OBG Management

“TREATING POLYCYSTIC OVARY SYNDROME: START USING DUAL MEDICAL THERAPY”

ROBERT L. BARBIERI, MD (EDITORIAL; APRIL 2017)

Why extended release metformin?

I read with interest Dr. Barbieri’s editorial on polycystic ovary syndrome. It left me wondering: Is there a metabolic or pharmacologic reason why you give metformin XR 1,500 mg with dinner instead of 750 mg orally twice per day?

Marcelo Andreoli, MD
Vienna, Virginia

Dr. Barbieri responds

I thank Dr. Andreoli for the important clinical question about one-time or multiple dosing of metformin. To improve patient adherence with metformin treatment, I think once-daily dosing at dinner with an extended-release formulation is more convenient than twice-daily dosing with immediate-release metformin. Following ingestion of immediate- or extended-release metformin, peak metformin blood concentrations are achieved after 2 and 7 hours, respectively.¹ There is some evidence that extended-release metformin has fewer gastrointestinal (GI) adverse effects than immediate-release metformin.² In one study, the reported rates of GI adverse effects were 29% versus 39% with extended-release and immediate-release formulations, respectively.²

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“TREATING POLYCYSTIC OVARY SYNDROME: START USING DUAL MEDICAL THERAPY”

ROBERT L. BARBIERI, MD (EDITORIAL; APRIL 2017)

Why extended release metformin?

I read with interest Dr. Barbieri’s editorial on polycystic ovary syndrome. It left me wondering: Is there a metabolic or pharmacologic reason why you give metformin XR 1,500 mg with dinner instead of 750 mg orally twice per day?

Marcelo Andreoli, MD
Vienna, Virginia

Dr. Barbieri responds

I thank Dr. Andreoli for the important clinical question about one-time or multiple dosing of metformin. To improve patient adherence with metformin treatment, I think once-daily dosing at dinner with an extended-release formulation is more convenient than twice-daily dosing with immediate-release metformin. Following ingestion of immediate- or extended-release metformin, peak metformin blood concentrations are achieved after 2 and 7 hours, respectively.¹ There is some evidence that extended-release metformin has fewer gastrointestinal (GI) adverse effects than immediate-release metformin.² In one study, the reported rates of GI adverse effects were 29% versus 39% with extended-release and immediate-release formulations, respectively.²

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“TREATING POLYCYSTIC OVARY SYNDROME: START USING DUAL MEDICAL THERAPY”

ROBERT L. BARBIERI, MD (EDITORIAL; APRIL 2017)

Why extended release metformin?

I read with interest Dr. Barbieri’s editorial on polycystic ovary syndrome. It left me wondering: Is there a metabolic or pharmacologic reason why you give metformin XR 1,500 mg with dinner instead of 750 mg orally twice per day?

Marcelo Andreoli, MD
Vienna, Virginia

Dr. Barbieri responds

I thank Dr. Andreoli for the important clinical question about one-time or multiple dosing of metformin. To improve patient adherence with metformin treatment, I think once-daily dosing at dinner with an extended-release formulation is more convenient than twice-daily dosing with immediate-release metformin. Following ingestion of immediate- or extended-release metformin, peak metformin blood concentrations are achieved after 2 and 7 hours, respectively.¹ There is some evidence that extended-release metformin has fewer gastrointestinal (GI) adverse effects than immediate-release metformin.² In one study, the reported rates of GI adverse effects were 29% versus 39% with extended-release and immediate-release formulations, respectively.²

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“WHY ARE THERE DELAYS IN THE DIAGNOSIS OF ENDOMETRIOSIS?”

ROBERT L. BARBIERI, MD (EDITORIAL; MARCH 2017)

Look for symptoms of IBS, PCOS, and PMS

I practiced reproductive endocrinology for 40 years and saw too many patients whose endometriosis had been ignored or undertreated. I found that the initial suspicion for the disease could be discovered by looking for symptoms of 3 comorbidities: irritable bowel syndrome, polycystic ovary syndrome, and premenstrual syndrome.

Wilbur (Dub) Howard, MD
Dallas, Texas

 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“WHY ARE THERE DELAYS IN THE DIAGNOSIS OF ENDOMETRIOSIS?”

ROBERT L. BARBIERI, MD (EDITORIAL; MARCH 2017)

Look for symptoms of IBS, PCOS, and PMS

I practiced reproductive endocrinology for 40 years and saw too many patients whose endometriosis had been ignored or undertreated. I found that the initial suspicion for the disease could be discovered by looking for symptoms of 3 comorbidities: irritable bowel syndrome, polycystic ovary syndrome, and premenstrual syndrome.

Wilbur (Dub) Howard, MD
Dallas, Texas

 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“WHY ARE THERE DELAYS IN THE DIAGNOSIS OF ENDOMETRIOSIS?”

ROBERT L. BARBIERI, MD (EDITORIAL; MARCH 2017)

Look for symptoms of IBS, PCOS, and PMS

I practiced reproductive endocrinology for 40 years and saw too many patients whose endometriosis had been ignored or undertreated. I found that the initial suspicion for the disease could be discovered by looking for symptoms of 3 comorbidities: irritable bowel syndrome, polycystic ovary syndrome, and premenstrual syndrome.

Wilbur (Dub) Howard, MD
Dallas, Texas

 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“ROBOT-ASSISTED LAPAROSCOPIC RESECTION OF A NONCOMMUNICATING CAVITARY RUDIMENTARY HORN”

OBIANUJU SANDRA MADUEKE-LAVEAUX, MD, MPH; BETH W. RACKOW, MD; AND ARNOLD P. ADVINCULA, MD (VIDEO; JANUARY 2017)

The fallopian tube should have been removed

I watched the video by Dr. Advincula and colleagues and as always was impressed with the surgical skills demonstrated. While the robot-assisted approach is quite nice, this case could have been accomplished with only three 5-mm lower abdominal port sites and traditional straight-stick laparoscopic methods. The cosmetic benefit to a 15-year-old patient of this alternative should have been considered.

More importantly, the fallopian tube separated from the rudimentary horn should have been removed. Leaving the right tube in situ exposes the patient to the possibility of a future ectopic pregnancy in that tube and provides no benefit to the patient.

David L. Zisow, MD
Baltimore, Maryland

 

Dr. Advincula and team respond

We appreciate Dr. Zisow’s perspective. As is known, tool selection is based on surgeon preference. Inherent to this point, a discussion about route of surgery, and any implications it would have, such as cosmesis, was had. Cosmesis was not an issue with this patient, and she was quite pleased with her cosmetic outcome.

We also discussed preoperatively, among our team and with the patient, the right fallopian tube. Although removal would have been optimal, there was concern intraoperatively of possible compromise to the ovary. Hence, a decision was made to forego removal particularly in light of the extremely rare risk of transperitoneal migration of spermatozoa weighed against the risk of compromising a perfectly healthy ovary in a 15-year-old woman.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“ROBOT-ASSISTED LAPAROSCOPIC RESECTION OF A NONCOMMUNICATING CAVITARY RUDIMENTARY HORN”

OBIANUJU SANDRA MADUEKE-LAVEAUX, MD, MPH; BETH W. RACKOW, MD; AND ARNOLD P. ADVINCULA, MD (VIDEO; JANUARY 2017)

The fallopian tube should have been removed

I watched the video by Dr. Advincula and colleagues and as always was impressed with the surgical skills demonstrated. While the robot-assisted approach is quite nice, this case could have been accomplished with only three 5-mm lower abdominal port sites and traditional straight-stick laparoscopic methods. The cosmetic benefit to a 15-year-old patient of this alternative should have been considered.

More importantly, the fallopian tube separated from the rudimentary horn should have been removed. Leaving the right tube in situ exposes the patient to the possibility of a future ectopic pregnancy in that tube and provides no benefit to the patient.

David L. Zisow, MD
Baltimore, Maryland

 

Dr. Advincula and team respond

We appreciate Dr. Zisow’s perspective. As is known, tool selection is based on surgeon preference. Inherent to this point, a discussion about route of surgery, and any implications it would have, such as cosmesis, was had. Cosmesis was not an issue with this patient, and she was quite pleased with her cosmetic outcome.

We also discussed preoperatively, among our team and with the patient, the right fallopian tube. Although removal would have been optimal, there was concern intraoperatively of possible compromise to the ovary. Hence, a decision was made to forego removal particularly in light of the extremely rare risk of transperitoneal migration of spermatozoa weighed against the risk of compromising a perfectly healthy ovary in a 15-year-old woman.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“ROBOT-ASSISTED LAPAROSCOPIC RESECTION OF A NONCOMMUNICATING CAVITARY RUDIMENTARY HORN”

OBIANUJU SANDRA MADUEKE-LAVEAUX, MD, MPH; BETH W. RACKOW, MD; AND ARNOLD P. ADVINCULA, MD (VIDEO; JANUARY 2017)

The fallopian tube should have been removed

I watched the video by Dr. Advincula and colleagues and as always was impressed with the surgical skills demonstrated. While the robot-assisted approach is quite nice, this case could have been accomplished with only three 5-mm lower abdominal port sites and traditional straight-stick laparoscopic methods. The cosmetic benefit to a 15-year-old patient of this alternative should have been considered.

More importantly, the fallopian tube separated from the rudimentary horn should have been removed. Leaving the right tube in situ exposes the patient to the possibility of a future ectopic pregnancy in that tube and provides no benefit to the patient.

David L. Zisow, MD
Baltimore, Maryland

 

Dr. Advincula and team respond

We appreciate Dr. Zisow’s perspective. As is known, tool selection is based on surgeon preference. Inherent to this point, a discussion about route of surgery, and any implications it would have, such as cosmesis, was had. Cosmesis was not an issue with this patient, and she was quite pleased with her cosmetic outcome.

We also discussed preoperatively, among our team and with the patient, the right fallopian tube. Although removal would have been optimal, there was concern intraoperatively of possible compromise to the ovary. Hence, a decision was made to forego removal particularly in light of the extremely rare risk of transperitoneal migration of spermatozoa weighed against the risk of compromising a perfectly healthy ovary in a 15-year-old woman.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“2017 UPDATE ON ABNORMAL UTERINE BLEEDING”

HOWARD T. SHARP, MD, AND MARISSA ADELMAN, MD (APRIL 2017)

Hysteroscopy equipment too expensive for employed or small-group practitioners

I could not agree more with Drs. Sharp and Adelman that diagnostic hysteroscopy should be performed in the office whenever possible. However, as a solo gynecologist in private practice, I could not afford or justify the cost of purchasing the equipment as well as its care and maintenance. Sometimes I was able to bring a third-party vendor to provide the equipment and a technician so that I could perform a diagnostic hysteroscopy in my office when I did an ablation with my own Thermachoice equipment and balloon system.

The hysteroscopy was bundled/required for the Current Procedural Terminology (CPT) code to work in the office. Most of these patients already had undergone an ultrasonography, endometrial biopsy, and some had an outpatient hysteroscopic dilation and curettage under general anesthesia, which did not resolve their bleeding. All of this adds to the cost and increased patient discomfort and inconvenience. Reimbursement for the office procedure was better than when performed at the hospital, and patients avoided $500 to $1,000 copays to the hospital and anesthesiologist.

When I closed my private practice and became employed by the hospital, I proposed that they purchase office hysteroscopy equipment for the other gynecologist and me to share. I continued to perform uterine ablations with my own equipment. Together we performed more than 100 outpatient diagnostic hysteroscopies per year, some with global endometrial ablation. Since there were only 2 gyns, the 2 new hysteroscopy sets they purchased sat in the closet most of the time.

I suggested they “lease” the equipment back to us on a case-by-case basis for office use since they owned and managed our practices. The hospital administration basically saw office procedures as taking away revenue from the hospital and decreasing operating room volume. The patients I treated in the office setting did well, preferred to avoid general anesthesia, and enjoyed the cost savings.

Large ObGyn groups with multiple providers and high volumes can justify the expenses of the equipment, but for those in solo practice or employed by a hospital, it may not be feasible. I sincerely hope that articles focusing on in-office hysteroscopy will open up the discussion to enable and encourage more physicians and hospital administrators to see the advantages of office-based procedures.

Steven R. Moffett, MD
Knoxville, Tennessee

 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“2017 UPDATE ON ABNORMAL UTERINE BLEEDING”

HOWARD T. SHARP, MD, AND MARISSA ADELMAN, MD (APRIL 2017)

Hysteroscopy equipment too expensive for employed or small-group practitioners

I could not agree more with Drs. Sharp and Adelman that diagnostic hysteroscopy should be performed in the office whenever possible. However, as a solo gynecologist in private practice, I could not afford or justify the cost of purchasing the equipment as well as its care and maintenance. Sometimes I was able to bring a third-party vendor to provide the equipment and a technician so that I could perform a diagnostic hysteroscopy in my office when I did an ablation with my own Thermachoice equipment and balloon system.

The hysteroscopy was bundled/required for the Current Procedural Terminology (CPT) code to work in the office. Most of these patients already had undergone an ultrasonography, endometrial biopsy, and some had an outpatient hysteroscopic dilation and curettage under general anesthesia, which did not resolve their bleeding. All of this adds to the cost and increased patient discomfort and inconvenience. Reimbursement for the office procedure was better than when performed at the hospital, and patients avoided $500 to $1,000 copays to the hospital and anesthesiologist.

When I closed my private practice and became employed by the hospital, I proposed that they purchase office hysteroscopy equipment for the other gynecologist and me to share. I continued to perform uterine ablations with my own equipment. Together we performed more than 100 outpatient diagnostic hysteroscopies per year, some with global endometrial ablation. Since there were only 2 gyns, the 2 new hysteroscopy sets they purchased sat in the closet most of the time.

I suggested they “lease” the equipment back to us on a case-by-case basis for office use since they owned and managed our practices. The hospital administration basically saw office procedures as taking away revenue from the hospital and decreasing operating room volume. The patients I treated in the office setting did well, preferred to avoid general anesthesia, and enjoyed the cost savings.

Large ObGyn groups with multiple providers and high volumes can justify the expenses of the equipment, but for those in solo practice or employed by a hospital, it may not be feasible. I sincerely hope that articles focusing on in-office hysteroscopy will open up the discussion to enable and encourage more physicians and hospital administrators to see the advantages of office-based procedures.

Steven R. Moffett, MD
Knoxville, Tennessee

 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

“2017 UPDATE ON ABNORMAL UTERINE BLEEDING”

HOWARD T. SHARP, MD, AND MARISSA ADELMAN, MD (APRIL 2017)

Hysteroscopy equipment too expensive for employed or small-group practitioners

I could not agree more with Drs. Sharp and Adelman that diagnostic hysteroscopy should be performed in the office whenever possible. However, as a solo gynecologist in private practice, I could not afford or justify the cost of purchasing the equipment as well as its care and maintenance. Sometimes I was able to bring a third-party vendor to provide the equipment and a technician so that I could perform a diagnostic hysteroscopy in my office when I did an ablation with my own Thermachoice equipment and balloon system.

The hysteroscopy was bundled/required for the Current Procedural Terminology (CPT) code to work in the office. Most of these patients already had undergone an ultrasonography, endometrial biopsy, and some had an outpatient hysteroscopic dilation and curettage under general anesthesia, which did not resolve their bleeding. All of this adds to the cost and increased patient discomfort and inconvenience. Reimbursement for the office procedure was better than when performed at the hospital, and patients avoided $500 to $1,000 copays to the hospital and anesthesiologist.

When I closed my private practice and became employed by the hospital, I proposed that they purchase office hysteroscopy equipment for the other gynecologist and me to share. I continued to perform uterine ablations with my own equipment. Together we performed more than 100 outpatient diagnostic hysteroscopies per year, some with global endometrial ablation. Since there were only 2 gyns, the 2 new hysteroscopy sets they purchased sat in the closet most of the time.

I suggested they “lease” the equipment back to us on a case-by-case basis for office use since they owned and managed our practices. The hospital administration basically saw office procedures as taking away revenue from the hospital and decreasing operating room volume. The patients I treated in the office setting did well, preferred to avoid general anesthesia, and enjoyed the cost savings.

Large ObGyn groups with multiple providers and high volumes can justify the expenses of the equipment, but for those in solo practice or employed by a hospital, it may not be feasible. I sincerely hope that articles focusing on in-office hysteroscopy will open up the discussion to enable and encourage more physicians and hospital administrators to see the advantages of office-based procedures.

Steven R. Moffett, MD
Knoxville, Tennessee

 

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

NONESTROGEN PRODUCT FOR DYSPAREUNIA

FOR MORE INFORMATION, VISIT: http://www.amagpharma.com

ORAL MAINTENANCE TX FOR RECURRENT CANCER

FOR MORE INFORMATION, VISIT: http://www.zejula.com

MIGS STAPLING SYSTEM WITH REAL-TIME FEEDBACK

FOR MORE INFORMATION, VISIT: http://www.medtronic.com

BONE BUILDING AGENT

FOR MORE INFORMATION, VISIT: http://www.radiuspharm.com

PROTEOMIC BREAST CANCER ASSAY

FOR MORE INFORMATION, VISIT: http://www.provistadx.com

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

NONESTROGEN PRODUCT FOR DYSPAREUNIA

FOR MORE INFORMATION, VISIT: http://www.amagpharma.com

ORAL MAINTENANCE TX FOR RECURRENT CANCER

FOR MORE INFORMATION, VISIT: http://www.zejula.com

MIGS STAPLING SYSTEM WITH REAL-TIME FEEDBACK

FOR MORE INFORMATION, VISIT: http://www.medtronic.com

BONE BUILDING AGENT

FOR MORE INFORMATION, VISIT: http://www.radiuspharm.com

PROTEOMIC BREAST CANCER ASSAY

FOR MORE INFORMATION, VISIT: http://www.provistadx.com

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

NONESTROGEN PRODUCT FOR DYSPAREUNIA

FOR MORE INFORMATION, VISIT: http://www.amagpharma.com

ORAL MAINTENANCE TX FOR RECURRENT CANCER

FOR MORE INFORMATION, VISIT: http://www.zejula.com

MIGS STAPLING SYSTEM WITH REAL-TIME FEEDBACK

FOR MORE INFORMATION, VISIT: http://www.medtronic.com

BONE BUILDING AGENT

FOR MORE INFORMATION, VISIT: http://www.radiuspharm.com

PROTEOMIC BREAST CANCER ASSAY

FOR MORE INFORMATION, VISIT: http://www.provistadx.com

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Since publication of initial findings of the Women’s Health Initiative (WHI) in 2002, use of systemic menopausal hormone therapy (HT) has declined by some 80% among US women.¹ Against this backdrop, this year’s Menopause Update highlights the “hot off the press” updated position statement on menopausal HT from The North American Menopause Society (NAMS), summarized by Dr. JoAnn V. Pinkerton. Although this guidance is chock full of practical, evidence-based guidance, the take-home message that Dr. Pinkerton and I would like to leave readers of OBG Management with is that for women with bothersome menopausal symptoms aged in their 50s or within 10 years of the onset of menopause who are free of contraindications, use of systemic HT is appropriate.

Related Article:
Dr. Andrew M. Kaunitz on prescribing systemic HT to older women

Although menopausal vasomotor and related symptoms improve as women age, in untreated women, vulvovaginal atrophy (VVA, also known as genitourinary syndrome of menopause, or GSM) tends to progress, causing vaginal dryness and sexual dysfunction, among other symptoms. When symptomatic GSM represents the only indication for treatment, low-dose local vaginal estrogen, ospemifene, or dehydroepiandrosterone (DHEA; prasterone) is safe and effective. However, as with systemic HT, specific treatments for GSM are substantially underutilized.² The current package labeling for low-dose vaginal estrogen deters many appropriate candidates from using this safe, effective treatment. In this Update, Dr. JoAnn E. Manson reviews the rationale for updating this labeling as well as recent efforts to accomplish the task.

Read about updated NAMS guidelines on HT

Guidelines on HT have been updated by The North American Menopause Society

The 2017 hormone therapy position statement of The North American Menopause Society [published online ahead of print June 2017]. Menopause.

The North American Menopause Society Hormone Therapy (HT) Position Statement Advisory Panel, composed of more than 20 experts in menopausal women's HT, including clinicians, researchers, and epidemiologists, reviewed the 2012 HT Position Statement, evaluated prior and new literature and used levels of evidence to identify the quality of the evidence and strength of the recommendations and to find consensus for the guidelines. The following information comes from the NAMS 2017 Hormone Therapy Position Statement.³

What are the major findings?

HT is the most effective treatment for vasomotor symptoms (VMS) and GSM and has been shown to prevent bone loss and fracture. Risks of HT may differ for women depending on type, dose, duration, route of administration, and timing of initiation and whether or not a progestogen is needed. Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation about benefits and risks of continuing or discontinuing HT.

For women who are younger than age 60 or within 10 years of menopause and have no contraindication, the clearest benefit of HT is for the treatment of VMS and prevention of bone loss in those at elevated risk.

The clinical guidelines were presented to NAMS audience at the 2016 annual clinical meeting, where NAMS recommended "determining the most appropriate type, dose, formulation, and duration of HT."⁴

When to initiate HT and duration of use

In its now-published 2017 guidelines on HT, NAMS affirms the safety and efficacy of HT for symptomatic menopausal women or those at high risk for bone loss who are under age 60 or within 10 years of menopause. NAMS encourages practitioners to employ shared decision making with their patients to find the appropriate type, dose, formulation, and duration of HT, making individualized decisions based on evidence-based information, the unique health risks of women, and with periodic reassessment.

In the clinical guidelines presented in the 2016 NAMS annual meeting,⁴ key recommendations taken from the 2017 Hormone Therapy Position Statement³ include the following: For women who are aged younger than 60 years or within 10 years of menopause and have no contraindications, the benefit/risk ratio appears favorable for treatment of bothersome VMS and in those at elevated risk for bone loss or fracture.

For women who initiate HT more than 10 years from menopause or after age 60, this benefit/risk ratio appears less favorable because of greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

What about extended use of hormone therapy? There is no evidence to support routine discontinuation of HT after age 65. Decisions about longer durations of HT should be individualized and considered for indications such as persistent VMS or bone loss, with shared decision making, documentation, and periodic reevaluation. Longer duration is more favorable for estrogen therapy than for estrogen-progestin therapy, based on the Women's Health Initiative (WHI) randomized controlled trials.⁵

What about only vaginal symptoms? For bothersome GSM not relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended and can be continued as long as indicated since there is minimal systemic absorption of estrogen, with serum levels remaining within the normal postmenopausal range.^6,7 For women with estrogen sensitive cancer, oncologists should be included in decision making, particularly for women on aromatase inhibitors.

Considerations for special populations Early menopause. For women with hypoestrogenism, primary ovarian insufficiency, or premature surgical menopause without contraindications, HT is recommended until at least the median age of menopause (52 years), as studies suggest that benefits outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.⁸

Family history of breast cancer. Observational evidence suggests that use of HT does not further alter the risk for breast cancer in women with a family history of breast cancer. Family history is one risk, among others, that should be assessed when counseling women regarding HT.

Women who are BRCA-positive without breast cancer. For women who are BRCA-positive (higher genetic risk of breast cancer, primarily estrogen-receptor-negative), and have undergone surgical menopause (bilateral salpingo-oophorectomy), the benefits of estrogen to decrease health risks caused by premature loss of estrogen need to be considered on an individual basis.⁹ On the basis of limited observational studies, consider offering systemic HT until the median age of menopause (52 years) with longer use individualized.³

Related Article:
Is menopausal hormone therapy safe when your patient carries a BRCA mutation?

Survivors of endometrial and breast cancer with bothersome VMS. For women with prior estrogen-sensitive cancers, non-HTs should be considered first, particularly those agents studied through randomized controlled trials in this population and found to be effective. If systemic estrogen is considered for persistent symptoms after non-HT or complementary options have been unsuccessful, decisions should be made for compelling reasons and after detailed counseling, with shared decision making and in conjunction with their oncologist.³ 

Bothersome GSM. On the basis of limited observational data, there appears to be minimal to no demonstrated elevation in risk for recurrence of endometrial or breast cancer using low-dose vaginal estrogen,^3,10 but decisions should be made in conjunction with an oncologist.

Related Article:
Focus on treating genital atrophy symptoms
 

The importance of relaying the new guidelines to patients

It is important for clinicians to talk to women about their menopausal symptoms and their options for relief of symptoms or prevention of bone loss. Discussion should take into account age and time from menopause, include evidence-based information^11-13 about benefits and risks of different types of therapy, and employ shared decision making to choose the most appropriate therapy to maximize benefits and minimize risks for the individual woman.

Following the WHI initial release in 2002, both women and providers became fearful of HT and believed media hype and celebrities that compounded bioidentical HT was safer than FDA-approved HTs. However, compounded products lack safety and efficacy data, are not monitored or regulated by the FDA, and have unique risks associated with compounding, including concerns about sterility, impurities, and overdosing or underdosing, which could increase cancer risk.³

Read about modifying low-dose vaginal estrogen’s black box warning

Physicians continue to underwhelmingly prescribe low-dose vaginal estrogen for GSM 

Kingsberg SA, Krychman M, Graham S, Bernick B, Mirkin S. The Women's EMPOWER survey: identifying women's perceptions on vulvar and vaginal atrophy and its treatment. J Sex Med. 2017;14(3):413-424.

GSM is seriously underrecognized and undertreated.^2,8,14 It has a major impact on women's lives--a silent epidemic affecting women's quality of life, sexual health, interpersonal relationships, and even physical health in terms of increased risk of urinary tract infections and urinary symptoms. Unfortunately, patients are reluctant to mention the problem to their clinicians, and they do not clearly recognize it as a medical condition that has available treatment options. Clinicians also rarely receive adequate training in the management of this condition and how to discuss it with their patients. Given busy schedules and time constraints, addressing this topic often falls through the cracks, representing a missed opportunity for helping our patients with safe and effective treatments. In a recent study by Kingsberg and colleagues, an astoundingly low percentageof women with GSM symptoms received treatment. 

Details of the study

The study authors evaluated women's perceptions of GSM and available treatment options. US women aged 45 and older who reported GSM symptoms were surveyed. Of 1,858 women with a median age of 58 (range, 45-90), the study authors found that 50% had never used any treatment; 25% used over-the-counter medications; 18% were former users of GSM treatments; and 7% currently used prescribed GSM therapies.

When GSM was discussed, women were more likely than their clinicians to initiate the conversation. The main reason for women not mentioning their symptoms was the perception that GSM symptoms were a natural and inevitable part of aging. Hormonal products were perceived by women as having several downsides, including risk of systemic absorption, messiness of local creams, and the need to reuse an applicator. Overall, clinicians recommended vaginal estrogen therapy to only 23% and oral HTs to 18% of women.

The results of the study are consistent with results of earlier surveys of menopausal women. Although the survey included nearly 2,000 women, it has the potential for selection biases inherent to most Internet-based surveys. In addition, the respondents tended to be white and have higher socieconomic status, with limited representation from other groups.

Calls for the current boxed warning to be revised

GSM is highly prevalent among postmenopausal women; the condition has adverse effects on quality of life and sexual health.^2,8,14 Safe and effective treatments are available but are underutilized.^1,8,15,16 A current boxed warning appears on low-dose vaginal estrogen--class labeling that appears on all medications in the class of estrogen or HT, regardless of dose or route of administration. These warnings are based on findings from the WHI and other studies of systemic estrogen or estrogen plus progestin, which demonstrated a complex pattern of risks and benefits of HT (including increased risk of venous thrombosis or pulmonary embolism, stroke, and breast cancer [with estrogen plus progestin]).

These findings, however, do not appear to be relevant to low-dose vaginal estrogen, given minimal if any systemic absorption and much lower blood levels of hormones than found with systemic HT. Blood levels of estradiol with low-dose vaginal estrogen remain in the normal postmenopausal range, compared to several-fold elevations in hormone levels with systemic HT.^8,15,16 Additionally, observational studies of low-dose vaginal estrogen, as well as short-term randomized clinical trials, show no evidence of an increased risk of venous thromboembolic events, heart disease, stroke, breast cancer, or dementia--the listed possible adverse effects in the boxed warning. The current warning is based on extrapolating findings from systemic HT, which is inappropriate and not evidence-based for low-dose vaginal estrogen.¹⁵

The inappropriate boxed warning contributes to the problem of undertreatment of GSM in women by discouraging clinicians from prescribing the medication and dissuading patients from taking it even after purchase. Testimonials from many clinicians caring for these women have underscored that women will fill their prescription, but after seeing the boxed warning will often become alarmed and decide not to take the medication. Clinicians reported that patients often say at their next appointment: "No, I never took it. I got very scared when I saw the boxed warning." As a result, clinicians often have to spend a great deal of time explaining the limitations of, and lack of evidence for, the boxed warning on low-dose vaginal estrogen.

Related Article:
2016 Update on menopause
 

Recommended label revisions

A modified label, without a boxed warning, would be safer for women because the key messages would not be obscured by the large amount of irrelevant information. Our Working Group recommended that the label explain that the listed risks were found in studies of systemic HT and their relevance to low-dose vaginal estrogen is unknown. The Group also recommended that warning text should be added in bold font to advise  patients to seek medical attention if they have vaginal bleeding or spotting while taking the medication. In addition, patients who have a history of breast cancer or other hormone-sensitive cancer should discuss the use of the medication with their oncologist.   

Status update on efforts to revise label. A citizen's petition was filed in the Spring of 2016, with signatures from more than 600 clinicians and patients and representatives of medical and professional organizations endorsing a more appropriate evidence-based label for low-dose vaginal estrogen. The FDA is continuing to review and deliberate on these issues but has not yet made a final decision.  

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Since publication of initial findings of the Women’s Health Initiative (WHI) in 2002, use of systemic menopausal hormone therapy (HT) has declined by some 80% among US women.¹ Against this backdrop, this year’s Menopause Update highlights the “hot off the press” updated position statement on menopausal HT from The North American Menopause Society (NAMS), summarized by Dr. JoAnn V. Pinkerton. Although this guidance is chock full of practical, evidence-based guidance, the take-home message that Dr. Pinkerton and I would like to leave readers of OBG Management with is that for women with bothersome menopausal symptoms aged in their 50s or within 10 years of the onset of menopause who are free of contraindications, use of systemic HT is appropriate.

Related Article:
Dr. Andrew M. Kaunitz on prescribing systemic HT to older women

Although menopausal vasomotor and related symptoms improve as women age, in untreated women, vulvovaginal atrophy (VVA, also known as genitourinary syndrome of menopause, or GSM) tends to progress, causing vaginal dryness and sexual dysfunction, among other symptoms. When symptomatic GSM represents the only indication for treatment, low-dose local vaginal estrogen, ospemifene, or dehydroepiandrosterone (DHEA; prasterone) is safe and effective. However, as with systemic HT, specific treatments for GSM are substantially underutilized.² The current package labeling for low-dose vaginal estrogen deters many appropriate candidates from using this safe, effective treatment. In this Update, Dr. JoAnn E. Manson reviews the rationale for updating this labeling as well as recent efforts to accomplish the task.

Read about updated NAMS guidelines on HT

Guidelines on HT have been updated by The North American Menopause Society

The 2017 hormone therapy position statement of The North American Menopause Society [published online ahead of print June 2017]. Menopause.

The North American Menopause Society Hormone Therapy (HT) Position Statement Advisory Panel, composed of more than 20 experts in menopausal women's HT, including clinicians, researchers, and epidemiologists, reviewed the 2012 HT Position Statement, evaluated prior and new literature and used levels of evidence to identify the quality of the evidence and strength of the recommendations and to find consensus for the guidelines. The following information comes from the NAMS 2017 Hormone Therapy Position Statement.³

What are the major findings?

HT is the most effective treatment for vasomotor symptoms (VMS) and GSM and has been shown to prevent bone loss and fracture. Risks of HT may differ for women depending on type, dose, duration, route of administration, and timing of initiation and whether or not a progestogen is needed. Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation about benefits and risks of continuing or discontinuing HT.

For women who are younger than age 60 or within 10 years of menopause and have no contraindication, the clearest benefit of HT is for the treatment of VMS and prevention of bone loss in those at elevated risk.

The clinical guidelines were presented to NAMS audience at the 2016 annual clinical meeting, where NAMS recommended "determining the most appropriate type, dose, formulation, and duration of HT."⁴

When to initiate HT and duration of use

In its now-published 2017 guidelines on HT, NAMS affirms the safety and efficacy of HT for symptomatic menopausal women or those at high risk for bone loss who are under age 60 or within 10 years of menopause. NAMS encourages practitioners to employ shared decision making with their patients to find the appropriate type, dose, formulation, and duration of HT, making individualized decisions based on evidence-based information, the unique health risks of women, and with periodic reassessment.

In the clinical guidelines presented in the 2016 NAMS annual meeting,⁴ key recommendations taken from the 2017 Hormone Therapy Position Statement³ include the following: For women who are aged younger than 60 years or within 10 years of menopause and have no contraindications, the benefit/risk ratio appears favorable for treatment of bothersome VMS and in those at elevated risk for bone loss or fracture.

For women who initiate HT more than 10 years from menopause or after age 60, this benefit/risk ratio appears less favorable because of greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

What about extended use of hormone therapy? There is no evidence to support routine discontinuation of HT after age 65. Decisions about longer durations of HT should be individualized and considered for indications such as persistent VMS or bone loss, with shared decision making, documentation, and periodic reevaluation. Longer duration is more favorable for estrogen therapy than for estrogen-progestin therapy, based on the Women's Health Initiative (WHI) randomized controlled trials.⁵

What about only vaginal symptoms? For bothersome GSM not relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended and can be continued as long as indicated since there is minimal systemic absorption of estrogen, with serum levels remaining within the normal postmenopausal range.^6,7 For women with estrogen sensitive cancer, oncologists should be included in decision making, particularly for women on aromatase inhibitors.

Considerations for special populations Early menopause. For women with hypoestrogenism, primary ovarian insufficiency, or premature surgical menopause without contraindications, HT is recommended until at least the median age of menopause (52 years), as studies suggest that benefits outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.⁸

Family history of breast cancer. Observational evidence suggests that use of HT does not further alter the risk for breast cancer in women with a family history of breast cancer. Family history is one risk, among others, that should be assessed when counseling women regarding HT.

Women who are BRCA-positive without breast cancer. For women who are BRCA-positive (higher genetic risk of breast cancer, primarily estrogen-receptor-negative), and have undergone surgical menopause (bilateral salpingo-oophorectomy), the benefits of estrogen to decrease health risks caused by premature loss of estrogen need to be considered on an individual basis.⁹ On the basis of limited observational studies, consider offering systemic HT until the median age of menopause (52 years) with longer use individualized.³

Related Article:
Is menopausal hormone therapy safe when your patient carries a BRCA mutation?

Survivors of endometrial and breast cancer with bothersome VMS. For women with prior estrogen-sensitive cancers, non-HTs should be considered first, particularly those agents studied through randomized controlled trials in this population and found to be effective. If systemic estrogen is considered for persistent symptoms after non-HT or complementary options have been unsuccessful, decisions should be made for compelling reasons and after detailed counseling, with shared decision making and in conjunction with their oncologist.³ 

Bothersome GSM. On the basis of limited observational data, there appears to be minimal to no demonstrated elevation in risk for recurrence of endometrial or breast cancer using low-dose vaginal estrogen,^3,10 but decisions should be made in conjunction with an oncologist.

Related Article:
Focus on treating genital atrophy symptoms
 

The importance of relaying the new guidelines to patients

It is important for clinicians to talk to women about their menopausal symptoms and their options for relief of symptoms or prevention of bone loss. Discussion should take into account age and time from menopause, include evidence-based information^11-13 about benefits and risks of different types of therapy, and employ shared decision making to choose the most appropriate therapy to maximize benefits and minimize risks for the individual woman.

Following the WHI initial release in 2002, both women and providers became fearful of HT and believed media hype and celebrities that compounded bioidentical HT was safer than FDA-approved HTs. However, compounded products lack safety and efficacy data, are not monitored or regulated by the FDA, and have unique risks associated with compounding, including concerns about sterility, impurities, and overdosing or underdosing, which could increase cancer risk.³

Read about modifying low-dose vaginal estrogen’s black box warning

Physicians continue to underwhelmingly prescribe low-dose vaginal estrogen for GSM 

Kingsberg SA, Krychman M, Graham S, Bernick B, Mirkin S. The Women's EMPOWER survey: identifying women's perceptions on vulvar and vaginal atrophy and its treatment. J Sex Med. 2017;14(3):413-424.

GSM is seriously underrecognized and undertreated.^2,8,14 It has a major impact on women's lives--a silent epidemic affecting women's quality of life, sexual health, interpersonal relationships, and even physical health in terms of increased risk of urinary tract infections and urinary symptoms. Unfortunately, patients are reluctant to mention the problem to their clinicians, and they do not clearly recognize it as a medical condition that has available treatment options. Clinicians also rarely receive adequate training in the management of this condition and how to discuss it with their patients. Given busy schedules and time constraints, addressing this topic often falls through the cracks, representing a missed opportunity for helping our patients with safe and effective treatments. In a recent study by Kingsberg and colleagues, an astoundingly low percentageof women with GSM symptoms received treatment. 

Details of the study

The study authors evaluated women's perceptions of GSM and available treatment options. US women aged 45 and older who reported GSM symptoms were surveyed. Of 1,858 women with a median age of 58 (range, 45-90), the study authors found that 50% had never used any treatment; 25% used over-the-counter medications; 18% were former users of GSM treatments; and 7% currently used prescribed GSM therapies.

When GSM was discussed, women were more likely than their clinicians to initiate the conversation. The main reason for women not mentioning their symptoms was the perception that GSM symptoms were a natural and inevitable part of aging. Hormonal products were perceived by women as having several downsides, including risk of systemic absorption, messiness of local creams, and the need to reuse an applicator. Overall, clinicians recommended vaginal estrogen therapy to only 23% and oral HTs to 18% of women.

The results of the study are consistent with results of earlier surveys of menopausal women. Although the survey included nearly 2,000 women, it has the potential for selection biases inherent to most Internet-based surveys. In addition, the respondents tended to be white and have higher socieconomic status, with limited representation from other groups.

Calls for the current boxed warning to be revised

GSM is highly prevalent among postmenopausal women; the condition has adverse effects on quality of life and sexual health.^2,8,14 Safe and effective treatments are available but are underutilized.^1,8,15,16 A current boxed warning appears on low-dose vaginal estrogen--class labeling that appears on all medications in the class of estrogen or HT, regardless of dose or route of administration. These warnings are based on findings from the WHI and other studies of systemic estrogen or estrogen plus progestin, which demonstrated a complex pattern of risks and benefits of HT (including increased risk of venous thrombosis or pulmonary embolism, stroke, and breast cancer [with estrogen plus progestin]).

These findings, however, do not appear to be relevant to low-dose vaginal estrogen, given minimal if any systemic absorption and much lower blood levels of hormones than found with systemic HT. Blood levels of estradiol with low-dose vaginal estrogen remain in the normal postmenopausal range, compared to several-fold elevations in hormone levels with systemic HT.^8,15,16 Additionally, observational studies of low-dose vaginal estrogen, as well as short-term randomized clinical trials, show no evidence of an increased risk of venous thromboembolic events, heart disease, stroke, breast cancer, or dementia--the listed possible adverse effects in the boxed warning. The current warning is based on extrapolating findings from systemic HT, which is inappropriate and not evidence-based for low-dose vaginal estrogen.¹⁵

The inappropriate boxed warning contributes to the problem of undertreatment of GSM in women by discouraging clinicians from prescribing the medication and dissuading patients from taking it even after purchase. Testimonials from many clinicians caring for these women have underscored that women will fill their prescription, but after seeing the boxed warning will often become alarmed and decide not to take the medication. Clinicians reported that patients often say at their next appointment: "No, I never took it. I got very scared when I saw the boxed warning." As a result, clinicians often have to spend a great deal of time explaining the limitations of, and lack of evidence for, the boxed warning on low-dose vaginal estrogen.

Related Article:
2016 Update on menopause
 

Recommended label revisions

A modified label, without a boxed warning, would be safer for women because the key messages would not be obscured by the large amount of irrelevant information. Our Working Group recommended that the label explain that the listed risks were found in studies of systemic HT and their relevance to low-dose vaginal estrogen is unknown. The Group also recommended that warning text should be added in bold font to advise  patients to seek medical attention if they have vaginal bleeding or spotting while taking the medication. In addition, patients who have a history of breast cancer or other hormone-sensitive cancer should discuss the use of the medication with their oncologist.   

Status update on efforts to revise label. A citizen's petition was filed in the Spring of 2016, with signatures from more than 600 clinicians and patients and representatives of medical and professional organizations endorsing a more appropriate evidence-based label for low-dose vaginal estrogen. The FDA is continuing to review and deliberate on these issues but has not yet made a final decision.  

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Since publication of initial findings of the Women’s Health Initiative (WHI) in 2002, use of systemic menopausal hormone therapy (HT) has declined by some 80% among US women.¹ Against this backdrop, this year’s Menopause Update highlights the “hot off the press” updated position statement on menopausal HT from The North American Menopause Society (NAMS), summarized by Dr. JoAnn V. Pinkerton. Although this guidance is chock full of practical, evidence-based guidance, the take-home message that Dr. Pinkerton and I would like to leave readers of OBG Management with is that for women with bothersome menopausal symptoms aged in their 50s or within 10 years of the onset of menopause who are free of contraindications, use of systemic HT is appropriate.

Related Article:
Dr. Andrew M. Kaunitz on prescribing systemic HT to older women

Although menopausal vasomotor and related symptoms improve as women age, in untreated women, vulvovaginal atrophy (VVA, also known as genitourinary syndrome of menopause, or GSM) tends to progress, causing vaginal dryness and sexual dysfunction, among other symptoms. When symptomatic GSM represents the only indication for treatment, low-dose local vaginal estrogen, ospemifene, or dehydroepiandrosterone (DHEA; prasterone) is safe and effective. However, as with systemic HT, specific treatments for GSM are substantially underutilized.² The current package labeling for low-dose vaginal estrogen deters many appropriate candidates from using this safe, effective treatment. In this Update, Dr. JoAnn E. Manson reviews the rationale for updating this labeling as well as recent efforts to accomplish the task.

Read about updated NAMS guidelines on HT

Guidelines on HT have been updated by The North American Menopause Society

The 2017 hormone therapy position statement of The North American Menopause Society [published online ahead of print June 2017]. Menopause.

The North American Menopause Society Hormone Therapy (HT) Position Statement Advisory Panel, composed of more than 20 experts in menopausal women's HT, including clinicians, researchers, and epidemiologists, reviewed the 2012 HT Position Statement, evaluated prior and new literature and used levels of evidence to identify the quality of the evidence and strength of the recommendations and to find consensus for the guidelines. The following information comes from the NAMS 2017 Hormone Therapy Position Statement.³

What are the major findings?

HT is the most effective treatment for vasomotor symptoms (VMS) and GSM and has been shown to prevent bone loss and fracture. Risks of HT may differ for women depending on type, dose, duration, route of administration, and timing of initiation and whether or not a progestogen is needed. Treatment should be individualized using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation about benefits and risks of continuing or discontinuing HT.

For women who are younger than age 60 or within 10 years of menopause and have no contraindication, the clearest benefit of HT is for the treatment of VMS and prevention of bone loss in those at elevated risk.

The clinical guidelines were presented to NAMS audience at the 2016 annual clinical meeting, where NAMS recommended "determining the most appropriate type, dose, formulation, and duration of HT."⁴

When to initiate HT and duration of use

In its now-published 2017 guidelines on HT, NAMS affirms the safety and efficacy of HT for symptomatic menopausal women or those at high risk for bone loss who are under age 60 or within 10 years of menopause. NAMS encourages practitioners to employ shared decision making with their patients to find the appropriate type, dose, formulation, and duration of HT, making individualized decisions based on evidence-based information, the unique health risks of women, and with periodic reassessment.

In the clinical guidelines presented in the 2016 NAMS annual meeting,⁴ key recommendations taken from the 2017 Hormone Therapy Position Statement³ include the following: For women who are aged younger than 60 years or within 10 years of menopause and have no contraindications, the benefit/risk ratio appears favorable for treatment of bothersome VMS and in those at elevated risk for bone loss or fracture.

For women who initiate HT more than 10 years from menopause or after age 60, this benefit/risk ratio appears less favorable because of greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

What about extended use of hormone therapy? There is no evidence to support routine discontinuation of HT after age 65. Decisions about longer durations of HT should be individualized and considered for indications such as persistent VMS or bone loss, with shared decision making, documentation, and periodic reevaluation. Longer duration is more favorable for estrogen therapy than for estrogen-progestin therapy, based on the Women's Health Initiative (WHI) randomized controlled trials.⁵

What about only vaginal symptoms? For bothersome GSM not relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended and can be continued as long as indicated since there is minimal systemic absorption of estrogen, with serum levels remaining within the normal postmenopausal range.^6,7 For women with estrogen sensitive cancer, oncologists should be included in decision making, particularly for women on aromatase inhibitors.

Considerations for special populations Early menopause. For women with hypoestrogenism, primary ovarian insufficiency, or premature surgical menopause without contraindications, HT is recommended until at least the median age of menopause (52 years), as studies suggest that benefits outweigh the risks for effects on bone, heart, cognition, GSM, sexual function, and mood.⁸

Family history of breast cancer. Observational evidence suggests that use of HT does not further alter the risk for breast cancer in women with a family history of breast cancer. Family history is one risk, among others, that should be assessed when counseling women regarding HT.

Women who are BRCA-positive without breast cancer. For women who are BRCA-positive (higher genetic risk of breast cancer, primarily estrogen-receptor-negative), and have undergone surgical menopause (bilateral salpingo-oophorectomy), the benefits of estrogen to decrease health risks caused by premature loss of estrogen need to be considered on an individual basis.⁹ On the basis of limited observational studies, consider offering systemic HT until the median age of menopause (52 years) with longer use individualized.³

Related Article:
Is menopausal hormone therapy safe when your patient carries a BRCA mutation?

Survivors of endometrial and breast cancer with bothersome VMS. For women with prior estrogen-sensitive cancers, non-HTs should be considered first, particularly those agents studied through randomized controlled trials in this population and found to be effective. If systemic estrogen is considered for persistent symptoms after non-HT or complementary options have been unsuccessful, decisions should be made for compelling reasons and after detailed counseling, with shared decision making and in conjunction with their oncologist.³ 

Bothersome GSM. On the basis of limited observational data, there appears to be minimal to no demonstrated elevation in risk for recurrence of endometrial or breast cancer using low-dose vaginal estrogen,^3,10 but decisions should be made in conjunction with an oncologist.

Related Article:
Focus on treating genital atrophy symptoms
 

The importance of relaying the new guidelines to patients

It is important for clinicians to talk to women about their menopausal symptoms and their options for relief of symptoms or prevention of bone loss. Discussion should take into account age and time from menopause, include evidence-based information^11-13 about benefits and risks of different types of therapy, and employ shared decision making to choose the most appropriate therapy to maximize benefits and minimize risks for the individual woman.

Following the WHI initial release in 2002, both women and providers became fearful of HT and believed media hype and celebrities that compounded bioidentical HT was safer than FDA-approved HTs. However, compounded products lack safety and efficacy data, are not monitored or regulated by the FDA, and have unique risks associated with compounding, including concerns about sterility, impurities, and overdosing or underdosing, which could increase cancer risk.³

Read about modifying low-dose vaginal estrogen’s black box warning

Physicians continue to underwhelmingly prescribe low-dose vaginal estrogen for GSM 

Kingsberg SA, Krychman M, Graham S, Bernick B, Mirkin S. The Women's EMPOWER survey: identifying women's perceptions on vulvar and vaginal atrophy and its treatment. J Sex Med. 2017;14(3):413-424.

GSM is seriously underrecognized and undertreated.^2,8,14 It has a major impact on women's lives--a silent epidemic affecting women's quality of life, sexual health, interpersonal relationships, and even physical health in terms of increased risk of urinary tract infections and urinary symptoms. Unfortunately, patients are reluctant to mention the problem to their clinicians, and they do not clearly recognize it as a medical condition that has available treatment options. Clinicians also rarely receive adequate training in the management of this condition and how to discuss it with their patients. Given busy schedules and time constraints, addressing this topic often falls through the cracks, representing a missed opportunity for helping our patients with safe and effective treatments. In a recent study by Kingsberg and colleagues, an astoundingly low percentageof women with GSM symptoms received treatment. 

Details of the study

The study authors evaluated women's perceptions of GSM and available treatment options. US women aged 45 and older who reported GSM symptoms were surveyed. Of 1,858 women with a median age of 58 (range, 45-90), the study authors found that 50% had never used any treatment; 25% used over-the-counter medications; 18% were former users of GSM treatments; and 7% currently used prescribed GSM therapies.

When GSM was discussed, women were more likely than their clinicians to initiate the conversation. The main reason for women not mentioning their symptoms was the perception that GSM symptoms were a natural and inevitable part of aging. Hormonal products were perceived by women as having several downsides, including risk of systemic absorption, messiness of local creams, and the need to reuse an applicator. Overall, clinicians recommended vaginal estrogen therapy to only 23% and oral HTs to 18% of women.

The results of the study are consistent with results of earlier surveys of menopausal women. Although the survey included nearly 2,000 women, it has the potential for selection biases inherent to most Internet-based surveys. In addition, the respondents tended to be white and have higher socieconomic status, with limited representation from other groups.

Calls for the current boxed warning to be revised

GSM is highly prevalent among postmenopausal women; the condition has adverse effects on quality of life and sexual health.^2,8,14 Safe and effective treatments are available but are underutilized.^1,8,15,16 A current boxed warning appears on low-dose vaginal estrogen--class labeling that appears on all medications in the class of estrogen or HT, regardless of dose or route of administration. These warnings are based on findings from the WHI and other studies of systemic estrogen or estrogen plus progestin, which demonstrated a complex pattern of risks and benefits of HT (including increased risk of venous thrombosis or pulmonary embolism, stroke, and breast cancer [with estrogen plus progestin]).

These findings, however, do not appear to be relevant to low-dose vaginal estrogen, given minimal if any systemic absorption and much lower blood levels of hormones than found with systemic HT. Blood levels of estradiol with low-dose vaginal estrogen remain in the normal postmenopausal range, compared to several-fold elevations in hormone levels with systemic HT.^8,15,16 Additionally, observational studies of low-dose vaginal estrogen, as well as short-term randomized clinical trials, show no evidence of an increased risk of venous thromboembolic events, heart disease, stroke, breast cancer, or dementia--the listed possible adverse effects in the boxed warning. The current warning is based on extrapolating findings from systemic HT, which is inappropriate and not evidence-based for low-dose vaginal estrogen.¹⁵

The inappropriate boxed warning contributes to the problem of undertreatment of GSM in women by discouraging clinicians from prescribing the medication and dissuading patients from taking it even after purchase. Testimonials from many clinicians caring for these women have underscored that women will fill their prescription, but after seeing the boxed warning will often become alarmed and decide not to take the medication. Clinicians reported that patients often say at their next appointment: "No, I never took it. I got very scared when I saw the boxed warning." As a result, clinicians often have to spend a great deal of time explaining the limitations of, and lack of evidence for, the boxed warning on low-dose vaginal estrogen.

Related Article:
2016 Update on menopause
 

Recommended label revisions

A modified label, without a boxed warning, would be safer for women because the key messages would not be obscured by the large amount of irrelevant information. Our Working Group recommended that the label explain that the listed risks were found in studies of systemic HT and their relevance to low-dose vaginal estrogen is unknown. The Group also recommended that warning text should be added in bold font to advise  patients to seek medical attention if they have vaginal bleeding or spotting while taking the medication. In addition, patients who have a history of breast cancer or other hormone-sensitive cancer should discuss the use of the medication with their oncologist.   

Status update on efforts to revise label. A citizen's petition was filed in the Spring of 2016, with signatures from more than 600 clinicians and patients and representatives of medical and professional organizations endorsing a more appropriate evidence-based label for low-dose vaginal estrogen. The FDA is continuing to review and deliberate on these issues but has not yet made a final decision.  

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE: Woman with short cervix, intra-amniotic sludge, and prior preterm delivery

An asymptomatic 32-year-old woman with a prior preterm delivery, presently pregnant with a singleton at 17 weeks of gestation, underwent transvaginal ultrasonography and was found to have a cervical length of 22 mm and dense intra-amniotic sludge. She received one dose of 17α-hydroxyprogesterone caproate (17P) at 16 weeks of gestation. What are your next steps in management?

Intra-amniotic sludge is a conundrum 

Intra-amniotic sludge is a sonographic finding of free-floating, hyperechoic, particulate matter in the amniotic fluid close to the internal os. The precise nature of this material varies, and it may include blood, meconium, or vernix and may signal inflammation or infection. In a retrospective case-control study, 27% of asymptomatic women with sludge and a short cervix had positive amniotic fluid cultures, and 27% had evidence of inflammation in the amniotic fluid (>50 white blood cells/mm3).¹ In a separate report, the authors proposed that "the detection of amniotic fluid 'sludge' represents a sign that microbial invasion of the amniotic cavity and an inflammatory process are in progress."²

Benefit of cerclage in high-risk women. Several systematic reviews have highlighted the benefit of cerclage for women with a singleton pregnancy, short cervix, and previous preterm birth or second-trimester loss (ultrasound-indicated cerclage for high-risk women).³ Cerclage is presumed to work by providing some degree of structural support and by maintaining a barrier to protect the fetal membranes against exposure to ascending pathogens.⁴

Since dense intra-amniotic sludge may represent chronic intra-amniotic infection, can cerclage still be expected to be beneficial when microbiologic invasion of the amniotic cavity already has occurred? Furthermore, intra-amniotic infection has been cited as a possible complication of ultrasound-indicated cerclage, with a rate of 10%.⁵ The traditional view is that the presence of subclinical intra-amniotic infection may further increase this risk and therefore should be considered a contraindication to cerclage.⁶

Evaluating the patient for cerclage placement

The patient history and physical examination should focus on the signs and symptoms of labor, vaginal bleeding, amniotic membrane rupture, and intra-amniotic infection. Particular attention should be paid to maternal temperature, pulse, and the presence of uterine tenderness or foul-smelling vaginal discharge. A sterile speculum examination followed by digital examination would complement the ultrasonography evaluation in assessing cervical dilation and effacement. The ultrasonography evaluation should be completed to confirm a viable pregnancy with accurate dating and the absence of detectable fetal anomalies.

Currently, evidence is insufficient for recommending routine amniocentesis to exclude intra-amniotic infection in an asymptomatic woman prior to ultrasound-indicated cerclage, even in the presence of intra-amniotic sludge, as there are no data demonstrating improved outcomes.⁴ In addition, intra-amniotic sludge has been associated with intra-amniotic infection and/or inflammation in the form of microbial biofilms, which may prevent detection of infection by routine culture techniques.⁷ 

Related Article:
Universal cervical length screening–saving babies lives

Study results offer limited guidance

Data are limited on the clinical implications of intra-amniotic sludge in women with cervical cerclage. In a retrospective cohort of 177 patients with cerclage, 60 had evidence of sludge and 46 of those with sludge underwent ultrasound-indicated cerclage.⁸ There were no significant differences in the mean gestational age at delivery, neonatal outcomes, rate of preterm delivery, preterm premature rupture of membranes, or intra-amniotic infection between women with or without intra-amniotic sludge. A subanalysis was performed comparing women with sludge detected before or after cerclage and, again, no difference was found in measured outcomes.

Similarly, in a small (N = 20) retrospective review of the Arabin pessary used as a noninvasive intervention for short cervix, the presence of intra-amniotic sludge in 5 cases did not appear to impact outcomes.⁹

Case patient: How would you manage her care?

Based on her obstetric history and ultrasonography findings, the patient described in the case vignette is at high risk for preterm delivery. The presence of both intra-amniotic sludge and short cervix is associated with an increased risk for spontaneous preterm delivery. After evaluating for clinical intra-amniotic infection and performing a work-up for other contraindications to cerclage placement, cerclage placement may be offered--even in the presence of intra-amniotic sludge.

The next practical question is whether 17P, already started, should be continued after cerclage placement. From the literature on 17P, it is unclear whether progesterone provides additional benefit. One randomized, placebo-controlled study in women with at least 2 preterm deliveries or mid-trimester losses and cerclage in place showed that the 17P-treated women had a significant reduction in preterm delivery compared with the control group, from 37.8% to 16.1%.¹⁰

By contrast, in a secondary analysis of a randomized trial evaluating cerclage in high-risk women with short cervix in the current pregnancy, addition of 17P to cerclage was not beneficial.¹¹ Results of 2 retrospective cohort studies showed the same lack of difference on preterm delivery rates with the addition of 17P.^12,13

Accepting that the interpretation of these data is challenging, in our practice we would choose to continue the progesterone supplementation, siding with other recently expressed expert opinions.¹⁴

The bottom line

While clinical intra-amniotic infection is a contraindication to cerclage, there is no evidence to support withholding cerclage from eligible women due to the presence of intra-amniotic fluid sludge alone.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE: Woman with short cervix, intra-amniotic sludge, and prior preterm delivery

An asymptomatic 32-year-old woman with a prior preterm delivery, presently pregnant with a singleton at 17 weeks of gestation, underwent transvaginal ultrasonography and was found to have a cervical length of 22 mm and dense intra-amniotic sludge. She received one dose of 17α-hydroxyprogesterone caproate (17P) at 16 weeks of gestation. What are your next steps in management?

Intra-amniotic sludge is a conundrum 

Intra-amniotic sludge is a sonographic finding of free-floating, hyperechoic, particulate matter in the amniotic fluid close to the internal os. The precise nature of this material varies, and it may include blood, meconium, or vernix and may signal inflammation or infection. In a retrospective case-control study, 27% of asymptomatic women with sludge and a short cervix had positive amniotic fluid cultures, and 27% had evidence of inflammation in the amniotic fluid (>50 white blood cells/mm3).¹ In a separate report, the authors proposed that "the detection of amniotic fluid 'sludge' represents a sign that microbial invasion of the amniotic cavity and an inflammatory process are in progress."²

Benefit of cerclage in high-risk women. Several systematic reviews have highlighted the benefit of cerclage for women with a singleton pregnancy, short cervix, and previous preterm birth or second-trimester loss (ultrasound-indicated cerclage for high-risk women).³ Cerclage is presumed to work by providing some degree of structural support and by maintaining a barrier to protect the fetal membranes against exposure to ascending pathogens.⁴

Since dense intra-amniotic sludge may represent chronic intra-amniotic infection, can cerclage still be expected to be beneficial when microbiologic invasion of the amniotic cavity already has occurred? Furthermore, intra-amniotic infection has been cited as a possible complication of ultrasound-indicated cerclage, with a rate of 10%.⁵ The traditional view is that the presence of subclinical intra-amniotic infection may further increase this risk and therefore should be considered a contraindication to cerclage.⁶

Evaluating the patient for cerclage placement

The patient history and physical examination should focus on the signs and symptoms of labor, vaginal bleeding, amniotic membrane rupture, and intra-amniotic infection. Particular attention should be paid to maternal temperature, pulse, and the presence of uterine tenderness or foul-smelling vaginal discharge. A sterile speculum examination followed by digital examination would complement the ultrasonography evaluation in assessing cervical dilation and effacement. The ultrasonography evaluation should be completed to confirm a viable pregnancy with accurate dating and the absence of detectable fetal anomalies.

Currently, evidence is insufficient for recommending routine amniocentesis to exclude intra-amniotic infection in an asymptomatic woman prior to ultrasound-indicated cerclage, even in the presence of intra-amniotic sludge, as there are no data demonstrating improved outcomes.⁴ In addition, intra-amniotic sludge has been associated with intra-amniotic infection and/or inflammation in the form of microbial biofilms, which may prevent detection of infection by routine culture techniques.⁷ 

Related Article:
Universal cervical length screening–saving babies lives

Study results offer limited guidance

Data are limited on the clinical implications of intra-amniotic sludge in women with cervical cerclage. In a retrospective cohort of 177 patients with cerclage, 60 had evidence of sludge and 46 of those with sludge underwent ultrasound-indicated cerclage.⁸ There were no significant differences in the mean gestational age at delivery, neonatal outcomes, rate of preterm delivery, preterm premature rupture of membranes, or intra-amniotic infection between women with or without intra-amniotic sludge. A subanalysis was performed comparing women with sludge detected before or after cerclage and, again, no difference was found in measured outcomes.

Similarly, in a small (N = 20) retrospective review of the Arabin pessary used as a noninvasive intervention for short cervix, the presence of intra-amniotic sludge in 5 cases did not appear to impact outcomes.⁹

Case patient: How would you manage her care?

Based on her obstetric history and ultrasonography findings, the patient described in the case vignette is at high risk for preterm delivery. The presence of both intra-amniotic sludge and short cervix is associated with an increased risk for spontaneous preterm delivery. After evaluating for clinical intra-amniotic infection and performing a work-up for other contraindications to cerclage placement, cerclage placement may be offered--even in the presence of intra-amniotic sludge.

The next practical question is whether 17P, already started, should be continued after cerclage placement. From the literature on 17P, it is unclear whether progesterone provides additional benefit. One randomized, placebo-controlled study in women with at least 2 preterm deliveries or mid-trimester losses and cerclage in place showed that the 17P-treated women had a significant reduction in preterm delivery compared with the control group, from 37.8% to 16.1%.¹⁰

By contrast, in a secondary analysis of a randomized trial evaluating cerclage in high-risk women with short cervix in the current pregnancy, addition of 17P to cerclage was not beneficial.¹¹ Results of 2 retrospective cohort studies showed the same lack of difference on preterm delivery rates with the addition of 17P.^12,13

Accepting that the interpretation of these data is challenging, in our practice we would choose to continue the progesterone supplementation, siding with other recently expressed expert opinions.¹⁴

The bottom line

While clinical intra-amniotic infection is a contraindication to cerclage, there is no evidence to support withholding cerclage from eligible women due to the presence of intra-amniotic fluid sludge alone.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE: Woman with short cervix, intra-amniotic sludge, and prior preterm delivery

An asymptomatic 32-year-old woman with a prior preterm delivery, presently pregnant with a singleton at 17 weeks of gestation, underwent transvaginal ultrasonography and was found to have a cervical length of 22 mm and dense intra-amniotic sludge. She received one dose of 17α-hydroxyprogesterone caproate (17P) at 16 weeks of gestation. What are your next steps in management?

Intra-amniotic sludge is a conundrum 

Intra-amniotic sludge is a sonographic finding of free-floating, hyperechoic, particulate matter in the amniotic fluid close to the internal os. The precise nature of this material varies, and it may include blood, meconium, or vernix and may signal inflammation or infection. In a retrospective case-control study, 27% of asymptomatic women with sludge and a short cervix had positive amniotic fluid cultures, and 27% had evidence of inflammation in the amniotic fluid (>50 white blood cells/mm3).¹ In a separate report, the authors proposed that "the detection of amniotic fluid 'sludge' represents a sign that microbial invasion of the amniotic cavity and an inflammatory process are in progress."²

Benefit of cerclage in high-risk women. Several systematic reviews have highlighted the benefit of cerclage for women with a singleton pregnancy, short cervix, and previous preterm birth or second-trimester loss (ultrasound-indicated cerclage for high-risk women).³ Cerclage is presumed to work by providing some degree of structural support and by maintaining a barrier to protect the fetal membranes against exposure to ascending pathogens.⁴

Since dense intra-amniotic sludge may represent chronic intra-amniotic infection, can cerclage still be expected to be beneficial when microbiologic invasion of the amniotic cavity already has occurred? Furthermore, intra-amniotic infection has been cited as a possible complication of ultrasound-indicated cerclage, with a rate of 10%.⁵ The traditional view is that the presence of subclinical intra-amniotic infection may further increase this risk and therefore should be considered a contraindication to cerclage.⁶

Evaluating the patient for cerclage placement

The patient history and physical examination should focus on the signs and symptoms of labor, vaginal bleeding, amniotic membrane rupture, and intra-amniotic infection. Particular attention should be paid to maternal temperature, pulse, and the presence of uterine tenderness or foul-smelling vaginal discharge. A sterile speculum examination followed by digital examination would complement the ultrasonography evaluation in assessing cervical dilation and effacement. The ultrasonography evaluation should be completed to confirm a viable pregnancy with accurate dating and the absence of detectable fetal anomalies.

Currently, evidence is insufficient for recommending routine amniocentesis to exclude intra-amniotic infection in an asymptomatic woman prior to ultrasound-indicated cerclage, even in the presence of intra-amniotic sludge, as there are no data demonstrating improved outcomes.⁴ In addition, intra-amniotic sludge has been associated with intra-amniotic infection and/or inflammation in the form of microbial biofilms, which may prevent detection of infection by routine culture techniques.⁷ 

Related Article:
Universal cervical length screening–saving babies lives

Study results offer limited guidance

Data are limited on the clinical implications of intra-amniotic sludge in women with cervical cerclage. In a retrospective cohort of 177 patients with cerclage, 60 had evidence of sludge and 46 of those with sludge underwent ultrasound-indicated cerclage.⁸ There were no significant differences in the mean gestational age at delivery, neonatal outcomes, rate of preterm delivery, preterm premature rupture of membranes, or intra-amniotic infection between women with or without intra-amniotic sludge. A subanalysis was performed comparing women with sludge detected before or after cerclage and, again, no difference was found in measured outcomes.

Similarly, in a small (N = 20) retrospective review of the Arabin pessary used as a noninvasive intervention for short cervix, the presence of intra-amniotic sludge in 5 cases did not appear to impact outcomes.⁹

Case patient: How would you manage her care?

Based on her obstetric history and ultrasonography findings, the patient described in the case vignette is at high risk for preterm delivery. The presence of both intra-amniotic sludge and short cervix is associated with an increased risk for spontaneous preterm delivery. After evaluating for clinical intra-amniotic infection and performing a work-up for other contraindications to cerclage placement, cerclage placement may be offered--even in the presence of intra-amniotic sludge.

The next practical question is whether 17P, already started, should be continued after cerclage placement. From the literature on 17P, it is unclear whether progesterone provides additional benefit. One randomized, placebo-controlled study in women with at least 2 preterm deliveries or mid-trimester losses and cerclage in place showed that the 17P-treated women had a significant reduction in preterm delivery compared with the control group, from 37.8% to 16.1%.¹⁰

By contrast, in a secondary analysis of a randomized trial evaluating cerclage in high-risk women with short cervix in the current pregnancy, addition of 17P to cerclage was not beneficial.¹¹ Results of 2 retrospective cohort studies showed the same lack of difference on preterm delivery rates with the addition of 17P.^12,13

Accepting that the interpretation of these data is challenging, in our practice we would choose to continue the progesterone supplementation, siding with other recently expressed expert opinions.¹⁴

The bottom line

While clinical intra-amniotic infection is a contraindication to cerclage, there is no evidence to support withholding cerclage from eligible women due to the presence of intra-amniotic fluid sludge alone.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

WHAT LIES AHEAD FOR WOMEN’S HEALTH? CHALLENGES, AND OPPORTUNITIES, AS ACOG AND US LEADERSHIP TRANSITION

LUCIA DIVENERE, MA

Politics and Planned Parenthood

As obstetricians and gynecologists, we are all dedicated to women's health care. Many of us are Pro-Life and resent your unqualified support of Planned Parenthood, the world’s largest provider and supporter of unrestricted abortion. There are many venues to deliver women's health care. We should not be cheerleaders for the Planned Parenthood/Democratic party propaganda. As you stated, we should be truly a-political.

Laurence Burns, DO
Grand Rapids, Michigan

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

WHAT LIES AHEAD FOR WOMEN’S HEALTH? CHALLENGES, AND OPPORTUNITIES, AS ACOG AND US LEADERSHIP TRANSITION

LUCIA DIVENERE, MA

Politics and Planned Parenthood

As obstetricians and gynecologists, we are all dedicated to women's health care. Many of us are Pro-Life and resent your unqualified support of Planned Parenthood, the world’s largest provider and supporter of unrestricted abortion. There are many venues to deliver women's health care. We should not be cheerleaders for the Planned Parenthood/Democratic party propaganda. As you stated, we should be truly a-political.

Laurence Burns, DO
Grand Rapids, Michigan

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

WHAT LIES AHEAD FOR WOMEN’S HEALTH? CHALLENGES, AND OPPORTUNITIES, AS ACOG AND US LEADERSHIP TRANSITION

LUCIA DIVENERE, MA

Politics and Planned Parenthood

As obstetricians and gynecologists, we are all dedicated to women's health care. Many of us are Pro-Life and resent your unqualified support of Planned Parenthood, the world’s largest provider and supporter of unrestricted abortion. There are many venues to deliver women's health care. We should not be cheerleaders for the Planned Parenthood/Democratic party propaganda. As you stated, we should be truly a-political.

Laurence Burns, DO
Grand Rapids, Michigan

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.