Gynecology

VANCOUVER, B.C.– A thorough preop work-up can just about eliminate the risk of accidentally morcellating an occult uterine sarcoma, according to a prospective series of 2,824 women referred for minimally invasive myomectomy to a French university hospital from 2002 to 2013.

The message came just days before the Food and Drug Administration’s Nov. 24 advice not to use power morcellationin the majority of women undergoing hysterectomy or myomectomy for uterine fibroids because “there is no reliable method for predicting whether a woman with fibroids may have a uterine sarcoma” that morcellation could spread. The agency estimated that about 1 in 350 fibroid patients actually have an occult sarcoma.

That’s close to the 1 in 400 incidence investigators at the Lariboisière Hospital in Paris found; the difference is that the French investigators detected all but one of the seven sarcomas in their series before entering the operating room, using a heightened screening protocol. “That’s the major difference between our series and the other series that the” FDA relied on for their advice, said lead investigator and gynecologic surgeon Dr. Afshin Fazel, an assistant professor of obstetrics and gynecology at Lariboisière Hospital.

Physicians at the hospital go further than some to rule out sarcomas prior to fibroid surgery. “Every single patient with a pelvic mass gets an MRI,” as well as a clinical exam and pelvic ultrasound. “If the endometrium is thicker than 4 mm, every patient older than 40 [years old] has endometrial sampling, and if there’s bleeding, every single patient has an office hysteroscopy.” A multidisciplinary team – oncologists, radiologists, gynecologists, and surgeons – review the results and select the appropriate surgical approach, Dr. Fazel said at a meeting sponsored by AAGL.

The screening protocol caught five of the seven sarcomas before surgery. A sixth case, a ruptured uterine sarcoma, presented emergently. All seven women had open surgeries, most had a hysterectomy as their initial operation, and none were morcellated. “The take-home message is that you need all the cards in your hand” to rule out sarcomas before myomectomy. No one screening test is sufficient. Some sarcomas, for instance, don’t have the usual MRI signs; of the three sarcomas the team had detected so far in 2014 – not included in the reported series – just one was found on MRI; the other two were found by endometrial sampling. “Preoperative diagnosis is the key to preventing [accidental] morcellation,” Dr. Fazel said.

The second message is that although “1 out of 400 fibroids in our series were actually sarcomas,” the extra screening meant that “the undiagnosed rate of sarcoma was” 0.035% (or 1 in 2,824), he said.

One of the sarcoma patients was from Taiwan, another was African, and the rest were French. Their age ranged from 38 to 78 years, with a mean age 50 years; two were postmenopausal. They had heavy bleeding and pain, and two had multiple masses. The average size of the uterus was 1,136 cc, and the average size of the mass 891 cc. Four of the seven patients died within 2 years of their surgery.

Among all 2,824 women, two-thirds had minimally invasive approaches, including 743 laparoscopic, 510 hysteroscopic, and 336 vaginal procedures; 262 had uterine artery embolization, which was pioneered by Lariboisière in the late 1980s.

Dr. Fazel said he has no disclosures.

aotto@frontlinemedcom.com

VANCOUVER, B.C.– A thorough preop work-up can just about eliminate the risk of accidentally morcellating an occult uterine sarcoma, according to a prospective series of 2,824 women referred for minimally invasive myomectomy to a French university hospital from 2002 to 2013.

The message came just days before the Food and Drug Administration’s Nov. 24 advice not to use power morcellationin the majority of women undergoing hysterectomy or myomectomy for uterine fibroids because “there is no reliable method for predicting whether a woman with fibroids may have a uterine sarcoma” that morcellation could spread. The agency estimated that about 1 in 350 fibroid patients actually have an occult sarcoma.

That’s close to the 1 in 400 incidence investigators at the Lariboisière Hospital in Paris found; the difference is that the French investigators detected all but one of the seven sarcomas in their series before entering the operating room, using a heightened screening protocol. “That’s the major difference between our series and the other series that the” FDA relied on for their advice, said lead investigator and gynecologic surgeon Dr. Afshin Fazel, an assistant professor of obstetrics and gynecology at Lariboisière Hospital.

Physicians at the hospital go further than some to rule out sarcomas prior to fibroid surgery. “Every single patient with a pelvic mass gets an MRI,” as well as a clinical exam and pelvic ultrasound. “If the endometrium is thicker than 4 mm, every patient older than 40 [years old] has endometrial sampling, and if there’s bleeding, every single patient has an office hysteroscopy.” A multidisciplinary team – oncologists, radiologists, gynecologists, and surgeons – review the results and select the appropriate surgical approach, Dr. Fazel said at a meeting sponsored by AAGL.

The screening protocol caught five of the seven sarcomas before surgery. A sixth case, a ruptured uterine sarcoma, presented emergently. All seven women had open surgeries, most had a hysterectomy as their initial operation, and none were morcellated. “The take-home message is that you need all the cards in your hand” to rule out sarcomas before myomectomy. No one screening test is sufficient. Some sarcomas, for instance, don’t have the usual MRI signs; of the three sarcomas the team had detected so far in 2014 – not included in the reported series – just one was found on MRI; the other two were found by endometrial sampling. “Preoperative diagnosis is the key to preventing [accidental] morcellation,” Dr. Fazel said.

The second message is that although “1 out of 400 fibroids in our series were actually sarcomas,” the extra screening meant that “the undiagnosed rate of sarcoma was” 0.035% (or 1 in 2,824), he said.

One of the sarcoma patients was from Taiwan, another was African, and the rest were French. Their age ranged from 38 to 78 years, with a mean age 50 years; two were postmenopausal. They had heavy bleeding and pain, and two had multiple masses. The average size of the uterus was 1,136 cc, and the average size of the mass 891 cc. Four of the seven patients died within 2 years of their surgery.

Among all 2,824 women, two-thirds had minimally invasive approaches, including 743 laparoscopic, 510 hysteroscopic, and 336 vaginal procedures; 262 had uterine artery embolization, which was pioneered by Lariboisière in the late 1980s.

Dr. Fazel said he has no disclosures.

aotto@frontlinemedcom.com

VANCOUVER, B.C.– A thorough preop work-up can just about eliminate the risk of accidentally morcellating an occult uterine sarcoma, according to a prospective series of 2,824 women referred for minimally invasive myomectomy to a French university hospital from 2002 to 2013.

The message came just days before the Food and Drug Administration’s Nov. 24 advice not to use power morcellationin the majority of women undergoing hysterectomy or myomectomy for uterine fibroids because “there is no reliable method for predicting whether a woman with fibroids may have a uterine sarcoma” that morcellation could spread. The agency estimated that about 1 in 350 fibroid patients actually have an occult sarcoma.

That’s close to the 1 in 400 incidence investigators at the Lariboisière Hospital in Paris found; the difference is that the French investigators detected all but one of the seven sarcomas in their series before entering the operating room, using a heightened screening protocol. “That’s the major difference between our series and the other series that the” FDA relied on for their advice, said lead investigator and gynecologic surgeon Dr. Afshin Fazel, an assistant professor of obstetrics and gynecology at Lariboisière Hospital.

Physicians at the hospital go further than some to rule out sarcomas prior to fibroid surgery. “Every single patient with a pelvic mass gets an MRI,” as well as a clinical exam and pelvic ultrasound. “If the endometrium is thicker than 4 mm, every patient older than 40 [years old] has endometrial sampling, and if there’s bleeding, every single patient has an office hysteroscopy.” A multidisciplinary team – oncologists, radiologists, gynecologists, and surgeons – review the results and select the appropriate surgical approach, Dr. Fazel said at a meeting sponsored by AAGL.

The screening protocol caught five of the seven sarcomas before surgery. A sixth case, a ruptured uterine sarcoma, presented emergently. All seven women had open surgeries, most had a hysterectomy as their initial operation, and none were morcellated. “The take-home message is that you need all the cards in your hand” to rule out sarcomas before myomectomy. No one screening test is sufficient. Some sarcomas, for instance, don’t have the usual MRI signs; of the three sarcomas the team had detected so far in 2014 – not included in the reported series – just one was found on MRI; the other two were found by endometrial sampling. “Preoperative diagnosis is the key to preventing [accidental] morcellation,” Dr. Fazel said.

The second message is that although “1 out of 400 fibroids in our series were actually sarcomas,” the extra screening meant that “the undiagnosed rate of sarcoma was” 0.035% (or 1 in 2,824), he said.

One of the sarcoma patients was from Taiwan, another was African, and the rest were French. Their age ranged from 38 to 78 years, with a mean age 50 years; two were postmenopausal. They had heavy bleeding and pain, and two had multiple masses. The average size of the uterus was 1,136 cc, and the average size of the mass 891 cc. Four of the seven patients died within 2 years of their surgery.

Among all 2,824 women, two-thirds had minimally invasive approaches, including 743 laparoscopic, 510 hysteroscopic, and 336 vaginal procedures; 262 had uterine artery embolization, which was pioneered by Lariboisière in the late 1980s.

Dr. Fazel said he has no disclosures.

aotto@frontlinemedcom.com

MELBOURNE – Staging endometrial cancer using sentinel lymph node mapping reduces side effects for patients, and enables selection of lymph nodes for pathology that are more likely to have disease in them, an investigator reported at the biennial meeting of the International Gynecologic Cancer Society.

The procedure results in fewer lymph nodes being removed – usually two to three on each side, and no more than ten – which meant less side effects such as lymphedema, and potentially avoided the need for pelvic lymphadenectomy said Dr. Nadeem Abu-Rustum, chief of the gynecology service at Memorial Sloan Kettering Cancer Center, New York.

“One, you are removing fewer lymph nodes so there’s less radicality in surgery and less side effects; two, it makes the operating time faster, and three, you give the pathologist fewer lymph nodes but they can work on them in more depth to try to find low-volume metastases,” Dr. Abu-Rustum said in an interview.

Bianca Nogrady/Frontline Medical News

“It’s a win-win situation for the patient.”

Dr. Abu-Rustum and colleagues at Memorial Sloan-Kettering have developed a sentinel lymph node mapping algorithm for stage I cervical or endometrial cancers.

“It is applicable for any women who has endometrial cancer where the surgeon feels that the cancer is contained, and you need staging information,” he said.

However he stressed it was not applicable in patients with obvious metastases or with abnormal lymph nodes.

“This is for normal-appearing lymph nodes, clinical stage I, and the algorithm checklist really protects you because it will exclude those patients [with abnormal lymph nodes].”

While there was ongoing debate about where to inject the dye to best identify the sentinel node, Dr. Abu-Rustum told the conference that he and his colleagues believed injecting into the cervix at the three o’clock and nine o’clock positions was the most reasonable option.

He also commented on the different dyes used, saying that while methylene blue or lymphazurin had been the traditional choice – with or without technetium-99 – the near-infrared fluorescing indocyanine green and use of a laser significantly improved accuracy of the procedure.

“Now you’re able to increase the chance of finding the lymph node from 80% to almost 100%, and finding it on the right and the left was 60%, now it’s 80%,” he said.

In another presentation, a speaker reported an overall sentinel lymph node detection rate of 92%, and a 74% rate of bilateral detection, using a combination of methylene blue, technetium-99, and indocyanine green, in 100 patients who underwent sentinel lymph node mapping for endometrial cancer.

Among the 10 patients in the prospective study who had metastatic disease, 9 had a positive sentinel lymph node. The sentinel node was found to be the only positive node in 66% of these patients, suggesting that this was the most clinically relevant node. There was one case of a false negative for a sentinel lymph node, reported Dr. Jeffrey How, obstetrics and gynecology resident at the McGill University Health Centre, Montreal.

The addition of indocyanine green increased the precision of in vivo detection of sentinel lymph nodes, aiding detection of the highest-yield lymph nodes for pathology, he said.

No conflicts of interest were declared.

MELBOURNE – Staging endometrial cancer using sentinel lymph node mapping reduces side effects for patients, and enables selection of lymph nodes for pathology that are more likely to have disease in them, an investigator reported at the biennial meeting of the International Gynecologic Cancer Society.

The procedure results in fewer lymph nodes being removed – usually two to three on each side, and no more than ten – which meant less side effects such as lymphedema, and potentially avoided the need for pelvic lymphadenectomy said Dr. Nadeem Abu-Rustum, chief of the gynecology service at Memorial Sloan Kettering Cancer Center, New York.

“One, you are removing fewer lymph nodes so there’s less radicality in surgery and less side effects; two, it makes the operating time faster, and three, you give the pathologist fewer lymph nodes but they can work on them in more depth to try to find low-volume metastases,” Dr. Abu-Rustum said in an interview.

Bianca Nogrady/Frontline Medical News

“It’s a win-win situation for the patient.”

Dr. Abu-Rustum and colleagues at Memorial Sloan-Kettering have developed a sentinel lymph node mapping algorithm for stage I cervical or endometrial cancers.

“It is applicable for any women who has endometrial cancer where the surgeon feels that the cancer is contained, and you need staging information,” he said.

However he stressed it was not applicable in patients with obvious metastases or with abnormal lymph nodes.

“This is for normal-appearing lymph nodes, clinical stage I, and the algorithm checklist really protects you because it will exclude those patients [with abnormal lymph nodes].”

While there was ongoing debate about where to inject the dye to best identify the sentinel node, Dr. Abu-Rustum told the conference that he and his colleagues believed injecting into the cervix at the three o’clock and nine o’clock positions was the most reasonable option.

He also commented on the different dyes used, saying that while methylene blue or lymphazurin had been the traditional choice – with or without technetium-99 – the near-infrared fluorescing indocyanine green and use of a laser significantly improved accuracy of the procedure.

“Now you’re able to increase the chance of finding the lymph node from 80% to almost 100%, and finding it on the right and the left was 60%, now it’s 80%,” he said.

In another presentation, a speaker reported an overall sentinel lymph node detection rate of 92%, and a 74% rate of bilateral detection, using a combination of methylene blue, technetium-99, and indocyanine green, in 100 patients who underwent sentinel lymph node mapping for endometrial cancer.

Among the 10 patients in the prospective study who had metastatic disease, 9 had a positive sentinel lymph node. The sentinel node was found to be the only positive node in 66% of these patients, suggesting that this was the most clinically relevant node. There was one case of a false negative for a sentinel lymph node, reported Dr. Jeffrey How, obstetrics and gynecology resident at the McGill University Health Centre, Montreal.

The addition of indocyanine green increased the precision of in vivo detection of sentinel lymph nodes, aiding detection of the highest-yield lymph nodes for pathology, he said.

No conflicts of interest were declared.

MELBOURNE – Staging endometrial cancer using sentinel lymph node mapping reduces side effects for patients, and enables selection of lymph nodes for pathology that are more likely to have disease in them, an investigator reported at the biennial meeting of the International Gynecologic Cancer Society.

The procedure results in fewer lymph nodes being removed – usually two to three on each side, and no more than ten – which meant less side effects such as lymphedema, and potentially avoided the need for pelvic lymphadenectomy said Dr. Nadeem Abu-Rustum, chief of the gynecology service at Memorial Sloan Kettering Cancer Center, New York.

“One, you are removing fewer lymph nodes so there’s less radicality in surgery and less side effects; two, it makes the operating time faster, and three, you give the pathologist fewer lymph nodes but they can work on them in more depth to try to find low-volume metastases,” Dr. Abu-Rustum said in an interview.

Bianca Nogrady/Frontline Medical News

“It’s a win-win situation for the patient.”

Dr. Abu-Rustum and colleagues at Memorial Sloan-Kettering have developed a sentinel lymph node mapping algorithm for stage I cervical or endometrial cancers.

“It is applicable for any women who has endometrial cancer where the surgeon feels that the cancer is contained, and you need staging information,” he said.

However he stressed it was not applicable in patients with obvious metastases or with abnormal lymph nodes.

“This is for normal-appearing lymph nodes, clinical stage I, and the algorithm checklist really protects you because it will exclude those patients [with abnormal lymph nodes].”

While there was ongoing debate about where to inject the dye to best identify the sentinel node, Dr. Abu-Rustum told the conference that he and his colleagues believed injecting into the cervix at the three o’clock and nine o’clock positions was the most reasonable option.

He also commented on the different dyes used, saying that while methylene blue or lymphazurin had been the traditional choice – with or without technetium-99 – the near-infrared fluorescing indocyanine green and use of a laser significantly improved accuracy of the procedure.

“Now you’re able to increase the chance of finding the lymph node from 80% to almost 100%, and finding it on the right and the left was 60%, now it’s 80%,” he said.

In another presentation, a speaker reported an overall sentinel lymph node detection rate of 92%, and a 74% rate of bilateral detection, using a combination of methylene blue, technetium-99, and indocyanine green, in 100 patients who underwent sentinel lymph node mapping for endometrial cancer.

Among the 10 patients in the prospective study who had metastatic disease, 9 had a positive sentinel lymph node. The sentinel node was found to be the only positive node in 66% of these patients, suggesting that this was the most clinically relevant node. There was one case of a false negative for a sentinel lymph node, reported Dr. Jeffrey How, obstetrics and gynecology resident at the McGill University Health Centre, Montreal.

The addition of indocyanine green increased the precision of in vivo detection of sentinel lymph nodes, aiding detection of the highest-yield lymph nodes for pathology, he said.

No conflicts of interest were declared.

Physicians should consider collecting additional biopsies during colposcopy if multiple lesions are present, according to the authors of a study finding the practice increases the detection of high-grade squamous intraepithelial lesions.

An observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results found sensitivity for detecting high-grade squamous intraepithelial lesions (HSILs) increased from 60.6% with a single biopsy to 85.6% with two biopsies and 95.6% with three biopsies.

“The incremental benefit of taking multiple biopsies was present regardless of referral cytology, HPV-16 status, and colposcopic impression; for example, even when there was a high-grade colposcopic impression, a single biopsy did not identify a prevalent HSIL in 35% of the women,” wrote Dr. Nicolas Wentzensen of the National Cancer Institute, Bethesda, Md., and colleagues.

Researchers found an increase in sensitivity of multiple biopsies across a range of subgroups, although the additional biopsies found more disease among women with more severe referral cytology, higher-risk HPV status, and higher-risk colposcopic impression, according to the study, published online Nov. 24 in the Journal of Clinical Oncology [doi:10.1200/JCO.2014.55.9948].

Physicians should consider collecting additional biopsies during colposcopy if multiple lesions are present, according to the authors of a study finding the practice increases the detection of high-grade squamous intraepithelial lesions.

An observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results found sensitivity for detecting high-grade squamous intraepithelial lesions (HSILs) increased from 60.6% with a single biopsy to 85.6% with two biopsies and 95.6% with three biopsies.

“The incremental benefit of taking multiple biopsies was present regardless of referral cytology, HPV-16 status, and colposcopic impression; for example, even when there was a high-grade colposcopic impression, a single biopsy did not identify a prevalent HSIL in 35% of the women,” wrote Dr. Nicolas Wentzensen of the National Cancer Institute, Bethesda, Md., and colleagues.

Researchers found an increase in sensitivity of multiple biopsies across a range of subgroups, although the additional biopsies found more disease among women with more severe referral cytology, higher-risk HPV status, and higher-risk colposcopic impression, according to the study, published online Nov. 24 in the Journal of Clinical Oncology [doi:10.1200/JCO.2014.55.9948].

Physicians should consider collecting additional biopsies during colposcopy if multiple lesions are present, according to the authors of a study finding the practice increases the detection of high-grade squamous intraepithelial lesions.

An observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results found sensitivity for detecting high-grade squamous intraepithelial lesions (HSILs) increased from 60.6% with a single biopsy to 85.6% with two biopsies and 95.6% with three biopsies.

“The incremental benefit of taking multiple biopsies was present regardless of referral cytology, HPV-16 status, and colposcopic impression; for example, even when there was a high-grade colposcopic impression, a single biopsy did not identify a prevalent HSIL in 35% of the women,” wrote Dr. Nicolas Wentzensen of the National Cancer Institute, Bethesda, Md., and colleagues.

Researchers found an increase in sensitivity of multiple biopsies across a range of subgroups, although the additional biopsies found more disease among women with more severe referral cytology, higher-risk HPV status, and higher-risk colposcopic impression, according to the study, published online Nov. 24 in the Journal of Clinical Oncology [doi:10.1200/JCO.2014.55.9948].

The laparoscopic power morcellator, in wide use for years, should not be used in the “vast majority” of women undergoing a hysterectomy or myomectomy, the Food and Drug Administration announced.

The updated safety communication regarding the use of laparoscopic power morcellators to treat uterine fibroids includes an Immediately in Effect guidance to manufacturers of the devices that the labels should include “specific safety statements” in the form of a boxed warning and two contraindications on proper usage.

“The FDA’s primary concern is the safety and well-being of patients and taking these steps will help the agency’s safety recommendations to be implemented as quickly as possible,” Dr. William Maisel, deputy director for science and chief scientist at the FDA’s Center for Devices and Radiological Health, said in a statement. “Updating the device label with a boxed warning and contraindications will provide clinicians and patients with critical information about the risk of spreading cancerous tissue when these procedures are performed.”

According to the FDA announcement, the boxed warning on future labels should say, “Uterine tissue may contain unsuspected cancer. The use of laparoscopic power morcellators during fibroid surgery may spread cancer and decrease the long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.”

The first of the two contraindications, both of which also would be included on all future laparoscopic power morcellator labels, warns against using the devices for removal of uterine tissue that possibly contains fibroids in patients who are perimenopausal or postmenopausal, and candidates for en bloc tissue removal through the vagina or minilaparotomy incision, as these groups of women “represent the majority of women with fibroids who undergo hysterectomy and myomectomy.” The second contraindication cautions against using laparoscopic power morcellators “in gynecologic surgery in which the tissue to be morcellated is known or suspected to be cancerous.”

“The FDA strongly encourages doctors to inform their patients of the risk of spreading unsuspected cancer from the use of these devices in fibroid surgery and discuss the benefits and risks associated with all treatment options,” Dr. Maisel said in a statement.

This announcement appears to be stronger than the previous statement, “perhaps geared to those select few who have not ceased using the laparoscopic power morcellator,” Dr. David Jaspan, chairman of the department of obstetrics and gynecology at Einstein Medical Center, Philadelphia, said in an interview. “Gynecologic surgeons must collaborate with medical engineers to create equipment that will enable women to once again enjoy the advantages of minimally invasive techniques that we have worked so hard to develop,” he added. “We have seen an increased number of laparotomies, and thus increased women’s risk for postoperative morbidity. I am hopeful that novel approaches will soon be made available for our patients.”

This latest set of warnings is an update of guidelines originally issued by the FDA in April 2014, in which the federal agency stated that use of laparoscopic power morcellators for hysterectomy or myomectomy can significantly increase the risk of spreading “unsuspected” cancer found in the tissue of the uterine wall. A quantitative analysis released by the FDA estimated that 1 in 350 women who undergo hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma.

The agency announced that its Immediately in Effect (IIE) guidance applies to all new and currently marketed laparoscopic power morcellators used for “general and specific gynecological indications.”

The campaign to highlight the risks of morcellators has been led by Dr. Hooman Noorchashm, a cardiothoracic surgeon, and his wife, Dr. Amy Reed, an anesthesiologist who was diagnosed with stage 4 leiomyosarcoma after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids. Dr. Noorchashm and Dr. Reed have called for a ban on the use of laparoscopic power morcellators.

Asked to comment on the FDA announcement, Dr. Noorchashm said the decision represents “ a massive and historic regulatory failure on the part of FDA Center for Devices and Radiological Health.”

In an interview, he added, “The evidence of avoidable deadly harm was beyond doubt in this case. But the FDA CDRH could not bring itself to fully protect those at risk. This demonstrates that the FDA is a ‘captured agency’ with more loyalty to corporate and industry interests than to patient safety. I think the United States Congress needs to conduct a hearing and overhaul and clarify the FDA’s overall mission. And in particular medical device safety legislation. Corporations have power, people don’t. And without cogent federal government, lives are left exposed.”

--Elizabeth Mechcatie contributed to this article.

dchitnis@frontlinemedcom.com 

*This article was updated November 24, 2014.

The laparoscopic power morcellator, in wide use for years, should not be used in the “vast majority” of women undergoing a hysterectomy or myomectomy, the Food and Drug Administration announced.

The updated safety communication regarding the use of laparoscopic power morcellators to treat uterine fibroids includes an Immediately in Effect guidance to manufacturers of the devices that the labels should include “specific safety statements” in the form of a boxed warning and two contraindications on proper usage.

“The FDA’s primary concern is the safety and well-being of patients and taking these steps will help the agency’s safety recommendations to be implemented as quickly as possible,” Dr. William Maisel, deputy director for science and chief scientist at the FDA’s Center for Devices and Radiological Health, said in a statement. “Updating the device label with a boxed warning and contraindications will provide clinicians and patients with critical information about the risk of spreading cancerous tissue when these procedures are performed.”

According to the FDA announcement, the boxed warning on future labels should say, “Uterine tissue may contain unsuspected cancer. The use of laparoscopic power morcellators during fibroid surgery may spread cancer and decrease the long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.”

The first of the two contraindications, both of which also would be included on all future laparoscopic power morcellator labels, warns against using the devices for removal of uterine tissue that possibly contains fibroids in patients who are perimenopausal or postmenopausal, and candidates for en bloc tissue removal through the vagina or minilaparotomy incision, as these groups of women “represent the majority of women with fibroids who undergo hysterectomy and myomectomy.” The second contraindication cautions against using laparoscopic power morcellators “in gynecologic surgery in which the tissue to be morcellated is known or suspected to be cancerous.”

“The FDA strongly encourages doctors to inform their patients of the risk of spreading unsuspected cancer from the use of these devices in fibroid surgery and discuss the benefits and risks associated with all treatment options,” Dr. Maisel said in a statement.

This announcement appears to be stronger than the previous statement, “perhaps geared to those select few who have not ceased using the laparoscopic power morcellator,” Dr. David Jaspan, chairman of the department of obstetrics and gynecology at Einstein Medical Center, Philadelphia, said in an interview. “Gynecologic surgeons must collaborate with medical engineers to create equipment that will enable women to once again enjoy the advantages of minimally invasive techniques that we have worked so hard to develop,” he added. “We have seen an increased number of laparotomies, and thus increased women’s risk for postoperative morbidity. I am hopeful that novel approaches will soon be made available for our patients.”

This latest set of warnings is an update of guidelines originally issued by the FDA in April 2014, in which the federal agency stated that use of laparoscopic power morcellators for hysterectomy or myomectomy can significantly increase the risk of spreading “unsuspected” cancer found in the tissue of the uterine wall. A quantitative analysis released by the FDA estimated that 1 in 350 women who undergo hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma.

The agency announced that its Immediately in Effect (IIE) guidance applies to all new and currently marketed laparoscopic power morcellators used for “general and specific gynecological indications.”

The campaign to highlight the risks of morcellators has been led by Dr. Hooman Noorchashm, a cardiothoracic surgeon, and his wife, Dr. Amy Reed, an anesthesiologist who was diagnosed with stage 4 leiomyosarcoma after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids. Dr. Noorchashm and Dr. Reed have called for a ban on the use of laparoscopic power morcellators.

Asked to comment on the FDA announcement, Dr. Noorchashm said the decision represents “ a massive and historic regulatory failure on the part of FDA Center for Devices and Radiological Health.”

In an interview, he added, “The evidence of avoidable deadly harm was beyond doubt in this case. But the FDA CDRH could not bring itself to fully protect those at risk. This demonstrates that the FDA is a ‘captured agency’ with more loyalty to corporate and industry interests than to patient safety. I think the United States Congress needs to conduct a hearing and overhaul and clarify the FDA’s overall mission. And in particular medical device safety legislation. Corporations have power, people don’t. And without cogent federal government, lives are left exposed.”

--Elizabeth Mechcatie contributed to this article.

dchitnis@frontlinemedcom.com 

*This article was updated November 24, 2014.

The laparoscopic power morcellator, in wide use for years, should not be used in the “vast majority” of women undergoing a hysterectomy or myomectomy, the Food and Drug Administration announced.

The updated safety communication regarding the use of laparoscopic power morcellators to treat uterine fibroids includes an Immediately in Effect guidance to manufacturers of the devices that the labels should include “specific safety statements” in the form of a boxed warning and two contraindications on proper usage.

“The FDA’s primary concern is the safety and well-being of patients and taking these steps will help the agency’s safety recommendations to be implemented as quickly as possible,” Dr. William Maisel, deputy director for science and chief scientist at the FDA’s Center for Devices and Radiological Health, said in a statement. “Updating the device label with a boxed warning and contraindications will provide clinicians and patients with critical information about the risk of spreading cancerous tissue when these procedures are performed.”

According to the FDA announcement, the boxed warning on future labels should say, “Uterine tissue may contain unsuspected cancer. The use of laparoscopic power morcellators during fibroid surgery may spread cancer and decrease the long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.”

The first of the two contraindications, both of which also would be included on all future laparoscopic power morcellator labels, warns against using the devices for removal of uterine tissue that possibly contains fibroids in patients who are perimenopausal or postmenopausal, and candidates for en bloc tissue removal through the vagina or minilaparotomy incision, as these groups of women “represent the majority of women with fibroids who undergo hysterectomy and myomectomy.” The second contraindication cautions against using laparoscopic power morcellators “in gynecologic surgery in which the tissue to be morcellated is known or suspected to be cancerous.”

“The FDA strongly encourages doctors to inform their patients of the risk of spreading unsuspected cancer from the use of these devices in fibroid surgery and discuss the benefits and risks associated with all treatment options,” Dr. Maisel said in a statement.

This announcement appears to be stronger than the previous statement, “perhaps geared to those select few who have not ceased using the laparoscopic power morcellator,” Dr. David Jaspan, chairman of the department of obstetrics and gynecology at Einstein Medical Center, Philadelphia, said in an interview. “Gynecologic surgeons must collaborate with medical engineers to create equipment that will enable women to once again enjoy the advantages of minimally invasive techniques that we have worked so hard to develop,” he added. “We have seen an increased number of laparotomies, and thus increased women’s risk for postoperative morbidity. I am hopeful that novel approaches will soon be made available for our patients.”

This latest set of warnings is an update of guidelines originally issued by the FDA in April 2014, in which the federal agency stated that use of laparoscopic power morcellators for hysterectomy or myomectomy can significantly increase the risk of spreading “unsuspected” cancer found in the tissue of the uterine wall. A quantitative analysis released by the FDA estimated that 1 in 350 women who undergo hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma.

The agency announced that its Immediately in Effect (IIE) guidance applies to all new and currently marketed laparoscopic power morcellators used for “general and specific gynecological indications.”

The campaign to highlight the risks of morcellators has been led by Dr. Hooman Noorchashm, a cardiothoracic surgeon, and his wife, Dr. Amy Reed, an anesthesiologist who was diagnosed with stage 4 leiomyosarcoma after undergoing a hysterectomy with morcellation at the age of 40 for what was thought to be benign fibroids. Dr. Noorchashm and Dr. Reed have called for a ban on the use of laparoscopic power morcellators.

Asked to comment on the FDA announcement, Dr. Noorchashm said the decision represents “ a massive and historic regulatory failure on the part of FDA Center for Devices and Radiological Health.”

In an interview, he added, “The evidence of avoidable deadly harm was beyond doubt in this case. But the FDA CDRH could not bring itself to fully protect those at risk. This demonstrates that the FDA is a ‘captured agency’ with more loyalty to corporate and industry interests than to patient safety. I think the United States Congress needs to conduct a hearing and overhaul and clarify the FDA’s overall mission. And in particular medical device safety legislation. Corporations have power, people don’t. And without cogent federal government, lives are left exposed.”

--Elizabeth Mechcatie contributed to this article.

dchitnis@frontlinemedcom.com 

*This article was updated November 24, 2014.

Testosterone supplementation is not recommended for women, unless they have a clinical diagnosis of hypoactive sexual desire disorder, a joint task force led by the Endocrine Society has determined.

While a number of studies have shown that testosterone supplementation helps improve sexual desire, cognition, and other outcomes, most are either too small, too short, or confounded by other factors to provide irrefutable evidence of the hormone’s benefit for any indication other than hypoactive sexual desire disorder (HSDD), Dr. Margaret E. Wierman and her colleagues wrote in the Journal of Clinical Endocrinology and Metabolism (J. Clin. Endocrinol. Metab. 2014;99:3489-510).

A trial of testosterone is only appropriate for postmenopausal women with a diagnosed HSDD, wrote the task force, which also noted that libido and response improvements don’t necessarily correlate with testosterone serum levels. If there’s no clinical response after a 6-month trial, the hormone should be discontinued.

The hormone-health connection is clearly important to women, and many have already done Internet research on the topic, said Dr. Margery Gass, executive director of the North American Menopause Society. A Google query for “hormones to control aging” turned up 9.5 million results, she said.

Although NAMS was not involved in creating the new clinical guideline, the society supports it, she said in an interview.

“The Endocrine Society has published an excellent set of guidelines on the use of androgen therapy in women. These guidelines are in harmony with NAMS’ comments on the use of testosterone and dehydroepiandrosterones,” included in the group’s clinical practice guideline for the care of midlife women (Menopause 2014;21:1038-62). That paper also recommends a trial of testosterone therapy “in carefully selected postmenopausal women with female sexual interest/arousal disorder and no other etiology for their sexual problems.”

Dr. Gass continued, “I encourage clinicians to use both publications to help women understand the misinformation about testosterone and other androgens that they are seeing on the Internet.”

Dr. Wierman, chief of endocrinology at the University of Colorado, Aurora, led the task force, composed of representatives from the American Society for Reproductive Medicine, the American Congress of Obstetricians and Gynecologists, the European Society of Endocrinology, and the International Menopause Society. Together, they reviewed the extant literature and, in addition, commissioned meta-analyses to examine the issue of androgen supplementation in premenopausal and postmenopausal women – either healthy or with specific conditions. Evidence was graded as level 1 (strong) or level 2 (weak).

The group considered androgen supplementation for a number of indications: infertility; sexual dysfunction; cognition; cardiovascular, metabolic, and bone health; and general well-being. It found little strong data to support the practice in any of these except HSDD.

As a basic tenet, the task force agreed that androgen testing for most women is inaccurate, and thus virtually incapable of providing useful diagnostic information. Testosterone levels vary among women and within their different hormonal life stages, and there are no validated reference ranges.

Sexual function

A controversial issue, women’s sexual health remains somewhat of a mystery, the team noted – a complex web of physical, emotional, and psychological factors. Evidence derived from testosterone therapy in postmenopausal women shows that the hormone may influence all aspects of sexual response by improving desire, subjective arousal, and vaginal blood flow, and increasing frequency of orgasm.

However, decreasing sexuality is a common phenomenon for women, and is not dependent on physiologic testosterone levels. While response to testosterone therapy didn’t always correlate with plasma levels, most trials found that a daily dose of 300 mcg provided optimal benefit. One study found a more than 115% increase in reported orgasms, compared with a 38% increase in the placebo group, and another found 2.12 more satisfactory sexual events per month, compared with 0.73 per month with placebo.

One trial of a testosterone gel was negative, but was only available as an abstract. A large randomized trial of transdermal testosterone gel that recruited 3,565 naturally and surgically postmenopausal women, and accrued several thousand women-years of data, has yet to be published.

For postmenopausal women with properly diagnosed HSDD, the task force recommended a 3- to 6-month trial of testosterone for those who request therapy and in whom it is not contraindicated.

Testosterone levels should be measured at baseline and after 3-6 weeks of initial treatment to assess patient overuse. In cases of ongoing testosterone therapy, levels should be reviewed every 6 months to monitor for excessive use and signs of androgen excess.

Other indications

The task force noted insufficient evidence for the following indications:

• Infertility. One meta-analysis reported an overall 11% increase in live births; another found no benefit. The individual studies were marred by methodological issues, the team said.

• Bone. Several small studies showed increased bone density in some locations after testosterone therapy. However, many women received concomitant estrogens, so the studies were confounded, the team noted.

• Cognition. Several studies have hinted that testosterone may be protective against Alzheimer’s and other dementias in women, possibly by mediating the accumulation of neurotoxic amyloid beta brain plaques. Women taking the hormone scored better on cognitive tests, including verbal memory, as well as spatial and mathematical reasoning. “In addition to having neuroprotective effects, testosterone has positive effects on endothelial function and acts as a vasodilator, providing another potential pathway through which testosterone may confer neuroprotection,” the investigators said. Again, however, they felt that the body and quality of evidence were not enough to justify a recommendation.

• Cardiovascular. Higher endogenous testosterone in women has been associated with better endothelial function and lower carotid intima-medial thickness; exogenous testosterone has not been adequately studied. However, testosterone supplementation does not seem to negatively affect lipids or increase other cardiovascular risk markers.

• Body composition. Several large studies of women with testosterone-alone and testosterone-estradiol therapy found increased lean muscle mass and lower body fat mass. These results were seen in healthy women as well as those with Turner syndrome, anorexia nervosa, and HIV infections. “Thus,” the investigators concluded, “testosterone increases lean body mass and may decrease fat mass in women, but effects are less dramatic than in men.”

• Mood. Testosterone therapy resulted in improved mood and lower depression scores in several studies, but subjects in some were not screened for comorbidities, including sexual dysfunction.

• Side effects. The potential for masculinizing effects – acne, hirsutism, deepening of the voice, and androgenic alopecia – exists. They are dose dependent, uncommon, and short-lived once supraphysiologic levels are decreased. Findings on breast cancer risk are contradictory; the team said more study is necessary.

The task force commissioned a testosterone therapy meta-analysis of published randomized trials of testosterone-alone or in addition to hormone replacement therapy. “Across all trials, testosterone use was associated with a statistically significant improvement in satisfaction, pleasure, orgasm, and libido. The quality of evidence was moderate to high for pleasure and orgasm outcomes, and moderate for satisfaction and libido outcomes,” with minimal effect on lipids and none on hair growth or loss.

“However,” the task force wrote, “data on adverse effects were not extensive, particularly for long-term use,” with a follow-up of 6 weeks to 2 years.

Dr. Wierman had no financial disclosures. However, several coauthors had numerous disclosures, including financial ties with pharmaceutical companies.

sullivan@frontlinemedcom.com 


On Twitter @alz_gal

Testosterone supplementation is not recommended for women, unless they have a clinical diagnosis of hypoactive sexual desire disorder, a joint task force led by the Endocrine Society has determined.

While a number of studies have shown that testosterone supplementation helps improve sexual desire, cognition, and other outcomes, most are either too small, too short, or confounded by other factors to provide irrefutable evidence of the hormone’s benefit for any indication other than hypoactive sexual desire disorder (HSDD), Dr. Margaret E. Wierman and her colleagues wrote in the Journal of Clinical Endocrinology and Metabolism (J. Clin. Endocrinol. Metab. 2014;99:3489-510).

A trial of testosterone is only appropriate for postmenopausal women with a diagnosed HSDD, wrote the task force, which also noted that libido and response improvements don’t necessarily correlate with testosterone serum levels. If there’s no clinical response after a 6-month trial, the hormone should be discontinued.

The hormone-health connection is clearly important to women, and many have already done Internet research on the topic, said Dr. Margery Gass, executive director of the North American Menopause Society. A Google query for “hormones to control aging” turned up 9.5 million results, she said.

Although NAMS was not involved in creating the new clinical guideline, the society supports it, she said in an interview.

“The Endocrine Society has published an excellent set of guidelines on the use of androgen therapy in women. These guidelines are in harmony with NAMS’ comments on the use of testosterone and dehydroepiandrosterones,” included in the group’s clinical practice guideline for the care of midlife women (Menopause 2014;21:1038-62). That paper also recommends a trial of testosterone therapy “in carefully selected postmenopausal women with female sexual interest/arousal disorder and no other etiology for their sexual problems.”

Dr. Gass continued, “I encourage clinicians to use both publications to help women understand the misinformation about testosterone and other androgens that they are seeing on the Internet.”

Dr. Wierman, chief of endocrinology at the University of Colorado, Aurora, led the task force, composed of representatives from the American Society for Reproductive Medicine, the American Congress of Obstetricians and Gynecologists, the European Society of Endocrinology, and the International Menopause Society. Together, they reviewed the extant literature and, in addition, commissioned meta-analyses to examine the issue of androgen supplementation in premenopausal and postmenopausal women – either healthy or with specific conditions. Evidence was graded as level 1 (strong) or level 2 (weak).

The group considered androgen supplementation for a number of indications: infertility; sexual dysfunction; cognition; cardiovascular, metabolic, and bone health; and general well-being. It found little strong data to support the practice in any of these except HSDD.

As a basic tenet, the task force agreed that androgen testing for most women is inaccurate, and thus virtually incapable of providing useful diagnostic information. Testosterone levels vary among women and within their different hormonal life stages, and there are no validated reference ranges.

Sexual function

A controversial issue, women’s sexual health remains somewhat of a mystery, the team noted – a complex web of physical, emotional, and psychological factors. Evidence derived from testosterone therapy in postmenopausal women shows that the hormone may influence all aspects of sexual response by improving desire, subjective arousal, and vaginal blood flow, and increasing frequency of orgasm.

However, decreasing sexuality is a common phenomenon for women, and is not dependent on physiologic testosterone levels. While response to testosterone therapy didn’t always correlate with plasma levels, most trials found that a daily dose of 300 mcg provided optimal benefit. One study found a more than 115% increase in reported orgasms, compared with a 38% increase in the placebo group, and another found 2.12 more satisfactory sexual events per month, compared with 0.73 per month with placebo.

One trial of a testosterone gel was negative, but was only available as an abstract. A large randomized trial of transdermal testosterone gel that recruited 3,565 naturally and surgically postmenopausal women, and accrued several thousand women-years of data, has yet to be published.

For postmenopausal women with properly diagnosed HSDD, the task force recommended a 3- to 6-month trial of testosterone for those who request therapy and in whom it is not contraindicated.

Testosterone levels should be measured at baseline and after 3-6 weeks of initial treatment to assess patient overuse. In cases of ongoing testosterone therapy, levels should be reviewed every 6 months to monitor for excessive use and signs of androgen excess.

Other indications

The task force noted insufficient evidence for the following indications:

• Infertility. One meta-analysis reported an overall 11% increase in live births; another found no benefit. The individual studies were marred by methodological issues, the team said.

• Bone. Several small studies showed increased bone density in some locations after testosterone therapy. However, many women received concomitant estrogens, so the studies were confounded, the team noted.

• Cognition. Several studies have hinted that testosterone may be protective against Alzheimer’s and other dementias in women, possibly by mediating the accumulation of neurotoxic amyloid beta brain plaques. Women taking the hormone scored better on cognitive tests, including verbal memory, as well as spatial and mathematical reasoning. “In addition to having neuroprotective effects, testosterone has positive effects on endothelial function and acts as a vasodilator, providing another potential pathway through which testosterone may confer neuroprotection,” the investigators said. Again, however, they felt that the body and quality of evidence were not enough to justify a recommendation.

• Cardiovascular. Higher endogenous testosterone in women has been associated with better endothelial function and lower carotid intima-medial thickness; exogenous testosterone has not been adequately studied. However, testosterone supplementation does not seem to negatively affect lipids or increase other cardiovascular risk markers.

• Body composition. Several large studies of women with testosterone-alone and testosterone-estradiol therapy found increased lean muscle mass and lower body fat mass. These results were seen in healthy women as well as those with Turner syndrome, anorexia nervosa, and HIV infections. “Thus,” the investigators concluded, “testosterone increases lean body mass and may decrease fat mass in women, but effects are less dramatic than in men.”

• Mood. Testosterone therapy resulted in improved mood and lower depression scores in several studies, but subjects in some were not screened for comorbidities, including sexual dysfunction.

• Side effects. The potential for masculinizing effects – acne, hirsutism, deepening of the voice, and androgenic alopecia – exists. They are dose dependent, uncommon, and short-lived once supraphysiologic levels are decreased. Findings on breast cancer risk are contradictory; the team said more study is necessary.

The task force commissioned a testosterone therapy meta-analysis of published randomized trials of testosterone-alone or in addition to hormone replacement therapy. “Across all trials, testosterone use was associated with a statistically significant improvement in satisfaction, pleasure, orgasm, and libido. The quality of evidence was moderate to high for pleasure and orgasm outcomes, and moderate for satisfaction and libido outcomes,” with minimal effect on lipids and none on hair growth or loss.

“However,” the task force wrote, “data on adverse effects were not extensive, particularly for long-term use,” with a follow-up of 6 weeks to 2 years.

Dr. Wierman had no financial disclosures. However, several coauthors had numerous disclosures, including financial ties with pharmaceutical companies.

sullivan@frontlinemedcom.com 


On Twitter @alz_gal

Testosterone supplementation is not recommended for women, unless they have a clinical diagnosis of hypoactive sexual desire disorder, a joint task force led by the Endocrine Society has determined.

While a number of studies have shown that testosterone supplementation helps improve sexual desire, cognition, and other outcomes, most are either too small, too short, or confounded by other factors to provide irrefutable evidence of the hormone’s benefit for any indication other than hypoactive sexual desire disorder (HSDD), Dr. Margaret E. Wierman and her colleagues wrote in the Journal of Clinical Endocrinology and Metabolism (J. Clin. Endocrinol. Metab. 2014;99:3489-510).

A trial of testosterone is only appropriate for postmenopausal women with a diagnosed HSDD, wrote the task force, which also noted that libido and response improvements don’t necessarily correlate with testosterone serum levels. If there’s no clinical response after a 6-month trial, the hormone should be discontinued.

The hormone-health connection is clearly important to women, and many have already done Internet research on the topic, said Dr. Margery Gass, executive director of the North American Menopause Society. A Google query for “hormones to control aging” turned up 9.5 million results, she said.

Although NAMS was not involved in creating the new clinical guideline, the society supports it, she said in an interview.

“The Endocrine Society has published an excellent set of guidelines on the use of androgen therapy in women. These guidelines are in harmony with NAMS’ comments on the use of testosterone and dehydroepiandrosterones,” included in the group’s clinical practice guideline for the care of midlife women (Menopause 2014;21:1038-62). That paper also recommends a trial of testosterone therapy “in carefully selected postmenopausal women with female sexual interest/arousal disorder and no other etiology for their sexual problems.”

Dr. Gass continued, “I encourage clinicians to use both publications to help women understand the misinformation about testosterone and other androgens that they are seeing on the Internet.”

Dr. Wierman, chief of endocrinology at the University of Colorado, Aurora, led the task force, composed of representatives from the American Society for Reproductive Medicine, the American Congress of Obstetricians and Gynecologists, the European Society of Endocrinology, and the International Menopause Society. Together, they reviewed the extant literature and, in addition, commissioned meta-analyses to examine the issue of androgen supplementation in premenopausal and postmenopausal women – either healthy or with specific conditions. Evidence was graded as level 1 (strong) or level 2 (weak).

The group considered androgen supplementation for a number of indications: infertility; sexual dysfunction; cognition; cardiovascular, metabolic, and bone health; and general well-being. It found little strong data to support the practice in any of these except HSDD.

As a basic tenet, the task force agreed that androgen testing for most women is inaccurate, and thus virtually incapable of providing useful diagnostic information. Testosterone levels vary among women and within their different hormonal life stages, and there are no validated reference ranges.

Sexual function

A controversial issue, women’s sexual health remains somewhat of a mystery, the team noted – a complex web of physical, emotional, and psychological factors. Evidence derived from testosterone therapy in postmenopausal women shows that the hormone may influence all aspects of sexual response by improving desire, subjective arousal, and vaginal blood flow, and increasing frequency of orgasm.

However, decreasing sexuality is a common phenomenon for women, and is not dependent on physiologic testosterone levels. While response to testosterone therapy didn’t always correlate with plasma levels, most trials found that a daily dose of 300 mcg provided optimal benefit. One study found a more than 115% increase in reported orgasms, compared with a 38% increase in the placebo group, and another found 2.12 more satisfactory sexual events per month, compared with 0.73 per month with placebo.

One trial of a testosterone gel was negative, but was only available as an abstract. A large randomized trial of transdermal testosterone gel that recruited 3,565 naturally and surgically postmenopausal women, and accrued several thousand women-years of data, has yet to be published.

For postmenopausal women with properly diagnosed HSDD, the task force recommended a 3- to 6-month trial of testosterone for those who request therapy and in whom it is not contraindicated.

Testosterone levels should be measured at baseline and after 3-6 weeks of initial treatment to assess patient overuse. In cases of ongoing testosterone therapy, levels should be reviewed every 6 months to monitor for excessive use and signs of androgen excess.

Other indications

The task force noted insufficient evidence for the following indications:

• Infertility. One meta-analysis reported an overall 11% increase in live births; another found no benefit. The individual studies were marred by methodological issues, the team said.

• Bone. Several small studies showed increased bone density in some locations after testosterone therapy. However, many women received concomitant estrogens, so the studies were confounded, the team noted.

• Cognition. Several studies have hinted that testosterone may be protective against Alzheimer’s and other dementias in women, possibly by mediating the accumulation of neurotoxic amyloid beta brain plaques. Women taking the hormone scored better on cognitive tests, including verbal memory, as well as spatial and mathematical reasoning. “In addition to having neuroprotective effects, testosterone has positive effects on endothelial function and acts as a vasodilator, providing another potential pathway through which testosterone may confer neuroprotection,” the investigators said. Again, however, they felt that the body and quality of evidence were not enough to justify a recommendation.

• Cardiovascular. Higher endogenous testosterone in women has been associated with better endothelial function and lower carotid intima-medial thickness; exogenous testosterone has not been adequately studied. However, testosterone supplementation does not seem to negatively affect lipids or increase other cardiovascular risk markers.

• Body composition. Several large studies of women with testosterone-alone and testosterone-estradiol therapy found increased lean muscle mass and lower body fat mass. These results were seen in healthy women as well as those with Turner syndrome, anorexia nervosa, and HIV infections. “Thus,” the investigators concluded, “testosterone increases lean body mass and may decrease fat mass in women, but effects are less dramatic than in men.”

• Mood. Testosterone therapy resulted in improved mood and lower depression scores in several studies, but subjects in some were not screened for comorbidities, including sexual dysfunction.

• Side effects. The potential for masculinizing effects – acne, hirsutism, deepening of the voice, and androgenic alopecia – exists. They are dose dependent, uncommon, and short-lived once supraphysiologic levels are decreased. Findings on breast cancer risk are contradictory; the team said more study is necessary.

The task force commissioned a testosterone therapy meta-analysis of published randomized trials of testosterone-alone or in addition to hormone replacement therapy. “Across all trials, testosterone use was associated with a statistically significant improvement in satisfaction, pleasure, orgasm, and libido. The quality of evidence was moderate to high for pleasure and orgasm outcomes, and moderate for satisfaction and libido outcomes,” with minimal effect on lipids and none on hair growth or loss.

“However,” the task force wrote, “data on adverse effects were not extensive, particularly for long-term use,” with a follow-up of 6 weeks to 2 years.

Dr. Wierman had no financial disclosures. However, several coauthors had numerous disclosures, including financial ties with pharmaceutical companies.

sullivan@frontlinemedcom.com 


On Twitter @alz_gal

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

msullivan@frontlinemedcom.com