulvovaginal atrophy, additional data are needed to confirm the favorable outcomes observed with laser therapy for the treatment of lichen sclerosus, and a significant amount of data are needed to evaluate the efficacy of laser treatment for urinary incontinence.

Until such evidence is available, fractionated CO2 vaginal laser therapy will remain a fee-for-service treatment option and will be inaccessible to patients who cannot afford the cost of treatment.

Continue to: Hydrogel urethral bulking...

Urethral bulking agents have been used for 5 decades in the treatment of stress urinary incontinence (SUI) in women. Unlike midurethral slings, in which many medical device companies use the same implant material (microporous, monofilament polypropylene mesh), the material for bulking agents has varied greatly. A 2017 Cochrane review of urethral bulking listed these agents used for this indication: autologous fat, carbon beads, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, glutaraldehyde cross-linked bovine collagen, hyaluronic acid with dextranomer, porcine dermal implant, polytetrafluoroethylene, and silicone particles.¹⁴ These agents can be injected through a transurethral or periurethral technique. The review failed to find superiority of one material or injection technique over another.

New bulking agent available

In January 2020, the FDA approved the premarket application for a new bulking agent. This new agent is a permanently implanted, nonresorbable hydrogel that consists of cross-linked polyacrylamide (2.5%) and water (97.5%). It is intended to be used with a transurethral bulking system that includes a rotatable sheath and two 23-guage needles; a total of 1.5 to 2.0 mL of the hydrogel is injected in 3 locations in the proximal urethra per session. Patients may undergo an additional 2 sessions, if needed, at least 4 weeks after the previous session.

Polyacrylamide hydrogel has been used as a bulking agent in cosmetic and ophthalmic surgery for many years, and it was first approved for medical use in Europe in 2001. The initial European data on its use as a urethral bulking agent was published in 2006.¹⁵ The first North American data came in 2014 from a multicenter, randomized trial that compared polyacrylamide hydrogel with collagen gel.¹⁶ This investigation followed 345 women for 12 months and concluded that the safety and efficacy of polyacrylamide hydrogel was not inferior to collagen, with a little over half of both cohorts demonstrating a 50% or greater decrease in incontinence episodes.

Since these initial studies, 3-year¹⁷ and 7-year safety and efficacy data¹⁸ have been reported, with reassuring findings, but both studies experienced significant attrition of the original group of patients. The most commonly reported adverse events associated with the procedure are pain at the injection site (4%–14%) and urinary tract infection (3%–7%); transient urinary retention rates range in incidence from 1.5% to 15%.¹⁹

Short procedure, long-term results

Given that a urethral bulking procedure can be done in less than 10 minutes in the office under local analgesia, this treatment may lend itself to use in more brittle patient populations. One study of women aged 80 or older showed a greater than 50% decrease in the number of daily pads used for up to 2 years after initial injection.²⁰ Another study found the greatest treatment success in women aged 60 years or older with fewer than 2.5 episodes of SUI per day.²¹

Platelet-rich plasma therapy

Platelet-rich plasma (PRP) therapy has been used in multiple disciplines for more than 2 decades as a treatment to regenerate damaged tissue, particularly in sports medicine for treating tendonitis as well as in plastic surgery, gynecology, urology, and ophthalmology, and good outcomes have been demonstrated with no serious adverse effects. PRP is a natural product in which high levels of platelets are concentrated through centrifugation with bioactive growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin growth factor (IGF).²² The activated platelets are then injected autologously back into the patient’s tissue. This process releases activated growth factors that accelerate tissue healing by stimulating the number of reparative cells to create collagen production, angiogenesis, and neurogenesis while fighting infection and downregulating the autoimmune system.

Continue to: Uses for PRP in gynecology...

In gynecology, dating back to 2007 PRP was shown to facilitate wound healing, when Fanning and colleagues reported PRP applications in gynecologic operative wounds, such as hysterectomies and urogynecologic procedures, to reduce postoperative pain.²³ In the last decade, there has been a dramatic increasing trend in the application of PRP injections as an alternative therapy in gynecology to improve intimate health. PRP has been used to treat lichen sclerosus, atrophic vaginitis, SUI, and female sexual dysfunction; however, there is a dearth of studies that compare PRP with traditional therapies.

Runels and colleagues described the effects of localized injections of autologous PRP for the treatment of sexual dysfunction early in 2014.²⁴ Those authors pioneered PRP use in women with dyspareunia and other symptoms related to sexual dysfunction. Women were offered PRP injections into the periurethral area of the Skene glands and the clitoris. Sexual satisfaction and pain were improved but results did not reach statistical significance. The results of this pilot study of 11 patients suggested that PRP injections could perhaps be an effective method to treat certain types of female sexual dysfunction, including desire, arousal, lubrication, and orgasm.

In another pilot study, Long and colleagues looked at the effectiveness of local injection of PRP for treating women with SUI.²⁵ In that study, younger patients with mild severity of SUI had promising results, with up to 75% cured or improved. Results in the older group, with 50% cured or improved, did not reach statistical significance. Other small, limited studies have been conducted under the hypothesis that PRP as an “O-shot” may be a promising treatment that is a safe, effective, nonsurgical, and nonhormonal option for women with dyspareunia from lack of lubrication and related sexual dysfunction, such as decreased libido or arousal.^26-29 A pilot study by Behnia-Willison and colleagues demonstrated clinical improvement in PRP use as an alternative to topical steroids for lichen sclerosus.³⁰ Several other studies also have shown efficacy for the treatment of lichen sclerosus.^31-34

More evidence of efficacy needed

To date, preliminary studies suggest that PRP holds promise for a host of gynecologic conditions. Since PRP is autologous, there are no significant contraindications, and thus far there have been no known serious adverse effects. However, most health insurers still do not cover this therapy, so for now patients must pay out-of-pocket fees for these treatments.

As we continue to investigate therapies in regenerative medicine, the continued efforts of our discipline are required to conduct well-designed prospective, randomized controlled studies. While initial series suggest that PRP is safe, it is unlikely that this therapy will be embraced widely in the paradigm as an alternative treatment option for many genitourinary symptoms of menopause and vulvar disorders until efficacy is better established.

Radiofrequency therapy

For the past 20 years, radiofrequency (RF) energy has been used through the vagina, urethra, and periurethral tissues for the treatment of genitourinary symptoms, with limited success. More recently, because some patients hesitate to receive mesh implants for treatment of urinary incontinence,³⁵ there has been gravitation to office-based procedures.

In contrast to lasers, which transmit energy through light, RF waves (measured in hertz) transform the kinetic energy of the intracellular atoms, which move and collide, generating thermal energy.^36,37 RF therapy has been shown to increase the proportion of smooth muscle and connective tissue; stimulate proliferation of the epithelium, neovascularization, and collagen formation in the lamina propria; and improve natural lubrication.^36,38 In addition, RF is:

• ablative when the heat is capable of generating ablation and/or necrosis of the epidermis and dermis
• microablative when energy fractionation produces microscopic columns of ablative thermal lesions in the epidermis and upper dermis, resulting in microscopic columns of treated tissue interspersed with areas of untreated skin,³⁹ and
• nonablative when trauma occurs only in the dermis by heating without causing ablation of the epidermis.³⁹

The RF devices discussed below are used with settings for microablation in the treatment of SUI and sexual health/vaginal laxity, and with nonablative settings in the treatment of GSM.

RF for the treatment of urinary incontinence

Studies with RF have shown its benefits in urinary symptoms as secondary outcomes, such as improvement of SUI.^38,40 One theory that favors energy devices as a treatment for SUI is that the treatment strengthens suburethral and pubocervical support, thereby decreasing urethral mobility.⁴¹

In 2016, the Viveve system (Viveve) received FDA 510(k) clearance for “use in general surgical procedures for electrocoagulation and hemostasis.” A single-site, randomized, nonblinded pilot study compared 1 treatment (group 1) versus 2 treatments (group 2) with the Viveve system for SUI in 35 participants.⁴² At 12 months, only for group 2 did mean scores on the Incontinence Impact Questionnaire Short Form (IIQ-7) and the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) decrease by the minimum clinically important difference of 16 and 2.52 points, respectively, compared with baseline.

The ThermiVa device (ThermiGen, LLC) received FDA clearance for “use in dermatological and general surgical procedures for electrocoagulation and hemostasis” in 2017. A single-site, prospective, double-blind, randomized controlled pilot trial evaluated the efficacy of this device for the treatment of SUI in 20 participants randomly assigned in a 1:1 fashion to active and sham groups.⁴³ At 12 weeks, mean scores of the Urogenital Distress Inventory (UDI-6) and the ICIQ-UI-SF decreased by the minimal clinically important difference only in the treatment group arm. Additionally, 70% of treatment group participants had a negative stress test at 12 weeks compared with 0% of control group participants.⁴³ In another study of 48 patients who were followed longitudinally for 5 months, a substantial improvement in genital appearance was observed.⁴⁴ Assessment based on validated instruments demonstrated significant improvements in sexual function and SUI.⁴⁴

A microablative RF device (Wavetronic 6000 Touch Device, Megapulse HF FRAXX system; Loktal Medical Electronics) consists of a vaginal probe with 64 microneedles at the tip, each capable of penetrating to a depth of 1 mm. During activation, delivery of RF energy, which results in vaporization of tissue at 100 °C, occurs in a preset sequence of 8 needles at a time, preventing the overheating of intervening tissue between adjacent needles.

Slongo and colleagues conducted a 3-arm randomized clinical trial that included 117 climacteric women with SUI.⁴⁵ In group 1, treatment consisted of 3 monthly sessions of RF; group 2 received 12 weekly sessions of pelvic floor muscle training (PFMT); and group 3 received RF treatment plus PFMT simultaneously. Assessments were conducted at baseline and 30 days after the end of therapy using validated questionnaires and scales for urinary, vaginal, and sexual functions, and cytology was used to assess vaginal atrophy. The association between RF and PFMT showed significant improvement in the SUI symptoms assessed by questionnaire. The vaginal symptoms and dryness showed more substantial improvement with the RF treatment, and vaginal laxity showed similar improvement in the 3 treatment groups.⁴⁵

Continue to: RF for the treatment of GSM...

RF for the treatment of GSM

For women who are not candidates for localized hormone therapy, as well as others who simply do not wish to use hormones, nonablative RF laser therapy may be an alternative for the management of GSM.

The VIVEVE I trial was one of the largest randomized, sham-controlled trials performed to determine the efficacy of vaginal rejuvenation using surface-cooled RF; 174 women received either RF treatment (90 J/cm²) or sham treatment (1 J/cm²).⁴⁶ Treated participants had a significant improvement in perception of vaginal laxity/looseness and sexual function up to 6 months posttreatment.⁴⁶ Overall, participants were satisfied with the treatment (77.8%–100%) and reported significant improvements in vaginal laxity and symptoms of atrophy. RF was well tolerated with minimal adverse effects, such as procedure-related erythema and edema of treated tissue, and vaginal discharge. One patient discontinued treatment because of procedural pain.^47,48

The ThermiVa system also was evaluated for efficacy in the treatment of GSM in a single-site, double-blind randomized controlled pilot study, the methods of which were previously described above.⁴³ GSM symptoms were evaluated at baseline and 12 weeks using the Vaginal Health Index (VHI) and visual analog scale (VAS). At the 12-week follow-up, compared with baseline scores, VHI scores were unchanged in the control group and improved in the treatment group. Additionally, VAS scores for dyspareunia decreased in the treatment group compared with baseline while VAS for dyspareunia in the sham group did not change from baseline to 12 weeks.

RF treatment for sexual health

The efficacy of the Viveve RF system for female sexual dysfunction was evaluated in an international, randomized, controlled, single-blinded study (n = 154) that compared 6-month outcomes of RF treatment versus sham treatment.⁴⁶ Although there was a statistically significant improvement in patient-reported sexual dysfunction on validated instruments, it is essential to note that the study was powered for the primary outcome of vaginal laxity. In addition, the study was not adequately powered to evaluate safety; however, the adverse events reported were mild, and the most frequently reported adverse event was vaginal discharge.

Microablative monopolar RF treatment for GSM has been evaluated in 2 single-arm clinical trials that included a total of 70 patients.^39,49 Pre- and posttreatment outcomes were analyzed after delivery of 3 treatment sessions 28 to 40 days apart. Although the only significant improvement in quality of life was in the health domain of the World Health Organization Quality of Life Adapted Questionnaire (P = .04), significant improvements in sexual functioning were seen in terms of the desire (P = .002), lubrication (P = .001), satisfaction (P = .003), and pain (P = .007) domains of the Female Sexual Function Index (FSFI) questionnaire except for excitation and orgasm.³⁹ Overall, 100% of participants reported being satisfied or very satisfied with treatments, and 13 of 14 women felt “cured” or “much better.”³⁹ After treatment, significant increases in vaginal Lactobacillus (P<.001), decreases in vaginal pH (P<.001), improvements in maturation of vaginal cellularity (decreased parabasal cells, P<.001; increased superficial cells, P<.001), and increased VHI score (P<.001) alone occurred.⁴⁹ No adverse events beyond self-limited vaginal burning and redness were reported.^39,49 In another study mentioned above, the combination of RF and PFMT in sexual function does not offer benefits superior to those achieved by the therapies alone.⁴⁵

Evidence on RF treatment does not support marketing efforts

Radiofrequency devices have been marketed for a variety of genitourinary problems in women, with limited high-quality, randomized, comparative evidence of efficacy and durability in the literature. It is unfortunate that RF treatment continues to be promoted by practitioners around the world who cite small, short-term studies that lack biostatistical rigor in their reporting of protocols and results. Statements from both AUGS and the International Urogynecological Association have heeded caution on the use of lasers but they could not even evaluate RF devices due to lack of evidence.^2,41

Informed counseling and shared decision making remain the bottom line

By the year 2025, all members of the Baby Boom generation will be aged 60 or older. While in the past there has been a reluctance to discuss women’s sexual health, urinary incontinence, and GSM, the need for open discussion and a variety of treatment options for these conditions has never been more critical.

Many patients prefer office-based therapies over hospital-based procedures, and others are leery of synthetic implants. These concerns are leading toward great interest in the types of treatments covered in this article. However, it is paramount that clinicians are aware of the evidence-based data behind these emerging options so that we can openly and accurately counsel our patients.

As we have shown, the quality of the data behind these officed-based therapies varies significantly. Until a greater body of research data is available, we must carefully balance our desire to meet patient wishes with solid, informed counseling and shared decision making. ●