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Refutes concept of overdiagnosis of breast cancer
“MORE THAN ONE-THIRD OF TUMORS FOUND ON BREAST CANCER SCREENING REPRESENT OVERDIAGNOSIS”
ANDREW M. KAUNITZ, MD (MARCH 2017)
Refutes concept of overdiagnosis of breast cancer
I read with interest and serious concern the commentary and conclusions of “overdiagnosed” breast cancer. Let us revisit a few time-honored principles. Are we throwing away the valued concept of the early diagnosis of node-negative breast cancer? Is it still true that 5-year and long-term survivals are markedly better for stage I and II disease as opposed to stage III and IV disease? Is it still true that treatments designed for cure are substantially less involved, more successful, and more likely to conserve the breast and require less chemotherapy in early stage disease? Is it still true that the majority of women diagnosed with breast cancer are in the lowest risk category, ie, no family history and negative for the BRCA gene? If so, then who can explain the statement that “an invasive breast cancer detected by any means is overdiagnosis”? Would this imply that screening and the biopsy required to make the diagnosis was time poorly spent, the breast cancer should not be treated, and/or we should simply wait for a lump to be found by the patient deep in a large breast most likely at that point representing advanced disease?
The last paragraph notes the current US Preventive Services Task Force (USPSTF) guidance: wait until 50 years of age to start biennial screening. If so, what do we say to women in their 40s who, through screening with mammography and/or ultrasound, were diagnosed with early node-negative invasive breast cancer? That all of that was unnecessary and would not have led to symptoms? Would extreme morbidity from advanced or recurrent disease and the horrors of treatment just to extend a few months of life qualify as a symptom to these investigators? Lax protocols are not for me, my colleagues, or patients that I know. One of the most common reasons for a lawsuit to be brought against a primary care or ObGyn provider is failure to diagnose breast cancer!
John T. Armstrong, MD
Napa, California
Dr. Kaunitz responds
I thank Dr. Armstrong for his interest in my commentary on screening mammography and overdiagnosis. As I indicated in my commentary, I continue to recommend screening mammography for my patients, encouraging average-risk women to begin biennial screens at age 50 (consistent with USPSTF guidance), when the likelihood that tumors found with mammograms representing overdiagnosis is lower. I also indicated that I recognize that some patients prefer to begin screening at a younger age and to be screened more frequently. Dr. Armstrong’s letter refers to the “horrors of treatment” of breast cancer. From my perspective, the most “horrible” treatment is that which is administered to a woman diagnosed with a tumor destined to not cause clinical problems during her lifetime (overdiagnosis). You also refer to a statement, “an invasive breast cancer detected by any means is overdiagnosis.” That statement does not appear in my commentary.
My commentary’s point is that overdiagnosis is common among tumors diagnosed by screening mammography, and likely explains why, in contrast with cervical cancer screening, screening mammography has failed to reduce the incidence of breast cancers presenting as advanced (metastatic) disease. Although this represents a confusing and disquieting reality for our patients, and for us their clinicians, I agree with Dr. Otis Brawley, Chief Medical and Scientific Officer of the American Cancer Society, that we must acknowledge to our patients that overdiagnosis is common, the benefits of screening have been overstated, and that some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.1
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis [published online ahead of print January 10, 2017]. Ann Intern Med. doi:10.7326/M16-2850.
“MORE THAN ONE-THIRD OF TUMORS FOUND ON BREAST CANCER SCREENING REPRESENT OVERDIAGNOSIS”
ANDREW M. KAUNITZ, MD (MARCH 2017)
Refutes concept of overdiagnosis of breast cancer
I read with interest and serious concern the commentary and conclusions of “overdiagnosed” breast cancer. Let us revisit a few time-honored principles. Are we throwing away the valued concept of the early diagnosis of node-negative breast cancer? Is it still true that 5-year and long-term survivals are markedly better for stage I and II disease as opposed to stage III and IV disease? Is it still true that treatments designed for cure are substantially less involved, more successful, and more likely to conserve the breast and require less chemotherapy in early stage disease? Is it still true that the majority of women diagnosed with breast cancer are in the lowest risk category, ie, no family history and negative for the BRCA gene? If so, then who can explain the statement that “an invasive breast cancer detected by any means is overdiagnosis”? Would this imply that screening and the biopsy required to make the diagnosis was time poorly spent, the breast cancer should not be treated, and/or we should simply wait for a lump to be found by the patient deep in a large breast most likely at that point representing advanced disease?
The last paragraph notes the current US Preventive Services Task Force (USPSTF) guidance: wait until 50 years of age to start biennial screening. If so, what do we say to women in their 40s who, through screening with mammography and/or ultrasound, were diagnosed with early node-negative invasive breast cancer? That all of that was unnecessary and would not have led to symptoms? Would extreme morbidity from advanced or recurrent disease and the horrors of treatment just to extend a few months of life qualify as a symptom to these investigators? Lax protocols are not for me, my colleagues, or patients that I know. One of the most common reasons for a lawsuit to be brought against a primary care or ObGyn provider is failure to diagnose breast cancer!
John T. Armstrong, MD
Napa, California
Dr. Kaunitz responds
I thank Dr. Armstrong for his interest in my commentary on screening mammography and overdiagnosis. As I indicated in my commentary, I continue to recommend screening mammography for my patients, encouraging average-risk women to begin biennial screens at age 50 (consistent with USPSTF guidance), when the likelihood that tumors found with mammograms representing overdiagnosis is lower. I also indicated that I recognize that some patients prefer to begin screening at a younger age and to be screened more frequently. Dr. Armstrong’s letter refers to the “horrors of treatment” of breast cancer. From my perspective, the most “horrible” treatment is that which is administered to a woman diagnosed with a tumor destined to not cause clinical problems during her lifetime (overdiagnosis). You also refer to a statement, “an invasive breast cancer detected by any means is overdiagnosis.” That statement does not appear in my commentary.
My commentary’s point is that overdiagnosis is common among tumors diagnosed by screening mammography, and likely explains why, in contrast with cervical cancer screening, screening mammography has failed to reduce the incidence of breast cancers presenting as advanced (metastatic) disease. Although this represents a confusing and disquieting reality for our patients, and for us their clinicians, I agree with Dr. Otis Brawley, Chief Medical and Scientific Officer of the American Cancer Society, that we must acknowledge to our patients that overdiagnosis is common, the benefits of screening have been overstated, and that some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.1
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
“MORE THAN ONE-THIRD OF TUMORS FOUND ON BREAST CANCER SCREENING REPRESENT OVERDIAGNOSIS”
ANDREW M. KAUNITZ, MD (MARCH 2017)
Refutes concept of overdiagnosis of breast cancer
I read with interest and serious concern the commentary and conclusions of “overdiagnosed” breast cancer. Let us revisit a few time-honored principles. Are we throwing away the valued concept of the early diagnosis of node-negative breast cancer? Is it still true that 5-year and long-term survivals are markedly better for stage I and II disease as opposed to stage III and IV disease? Is it still true that treatments designed for cure are substantially less involved, more successful, and more likely to conserve the breast and require less chemotherapy in early stage disease? Is it still true that the majority of women diagnosed with breast cancer are in the lowest risk category, ie, no family history and negative for the BRCA gene? If so, then who can explain the statement that “an invasive breast cancer detected by any means is overdiagnosis”? Would this imply that screening and the biopsy required to make the diagnosis was time poorly spent, the breast cancer should not be treated, and/or we should simply wait for a lump to be found by the patient deep in a large breast most likely at that point representing advanced disease?
The last paragraph notes the current US Preventive Services Task Force (USPSTF) guidance: wait until 50 years of age to start biennial screening. If so, what do we say to women in their 40s who, through screening with mammography and/or ultrasound, were diagnosed with early node-negative invasive breast cancer? That all of that was unnecessary and would not have led to symptoms? Would extreme morbidity from advanced or recurrent disease and the horrors of treatment just to extend a few months of life qualify as a symptom to these investigators? Lax protocols are not for me, my colleagues, or patients that I know. One of the most common reasons for a lawsuit to be brought against a primary care or ObGyn provider is failure to diagnose breast cancer!
John T. Armstrong, MD
Napa, California
Dr. Kaunitz responds
I thank Dr. Armstrong for his interest in my commentary on screening mammography and overdiagnosis. As I indicated in my commentary, I continue to recommend screening mammography for my patients, encouraging average-risk women to begin biennial screens at age 50 (consistent with USPSTF guidance), when the likelihood that tumors found with mammograms representing overdiagnosis is lower. I also indicated that I recognize that some patients prefer to begin screening at a younger age and to be screened more frequently. Dr. Armstrong’s letter refers to the “horrors of treatment” of breast cancer. From my perspective, the most “horrible” treatment is that which is administered to a woman diagnosed with a tumor destined to not cause clinical problems during her lifetime (overdiagnosis). You also refer to a statement, “an invasive breast cancer detected by any means is overdiagnosis.” That statement does not appear in my commentary.
My commentary’s point is that overdiagnosis is common among tumors diagnosed by screening mammography, and likely explains why, in contrast with cervical cancer screening, screening mammography has failed to reduce the incidence of breast cancers presenting as advanced (metastatic) disease. Although this represents a confusing and disquieting reality for our patients, and for us their clinicians, I agree with Dr. Otis Brawley, Chief Medical and Scientific Officer of the American Cancer Society, that we must acknowledge to our patients that overdiagnosis is common, the benefits of screening have been overstated, and that some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.1
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis [published online ahead of print January 10, 2017]. Ann Intern Med. doi:10.7326/M16-2850.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis [published online ahead of print January 10, 2017]. Ann Intern Med. doi:10.7326/M16-2850.
Highlights from new guidelines, and a chance to weigh in
Though the Society for Vascular Surgery has long published clinical practice guidelines, its 2017 annual meeting marks the first seminar dedicated to guidelines in progress, allowing for more interaction, debate, and feedback across the vascular community before these guidelines become final.
At Friday afternoon’s update on SVS clinical practice guidelines, speakers will present on four that are in advanced development, including new global vascular guidelines.
All too often, Dr. Forbes said, the guideline process can seem opaque, or top-town or cumbersome in soliciting and incorporating feedback – problems that this kind of interactive seminar can help rectify. “We don’t want to be Moses with the tablet from the mountain, handing them down and asking everybody to follow them without question,” he said.
Keith D. Calligaro, MD, who practices in Philadelphia, starts the seminar off with highlights from new guidelines on hospital privileges across practice settings, an update of SVS guidelines from 2008. The new guidelines “describe specific procedure-related training requirements that would then lead to privileges in a hospital setting. This is especially relevant in some of the practice environments in the U.S.,” Dr. Forbes said.
R. Eugene Zierler, MD, of the University of Washington in Seattle, will present broad-reaching new advice on the follow-up of patients after vascular procedures. These guidelines cover patients who’ve undergone a wide variety of procedures, “all the way from carotid to abdominal aortic aneurysm repairs to venous surgery – and offers specific, evidence-based recommendations for how patients should be followed up, how often they should undergo imaging, bloodwork, and other follow-up modalities,” Dr. Forbes said.
And Elliot Chaikof, MD, of Beth Israel Deaconess Medical Center in Boston, will discuss new guidelines on the care of patients with abdominal aortic aneurysms that incorporates “what we know today about the different therapeutic options: from medical management to endovascular and open repair to different treatment strategies for men and women – all this based on advances from the last couple years,” Dr. Forbes said.
Finally, in separate talks, two presenters will describe different elements of a new global vascular guideline developed jointly by the SVS, the European Society for Vascular Surgery, and the World Federation of Vascular Societies.
Andrew W. Bradbury, MD, of the University of Birmingham in the U.K. and Michael S. Conte of the University of California San Francisco will speak on some issues the guidelines are tackling, all with an aim to reflect a more inclusive, worldwide picture of vascular practice.
“This is the first time we’re going to hear what these recommendations are,” Dr. Forbes said. One highlight is likely to be a new global classification system for peripheral arterial disease. “This is a new and novel concept in vascular disease, and that is similar to the classification systems used for cancer,” Dr. Forbes said.
Dr. Forbes said that he hopes that a seminar focused on guidelines in progress will become a regular feature of the annual meeting, and that this year’s seminar will help shape the society’s approach to future guidelines as well.
“Members may know of areas of vascular surgery where there’s a real need for guidelines, or some evidence-based recommendations that we don’t have, and we’d love them to come forward and propose those topics,” he said. “We need practitioners in academic centers and community practitioners alike, to represent the breath of the work being done out there.”
Friday, June 2
3:30 p.m. - 5:00 p.m., SDCC, Room 4
C9: Update on Society for Vascular Surgery Clinical Practice Guidelines
Though the Society for Vascular Surgery has long published clinical practice guidelines, its 2017 annual meeting marks the first seminar dedicated to guidelines in progress, allowing for more interaction, debate, and feedback across the vascular community before these guidelines become final.
At Friday afternoon’s update on SVS clinical practice guidelines, speakers will present on four that are in advanced development, including new global vascular guidelines.
All too often, Dr. Forbes said, the guideline process can seem opaque, or top-town or cumbersome in soliciting and incorporating feedback – problems that this kind of interactive seminar can help rectify. “We don’t want to be Moses with the tablet from the mountain, handing them down and asking everybody to follow them without question,” he said.
Keith D. Calligaro, MD, who practices in Philadelphia, starts the seminar off with highlights from new guidelines on hospital privileges across practice settings, an update of SVS guidelines from 2008. The new guidelines “describe specific procedure-related training requirements that would then lead to privileges in a hospital setting. This is especially relevant in some of the practice environments in the U.S.,” Dr. Forbes said.
R. Eugene Zierler, MD, of the University of Washington in Seattle, will present broad-reaching new advice on the follow-up of patients after vascular procedures. These guidelines cover patients who’ve undergone a wide variety of procedures, “all the way from carotid to abdominal aortic aneurysm repairs to venous surgery – and offers specific, evidence-based recommendations for how patients should be followed up, how often they should undergo imaging, bloodwork, and other follow-up modalities,” Dr. Forbes said.
And Elliot Chaikof, MD, of Beth Israel Deaconess Medical Center in Boston, will discuss new guidelines on the care of patients with abdominal aortic aneurysms that incorporates “what we know today about the different therapeutic options: from medical management to endovascular and open repair to different treatment strategies for men and women – all this based on advances from the last couple years,” Dr. Forbes said.
Finally, in separate talks, two presenters will describe different elements of a new global vascular guideline developed jointly by the SVS, the European Society for Vascular Surgery, and the World Federation of Vascular Societies.
Andrew W. Bradbury, MD, of the University of Birmingham in the U.K. and Michael S. Conte of the University of California San Francisco will speak on some issues the guidelines are tackling, all with an aim to reflect a more inclusive, worldwide picture of vascular practice.
“This is the first time we’re going to hear what these recommendations are,” Dr. Forbes said. One highlight is likely to be a new global classification system for peripheral arterial disease. “This is a new and novel concept in vascular disease, and that is similar to the classification systems used for cancer,” Dr. Forbes said.
Dr. Forbes said that he hopes that a seminar focused on guidelines in progress will become a regular feature of the annual meeting, and that this year’s seminar will help shape the society’s approach to future guidelines as well.
“Members may know of areas of vascular surgery where there’s a real need for guidelines, or some evidence-based recommendations that we don’t have, and we’d love them to come forward and propose those topics,” he said. “We need practitioners in academic centers and community practitioners alike, to represent the breath of the work being done out there.”
Friday, June 2
3:30 p.m. - 5:00 p.m., SDCC, Room 4
C9: Update on Society for Vascular Surgery Clinical Practice Guidelines
Though the Society for Vascular Surgery has long published clinical practice guidelines, its 2017 annual meeting marks the first seminar dedicated to guidelines in progress, allowing for more interaction, debate, and feedback across the vascular community before these guidelines become final.
At Friday afternoon’s update on SVS clinical practice guidelines, speakers will present on four that are in advanced development, including new global vascular guidelines.
All too often, Dr. Forbes said, the guideline process can seem opaque, or top-town or cumbersome in soliciting and incorporating feedback – problems that this kind of interactive seminar can help rectify. “We don’t want to be Moses with the tablet from the mountain, handing them down and asking everybody to follow them without question,” he said.
Keith D. Calligaro, MD, who practices in Philadelphia, starts the seminar off with highlights from new guidelines on hospital privileges across practice settings, an update of SVS guidelines from 2008. The new guidelines “describe specific procedure-related training requirements that would then lead to privileges in a hospital setting. This is especially relevant in some of the practice environments in the U.S.,” Dr. Forbes said.
R. Eugene Zierler, MD, of the University of Washington in Seattle, will present broad-reaching new advice on the follow-up of patients after vascular procedures. These guidelines cover patients who’ve undergone a wide variety of procedures, “all the way from carotid to abdominal aortic aneurysm repairs to venous surgery – and offers specific, evidence-based recommendations for how patients should be followed up, how often they should undergo imaging, bloodwork, and other follow-up modalities,” Dr. Forbes said.
And Elliot Chaikof, MD, of Beth Israel Deaconess Medical Center in Boston, will discuss new guidelines on the care of patients with abdominal aortic aneurysms that incorporates “what we know today about the different therapeutic options: from medical management to endovascular and open repair to different treatment strategies for men and women – all this based on advances from the last couple years,” Dr. Forbes said.
Finally, in separate talks, two presenters will describe different elements of a new global vascular guideline developed jointly by the SVS, the European Society for Vascular Surgery, and the World Federation of Vascular Societies.
Andrew W. Bradbury, MD, of the University of Birmingham in the U.K. and Michael S. Conte of the University of California San Francisco will speak on some issues the guidelines are tackling, all with an aim to reflect a more inclusive, worldwide picture of vascular practice.
“This is the first time we’re going to hear what these recommendations are,” Dr. Forbes said. One highlight is likely to be a new global classification system for peripheral arterial disease. “This is a new and novel concept in vascular disease, and that is similar to the classification systems used for cancer,” Dr. Forbes said.
Dr. Forbes said that he hopes that a seminar focused on guidelines in progress will become a regular feature of the annual meeting, and that this year’s seminar will help shape the society’s approach to future guidelines as well.
“Members may know of areas of vascular surgery where there’s a real need for guidelines, or some evidence-based recommendations that we don’t have, and we’d love them to come forward and propose those topics,” he said. “We need practitioners in academic centers and community practitioners alike, to represent the breath of the work being done out there.”
Friday, June 2
3:30 p.m. - 5:00 p.m., SDCC, Room 4
C9: Update on Society for Vascular Surgery Clinical Practice Guidelines
How to get published in JVS and EJVES: Editors disclose secrets of success
Over the past year, the Journal of Vascular Surgery and its two affiliated journals have undergone a number of important changes.
Editorial boards have been revamped, disadvantageous limits on the number of contributing authors and on references have been scrapped, and editors’ videos accompany every new issue. New short abstracts, take-home messages, and extended tables of contents allow even the most time-crunched clinicians to get up to speed.
Even the look of the journals has changed – with a red color scheme for JVS, a blue one for JVS-VL, the venous and lymphatic disorders journal, and a mixed red and blue one for the open-access publication dedicated to cases and techniques.
On Saturday morning, Dr. Gloviczki, the editor in chief of JVS, and senior editor Peter F. Lawrence helm a seminar that describes not only what they’ve been doing since taking over the journals’ leadership in July 2016, but how more SVS members can take part by producing quality papers or reviewing for the journals.
Dr. Gloviczki and Dr. Lawrence have also invited Dr. Philip Kolh if the University of Liege in Liege, Belgium, to co-lead the seminar. Dr. Kolh, who is editor in chief of the European Journal of Vascular and Endovascular Surgery, will advise on what the EJVES is looking for in its reviews and submissions.
“We believe it is important for JVS and EJVES to work together, to develop joint guidelines, to avoid repetition and redundancy, and double-publish papers that are important for both readerships,” Dr. Gloviczki said.
Dr. Gloviczki will start the seminar off by discussing the sweeping changes aimed at raising the quality of all three JVS journals and, he hopes, will also affect their impact factor, currently at 3.45 for JVS.
In addition to increasing the scrutiny of the peer review and the number of statistical reviews performed by master statisticians, the editors are looking for systematic reviews, meta-analyses, practice guidelines, and reporting standards – and will publish paper types not previously accepted, such as study protocols.
The journal will retain many initiatives of the previous editors, including the international debates, and will continue recruiting international authors and reviewers. Having the best reviewers, Dr. Gloviczki noted, “is an important parallel to having top-quality studies.”
Dr. Lawrence, of the University of California Los Angeles, will discuss what makes a clinical research paper successful. “We want papers that are highly cited – and the highly cited papers are prospective studies, whether randomized controlled trials or single-arm cohort studies,” Dr. Gloviczki said. “We also favor large retrospective reviews of prospectively collected national or international registries.”
Peter Henke, MD, of the University of Michigan in Ann Arbor, Mich., will talk about what the JVS editors and reviewers want in basic science papers – which Dr. Gloviczki called an important and sometimes overlooked counterpart to the clinical studies. “We believe that our profession must be in charge of basic research, that whoever owns basic research in our field owns the disease,” he said.
“To understand vascular disease you have to start at the basics of anatomy, pathophysiology, etiology, prevention, presentation and finally treatment,” he said, noting that vascular surgeons at many academic centers are conducting experimental studies and other basic research, efforts often supported by SVS grants.
Last year the JVS editors re-named the journal’s basic science section and called it “From Bench to Bedside” to try and capture the importance of preclinical vascular studies. “It’s a relatively small section of our journal but it’s important,” Dr. Gloviczki said. “And now we are really pushing to get commentaries that emphasize the potential clinical application of the basic science research.”
Richard L. Amdur, MD, of George Washington University in Washington, DC, will talk about what the JVS journal editors want to see in terms of statistics, while Marc L. Schermerhorn, MD, of Beth Israel Deaconess Medical Center in Boston and Martin Bjorck, MD, PhD, of Uppsala University, Uppsala, Sweden, will both discuss mining the large vascular registries from the United States and Europe for studies attractive to JVS or EJVES.
“There are so many papers where real-world experience is given to us by analyzing these registries,” Dr. Gloviczki said. Studies from the SVS Vascular Quality Initiatives database, the American College of Surgeons’ National Surgical Quality Improvement Program, the National Inpatient Sample, the Swedish Vascular registry, VADUNET and the International Consortium of Vascular Registries, “have changed the way we practice vascular surgery, and we publish multiple papers from these in every issue.”
Saturday, June 3
6:30 a.m. - 8:00 a.m.
Breakfast Session B9: How to Write a Paper and Have it Accepted in the JVS or EJVES
Over the past year, the Journal of Vascular Surgery and its two affiliated journals have undergone a number of important changes.
Editorial boards have been revamped, disadvantageous limits on the number of contributing authors and on references have been scrapped, and editors’ videos accompany every new issue. New short abstracts, take-home messages, and extended tables of contents allow even the most time-crunched clinicians to get up to speed.
Even the look of the journals has changed – with a red color scheme for JVS, a blue one for JVS-VL, the venous and lymphatic disorders journal, and a mixed red and blue one for the open-access publication dedicated to cases and techniques.
On Saturday morning, Dr. Gloviczki, the editor in chief of JVS, and senior editor Peter F. Lawrence helm a seminar that describes not only what they’ve been doing since taking over the journals’ leadership in July 2016, but how more SVS members can take part by producing quality papers or reviewing for the journals.
Dr. Gloviczki and Dr. Lawrence have also invited Dr. Philip Kolh if the University of Liege in Liege, Belgium, to co-lead the seminar. Dr. Kolh, who is editor in chief of the European Journal of Vascular and Endovascular Surgery, will advise on what the EJVES is looking for in its reviews and submissions.
“We believe it is important for JVS and EJVES to work together, to develop joint guidelines, to avoid repetition and redundancy, and double-publish papers that are important for both readerships,” Dr. Gloviczki said.
Dr. Gloviczki will start the seminar off by discussing the sweeping changes aimed at raising the quality of all three JVS journals and, he hopes, will also affect their impact factor, currently at 3.45 for JVS.
In addition to increasing the scrutiny of the peer review and the number of statistical reviews performed by master statisticians, the editors are looking for systematic reviews, meta-analyses, practice guidelines, and reporting standards – and will publish paper types not previously accepted, such as study protocols.
The journal will retain many initiatives of the previous editors, including the international debates, and will continue recruiting international authors and reviewers. Having the best reviewers, Dr. Gloviczki noted, “is an important parallel to having top-quality studies.”
Dr. Lawrence, of the University of California Los Angeles, will discuss what makes a clinical research paper successful. “We want papers that are highly cited – and the highly cited papers are prospective studies, whether randomized controlled trials or single-arm cohort studies,” Dr. Gloviczki said. “We also favor large retrospective reviews of prospectively collected national or international registries.”
Peter Henke, MD, of the University of Michigan in Ann Arbor, Mich., will talk about what the JVS editors and reviewers want in basic science papers – which Dr. Gloviczki called an important and sometimes overlooked counterpart to the clinical studies. “We believe that our profession must be in charge of basic research, that whoever owns basic research in our field owns the disease,” he said.
“To understand vascular disease you have to start at the basics of anatomy, pathophysiology, etiology, prevention, presentation and finally treatment,” he said, noting that vascular surgeons at many academic centers are conducting experimental studies and other basic research, efforts often supported by SVS grants.
Last year the JVS editors re-named the journal’s basic science section and called it “From Bench to Bedside” to try and capture the importance of preclinical vascular studies. “It’s a relatively small section of our journal but it’s important,” Dr. Gloviczki said. “And now we are really pushing to get commentaries that emphasize the potential clinical application of the basic science research.”
Richard L. Amdur, MD, of George Washington University in Washington, DC, will talk about what the JVS journal editors want to see in terms of statistics, while Marc L. Schermerhorn, MD, of Beth Israel Deaconess Medical Center in Boston and Martin Bjorck, MD, PhD, of Uppsala University, Uppsala, Sweden, will both discuss mining the large vascular registries from the United States and Europe for studies attractive to JVS or EJVES.
“There are so many papers where real-world experience is given to us by analyzing these registries,” Dr. Gloviczki said. Studies from the SVS Vascular Quality Initiatives database, the American College of Surgeons’ National Surgical Quality Improvement Program, the National Inpatient Sample, the Swedish Vascular registry, VADUNET and the International Consortium of Vascular Registries, “have changed the way we practice vascular surgery, and we publish multiple papers from these in every issue.”
Saturday, June 3
6:30 a.m. - 8:00 a.m.
Breakfast Session B9: How to Write a Paper and Have it Accepted in the JVS or EJVES
Over the past year, the Journal of Vascular Surgery and its two affiliated journals have undergone a number of important changes.
Editorial boards have been revamped, disadvantageous limits on the number of contributing authors and on references have been scrapped, and editors’ videos accompany every new issue. New short abstracts, take-home messages, and extended tables of contents allow even the most time-crunched clinicians to get up to speed.
Even the look of the journals has changed – with a red color scheme for JVS, a blue one for JVS-VL, the venous and lymphatic disorders journal, and a mixed red and blue one for the open-access publication dedicated to cases and techniques.
On Saturday morning, Dr. Gloviczki, the editor in chief of JVS, and senior editor Peter F. Lawrence helm a seminar that describes not only what they’ve been doing since taking over the journals’ leadership in July 2016, but how more SVS members can take part by producing quality papers or reviewing for the journals.
Dr. Gloviczki and Dr. Lawrence have also invited Dr. Philip Kolh if the University of Liege in Liege, Belgium, to co-lead the seminar. Dr. Kolh, who is editor in chief of the European Journal of Vascular and Endovascular Surgery, will advise on what the EJVES is looking for in its reviews and submissions.
“We believe it is important for JVS and EJVES to work together, to develop joint guidelines, to avoid repetition and redundancy, and double-publish papers that are important for both readerships,” Dr. Gloviczki said.
Dr. Gloviczki will start the seminar off by discussing the sweeping changes aimed at raising the quality of all three JVS journals and, he hopes, will also affect their impact factor, currently at 3.45 for JVS.
In addition to increasing the scrutiny of the peer review and the number of statistical reviews performed by master statisticians, the editors are looking for systematic reviews, meta-analyses, practice guidelines, and reporting standards – and will publish paper types not previously accepted, such as study protocols.
The journal will retain many initiatives of the previous editors, including the international debates, and will continue recruiting international authors and reviewers. Having the best reviewers, Dr. Gloviczki noted, “is an important parallel to having top-quality studies.”
Dr. Lawrence, of the University of California Los Angeles, will discuss what makes a clinical research paper successful. “We want papers that are highly cited – and the highly cited papers are prospective studies, whether randomized controlled trials or single-arm cohort studies,” Dr. Gloviczki said. “We also favor large retrospective reviews of prospectively collected national or international registries.”
Peter Henke, MD, of the University of Michigan in Ann Arbor, Mich., will talk about what the JVS editors and reviewers want in basic science papers – which Dr. Gloviczki called an important and sometimes overlooked counterpart to the clinical studies. “We believe that our profession must be in charge of basic research, that whoever owns basic research in our field owns the disease,” he said.
“To understand vascular disease you have to start at the basics of anatomy, pathophysiology, etiology, prevention, presentation and finally treatment,” he said, noting that vascular surgeons at many academic centers are conducting experimental studies and other basic research, efforts often supported by SVS grants.
Last year the JVS editors re-named the journal’s basic science section and called it “From Bench to Bedside” to try and capture the importance of preclinical vascular studies. “It’s a relatively small section of our journal but it’s important,” Dr. Gloviczki said. “And now we are really pushing to get commentaries that emphasize the potential clinical application of the basic science research.”
Richard L. Amdur, MD, of George Washington University in Washington, DC, will talk about what the JVS journal editors want to see in terms of statistics, while Marc L. Schermerhorn, MD, of Beth Israel Deaconess Medical Center in Boston and Martin Bjorck, MD, PhD, of Uppsala University, Uppsala, Sweden, will both discuss mining the large vascular registries from the United States and Europe for studies attractive to JVS or EJVES.
“There are so many papers where real-world experience is given to us by analyzing these registries,” Dr. Gloviczki said. Studies from the SVS Vascular Quality Initiatives database, the American College of Surgeons’ National Surgical Quality Improvement Program, the National Inpatient Sample, the Swedish Vascular registry, VADUNET and the International Consortium of Vascular Registries, “have changed the way we practice vascular surgery, and we publish multiple papers from these in every issue.”
Saturday, June 3
6:30 a.m. - 8:00 a.m.
Breakfast Session B9: How to Write a Paper and Have it Accepted in the JVS or EJVES
Biologics after methotrexate fails: Huge cost, minimal benefit
Prescribing rheumatoid arthritis patients a biologic agent rather than triple therapy, when they fail to respond adequately to methotrexate, costs more than half a million dollars per quality-adjusted life year gained over a lifetime but provides only a minimal health benefit beyond triple therapy, according to a report published online May 30 in Annals of Internal Medicine.
The evidence is clear that triple therapy using sulfasalazine, hydroxychloroquine, and methotrexate is at least as effective as methotrexate plus an anti–tumor necrosis factor biologic (etanercept, adalimumab, infliximab, golimumab, or certolizumab pegol). Nevertheless, few RA patients are transitioned to triple therapy before escalating to biologics. This occurred in only 2.5% of patients in one Veterans Affairs study, said Nick Bansback, PhD, of the University of British Columbia and St. Paul’s Hospital, Vancouver, and his associates.
Dr. Bansback and his colleagues performed a cost-effectiveness study of proceeding directly to etanercept when RA fails to respond to methotrexate, using data from the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial. The RACAT study, a large international, randomized, double-blind trial, confirmed the clinical noninferiority of triple therapy versus etanercept plus methotrexate. In their analysis, Dr. Bansback and his associates calculated the costs and QALYs for both treatment strategies for 324 RACAT participants.
Switching directly to etanercept-methotrexate instead of triple therapy provided only a marginal advantage in QALYs, a difference of only 0.004 QALY over 24 weeks of treatment (0.358 with etanercept-methotrexate vs. 0.353 with triple therapy) and of only 0.016 QALY over 48 weeks of treatment (0.743 with etanercept-methotrexate vs. 0.726 with triple therapy). The associated costs were $11,295 for 24 weeks of etanercept-methotrexate, vs. $343 for 24 weeks of triple therapy, and $19,634 for 48 weeks of etanercept-methotrexate, vs. $3,680 for 48 weeks of triple therapy.
“The resultant ICER [incremental cost-effectiveness ratio] for first-line etanercept-methotrexate, vs. triple therapy, was $2.7 million per QALY gained over 24 weeks,” the investigators said (Ann Intern Med. 2017 May 29. doi: 10.7326/M16-0713).
When they extrapolated the data to determine the cost-effectiveness of the two treatment strategies over the course of the average patient’s lifetime, the model predicted an ICER of $521,520 per QALY gained for etanercept-methotrexate instead of triple therapy. These findings remained robust in numerous sensitivity and scenario analyses. For example, when the model assumed that radiographic and quality of life benefits of triple therapy were far lower than observed in the RACAT trial and far lower than what has been reported in the literature and that the tolerability of triple therapy was far worse than observed in the RACAT trial and reported in the literature, switching to etanercept-methotrexate instead of triple therapy still predicted an ICER of $350,000 per QALY per patient.
All of these ICERs far exceed the standard cost-effectiveness acceptability threshold ICER of $100,000 per QALY, Dr. Bansback and his associates noted.
This study demonstrates the substantial cost savings of prescribing triple therapy before a biologic. It shows that “for every patient who tries triple therapy before a biologic, payers will save an average of $78,000 over the patient’s lifetime, and most of the savings will accrue within the first 10 years,” the investigators wrote.
“Patients who receive triple therapy before a biologic will miss out on a benefit of approximately 0.15 QALY over their lifetime or a benefit of approximately 0.05 HAQ [Health Assessment Questionnaire] point at any point in time. To put these numbers in perspective, total hip arthroplasty in a patient with osteoarthritis who is approximately the same age as an average patient with RA provides an additional 6.9 QALYs. In terms of HAQ score, only differences greater than 0.2 points are considered minimally important to patients,” Dr. Bansback and his associates wrote.
Changing health care policy to require, rather than to just recommend, that triple therapy be prescribed before biologics would save millions of dollars in health care expenditures, they added.
This study was supported by the U.S. Department of Veterans Affairs Office of Research and Development, the Canadian Institutes for Health Research, the National Institutes of Health, and the American Recovery and Reinvestment Act. Dr. Bansback reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
The findings of Bansback et al., consistent with those of several other researchers, indicate that patients who have RA and no contraindications to triple-conventional, disease-modifying antirheumatic drug therapy should use therapy instead of biologics as the next regimen if methotrexate alone fails to control symptoms and radiographic progression.
Elena Losina, PhD, and Jeffrey N. Katz, MD, are at Brigham and Women’s Hospital in Boston. They disclosed having no conflicts of interest. Dr. Losina and Dr. Katz made these remarks in an editorial accompanying Dr. Bansback’s report (Ann Intern Med. 2017 May 29. doi: 10.7326/M17-1176).
The findings of Bansback et al., consistent with those of several other researchers, indicate that patients who have RA and no contraindications to triple-conventional, disease-modifying antirheumatic drug therapy should use therapy instead of biologics as the next regimen if methotrexate alone fails to control symptoms and radiographic progression.
Elena Losina, PhD, and Jeffrey N. Katz, MD, are at Brigham and Women’s Hospital in Boston. They disclosed having no conflicts of interest. Dr. Losina and Dr. Katz made these remarks in an editorial accompanying Dr. Bansback’s report (Ann Intern Med. 2017 May 29. doi: 10.7326/M17-1176).
The findings of Bansback et al., consistent with those of several other researchers, indicate that patients who have RA and no contraindications to triple-conventional, disease-modifying antirheumatic drug therapy should use therapy instead of biologics as the next regimen if methotrexate alone fails to control symptoms and radiographic progression.
Elena Losina, PhD, and Jeffrey N. Katz, MD, are at Brigham and Women’s Hospital in Boston. They disclosed having no conflicts of interest. Dr. Losina and Dr. Katz made these remarks in an editorial accompanying Dr. Bansback’s report (Ann Intern Med. 2017 May 29. doi: 10.7326/M17-1176).
Prescribing rheumatoid arthritis patients a biologic agent rather than triple therapy, when they fail to respond adequately to methotrexate, costs more than half a million dollars per quality-adjusted life year gained over a lifetime but provides only a minimal health benefit beyond triple therapy, according to a report published online May 30 in Annals of Internal Medicine.
The evidence is clear that triple therapy using sulfasalazine, hydroxychloroquine, and methotrexate is at least as effective as methotrexate plus an anti–tumor necrosis factor biologic (etanercept, adalimumab, infliximab, golimumab, or certolizumab pegol). Nevertheless, few RA patients are transitioned to triple therapy before escalating to biologics. This occurred in only 2.5% of patients in one Veterans Affairs study, said Nick Bansback, PhD, of the University of British Columbia and St. Paul’s Hospital, Vancouver, and his associates.
Dr. Bansback and his colleagues performed a cost-effectiveness study of proceeding directly to etanercept when RA fails to respond to methotrexate, using data from the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial. The RACAT study, a large international, randomized, double-blind trial, confirmed the clinical noninferiority of triple therapy versus etanercept plus methotrexate. In their analysis, Dr. Bansback and his associates calculated the costs and QALYs for both treatment strategies for 324 RACAT participants.
Switching directly to etanercept-methotrexate instead of triple therapy provided only a marginal advantage in QALYs, a difference of only 0.004 QALY over 24 weeks of treatment (0.358 with etanercept-methotrexate vs. 0.353 with triple therapy) and of only 0.016 QALY over 48 weeks of treatment (0.743 with etanercept-methotrexate vs. 0.726 with triple therapy). The associated costs were $11,295 for 24 weeks of etanercept-methotrexate, vs. $343 for 24 weeks of triple therapy, and $19,634 for 48 weeks of etanercept-methotrexate, vs. $3,680 for 48 weeks of triple therapy.
“The resultant ICER [incremental cost-effectiveness ratio] for first-line etanercept-methotrexate, vs. triple therapy, was $2.7 million per QALY gained over 24 weeks,” the investigators said (Ann Intern Med. 2017 May 29. doi: 10.7326/M16-0713).
When they extrapolated the data to determine the cost-effectiveness of the two treatment strategies over the course of the average patient’s lifetime, the model predicted an ICER of $521,520 per QALY gained for etanercept-methotrexate instead of triple therapy. These findings remained robust in numerous sensitivity and scenario analyses. For example, when the model assumed that radiographic and quality of life benefits of triple therapy were far lower than observed in the RACAT trial and far lower than what has been reported in the literature and that the tolerability of triple therapy was far worse than observed in the RACAT trial and reported in the literature, switching to etanercept-methotrexate instead of triple therapy still predicted an ICER of $350,000 per QALY per patient.
All of these ICERs far exceed the standard cost-effectiveness acceptability threshold ICER of $100,000 per QALY, Dr. Bansback and his associates noted.
This study demonstrates the substantial cost savings of prescribing triple therapy before a biologic. It shows that “for every patient who tries triple therapy before a biologic, payers will save an average of $78,000 over the patient’s lifetime, and most of the savings will accrue within the first 10 years,” the investigators wrote.
“Patients who receive triple therapy before a biologic will miss out on a benefit of approximately 0.15 QALY over their lifetime or a benefit of approximately 0.05 HAQ [Health Assessment Questionnaire] point at any point in time. To put these numbers in perspective, total hip arthroplasty in a patient with osteoarthritis who is approximately the same age as an average patient with RA provides an additional 6.9 QALYs. In terms of HAQ score, only differences greater than 0.2 points are considered minimally important to patients,” Dr. Bansback and his associates wrote.
Changing health care policy to require, rather than to just recommend, that triple therapy be prescribed before biologics would save millions of dollars in health care expenditures, they added.
This study was supported by the U.S. Department of Veterans Affairs Office of Research and Development, the Canadian Institutes for Health Research, the National Institutes of Health, and the American Recovery and Reinvestment Act. Dr. Bansback reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
Prescribing rheumatoid arthritis patients a biologic agent rather than triple therapy, when they fail to respond adequately to methotrexate, costs more than half a million dollars per quality-adjusted life year gained over a lifetime but provides only a minimal health benefit beyond triple therapy, according to a report published online May 30 in Annals of Internal Medicine.
The evidence is clear that triple therapy using sulfasalazine, hydroxychloroquine, and methotrexate is at least as effective as methotrexate plus an anti–tumor necrosis factor biologic (etanercept, adalimumab, infliximab, golimumab, or certolizumab pegol). Nevertheless, few RA patients are transitioned to triple therapy before escalating to biologics. This occurred in only 2.5% of patients in one Veterans Affairs study, said Nick Bansback, PhD, of the University of British Columbia and St. Paul’s Hospital, Vancouver, and his associates.
Dr. Bansback and his colleagues performed a cost-effectiveness study of proceeding directly to etanercept when RA fails to respond to methotrexate, using data from the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial. The RACAT study, a large international, randomized, double-blind trial, confirmed the clinical noninferiority of triple therapy versus etanercept plus methotrexate. In their analysis, Dr. Bansback and his associates calculated the costs and QALYs for both treatment strategies for 324 RACAT participants.
Switching directly to etanercept-methotrexate instead of triple therapy provided only a marginal advantage in QALYs, a difference of only 0.004 QALY over 24 weeks of treatment (0.358 with etanercept-methotrexate vs. 0.353 with triple therapy) and of only 0.016 QALY over 48 weeks of treatment (0.743 with etanercept-methotrexate vs. 0.726 with triple therapy). The associated costs were $11,295 for 24 weeks of etanercept-methotrexate, vs. $343 for 24 weeks of triple therapy, and $19,634 for 48 weeks of etanercept-methotrexate, vs. $3,680 for 48 weeks of triple therapy.
“The resultant ICER [incremental cost-effectiveness ratio] for first-line etanercept-methotrexate, vs. triple therapy, was $2.7 million per QALY gained over 24 weeks,” the investigators said (Ann Intern Med. 2017 May 29. doi: 10.7326/M16-0713).
When they extrapolated the data to determine the cost-effectiveness of the two treatment strategies over the course of the average patient’s lifetime, the model predicted an ICER of $521,520 per QALY gained for etanercept-methotrexate instead of triple therapy. These findings remained robust in numerous sensitivity and scenario analyses. For example, when the model assumed that radiographic and quality of life benefits of triple therapy were far lower than observed in the RACAT trial and far lower than what has been reported in the literature and that the tolerability of triple therapy was far worse than observed in the RACAT trial and reported in the literature, switching to etanercept-methotrexate instead of triple therapy still predicted an ICER of $350,000 per QALY per patient.
All of these ICERs far exceed the standard cost-effectiveness acceptability threshold ICER of $100,000 per QALY, Dr. Bansback and his associates noted.
This study demonstrates the substantial cost savings of prescribing triple therapy before a biologic. It shows that “for every patient who tries triple therapy before a biologic, payers will save an average of $78,000 over the patient’s lifetime, and most of the savings will accrue within the first 10 years,” the investigators wrote.
“Patients who receive triple therapy before a biologic will miss out on a benefit of approximately 0.15 QALY over their lifetime or a benefit of approximately 0.05 HAQ [Health Assessment Questionnaire] point at any point in time. To put these numbers in perspective, total hip arthroplasty in a patient with osteoarthritis who is approximately the same age as an average patient with RA provides an additional 6.9 QALYs. In terms of HAQ score, only differences greater than 0.2 points are considered minimally important to patients,” Dr. Bansback and his associates wrote.
Changing health care policy to require, rather than to just recommend, that triple therapy be prescribed before biologics would save millions of dollars in health care expenditures, they added.
This study was supported by the U.S. Department of Veterans Affairs Office of Research and Development, the Canadian Institutes for Health Research, the National Institutes of Health, and the American Recovery and Reinvestment Act. Dr. Bansback reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point:
Major finding: For every RA patient who tries triple therapy before a biologic, payers will save an average of $78,000 over the patient’s lifetime without sacrificing their health or quality of life.
Data source: A cost-effectiveness analysis using data from 324 participants in an international, randomized, double-blind trial.
Disclosures: This study was supported by the U.S. Department of Veterans Affairs Office of Research and Development, the Canadian Institutes for Health Research, the National Institutes of Health, and the American Recovery and Reinvestment Act. Dr. Bansback reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
Tafamidis Delays Progression of Rare Polyneuropathy
Tafamidis, an oral non-NSAID and highly specific stabilizer of the TTR protein, delays neurologic progression in early-stage transthyretin familial amyloid polyneuropathy (ATTR-FAP), according to research published online ahead of print April 10 in Amyloid.
ATTR-FAP is a progressive condition caused by mutations in the TTR gene that destabilize the TTR protein, thereby facilitating misfolding and aggregation. The neuropathy may be accompanied by cardiac, gastrointestinal, renal, or ocular symptoms, and death occurs at an average of 10 years after symptom onset.
A pivotal phase III trial compared tafamidis with placebo over 18 months in 128 patients with early-stage ATTR-FAP. Researchers observed a trend toward a smaller increase in Neuropathy Impairment Score for Lower Limbs (NIS-LL) with tafamidis, compared with placebo, but the result was not statistically significant. Baseline NIS-LL values were higher among controls than among actively treated patients, however, and many participants dropped out of the study for liver transplantation.
In a post hoc analysis, the investigators took these factors into account and reanalyzed change from baseline in NIS-LL in the trial. They also analyzed change in NIS-LL plus three small-fiber nerve tests (NIS-LL+Σ3) and NIS-LL plus seven nerve tests (NIS-LL+Σ7) without baseline measurements as covariates.
The analysis indicated a significant benefit of tafamidis, compared with placebo, at Months 12 and 18. The baseline-adjusted mean increase in NIS-LL from baseline to Month 12 was 1.5 points in the tafamidis group versus 4.5 points in the placebo group. By Month 18, the mean change from baseline was 2.9 points in the tafamidis group versus 5.6 points in the placebo group.
When the researchers applied sensitivity analysis based on multiple imputation for missing data by treatment group, the mean estimates of the increase in NIS-LL total score from baseline to Month 18 were significantly lower for tafamidis, compared with placebo. A more conservative model based on multiple imputation showed a benefit of tafamidis, but results did not reach statistical significance.
The researchers also found a statistically significant benefit of tafamidis, compared with placebo, on NIS-LL+Σ3 at Months 12 and 18. Significant differences favoring tafamidis also were observed on NIS-LL+Σ7 at Months 12 and 18. Four of the study’s five authors are employees of Pfizer, which owns tafamidis and sponsored the study.
—Erik Greb
Suggested Reading
Keohane D, Schwartz J, Gundapaneni B, et al. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Apr 10 [Epub ahead of print].
Tafamidis, an oral non-NSAID and highly specific stabilizer of the TTR protein, delays neurologic progression in early-stage transthyretin familial amyloid polyneuropathy (ATTR-FAP), according to research published online ahead of print April 10 in Amyloid.
ATTR-FAP is a progressive condition caused by mutations in the TTR gene that destabilize the TTR protein, thereby facilitating misfolding and aggregation. The neuropathy may be accompanied by cardiac, gastrointestinal, renal, or ocular symptoms, and death occurs at an average of 10 years after symptom onset.
A pivotal phase III trial compared tafamidis with placebo over 18 months in 128 patients with early-stage ATTR-FAP. Researchers observed a trend toward a smaller increase in Neuropathy Impairment Score for Lower Limbs (NIS-LL) with tafamidis, compared with placebo, but the result was not statistically significant. Baseline NIS-LL values were higher among controls than among actively treated patients, however, and many participants dropped out of the study for liver transplantation.
In a post hoc analysis, the investigators took these factors into account and reanalyzed change from baseline in NIS-LL in the trial. They also analyzed change in NIS-LL plus three small-fiber nerve tests (NIS-LL+Σ3) and NIS-LL plus seven nerve tests (NIS-LL+Σ7) without baseline measurements as covariates.
The analysis indicated a significant benefit of tafamidis, compared with placebo, at Months 12 and 18. The baseline-adjusted mean increase in NIS-LL from baseline to Month 12 was 1.5 points in the tafamidis group versus 4.5 points in the placebo group. By Month 18, the mean change from baseline was 2.9 points in the tafamidis group versus 5.6 points in the placebo group.
When the researchers applied sensitivity analysis based on multiple imputation for missing data by treatment group, the mean estimates of the increase in NIS-LL total score from baseline to Month 18 were significantly lower for tafamidis, compared with placebo. A more conservative model based on multiple imputation showed a benefit of tafamidis, but results did not reach statistical significance.
The researchers also found a statistically significant benefit of tafamidis, compared with placebo, on NIS-LL+Σ3 at Months 12 and 18. Significant differences favoring tafamidis also were observed on NIS-LL+Σ7 at Months 12 and 18. Four of the study’s five authors are employees of Pfizer, which owns tafamidis and sponsored the study.
—Erik Greb
Suggested Reading
Keohane D, Schwartz J, Gundapaneni B, et al. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Apr 10 [Epub ahead of print].
Tafamidis, an oral non-NSAID and highly specific stabilizer of the TTR protein, delays neurologic progression in early-stage transthyretin familial amyloid polyneuropathy (ATTR-FAP), according to research published online ahead of print April 10 in Amyloid.
ATTR-FAP is a progressive condition caused by mutations in the TTR gene that destabilize the TTR protein, thereby facilitating misfolding and aggregation. The neuropathy may be accompanied by cardiac, gastrointestinal, renal, or ocular symptoms, and death occurs at an average of 10 years after symptom onset.
A pivotal phase III trial compared tafamidis with placebo over 18 months in 128 patients with early-stage ATTR-FAP. Researchers observed a trend toward a smaller increase in Neuropathy Impairment Score for Lower Limbs (NIS-LL) with tafamidis, compared with placebo, but the result was not statistically significant. Baseline NIS-LL values were higher among controls than among actively treated patients, however, and many participants dropped out of the study for liver transplantation.
In a post hoc analysis, the investigators took these factors into account and reanalyzed change from baseline in NIS-LL in the trial. They also analyzed change in NIS-LL plus three small-fiber nerve tests (NIS-LL+Σ3) and NIS-LL plus seven nerve tests (NIS-LL+Σ7) without baseline measurements as covariates.
The analysis indicated a significant benefit of tafamidis, compared with placebo, at Months 12 and 18. The baseline-adjusted mean increase in NIS-LL from baseline to Month 12 was 1.5 points in the tafamidis group versus 4.5 points in the placebo group. By Month 18, the mean change from baseline was 2.9 points in the tafamidis group versus 5.6 points in the placebo group.
When the researchers applied sensitivity analysis based on multiple imputation for missing data by treatment group, the mean estimates of the increase in NIS-LL total score from baseline to Month 18 were significantly lower for tafamidis, compared with placebo. A more conservative model based on multiple imputation showed a benefit of tafamidis, but results did not reach statistical significance.
The researchers also found a statistically significant benefit of tafamidis, compared with placebo, on NIS-LL+Σ3 at Months 12 and 18. Significant differences favoring tafamidis also were observed on NIS-LL+Σ7 at Months 12 and 18. Four of the study’s five authors are employees of Pfizer, which owns tafamidis and sponsored the study.
—Erik Greb
Suggested Reading
Keohane D, Schwartz J, Gundapaneni B, et al. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Apr 10 [Epub ahead of print].
Friday - On Tap
What will happen Friday that people will be talking about Saturday? All of the below, and much more:
• 6:30 to 8:00 a.m. Breakfast Sessions: Pushing the boundaries in managing PAD, managing arterial infections and the aging of vascular surgeons. See Mobile App for room locations.
• 8:00 - 11:00 a.m.Plenary Sessions 4 through 6. Room 6 A/B. See Mobile App for abstracts and times.
• 11:00 a.m. Presidential address from Dr. Ronald M. Fairman. President-Elect Dr. R. Clement Darling, III, will introduce Dr. Fairman. Room 6 A/B.
• 3:30 to 5:00 p.m. Six Concurrent Sessions: the SVS/ESVS debate, joint sessions with the STS and AVF, an update on clinical practice guidelines and introduction of global vascular guidelines, and the Poster Competition. See Mobile App for details and room locations.
• 12:15 to 1:30 p.m. The Vascular Surgery Trainee Luncheon, Room 6C. Topics include how to find a job and “day in the life” stories from recent 5+2 and 0+5 graduates. Register at the Registration Counter.
• 5:00 to 6:30 p.m. Residency Fair. Exhibit Hall A.
What will happen Friday that people will be talking about Saturday? All of the below, and much more:
• 6:30 to 8:00 a.m. Breakfast Sessions: Pushing the boundaries in managing PAD, managing arterial infections and the aging of vascular surgeons. See Mobile App for room locations.
• 8:00 - 11:00 a.m.Plenary Sessions 4 through 6. Room 6 A/B. See Mobile App for abstracts and times.
• 11:00 a.m. Presidential address from Dr. Ronald M. Fairman. President-Elect Dr. R. Clement Darling, III, will introduce Dr. Fairman. Room 6 A/B.
• 3:30 to 5:00 p.m. Six Concurrent Sessions: the SVS/ESVS debate, joint sessions with the STS and AVF, an update on clinical practice guidelines and introduction of global vascular guidelines, and the Poster Competition. See Mobile App for details and room locations.
• 12:15 to 1:30 p.m. The Vascular Surgery Trainee Luncheon, Room 6C. Topics include how to find a job and “day in the life” stories from recent 5+2 and 0+5 graduates. Register at the Registration Counter.
• 5:00 to 6:30 p.m. Residency Fair. Exhibit Hall A.
What will happen Friday that people will be talking about Saturday? All of the below, and much more:
• 6:30 to 8:00 a.m. Breakfast Sessions: Pushing the boundaries in managing PAD, managing arterial infections and the aging of vascular surgeons. See Mobile App for room locations.
• 8:00 - 11:00 a.m.Plenary Sessions 4 through 6. Room 6 A/B. See Mobile App for abstracts and times.
• 11:00 a.m. Presidential address from Dr. Ronald M. Fairman. President-Elect Dr. R. Clement Darling, III, will introduce Dr. Fairman. Room 6 A/B.
• 3:30 to 5:00 p.m. Six Concurrent Sessions: the SVS/ESVS debate, joint sessions with the STS and AVF, an update on clinical practice guidelines and introduction of global vascular guidelines, and the Poster Competition. See Mobile App for details and room locations.
• 12:15 to 1:30 p.m. The Vascular Surgery Trainee Luncheon, Room 6C. Topics include how to find a job and “day in the life” stories from recent 5+2 and 0+5 graduates. Register at the Registration Counter.
• 5:00 to 6:30 p.m. Residency Fair. Exhibit Hall A.
Stop By, Say Hi! 6 Great Reasons to Visit the Membership Booth
While you’re in the neighborhood, why not stop by the SVS Membership Booth, located just outside the plenary doors?
Whether you are a member of SVS or not, we’d love to see you. Here are some reasons you’ll be glad you did:
Enter to win a $500 gift card if you update your SVS member profile or fill out a membership form.
Pick up a memento – SVS pens, notebooks, even saltwater taffy – of your visit (while supplies last).
Members are encouraged to update their personal information – emails, addresses, and even names can change. Don’t let yourself fall off the contact lists!
Inquire about membership options; learn about the benefits of belonging.
Get help with your mobile app.
Bonus: If you update your member details AND make a donation to the SVS Foundation (adjoining booth), you can enter the contest twice.
While you’re in the neighborhood, why not stop by the SVS Membership Booth, located just outside the plenary doors?
Whether you are a member of SVS or not, we’d love to see you. Here are some reasons you’ll be glad you did:
Enter to win a $500 gift card if you update your SVS member profile or fill out a membership form.
Pick up a memento – SVS pens, notebooks, even saltwater taffy – of your visit (while supplies last).
Members are encouraged to update their personal information – emails, addresses, and even names can change. Don’t let yourself fall off the contact lists!
Inquire about membership options; learn about the benefits of belonging.
Get help with your mobile app.
Bonus: If you update your member details AND make a donation to the SVS Foundation (adjoining booth), you can enter the contest twice.
While you’re in the neighborhood, why not stop by the SVS Membership Booth, located just outside the plenary doors?
Whether you are a member of SVS or not, we’d love to see you. Here are some reasons you’ll be glad you did:
Enter to win a $500 gift card if you update your SVS member profile or fill out a membership form.
Pick up a memento – SVS pens, notebooks, even saltwater taffy – of your visit (while supplies last).
Members are encouraged to update their personal information – emails, addresses, and even names can change. Don’t let yourself fall off the contact lists!
Inquire about membership options; learn about the benefits of belonging.
Get help with your mobile app.
Bonus: If you update your member details AND make a donation to the SVS Foundation (adjoining booth), you can enter the contest twice.
At Opening Reception: Vendors, Posters, Raffle
Meet up with friends, visit vendor booths to see the latest and greatest in all things vascular, peruse the posters.
And enter a high-tech raffle to win a high-flying prize: two airline tickets to anywhere in the continental United States AND complimentary registration for the 2018 Vascular Annual Meeting. While traversing the Exhibit Hall, be sure to look for placards with QR codes in select exhibitor booths; scan the QR code and be automatically entered into the raffle. No pens, no paper required, just a smart phone and the QR code.
Industry support is vital to VAM, permitting registration fees considerably lower than those assessed at comparable annual meetings. Please show your support by visiting our vendors.
The reception coincides with the end of the Interactive Poster Session, set for 5:00 to 6:30 p.m. in the same location.
Thursday, June 1
5:00 – 6:30 p.m.
Exhibit Hall B
Interactive Poster Session
5:30 – 6:30 p.m.
Exhibit Hall B
Opening Reception
Meet up with friends, visit vendor booths to see the latest and greatest in all things vascular, peruse the posters.
And enter a high-tech raffle to win a high-flying prize: two airline tickets to anywhere in the continental United States AND complimentary registration for the 2018 Vascular Annual Meeting. While traversing the Exhibit Hall, be sure to look for placards with QR codes in select exhibitor booths; scan the QR code and be automatically entered into the raffle. No pens, no paper required, just a smart phone and the QR code.
Industry support is vital to VAM, permitting registration fees considerably lower than those assessed at comparable annual meetings. Please show your support by visiting our vendors.
The reception coincides with the end of the Interactive Poster Session, set for 5:00 to 6:30 p.m. in the same location.
Thursday, June 1
5:00 – 6:30 p.m.
Exhibit Hall B
Interactive Poster Session
5:30 – 6:30 p.m.
Exhibit Hall B
Opening Reception
Meet up with friends, visit vendor booths to see the latest and greatest in all things vascular, peruse the posters.
And enter a high-tech raffle to win a high-flying prize: two airline tickets to anywhere in the continental United States AND complimentary registration for the 2018 Vascular Annual Meeting. While traversing the Exhibit Hall, be sure to look for placards with QR codes in select exhibitor booths; scan the QR code and be automatically entered into the raffle. No pens, no paper required, just a smart phone and the QR code.
Industry support is vital to VAM, permitting registration fees considerably lower than those assessed at comparable annual meetings. Please show your support by visiting our vendors.
The reception coincides with the end of the Interactive Poster Session, set for 5:00 to 6:30 p.m. in the same location.
Thursday, June 1
5:00 – 6:30 p.m.
Exhibit Hall B
Interactive Poster Session
5:30 – 6:30 p.m.
Exhibit Hall B
Opening Reception
Does laparoscopic versus open abdominal surgery for stage I endometrial cancer affect oncologic outcomes?
EXPERT COMMENTARY
The objective of the study by Janda and colleagues (known as the “LACE” trial) was to evaluate the equivalency of total laparoscopic hysterectomy (TLH) with staging versus the standard procedure, which is total abdominal hysterectomy (TAH) with staging, for surgical management of women with presumed low-risk, early-stage endometrial cancer.
Related Article:
2016 Update on cancer
Details of the study
This nonblinded, randomized controlled multicenter equivalency trial included 760 women from Australia, New Zealand, and Hong Kong undergoing surgical management of presumed stage I uterine endometrioid adenocarcinoma. All surgeries were performed or supervised by trained gynecologic oncologists. Pelvic lymph node sampling was required but omission was permitted for: morbid obesity, low risk of metastasis based on frozen section results, medically unfit status, or institutional guidelines prohibiting the procedure. Patients were excluded for preoperative nonendometrioid histology, suspected ultimate FIGO stage II–IV based on preoperative imaging, or uterine size greater than 10 weeks’ gestation.
The primary outcome was disease-free survival, defined as the time from surgery to the date of first recurrence, which included disease progression, development of a new primary malignancy, or death. Secondary outcomes included disease recurrence, patterns of recurrence, and overall survival. A 7% difference in disease-free survival at 4.5 years postoperatively was prespecified and determined based on previously published literature.1–4
By Kaplan-Meier estimates, disease-free survival at 4.5 years was 81.3% in the TAH group and 81.6% in the TLH group, a 0.3% difference. In addition, there were no differences noted in secondary outcomes, further supporting equivalency of the surgical modalities. The only significantly different surgical findings included decreased operative time in the TAH group and decreased lymph node dissection completion in the TLH group.
Related Article:
Can we reduce the use of abdominal hysterectomy and increase the use of vaginal and laparoscopic approaches?
Study strengths and weaknesses
The largest previous trial of more than 2,000 patients examining the method of surgical management was the Gynecologic Oncology Group’s (GOG) noninferiority LAP2 trial.3 This trial has been used widely to promote a minimally invasive approach, but did not actually reach the prespecified statistical goals. The LACE trial, however, successfully reached its statistical targets and is now the largest randomized trial supporting an equivalence in oncologic outcomes.
It is important to recognize the limitations of the LACE trial in the current medical environment. The study population was a very specific group of low-risk women without high-risk histologic subtypes or even moderately enlarged uteri; many institutions would consider offering a minimally invasive approach to these women. In addition, this study did not include robotic minimally invasive surgery, which in many regions of the country is rapidly becoming accepted as the first choice procedure over traditional laparoscopy.5 Furthermore, the FIRES trial and others6–8 have demonstrated that utilizing a minimally invasive approach that includes sentinel lymph node identification and removal may be as diagnostic as a full dissection, adding considerations to surgical modality selection.
--Kathryn A. Mills, MD, and David G. Mutch, MD
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Fleshman J, Branda M, Sargent DJ, et al. Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial. JAMA. 2015;314(13):1346–1355.
- Stevenson AR, Solomon MJ, Lumley JW, et al; ALaCaRT Investigators. Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: the ALaCaRT randomized clinical trial. JAMA. 2015;314(13):1356–1363.
- Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30(7):695–700.
- Creutzberg CL, van Putten WL, Koper PC, et al; Post Operative Radiation Therapy in Endometrial Carcinoma. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Lancet. 2000;355(9213):1404–1411.
- Wright JD, Burke WM, Tergas AI, et al. Comparative effectiveness of minimally invasive hysterectomy for endometrial cancer. J Clin Oncol. 2016;34(10):1087–1096.
- Rossi EC, Kowalski LD, Scalici JS, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384–392.
- Barlin JN, Khoury-Collado F, Kim CH, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol Oncol. 2012;12(3):531–535.
- Darai E, Dubernard G, Bats AS, et al. Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study. Gynecol Oncol. 2015;136(1):54-59.
EXPERT COMMENTARY
The objective of the study by Janda and colleagues (known as the “LACE” trial) was to evaluate the equivalency of total laparoscopic hysterectomy (TLH) with staging versus the standard procedure, which is total abdominal hysterectomy (TAH) with staging, for surgical management of women with presumed low-risk, early-stage endometrial cancer.
Related Article:
2016 Update on cancer
Details of the study
This nonblinded, randomized controlled multicenter equivalency trial included 760 women from Australia, New Zealand, and Hong Kong undergoing surgical management of presumed stage I uterine endometrioid adenocarcinoma. All surgeries were performed or supervised by trained gynecologic oncologists. Pelvic lymph node sampling was required but omission was permitted for: morbid obesity, low risk of metastasis based on frozen section results, medically unfit status, or institutional guidelines prohibiting the procedure. Patients were excluded for preoperative nonendometrioid histology, suspected ultimate FIGO stage II–IV based on preoperative imaging, or uterine size greater than 10 weeks’ gestation.
The primary outcome was disease-free survival, defined as the time from surgery to the date of first recurrence, which included disease progression, development of a new primary malignancy, or death. Secondary outcomes included disease recurrence, patterns of recurrence, and overall survival. A 7% difference in disease-free survival at 4.5 years postoperatively was prespecified and determined based on previously published literature.1–4
By Kaplan-Meier estimates, disease-free survival at 4.5 years was 81.3% in the TAH group and 81.6% in the TLH group, a 0.3% difference. In addition, there were no differences noted in secondary outcomes, further supporting equivalency of the surgical modalities. The only significantly different surgical findings included decreased operative time in the TAH group and decreased lymph node dissection completion in the TLH group.
Related Article:
Can we reduce the use of abdominal hysterectomy and increase the use of vaginal and laparoscopic approaches?
Study strengths and weaknesses
The largest previous trial of more than 2,000 patients examining the method of surgical management was the Gynecologic Oncology Group’s (GOG) noninferiority LAP2 trial.3 This trial has been used widely to promote a minimally invasive approach, but did not actually reach the prespecified statistical goals. The LACE trial, however, successfully reached its statistical targets and is now the largest randomized trial supporting an equivalence in oncologic outcomes.
It is important to recognize the limitations of the LACE trial in the current medical environment. The study population was a very specific group of low-risk women without high-risk histologic subtypes or even moderately enlarged uteri; many institutions would consider offering a minimally invasive approach to these women. In addition, this study did not include robotic minimally invasive surgery, which in many regions of the country is rapidly becoming accepted as the first choice procedure over traditional laparoscopy.5 Furthermore, the FIRES trial and others6–8 have demonstrated that utilizing a minimally invasive approach that includes sentinel lymph node identification and removal may be as diagnostic as a full dissection, adding considerations to surgical modality selection.
--Kathryn A. Mills, MD, and David G. Mutch, MD
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
EXPERT COMMENTARY
The objective of the study by Janda and colleagues (known as the “LACE” trial) was to evaluate the equivalency of total laparoscopic hysterectomy (TLH) with staging versus the standard procedure, which is total abdominal hysterectomy (TAH) with staging, for surgical management of women with presumed low-risk, early-stage endometrial cancer.
Related Article:
2016 Update on cancer
Details of the study
This nonblinded, randomized controlled multicenter equivalency trial included 760 women from Australia, New Zealand, and Hong Kong undergoing surgical management of presumed stage I uterine endometrioid adenocarcinoma. All surgeries were performed or supervised by trained gynecologic oncologists. Pelvic lymph node sampling was required but omission was permitted for: morbid obesity, low risk of metastasis based on frozen section results, medically unfit status, or institutional guidelines prohibiting the procedure. Patients were excluded for preoperative nonendometrioid histology, suspected ultimate FIGO stage II–IV based on preoperative imaging, or uterine size greater than 10 weeks’ gestation.
The primary outcome was disease-free survival, defined as the time from surgery to the date of first recurrence, which included disease progression, development of a new primary malignancy, or death. Secondary outcomes included disease recurrence, patterns of recurrence, and overall survival. A 7% difference in disease-free survival at 4.5 years postoperatively was prespecified and determined based on previously published literature.1–4
By Kaplan-Meier estimates, disease-free survival at 4.5 years was 81.3% in the TAH group and 81.6% in the TLH group, a 0.3% difference. In addition, there were no differences noted in secondary outcomes, further supporting equivalency of the surgical modalities. The only significantly different surgical findings included decreased operative time in the TAH group and decreased lymph node dissection completion in the TLH group.
Related Article:
Can we reduce the use of abdominal hysterectomy and increase the use of vaginal and laparoscopic approaches?
Study strengths and weaknesses
The largest previous trial of more than 2,000 patients examining the method of surgical management was the Gynecologic Oncology Group’s (GOG) noninferiority LAP2 trial.3 This trial has been used widely to promote a minimally invasive approach, but did not actually reach the prespecified statistical goals. The LACE trial, however, successfully reached its statistical targets and is now the largest randomized trial supporting an equivalence in oncologic outcomes.
It is important to recognize the limitations of the LACE trial in the current medical environment. The study population was a very specific group of low-risk women without high-risk histologic subtypes or even moderately enlarged uteri; many institutions would consider offering a minimally invasive approach to these women. In addition, this study did not include robotic minimally invasive surgery, which in many regions of the country is rapidly becoming accepted as the first choice procedure over traditional laparoscopy.5 Furthermore, the FIRES trial and others6–8 have demonstrated that utilizing a minimally invasive approach that includes sentinel lymph node identification and removal may be as diagnostic as a full dissection, adding considerations to surgical modality selection.
--Kathryn A. Mills, MD, and David G. Mutch, MD
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Fleshman J, Branda M, Sargent DJ, et al. Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial. JAMA. 2015;314(13):1346–1355.
- Stevenson AR, Solomon MJ, Lumley JW, et al; ALaCaRT Investigators. Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: the ALaCaRT randomized clinical trial. JAMA. 2015;314(13):1356–1363.
- Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30(7):695–700.
- Creutzberg CL, van Putten WL, Koper PC, et al; Post Operative Radiation Therapy in Endometrial Carcinoma. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Lancet. 2000;355(9213):1404–1411.
- Wright JD, Burke WM, Tergas AI, et al. Comparative effectiveness of minimally invasive hysterectomy for endometrial cancer. J Clin Oncol. 2016;34(10):1087–1096.
- Rossi EC, Kowalski LD, Scalici JS, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384–392.
- Barlin JN, Khoury-Collado F, Kim CH, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol Oncol. 2012;12(3):531–535.
- Darai E, Dubernard G, Bats AS, et al. Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study. Gynecol Oncol. 2015;136(1):54-59.
- Fleshman J, Branda M, Sargent DJ, et al. Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial. JAMA. 2015;314(13):1346–1355.
- Stevenson AR, Solomon MJ, Lumley JW, et al; ALaCaRT Investigators. Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: the ALaCaRT randomized clinical trial. JAMA. 2015;314(13):1356–1363.
- Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30(7):695–700.
- Creutzberg CL, van Putten WL, Koper PC, et al; Post Operative Radiation Therapy in Endometrial Carcinoma. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Lancet. 2000;355(9213):1404–1411.
- Wright JD, Burke WM, Tergas AI, et al. Comparative effectiveness of minimally invasive hysterectomy for endometrial cancer. J Clin Oncol. 2016;34(10):1087–1096.
- Rossi EC, Kowalski LD, Scalici JS, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384–392.
- Barlin JN, Khoury-Collado F, Kim CH, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol Oncol. 2012;12(3):531–535.
- Darai E, Dubernard G, Bats AS, et al. Sentinel node biopsy for the management of early stage endometrial cancer: long-term results of the SENTI-ENDO study. Gynecol Oncol. 2015;136(1):54-59.
Caring for the transgender patient: The role of the gynecologist
CASE: Transgender man consults gynecologist for fertility options
A 36-year-old transgender man considering the possibility of having his own biological children presents to the gynecology office to discuss hysterectomy as gender dysphoria treatment as well as his fertility preservation options. He has never had a gynecologic examination. Since age 24, he has been on testosterone therapy. Although his menses initially ceased, each month over the past 2 years he has had breakthrough spotting lasting 2 to 4 days, sometimes accompanied by pelvic pain and cramping. These symptoms have caused him distress and anxiety, which have led to his missing work 1 to 3 days each month. On presentation, he appears anxious and makes little eye contact. His girlfriend of 6 years has come in with him and is very supportive.
Over the past decade, transgender health care has moved to the forefront of the medical conversation. At many prominent medical centers across the United States, clinicians are forming multidisciplinary teams to help improve the health care of this patient population. Outcomes are being studied, and the literature is becoming more robust.
People tend to think of transgender women—male-assigned persons who self-identify as female—as the typical prototype for transgender people, but this focus is skewed in both society and the medical community. Transgender men—female-assigned persons who self-identify as male—remain underrepresented, mostly because they want to stay “under the radar,” especially with respect to medical care and, more specifically, routine gynecologic care.
Although the transgender woman has unique health needs and may present to a gynecologist for care after gender-affirmationsurgery, the transgender man’s many health care needs and their subtleties can be addressed only by a gynecologist. In this article, I review these intricacies of care to help increase clinician comfort in treating these patients.
Clinicians can take steps to:
- ensure all patients have the correct identifiers in their medical records
- provide staff with the proper education and diversity training
- instruct staff in proper use of pronouns
- set up unisex or gender-nonbinary restrooms with appropriate signage
- make the decor gender nonspecific.
Beth Cronin, MD, a practicing general gynecologist in Providence, Rhode Island, says that you also should consider a general sign, placed in a highly visible area, that represents your nondiscrimination policy. The AMA offers this wording: "This office appreciates the diversity of human beings and does not discriminate based on race, age, religion, ability, marital status, sexual orientation, sex or gender identity." She also recommends having education and marketing materials with affirmative imagery and content and providing educational brochures on transgender health topics.
Why transgender patients may delay seeking health care
Transgender patients remain underserved because of the health care barriers they encounter. Factors contributing to poor access include lack of health insurance, inability to pay for services, clinician insensitivity and hostility, and fear of exposure of transgender status during health care encounters.1 In a recent large survey study, 30% of transgender respondents indicated that they delayed or did not seek medical care as a result of discrimination, and those who had needed to teach their clinicians about transgenderism were 4 times more likely to postpone or not seek care.2
In a 2015 survey of ObGyns’ current knowledge and practice regarding LGBT (lesbian, gay, bisexual, transgender) care, only one-third of respondents indicated they were comfortable caring for transgender patients.3 In addition, only one-third indicated being knowledgeable about the steps transgender patients must take to transition to their self-identified gender, and less than half were familiar with the recommendations for the routine health maintenance and screening of these patients.
Much of this discomfort derives from the lack of incorporation of LGBT-specific topics in medical curricula. In 2011, Obedin-Maliver and colleagues found that, at 176 US and Canadian allopathic and osteopathic medical schools, the median time dedicated to LGBT health care needs and related topics was unsatisfactory.4 This deficiency is slowly being reduced with changes in the curricula of many health care specialties. In ObGyn residency programs, for example, transgender-specific questions have been added to annual in-service examinations. The hope is that, as education initiatives improve, clinicians will become more comfortable caring for gender-minority patients, who with improved access to care will no longer need to seek subspecialists in transgender services.
Read about the need for gyn exams, managing benign disorders, and cervical cancer screening
Considerations for the gynecologic visit and examination
Transgender men visit the gynecology office for many reasons, including routine gynecologic care and health maintenance, care for acute and chronic gynecologic conditions (abnormal bleeding, pelvic pain, vaginitis), evaluation and management of pelvic floor disorders, consultation on hysterectomy for gender transition, and fertility counseling.
However, transgender men who reach their third, fourth, or fifth decade without having had a pelvic examination cite many reasons for avoiding the gynecology office. Most commonly, gynecologic visits and genital examination can severely exacerbate these patients’ gender dysphoria. In addition, many patients who do not engage in penetrative vaginal sex think their health risks are so low that they can forgo or delay pelvic exams. Patients who have stopped menstruating while on testosterone therapy may think there is no need for routine gynecologic care. Other reasons for avoiding pelvic exams are pain and traumatic sexual memories.5
Related Article:
Four pillars of a successful practice: 4. Motivate your staff
Transgender men need to receive the regular guideline-recommended pelvic exams and screenings used for cisgender women. (Cisgender refers to a person whose sense of gender identity corresponds with their birth sex.) We need to educate patients in this regard and to discuss several issues before performing an examination. First, take a thorough history and avoid making assumptions about sexual orientation and sex practices. Some patients have penetrative vaginal intercourse with either men or women. For some patients, the exam may cause dysphoria symptoms, and we need to validate patients’ fears. Discussing these issues ahead of time helps patients get used to the idea of undergoing an exam and assures them that the clinician is experienced in performing these exams for transgender men. In my practice, we explain the exam’s purpose (screening or diagnosis) and importance. We also counsel patients that they may experience some normal, and temporary, spotting after the exam. For those who experience severe dysphoria with vaginal bleeding of any kind, we acknowledge that postexam spotting may cause some anxiety. Patients with severe anxiety before the exam may be premedicated with an anxiolytic agent as long as someone can transport them to and from the office.
The bimanual exam should be performed with care and efficiency and with the patient given as much control as possible. In most cases, we ask patients to undress only from the waist down, and their genitals stay covered. Patients uncomfortable in stirrups are asked to show us the position that suits them best, and we try to accommodate them. Although speed is a goal, remember that many patients are nulliparous, have had limited or no vaginal penetration, or are on testosterone and have significant vaginal dryness. Use the smallest speculum possible, a pediatric or long and narrow adult speculum, and apply lubricant copiously. Pre-exam application of topical lidocaine jelly to the introitus can help reduce pain. To help a patient relax the pelvic floor muscles and habituate to the presence of a foreign object in the vagina, start the exam by inserting a single digit. In addition, ask the patient about speculum placement inside the vagina: Does he want to place the speculum himself or guide the clinician’s hand? Open the speculum only as much as needed to adequately visualize the cervix and then remove it with care.
Managing benign gynecologic disorders
The same algorithms are used to evaluate abnormal bleeding in all patients, but the differential diagnosis expands for those on testosterone therapy. Testosterone may no longer be suppressing their cycles, and abnormal bleeding could simply be the return of menses, which would present as regular cyclic bleeding. Increasing the testosterone dosing or changing the testosterone formulation may help, and the gynecologist should discuss these options with the patient’s prescribing clinician. In addition, progesterone in any form (for example, medroxyprogesterone acetate 5 to 30 mg daily) can be added to testosterone regimens to help suppress menses. The levonorgestrel-releasing intrauterine device (LNG-IUD) can be very effective, but placement can induce anxiety, and some patients decline this treatment option.
In patients with intermenstrual spotting, assess the vagina for atrophy. Both over-the-counter vaginal moisturizers and DHEA (dehydroepiandrosterone) suppositories (1% compounded) can help treat atrophy, but not all patients are comfortable using them. Most patients decline vaginal estrogen products for symptomatic vaginal atrophy even though the systemic effects are minimal.
The historic literature suggests that female-to-male patients’ long-term exposure to androgens leads to atrophic changes in the endometrium and myometrium, and clinical studies of menopausal women who take exogenous androgens have confirmed this effect.6 However, new data point to a different histologic scenario. A recent study found a possible association between long-term testosterone use in transgender men of reproductive age and a low proliferative active endometrium, as well as hypertrophic changes in the myometrium.7 The causes may be peripheral aromatization of androgens and expression and up-regulation of androgen receptors within the endometrial stroma and myometrial cells.8 Given these emerging data and anecdotal cases reported by clinicians who perform hysterectomies for transgender men, imaging and tissue sampling should be used to evaluate abnormal uterine bleeding, particularly in patients previously amenorrheic on testosterone. Be aware that transvaginal ultrasound or endometrial biopsy are challenging procedures for these patients. Counsel patients to ensure that they adhere to follow-up.
Related Article:
2017 Update on cervical disease
The ongoing need for cervical cancer screening
The concept of “original gender surveillance” was presented in a 2-case series of transgender men with uterine and cervical cancer that might have been detected earlier with better screening and routine care.9 There is no evidence, however, that long-term high-dose androgen therapy causes endometrial or cervical cancer,10 and the data on endometrial cancer in patients on cross-sex hormone therapy are limited such that a causal relationship between testosterone and these malignancies cannot be established.9,11–14
The rate of unsatisfactory Pap smears is higher in transgender men than in cisgender women. The difference was anecdotally noted by clinicians who routinely cared for transgender patients over time and was confirmed with a retrospective chart review.15
Peitzmeier and colleagues reviewed the records of 233 transgender men and 3,625 cisgender women with Pap tests performed at an urban community health center over 6 years.15 The transgender cohort, with its prevalence rate of 10%, was 10 times more likely to have an unsatisfactory or inadequate Pap smear. Moreover, the transgender patients were more likely to have longer latency to follow-up for a repeat Pap test. In addition, testosterone therapy was more likely associated with inadequate Pap smears, and time on testosterone therapy was associated with higher odds of Pap smear inadequacy. Besides the exogenous hormone therapy, clinician comfort level and experience may have contributed to the high prevalence of inadequate Pap smears.
As mentioned earlier, it is important to become comfortable performing pelvic exams for transgender men and to prepare patients for the possibility that a Pap smear might be inadequate, making a follow-up visit and repeat Pap test necessary.16
Read about hysterectomy, oophorectomy, and vaginectomy choices
Consultation for hysterectomy: Perioperative considerations
Transgender men may undergo hysterectomy, oophorectomy, and/or vaginectomy. The TABLE summarizes the indications and perioperative considerations for each procedure.
Some transgender men undergo hysterectomy for benign gynecologic disease. Counseling and perioperative planning are the same for these patients as for cisgender women, although some of the considerations discussed here remain important.
Other patients undergo hysterectomy as part of transitioning to their self-affirmed gender. The World Professional Association for Transgender Health (WPATH) Standards of Care should be used to guide counseling and treatment.17 These guidelines were designed as a framework for performing hysterectomy and other gender-affirming procedures. According to the WPATH standards, the criteria for hysterectomy and oophorectomy are:
- 2 referral letters from qualified mental health professionals
- well-documented persistent gender dysphoria
- capacity to make fully informed decisions and to consent to treatment
- age of majority in given country
- good control of any concurrent medical or mental health concerns, and
- hormone therapy for 12 continuous months, as appropriate to gender goals, unless the patient has a medical contraindication or is otherwise unable or unwilling to take hormones.
As the guidelines emphasize, these criteria do not apply to patients undergoing either procedure for medical indications other than gender dysphoria.
Hysterectomy approach. Most surgeons perform gender-affirming hysterectomies laparoscopically. Many clinicians hesitate to perform these hysterectomies vaginally, as the patients are often nulliparous. In general, the best operative route is the one the surgeon feels most comfortable performing safely and efficiently. For a nulliparous patient with minimal pelvic organ descensus and a narrow pelvis, the laparoscopic approach is reasonable. A recent study in a small cohort of transgender men found that vaginal hysterectomy was successful in only 1 in 4 patients.18 Nevertheless, the American College of Obstetricians and Gynecologists (ACOG) recommends vaginal hysterectomy, when appropriate, for limiting complications and morbidity while maximizing cost-effectiveness.19 Although data are limited, vaginal hysterectomy seems feasible and should be considered in a subset of patients who pre‑sent for gender-affirming hysterectomy.
Related Article:
Total laparoscopic versus laparoscopic supracervical hysterectomy
The oophorectomy debate
Oophorectomy concurrent with hysterectomy remains a topic of debate among gynecologists who perform hysterectomy for gender transition. Some clinicians think gonadectomy poses a significant risk for bone health compromise at an early age. The long-term effects of testosterone on bone have not been well studied. Although bone metabolism is thought to increase over the short term, there are no major changes in bone density over the long term. In fact, in the setting of long-term testosterone therapy, cortical bone was found to be larger in transgender men than in cisgender women.20 The issue is for patients who stop taking exogenous testosterone after oophorectomy. This subset of patients has not been well studied but clearly needs bone health surveillance and supplementation.
Another concern about oophorectomy is its effect on fertility. Because it is important to discuss fertility-preserving options, during consultation for a hysterectomy I spend a large portion of time addressing fertility goals. Patients who want to become a parent but do not want to carry a child (they want a current or future partner or surrogate to carry) are candidates for hysterectomy; those who do not want a genetic child are candidates for oophorectomy; and those who do not want to preserve their fertility (or have already ended it) and who meet the WPATH criteria for surgery are candidates for oophorectomy concurrent with hysterectomy. The discussion can be particularly challenging with young transgender men, since their ability to project their family planning goals may be compromised by their gender dysphoria. Clinicians can counsel patients about another option: isolated hysterectomy with subsequent staged oophorectomy.
Similar to cisgender women with polycystic ovary syndrome, transgender men on exogenous testosterone therapy are at risk for ovarian cysts,7 which can cause pain and should be evaluated and managed. As mentioned, these patients may find it difficult to visit a gynecologist and tolerate a vaginal examination, and many fear presenting to an emergency room, as they will need to disclose their transgender status and risk being discriminated against or, worse, not being triaged or cared for properly. Patients should be thoroughly counseled about the risks and benefits of having oophorectomy performed concurrently with hysterectomy.
Related Article:
Vaginal hysterectomy with basic instrumentation
The question of vaginectomy
Patients and clinicians often ask about concurrent vaginectomy procedures. In some cases, patients with severe gender dysphoria and absence of penetrative vaginal activity request excision or obliteration of the vagina. There is no standard of care, however. Vaginectomy can be done transvaginally or abdominally: open, laparoscopically, or robotically. It therefore should be performed by surgeons experienced in the procedure. Patients should be advised that a portion of the vaginal epithelium is sometimes used for certain phalloplasty procedures and that, if they are considering genital reconstruction in the future, it may be beneficial to preserve the vagina until that time.
There are no guidelines on stopping or continuing testosterone therapy perioperatively. Some clinicians are concerned about possible venous thromboembolic events related to perioperative use of testosterone, but there are no data supporting increased risk. The risk of postoperative vaginal cuff bleeding in patients on and off testosterone has not been well studied. Since patients who stop taking testosterone may develop severe mood swings and malaise, they should be counseled on recognizing and managing such changes. There are also no data on the risk of vaginal cuff dehiscence in this patient population. Testosterone usually causes the vagina to become very atrophic, so proper closure should be ensured to avoid cuff evisceration. In my practice, the vaginal cuff is closed in 2 layers using at least 1 layer of delayed absorbable suture.
Read about addressing fertility, contraception, OB care, and your role
Addressing fertility, contraception, and obstetric care
Most transgender men are able to conceive a child.21 Data in this area, however, are sparse. Most of the literature on reproductive health in this patient population is focused on human immunodeficiency virus (HIV) and other sexually transmitted infections.22 Nevertheless, patient-physician dialogue on fertility and reproductive health has increased since more patients started seeking surgical transition services (likely a result of improved coverage for these surgeries). In addition, we are learning more about patients’ ability and desire to conceive after long-term use of cross-sex hormone therapy. The importance of this dialogue is becoming apparent. One survey study found that more than half of the transgender men who had undergone affirmation surgery wanted to become parents.23
Before initiating cross-sex hormone therapy or before undergoing hysterectomy and/or oophorectomy, patients must be counseled about their fertility options. Testosterone may affect fertility and fecundity, but there are case reports of successful pregnancy after discontinuation of testosterone.21 Reproductive endocrinology and fertility specialists have begun to recognize the importance of fertility preservation in this patient population and to apply the principles of oncofertility care beyond patients with cancer. In a 2015 opinion paper on access to fertility services by transgender persons, the Ethics Committee of the American Society for Reproductive Medicine focused on this population’s unique fertility needs.24 Currently, oocyte and embryo cryopreservation are options for transgender men planning to start cross-sex hormones or undergo surgery.25 Other methods being investigated may become options in the future.25
There are even fewer data on transgender men’s contraceptive needs. Many clinicians mistakenly think these patients are at low risk for pregnancy. Some patients have male partners and engage in penetrative penile-vaginal intercourse; others are not on testosterone therapy; and still others, despite taking testosterone, are not always amenorrheic and may be ovulating. In a small cross-sectional study, Light and colleagues found that 12% of transgender men who were surveyed after conceiving had been amenorrheic on testosterone therapy, and 24% of these pregnancies were not planned.21
In a study by Cipres and colleagues, half of the 26 transgender men were considered at risk for pregnancy: These patients still had a uterus, not all were on testosterone, not all on testosterone were amenorrheic, they were having vaginal intercourse with cisgender men, and none were using condoms or other contraception.26 The authors noted several potential underlying reasons for poor counseling on contraceptive needs: patients feel stigmatized, clinicians assume these patients are not candidates for “female” hormone therapy, patients fear these modalities may feminize them and compromise their affirmed identities, patients poorly understand how testosterone works and have mistaken ideas about its contraceptive properties, and clinician discomfort with broaching fertility and reproductive health discussions.
Data are also limited on pregnancy in transgender men. We do know that clinicians are not well equipped to help patients during the peripartum period and better resources are needed.21 Gender dysphoria can worsen during and immediately after pregnancy, and patients may be at significant risk for postpartum depression. More research is needed.
Related Article:
Care of the transgender patient: What is the gynecologist's role?
Gynecologists play key role in transgender care
Transgender men’s unique health care needs can be addressed only by gynecologists.It is important to become comfortable with and educated about these needs and their subtleties. This starts with understanding transgender patients’ gender dysphoria associated with the gynecologic visit and examination. Learning more about these patients and their needs will improve health care delivery.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Xavier JM, Simmons R. The Washington Transgender Needs Assessment Survey, 2000. http://www.glaa.org/archive/2000/tgneedsassessment1112.shtml. Accessed January 2, 2017.
- Jaffee KD, Shires DA, Stroumsa D. Discrimination and delayed health care among transgender women and men: implications for improving medical education and health care delivery. Med Care. 2016;54(11):1010–1016.
- Unger CA. Care of the transgender patient: a survey of gynecologists’ current knowledge and practice. J Womens Health. 2015;24(2):114–118.
- Obedin-Maliver J, Goldsmith ES, Stewart L, et al. Lesbian, gay, bisexual, and transgender-related content in undergraduate medical education. JAMA. 2011;306(9):971–977.
- Feldman J. Medical and surgical management of the transgender patient: what the primary care clinician needs to know. In: Makadon H, Mayer K, Potter J, Goldhammer H, eds. Fenway Guide to Lesbian, Gay, Bisexual, and Transgender Health. Philadelphia, PA: American College of Physicians; 2008:365–392.
- Hickok LR, Toomey C, Speroff L. A comparison of esterified estrogens with and without methyltestosterone: effects on endometrial histology and serum lipoproteins in postmenopausal women. Obstet Gynecol. 1993;82(6):919–924.
- Loverro G, Resta L, Dellino M, et al. Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals. Taiwan J Obstet Gynecol. 2016;55(5):686–691.
- Mertens HJ, Heineman MJ, Koudstaal J, Theunissen P, Evers JL. Androgen receptor content in human endometrium. Eur J Obstet Gynecol Reprod Biol. 1996;70(1):11–13.
- Urban RR, Teng NN, Kapp DS. Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance. Am J Obstet Gynecol. 2011;204(5):e9–e12.
- Mueller A, Gooren L. Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2008;159(3):197–202.
- Allen NE, Key TJ, Dossus L, et al. Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2008;15(2):485–497.
- Hage JJ, Dekker JJ, Karim RB, Verheijen RH, Bloemena E. Ovarian cancer in female-to-male transsexuals: report of two cases. Gynecol Oncol. 2000;76(3):413–415.
- Dizon DS, Tejada-Berges T, Keolliker S, Steinhoff M, Grania CO. Ovarian cancer associated with testosterone supplementation in a female-to-male transsexual patient. Gynecol Oncol Invest. 2006;62(4):226–228.
- Schenck TL, Holzbach T, Zantl N, et al. Vaginal carcinoma in a female-to-male transsexual. J Sex Med. 2010;7(8):2899–2902.
- Peitzmeier SM, Reisner SL, Harigopal P, Potter J. Female-to-male patients have high prevalence of unsatisfactory Paps compared to non-transgender females: implications for cervical cancer screening. J Gen Intern Med. 2014;29(5):778–784.
- Potter J, Peitzmeier SM, Bernstein I, et al. Cervical cancer screening for patients on the female-to-male spectrum: a narrative review and guide for clinicians. J Gen Intern Med. 2015;30(12):1857–1864.
- Coleman E, Bockting W, Botzer M, et al; World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, Version 7. https://s3.amazonaws.com/amo_hub_content/Association140/files/Standards_of_Care_V7_2011_WPATH(2)(1).pdf. Published 2011. Accessed January 21, 2017.
- Obedin-Maliver J, Light A, de Haan G, Jackson RA. Feasibility of vaginal hysterectomy for female-to-male transgender men. Obstet Gynecol. 2017;129(3):457–463.
- American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 444: Choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156–1158.
- Van Caenegem E, T’Sjoen G. Bone in trans persons. Curr Opin Endocrinol Diabetes Obes. 2015;22(6):459–466.
- Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014;124(6):1120–1127.
- Stephens SC, Bernstein KT, Philip SS. Male to female and female to male transgender persons have different sexual risk behaviors yet similar rates of STDs and HIV. AIDS Behav. 2011;15(3):683–686.
- Wierckx K, Van Caenegem E, Pennings G, et al. Reproductive wish in transsexual men. Hum Reprod. 2012;27(2):483–487.
- Ethics Committee of the American Society for Reproductive Medicine. Access to fertility services by transgender persons: an Ethics Committee opinion. Fertil Steril. 2015;104(5):1111–1115.
- Wallace SA, Blough KL, Kondapalli LA. Fertility preservation in the transgender patient: expanding oncofertility care beyond cancer. Gynecol Endocrinol. 2014;30(12):868–871.
- Cipres D, Seidman D, Cloniger C 3rd, Nova C, O’Shea A, Obedin-Maliver J. Contraceptive use and pregnancy intentions among transgender men presenting to a clinic for sex workers and their families in San Francisco. Contraception. 2016;95(2):186–189.
Dr. Unger is a gynecologic surgeon at the Center for Urogynecology and Pelvic Reconstructive Surgery and the Center for LGBT Care at the Obstetrics, Gynecology, and Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio.
The author reports no financial relationships relevant to this article.
Dr. Unger is a gynecologic surgeon at the Center for Urogynecology and Pelvic Reconstructive Surgery and the Center for LGBT Care at the Obstetrics, Gynecology, and Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio.
The author reports no financial relationships relevant to this article.
Dr. Unger is a gynecologic surgeon at the Center for Urogynecology and Pelvic Reconstructive Surgery and the Center for LGBT Care at the Obstetrics, Gynecology, and Women’s Health Institute, Cleveland Clinic, Cleveland, Ohio.
The author reports no financial relationships relevant to this article.
CASE: Transgender man consults gynecologist for fertility options
A 36-year-old transgender man considering the possibility of having his own biological children presents to the gynecology office to discuss hysterectomy as gender dysphoria treatment as well as his fertility preservation options. He has never had a gynecologic examination. Since age 24, he has been on testosterone therapy. Although his menses initially ceased, each month over the past 2 years he has had breakthrough spotting lasting 2 to 4 days, sometimes accompanied by pelvic pain and cramping. These symptoms have caused him distress and anxiety, which have led to his missing work 1 to 3 days each month. On presentation, he appears anxious and makes little eye contact. His girlfriend of 6 years has come in with him and is very supportive.
Over the past decade, transgender health care has moved to the forefront of the medical conversation. At many prominent medical centers across the United States, clinicians are forming multidisciplinary teams to help improve the health care of this patient population. Outcomes are being studied, and the literature is becoming more robust.
People tend to think of transgender women—male-assigned persons who self-identify as female—as the typical prototype for transgender people, but this focus is skewed in both society and the medical community. Transgender men—female-assigned persons who self-identify as male—remain underrepresented, mostly because they want to stay “under the radar,” especially with respect to medical care and, more specifically, routine gynecologic care.
Although the transgender woman has unique health needs and may present to a gynecologist for care after gender-affirmationsurgery, the transgender man’s many health care needs and their subtleties can be addressed only by a gynecologist. In this article, I review these intricacies of care to help increase clinician comfort in treating these patients.
Clinicians can take steps to:
- ensure all patients have the correct identifiers in their medical records
- provide staff with the proper education and diversity training
- instruct staff in proper use of pronouns
- set up unisex or gender-nonbinary restrooms with appropriate signage
- make the decor gender nonspecific.
Beth Cronin, MD, a practicing general gynecologist in Providence, Rhode Island, says that you also should consider a general sign, placed in a highly visible area, that represents your nondiscrimination policy. The AMA offers this wording: "This office appreciates the diversity of human beings and does not discriminate based on race, age, religion, ability, marital status, sexual orientation, sex or gender identity." She also recommends having education and marketing materials with affirmative imagery and content and providing educational brochures on transgender health topics.
Why transgender patients may delay seeking health care
Transgender patients remain underserved because of the health care barriers they encounter. Factors contributing to poor access include lack of health insurance, inability to pay for services, clinician insensitivity and hostility, and fear of exposure of transgender status during health care encounters.1 In a recent large survey study, 30% of transgender respondents indicated that they delayed or did not seek medical care as a result of discrimination, and those who had needed to teach their clinicians about transgenderism were 4 times more likely to postpone or not seek care.2
In a 2015 survey of ObGyns’ current knowledge and practice regarding LGBT (lesbian, gay, bisexual, transgender) care, only one-third of respondents indicated they were comfortable caring for transgender patients.3 In addition, only one-third indicated being knowledgeable about the steps transgender patients must take to transition to their self-identified gender, and less than half were familiar with the recommendations for the routine health maintenance and screening of these patients.
Much of this discomfort derives from the lack of incorporation of LGBT-specific topics in medical curricula. In 2011, Obedin-Maliver and colleagues found that, at 176 US and Canadian allopathic and osteopathic medical schools, the median time dedicated to LGBT health care needs and related topics was unsatisfactory.4 This deficiency is slowly being reduced with changes in the curricula of many health care specialties. In ObGyn residency programs, for example, transgender-specific questions have been added to annual in-service examinations. The hope is that, as education initiatives improve, clinicians will become more comfortable caring for gender-minority patients, who with improved access to care will no longer need to seek subspecialists in transgender services.
Read about the need for gyn exams, managing benign disorders, and cervical cancer screening
Considerations for the gynecologic visit and examination
Transgender men visit the gynecology office for many reasons, including routine gynecologic care and health maintenance, care for acute and chronic gynecologic conditions (abnormal bleeding, pelvic pain, vaginitis), evaluation and management of pelvic floor disorders, consultation on hysterectomy for gender transition, and fertility counseling.
However, transgender men who reach their third, fourth, or fifth decade without having had a pelvic examination cite many reasons for avoiding the gynecology office. Most commonly, gynecologic visits and genital examination can severely exacerbate these patients’ gender dysphoria. In addition, many patients who do not engage in penetrative vaginal sex think their health risks are so low that they can forgo or delay pelvic exams. Patients who have stopped menstruating while on testosterone therapy may think there is no need for routine gynecologic care. Other reasons for avoiding pelvic exams are pain and traumatic sexual memories.5
Related Article:
Four pillars of a successful practice: 4. Motivate your staff
Transgender men need to receive the regular guideline-recommended pelvic exams and screenings used for cisgender women. (Cisgender refers to a person whose sense of gender identity corresponds with their birth sex.) We need to educate patients in this regard and to discuss several issues before performing an examination. First, take a thorough history and avoid making assumptions about sexual orientation and sex practices. Some patients have penetrative vaginal intercourse with either men or women. For some patients, the exam may cause dysphoria symptoms, and we need to validate patients’ fears. Discussing these issues ahead of time helps patients get used to the idea of undergoing an exam and assures them that the clinician is experienced in performing these exams for transgender men. In my practice, we explain the exam’s purpose (screening or diagnosis) and importance. We also counsel patients that they may experience some normal, and temporary, spotting after the exam. For those who experience severe dysphoria with vaginal bleeding of any kind, we acknowledge that postexam spotting may cause some anxiety. Patients with severe anxiety before the exam may be premedicated with an anxiolytic agent as long as someone can transport them to and from the office.
The bimanual exam should be performed with care and efficiency and with the patient given as much control as possible. In most cases, we ask patients to undress only from the waist down, and their genitals stay covered. Patients uncomfortable in stirrups are asked to show us the position that suits them best, and we try to accommodate them. Although speed is a goal, remember that many patients are nulliparous, have had limited or no vaginal penetration, or are on testosterone and have significant vaginal dryness. Use the smallest speculum possible, a pediatric or long and narrow adult speculum, and apply lubricant copiously. Pre-exam application of topical lidocaine jelly to the introitus can help reduce pain. To help a patient relax the pelvic floor muscles and habituate to the presence of a foreign object in the vagina, start the exam by inserting a single digit. In addition, ask the patient about speculum placement inside the vagina: Does he want to place the speculum himself or guide the clinician’s hand? Open the speculum only as much as needed to adequately visualize the cervix and then remove it with care.
Managing benign gynecologic disorders
The same algorithms are used to evaluate abnormal bleeding in all patients, but the differential diagnosis expands for those on testosterone therapy. Testosterone may no longer be suppressing their cycles, and abnormal bleeding could simply be the return of menses, which would present as regular cyclic bleeding. Increasing the testosterone dosing or changing the testosterone formulation may help, and the gynecologist should discuss these options with the patient’s prescribing clinician. In addition, progesterone in any form (for example, medroxyprogesterone acetate 5 to 30 mg daily) can be added to testosterone regimens to help suppress menses. The levonorgestrel-releasing intrauterine device (LNG-IUD) can be very effective, but placement can induce anxiety, and some patients decline this treatment option.
In patients with intermenstrual spotting, assess the vagina for atrophy. Both over-the-counter vaginal moisturizers and DHEA (dehydroepiandrosterone) suppositories (1% compounded) can help treat atrophy, but not all patients are comfortable using them. Most patients decline vaginal estrogen products for symptomatic vaginal atrophy even though the systemic effects are minimal.
The historic literature suggests that female-to-male patients’ long-term exposure to androgens leads to atrophic changes in the endometrium and myometrium, and clinical studies of menopausal women who take exogenous androgens have confirmed this effect.6 However, new data point to a different histologic scenario. A recent study found a possible association between long-term testosterone use in transgender men of reproductive age and a low proliferative active endometrium, as well as hypertrophic changes in the myometrium.7 The causes may be peripheral aromatization of androgens and expression and up-regulation of androgen receptors within the endometrial stroma and myometrial cells.8 Given these emerging data and anecdotal cases reported by clinicians who perform hysterectomies for transgender men, imaging and tissue sampling should be used to evaluate abnormal uterine bleeding, particularly in patients previously amenorrheic on testosterone. Be aware that transvaginal ultrasound or endometrial biopsy are challenging procedures for these patients. Counsel patients to ensure that they adhere to follow-up.
Related Article:
2017 Update on cervical disease
The ongoing need for cervical cancer screening
The concept of “original gender surveillance” was presented in a 2-case series of transgender men with uterine and cervical cancer that might have been detected earlier with better screening and routine care.9 There is no evidence, however, that long-term high-dose androgen therapy causes endometrial or cervical cancer,10 and the data on endometrial cancer in patients on cross-sex hormone therapy are limited such that a causal relationship between testosterone and these malignancies cannot be established.9,11–14
The rate of unsatisfactory Pap smears is higher in transgender men than in cisgender women. The difference was anecdotally noted by clinicians who routinely cared for transgender patients over time and was confirmed with a retrospective chart review.15
Peitzmeier and colleagues reviewed the records of 233 transgender men and 3,625 cisgender women with Pap tests performed at an urban community health center over 6 years.15 The transgender cohort, with its prevalence rate of 10%, was 10 times more likely to have an unsatisfactory or inadequate Pap smear. Moreover, the transgender patients were more likely to have longer latency to follow-up for a repeat Pap test. In addition, testosterone therapy was more likely associated with inadequate Pap smears, and time on testosterone therapy was associated with higher odds of Pap smear inadequacy. Besides the exogenous hormone therapy, clinician comfort level and experience may have contributed to the high prevalence of inadequate Pap smears.
As mentioned earlier, it is important to become comfortable performing pelvic exams for transgender men and to prepare patients for the possibility that a Pap smear might be inadequate, making a follow-up visit and repeat Pap test necessary.16
Read about hysterectomy, oophorectomy, and vaginectomy choices
Consultation for hysterectomy: Perioperative considerations
Transgender men may undergo hysterectomy, oophorectomy, and/or vaginectomy. The TABLE summarizes the indications and perioperative considerations for each procedure.
Some transgender men undergo hysterectomy for benign gynecologic disease. Counseling and perioperative planning are the same for these patients as for cisgender women, although some of the considerations discussed here remain important.
Other patients undergo hysterectomy as part of transitioning to their self-affirmed gender. The World Professional Association for Transgender Health (WPATH) Standards of Care should be used to guide counseling and treatment.17 These guidelines were designed as a framework for performing hysterectomy and other gender-affirming procedures. According to the WPATH standards, the criteria for hysterectomy and oophorectomy are:
- 2 referral letters from qualified mental health professionals
- well-documented persistent gender dysphoria
- capacity to make fully informed decisions and to consent to treatment
- age of majority in given country
- good control of any concurrent medical or mental health concerns, and
- hormone therapy for 12 continuous months, as appropriate to gender goals, unless the patient has a medical contraindication or is otherwise unable or unwilling to take hormones.
As the guidelines emphasize, these criteria do not apply to patients undergoing either procedure for medical indications other than gender dysphoria.
Hysterectomy approach. Most surgeons perform gender-affirming hysterectomies laparoscopically. Many clinicians hesitate to perform these hysterectomies vaginally, as the patients are often nulliparous. In general, the best operative route is the one the surgeon feels most comfortable performing safely and efficiently. For a nulliparous patient with minimal pelvic organ descensus and a narrow pelvis, the laparoscopic approach is reasonable. A recent study in a small cohort of transgender men found that vaginal hysterectomy was successful in only 1 in 4 patients.18 Nevertheless, the American College of Obstetricians and Gynecologists (ACOG) recommends vaginal hysterectomy, when appropriate, for limiting complications and morbidity while maximizing cost-effectiveness.19 Although data are limited, vaginal hysterectomy seems feasible and should be considered in a subset of patients who pre‑sent for gender-affirming hysterectomy.
Related Article:
Total laparoscopic versus laparoscopic supracervical hysterectomy
The oophorectomy debate
Oophorectomy concurrent with hysterectomy remains a topic of debate among gynecologists who perform hysterectomy for gender transition. Some clinicians think gonadectomy poses a significant risk for bone health compromise at an early age. The long-term effects of testosterone on bone have not been well studied. Although bone metabolism is thought to increase over the short term, there are no major changes in bone density over the long term. In fact, in the setting of long-term testosterone therapy, cortical bone was found to be larger in transgender men than in cisgender women.20 The issue is for patients who stop taking exogenous testosterone after oophorectomy. This subset of patients has not been well studied but clearly needs bone health surveillance and supplementation.
Another concern about oophorectomy is its effect on fertility. Because it is important to discuss fertility-preserving options, during consultation for a hysterectomy I spend a large portion of time addressing fertility goals. Patients who want to become a parent but do not want to carry a child (they want a current or future partner or surrogate to carry) are candidates for hysterectomy; those who do not want a genetic child are candidates for oophorectomy; and those who do not want to preserve their fertility (or have already ended it) and who meet the WPATH criteria for surgery are candidates for oophorectomy concurrent with hysterectomy. The discussion can be particularly challenging with young transgender men, since their ability to project their family planning goals may be compromised by their gender dysphoria. Clinicians can counsel patients about another option: isolated hysterectomy with subsequent staged oophorectomy.
Similar to cisgender women with polycystic ovary syndrome, transgender men on exogenous testosterone therapy are at risk for ovarian cysts,7 which can cause pain and should be evaluated and managed. As mentioned, these patients may find it difficult to visit a gynecologist and tolerate a vaginal examination, and many fear presenting to an emergency room, as they will need to disclose their transgender status and risk being discriminated against or, worse, not being triaged or cared for properly. Patients should be thoroughly counseled about the risks and benefits of having oophorectomy performed concurrently with hysterectomy.
Related Article:
Vaginal hysterectomy with basic instrumentation
The question of vaginectomy
Patients and clinicians often ask about concurrent vaginectomy procedures. In some cases, patients with severe gender dysphoria and absence of penetrative vaginal activity request excision or obliteration of the vagina. There is no standard of care, however. Vaginectomy can be done transvaginally or abdominally: open, laparoscopically, or robotically. It therefore should be performed by surgeons experienced in the procedure. Patients should be advised that a portion of the vaginal epithelium is sometimes used for certain phalloplasty procedures and that, if they are considering genital reconstruction in the future, it may be beneficial to preserve the vagina until that time.
There are no guidelines on stopping or continuing testosterone therapy perioperatively. Some clinicians are concerned about possible venous thromboembolic events related to perioperative use of testosterone, but there are no data supporting increased risk. The risk of postoperative vaginal cuff bleeding in patients on and off testosterone has not been well studied. Since patients who stop taking testosterone may develop severe mood swings and malaise, they should be counseled on recognizing and managing such changes. There are also no data on the risk of vaginal cuff dehiscence in this patient population. Testosterone usually causes the vagina to become very atrophic, so proper closure should be ensured to avoid cuff evisceration. In my practice, the vaginal cuff is closed in 2 layers using at least 1 layer of delayed absorbable suture.
Read about addressing fertility, contraception, OB care, and your role
Addressing fertility, contraception, and obstetric care
Most transgender men are able to conceive a child.21 Data in this area, however, are sparse. Most of the literature on reproductive health in this patient population is focused on human immunodeficiency virus (HIV) and other sexually transmitted infections.22 Nevertheless, patient-physician dialogue on fertility and reproductive health has increased since more patients started seeking surgical transition services (likely a result of improved coverage for these surgeries). In addition, we are learning more about patients’ ability and desire to conceive after long-term use of cross-sex hormone therapy. The importance of this dialogue is becoming apparent. One survey study found that more than half of the transgender men who had undergone affirmation surgery wanted to become parents.23
Before initiating cross-sex hormone therapy or before undergoing hysterectomy and/or oophorectomy, patients must be counseled about their fertility options. Testosterone may affect fertility and fecundity, but there are case reports of successful pregnancy after discontinuation of testosterone.21 Reproductive endocrinology and fertility specialists have begun to recognize the importance of fertility preservation in this patient population and to apply the principles of oncofertility care beyond patients with cancer. In a 2015 opinion paper on access to fertility services by transgender persons, the Ethics Committee of the American Society for Reproductive Medicine focused on this population’s unique fertility needs.24 Currently, oocyte and embryo cryopreservation are options for transgender men planning to start cross-sex hormones or undergo surgery.25 Other methods being investigated may become options in the future.25
There are even fewer data on transgender men’s contraceptive needs. Many clinicians mistakenly think these patients are at low risk for pregnancy. Some patients have male partners and engage in penetrative penile-vaginal intercourse; others are not on testosterone therapy; and still others, despite taking testosterone, are not always amenorrheic and may be ovulating. In a small cross-sectional study, Light and colleagues found that 12% of transgender men who were surveyed after conceiving had been amenorrheic on testosterone therapy, and 24% of these pregnancies were not planned.21
In a study by Cipres and colleagues, half of the 26 transgender men were considered at risk for pregnancy: These patients still had a uterus, not all were on testosterone, not all on testosterone were amenorrheic, they were having vaginal intercourse with cisgender men, and none were using condoms or other contraception.26 The authors noted several potential underlying reasons for poor counseling on contraceptive needs: patients feel stigmatized, clinicians assume these patients are not candidates for “female” hormone therapy, patients fear these modalities may feminize them and compromise their affirmed identities, patients poorly understand how testosterone works and have mistaken ideas about its contraceptive properties, and clinician discomfort with broaching fertility and reproductive health discussions.
Data are also limited on pregnancy in transgender men. We do know that clinicians are not well equipped to help patients during the peripartum period and better resources are needed.21 Gender dysphoria can worsen during and immediately after pregnancy, and patients may be at significant risk for postpartum depression. More research is needed.
Related Article:
Care of the transgender patient: What is the gynecologist's role?
Gynecologists play key role in transgender care
Transgender men’s unique health care needs can be addressed only by gynecologists.It is important to become comfortable with and educated about these needs and their subtleties. This starts with understanding transgender patients’ gender dysphoria associated with the gynecologic visit and examination. Learning more about these patients and their needs will improve health care delivery.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
CASE: Transgender man consults gynecologist for fertility options
A 36-year-old transgender man considering the possibility of having his own biological children presents to the gynecology office to discuss hysterectomy as gender dysphoria treatment as well as his fertility preservation options. He has never had a gynecologic examination. Since age 24, he has been on testosterone therapy. Although his menses initially ceased, each month over the past 2 years he has had breakthrough spotting lasting 2 to 4 days, sometimes accompanied by pelvic pain and cramping. These symptoms have caused him distress and anxiety, which have led to his missing work 1 to 3 days each month. On presentation, he appears anxious and makes little eye contact. His girlfriend of 6 years has come in with him and is very supportive.
Over the past decade, transgender health care has moved to the forefront of the medical conversation. At many prominent medical centers across the United States, clinicians are forming multidisciplinary teams to help improve the health care of this patient population. Outcomes are being studied, and the literature is becoming more robust.
People tend to think of transgender women—male-assigned persons who self-identify as female—as the typical prototype for transgender people, but this focus is skewed in both society and the medical community. Transgender men—female-assigned persons who self-identify as male—remain underrepresented, mostly because they want to stay “under the radar,” especially with respect to medical care and, more specifically, routine gynecologic care.
Although the transgender woman has unique health needs and may present to a gynecologist for care after gender-affirmationsurgery, the transgender man’s many health care needs and their subtleties can be addressed only by a gynecologist. In this article, I review these intricacies of care to help increase clinician comfort in treating these patients.
Clinicians can take steps to:
- ensure all patients have the correct identifiers in their medical records
- provide staff with the proper education and diversity training
- instruct staff in proper use of pronouns
- set up unisex or gender-nonbinary restrooms with appropriate signage
- make the decor gender nonspecific.
Beth Cronin, MD, a practicing general gynecologist in Providence, Rhode Island, says that you also should consider a general sign, placed in a highly visible area, that represents your nondiscrimination policy. The AMA offers this wording: "This office appreciates the diversity of human beings and does not discriminate based on race, age, religion, ability, marital status, sexual orientation, sex or gender identity." She also recommends having education and marketing materials with affirmative imagery and content and providing educational brochures on transgender health topics.
Why transgender patients may delay seeking health care
Transgender patients remain underserved because of the health care barriers they encounter. Factors contributing to poor access include lack of health insurance, inability to pay for services, clinician insensitivity and hostility, and fear of exposure of transgender status during health care encounters.1 In a recent large survey study, 30% of transgender respondents indicated that they delayed or did not seek medical care as a result of discrimination, and those who had needed to teach their clinicians about transgenderism were 4 times more likely to postpone or not seek care.2
In a 2015 survey of ObGyns’ current knowledge and practice regarding LGBT (lesbian, gay, bisexual, transgender) care, only one-third of respondents indicated they were comfortable caring for transgender patients.3 In addition, only one-third indicated being knowledgeable about the steps transgender patients must take to transition to their self-identified gender, and less than half were familiar with the recommendations for the routine health maintenance and screening of these patients.
Much of this discomfort derives from the lack of incorporation of LGBT-specific topics in medical curricula. In 2011, Obedin-Maliver and colleagues found that, at 176 US and Canadian allopathic and osteopathic medical schools, the median time dedicated to LGBT health care needs and related topics was unsatisfactory.4 This deficiency is slowly being reduced with changes in the curricula of many health care specialties. In ObGyn residency programs, for example, transgender-specific questions have been added to annual in-service examinations. The hope is that, as education initiatives improve, clinicians will become more comfortable caring for gender-minority patients, who with improved access to care will no longer need to seek subspecialists in transgender services.
Read about the need for gyn exams, managing benign disorders, and cervical cancer screening
Considerations for the gynecologic visit and examination
Transgender men visit the gynecology office for many reasons, including routine gynecologic care and health maintenance, care for acute and chronic gynecologic conditions (abnormal bleeding, pelvic pain, vaginitis), evaluation and management of pelvic floor disorders, consultation on hysterectomy for gender transition, and fertility counseling.
However, transgender men who reach their third, fourth, or fifth decade without having had a pelvic examination cite many reasons for avoiding the gynecology office. Most commonly, gynecologic visits and genital examination can severely exacerbate these patients’ gender dysphoria. In addition, many patients who do not engage in penetrative vaginal sex think their health risks are so low that they can forgo or delay pelvic exams. Patients who have stopped menstruating while on testosterone therapy may think there is no need for routine gynecologic care. Other reasons for avoiding pelvic exams are pain and traumatic sexual memories.5
Related Article:
Four pillars of a successful practice: 4. Motivate your staff
Transgender men need to receive the regular guideline-recommended pelvic exams and screenings used for cisgender women. (Cisgender refers to a person whose sense of gender identity corresponds with their birth sex.) We need to educate patients in this regard and to discuss several issues before performing an examination. First, take a thorough history and avoid making assumptions about sexual orientation and sex practices. Some patients have penetrative vaginal intercourse with either men or women. For some patients, the exam may cause dysphoria symptoms, and we need to validate patients’ fears. Discussing these issues ahead of time helps patients get used to the idea of undergoing an exam and assures them that the clinician is experienced in performing these exams for transgender men. In my practice, we explain the exam’s purpose (screening or diagnosis) and importance. We also counsel patients that they may experience some normal, and temporary, spotting after the exam. For those who experience severe dysphoria with vaginal bleeding of any kind, we acknowledge that postexam spotting may cause some anxiety. Patients with severe anxiety before the exam may be premedicated with an anxiolytic agent as long as someone can transport them to and from the office.
The bimanual exam should be performed with care and efficiency and with the patient given as much control as possible. In most cases, we ask patients to undress only from the waist down, and their genitals stay covered. Patients uncomfortable in stirrups are asked to show us the position that suits them best, and we try to accommodate them. Although speed is a goal, remember that many patients are nulliparous, have had limited or no vaginal penetration, or are on testosterone and have significant vaginal dryness. Use the smallest speculum possible, a pediatric or long and narrow adult speculum, and apply lubricant copiously. Pre-exam application of topical lidocaine jelly to the introitus can help reduce pain. To help a patient relax the pelvic floor muscles and habituate to the presence of a foreign object in the vagina, start the exam by inserting a single digit. In addition, ask the patient about speculum placement inside the vagina: Does he want to place the speculum himself or guide the clinician’s hand? Open the speculum only as much as needed to adequately visualize the cervix and then remove it with care.
Managing benign gynecologic disorders
The same algorithms are used to evaluate abnormal bleeding in all patients, but the differential diagnosis expands for those on testosterone therapy. Testosterone may no longer be suppressing their cycles, and abnormal bleeding could simply be the return of menses, which would present as regular cyclic bleeding. Increasing the testosterone dosing or changing the testosterone formulation may help, and the gynecologist should discuss these options with the patient’s prescribing clinician. In addition, progesterone in any form (for example, medroxyprogesterone acetate 5 to 30 mg daily) can be added to testosterone regimens to help suppress menses. The levonorgestrel-releasing intrauterine device (LNG-IUD) can be very effective, but placement can induce anxiety, and some patients decline this treatment option.
In patients with intermenstrual spotting, assess the vagina for atrophy. Both over-the-counter vaginal moisturizers and DHEA (dehydroepiandrosterone) suppositories (1% compounded) can help treat atrophy, but not all patients are comfortable using them. Most patients decline vaginal estrogen products for symptomatic vaginal atrophy even though the systemic effects are minimal.
The historic literature suggests that female-to-male patients’ long-term exposure to androgens leads to atrophic changes in the endometrium and myometrium, and clinical studies of menopausal women who take exogenous androgens have confirmed this effect.6 However, new data point to a different histologic scenario. A recent study found a possible association between long-term testosterone use in transgender men of reproductive age and a low proliferative active endometrium, as well as hypertrophic changes in the myometrium.7 The causes may be peripheral aromatization of androgens and expression and up-regulation of androgen receptors within the endometrial stroma and myometrial cells.8 Given these emerging data and anecdotal cases reported by clinicians who perform hysterectomies for transgender men, imaging and tissue sampling should be used to evaluate abnormal uterine bleeding, particularly in patients previously amenorrheic on testosterone. Be aware that transvaginal ultrasound or endometrial biopsy are challenging procedures for these patients. Counsel patients to ensure that they adhere to follow-up.
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2017 Update on cervical disease
The ongoing need for cervical cancer screening
The concept of “original gender surveillance” was presented in a 2-case series of transgender men with uterine and cervical cancer that might have been detected earlier with better screening and routine care.9 There is no evidence, however, that long-term high-dose androgen therapy causes endometrial or cervical cancer,10 and the data on endometrial cancer in patients on cross-sex hormone therapy are limited such that a causal relationship between testosterone and these malignancies cannot be established.9,11–14
The rate of unsatisfactory Pap smears is higher in transgender men than in cisgender women. The difference was anecdotally noted by clinicians who routinely cared for transgender patients over time and was confirmed with a retrospective chart review.15
Peitzmeier and colleagues reviewed the records of 233 transgender men and 3,625 cisgender women with Pap tests performed at an urban community health center over 6 years.15 The transgender cohort, with its prevalence rate of 10%, was 10 times more likely to have an unsatisfactory or inadequate Pap smear. Moreover, the transgender patients were more likely to have longer latency to follow-up for a repeat Pap test. In addition, testosterone therapy was more likely associated with inadequate Pap smears, and time on testosterone therapy was associated with higher odds of Pap smear inadequacy. Besides the exogenous hormone therapy, clinician comfort level and experience may have contributed to the high prevalence of inadequate Pap smears.
As mentioned earlier, it is important to become comfortable performing pelvic exams for transgender men and to prepare patients for the possibility that a Pap smear might be inadequate, making a follow-up visit and repeat Pap test necessary.16
Read about hysterectomy, oophorectomy, and vaginectomy choices
Consultation for hysterectomy: Perioperative considerations
Transgender men may undergo hysterectomy, oophorectomy, and/or vaginectomy. The TABLE summarizes the indications and perioperative considerations for each procedure.
Some transgender men undergo hysterectomy for benign gynecologic disease. Counseling and perioperative planning are the same for these patients as for cisgender women, although some of the considerations discussed here remain important.
Other patients undergo hysterectomy as part of transitioning to their self-affirmed gender. The World Professional Association for Transgender Health (WPATH) Standards of Care should be used to guide counseling and treatment.17 These guidelines were designed as a framework for performing hysterectomy and other gender-affirming procedures. According to the WPATH standards, the criteria for hysterectomy and oophorectomy are:
- 2 referral letters from qualified mental health professionals
- well-documented persistent gender dysphoria
- capacity to make fully informed decisions and to consent to treatment
- age of majority in given country
- good control of any concurrent medical or mental health concerns, and
- hormone therapy for 12 continuous months, as appropriate to gender goals, unless the patient has a medical contraindication or is otherwise unable or unwilling to take hormones.
As the guidelines emphasize, these criteria do not apply to patients undergoing either procedure for medical indications other than gender dysphoria.
Hysterectomy approach. Most surgeons perform gender-affirming hysterectomies laparoscopically. Many clinicians hesitate to perform these hysterectomies vaginally, as the patients are often nulliparous. In general, the best operative route is the one the surgeon feels most comfortable performing safely and efficiently. For a nulliparous patient with minimal pelvic organ descensus and a narrow pelvis, the laparoscopic approach is reasonable. A recent study in a small cohort of transgender men found that vaginal hysterectomy was successful in only 1 in 4 patients.18 Nevertheless, the American College of Obstetricians and Gynecologists (ACOG) recommends vaginal hysterectomy, when appropriate, for limiting complications and morbidity while maximizing cost-effectiveness.19 Although data are limited, vaginal hysterectomy seems feasible and should be considered in a subset of patients who pre‑sent for gender-affirming hysterectomy.
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Total laparoscopic versus laparoscopic supracervical hysterectomy
The oophorectomy debate
Oophorectomy concurrent with hysterectomy remains a topic of debate among gynecologists who perform hysterectomy for gender transition. Some clinicians think gonadectomy poses a significant risk for bone health compromise at an early age. The long-term effects of testosterone on bone have not been well studied. Although bone metabolism is thought to increase over the short term, there are no major changes in bone density over the long term. In fact, in the setting of long-term testosterone therapy, cortical bone was found to be larger in transgender men than in cisgender women.20 The issue is for patients who stop taking exogenous testosterone after oophorectomy. This subset of patients has not been well studied but clearly needs bone health surveillance and supplementation.
Another concern about oophorectomy is its effect on fertility. Because it is important to discuss fertility-preserving options, during consultation for a hysterectomy I spend a large portion of time addressing fertility goals. Patients who want to become a parent but do not want to carry a child (they want a current or future partner or surrogate to carry) are candidates for hysterectomy; those who do not want a genetic child are candidates for oophorectomy; and those who do not want to preserve their fertility (or have already ended it) and who meet the WPATH criteria for surgery are candidates for oophorectomy concurrent with hysterectomy. The discussion can be particularly challenging with young transgender men, since their ability to project their family planning goals may be compromised by their gender dysphoria. Clinicians can counsel patients about another option: isolated hysterectomy with subsequent staged oophorectomy.
Similar to cisgender women with polycystic ovary syndrome, transgender men on exogenous testosterone therapy are at risk for ovarian cysts,7 which can cause pain and should be evaluated and managed. As mentioned, these patients may find it difficult to visit a gynecologist and tolerate a vaginal examination, and many fear presenting to an emergency room, as they will need to disclose their transgender status and risk being discriminated against or, worse, not being triaged or cared for properly. Patients should be thoroughly counseled about the risks and benefits of having oophorectomy performed concurrently with hysterectomy.
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Vaginal hysterectomy with basic instrumentation
The question of vaginectomy
Patients and clinicians often ask about concurrent vaginectomy procedures. In some cases, patients with severe gender dysphoria and absence of penetrative vaginal activity request excision or obliteration of the vagina. There is no standard of care, however. Vaginectomy can be done transvaginally or abdominally: open, laparoscopically, or robotically. It therefore should be performed by surgeons experienced in the procedure. Patients should be advised that a portion of the vaginal epithelium is sometimes used for certain phalloplasty procedures and that, if they are considering genital reconstruction in the future, it may be beneficial to preserve the vagina until that time.
There are no guidelines on stopping or continuing testosterone therapy perioperatively. Some clinicians are concerned about possible venous thromboembolic events related to perioperative use of testosterone, but there are no data supporting increased risk. The risk of postoperative vaginal cuff bleeding in patients on and off testosterone has not been well studied. Since patients who stop taking testosterone may develop severe mood swings and malaise, they should be counseled on recognizing and managing such changes. There are also no data on the risk of vaginal cuff dehiscence in this patient population. Testosterone usually causes the vagina to become very atrophic, so proper closure should be ensured to avoid cuff evisceration. In my practice, the vaginal cuff is closed in 2 layers using at least 1 layer of delayed absorbable suture.
Read about addressing fertility, contraception, OB care, and your role
Addressing fertility, contraception, and obstetric care
Most transgender men are able to conceive a child.21 Data in this area, however, are sparse. Most of the literature on reproductive health in this patient population is focused on human immunodeficiency virus (HIV) and other sexually transmitted infections.22 Nevertheless, patient-physician dialogue on fertility and reproductive health has increased since more patients started seeking surgical transition services (likely a result of improved coverage for these surgeries). In addition, we are learning more about patients’ ability and desire to conceive after long-term use of cross-sex hormone therapy. The importance of this dialogue is becoming apparent. One survey study found that more than half of the transgender men who had undergone affirmation surgery wanted to become parents.23
Before initiating cross-sex hormone therapy or before undergoing hysterectomy and/or oophorectomy, patients must be counseled about their fertility options. Testosterone may affect fertility and fecundity, but there are case reports of successful pregnancy after discontinuation of testosterone.21 Reproductive endocrinology and fertility specialists have begun to recognize the importance of fertility preservation in this patient population and to apply the principles of oncofertility care beyond patients with cancer. In a 2015 opinion paper on access to fertility services by transgender persons, the Ethics Committee of the American Society for Reproductive Medicine focused on this population’s unique fertility needs.24 Currently, oocyte and embryo cryopreservation are options for transgender men planning to start cross-sex hormones or undergo surgery.25 Other methods being investigated may become options in the future.25
There are even fewer data on transgender men’s contraceptive needs. Many clinicians mistakenly think these patients are at low risk for pregnancy. Some patients have male partners and engage in penetrative penile-vaginal intercourse; others are not on testosterone therapy; and still others, despite taking testosterone, are not always amenorrheic and may be ovulating. In a small cross-sectional study, Light and colleagues found that 12% of transgender men who were surveyed after conceiving had been amenorrheic on testosterone therapy, and 24% of these pregnancies were not planned.21
In a study by Cipres and colleagues, half of the 26 transgender men were considered at risk for pregnancy: These patients still had a uterus, not all were on testosterone, not all on testosterone were amenorrheic, they were having vaginal intercourse with cisgender men, and none were using condoms or other contraception.26 The authors noted several potential underlying reasons for poor counseling on contraceptive needs: patients feel stigmatized, clinicians assume these patients are not candidates for “female” hormone therapy, patients fear these modalities may feminize them and compromise their affirmed identities, patients poorly understand how testosterone works and have mistaken ideas about its contraceptive properties, and clinician discomfort with broaching fertility and reproductive health discussions.
Data are also limited on pregnancy in transgender men. We do know that clinicians are not well equipped to help patients during the peripartum period and better resources are needed.21 Gender dysphoria can worsen during and immediately after pregnancy, and patients may be at significant risk for postpartum depression. More research is needed.
Related Article:
Care of the transgender patient: What is the gynecologist's role?
Gynecologists play key role in transgender care
Transgender men’s unique health care needs can be addressed only by gynecologists.It is important to become comfortable with and educated about these needs and their subtleties. This starts with understanding transgender patients’ gender dysphoria associated with the gynecologic visit and examination. Learning more about these patients and their needs will improve health care delivery.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Xavier JM, Simmons R. The Washington Transgender Needs Assessment Survey, 2000. http://www.glaa.org/archive/2000/tgneedsassessment1112.shtml. Accessed January 2, 2017.
- Jaffee KD, Shires DA, Stroumsa D. Discrimination and delayed health care among transgender women and men: implications for improving medical education and health care delivery. Med Care. 2016;54(11):1010–1016.
- Unger CA. Care of the transgender patient: a survey of gynecologists’ current knowledge and practice. J Womens Health. 2015;24(2):114–118.
- Obedin-Maliver J, Goldsmith ES, Stewart L, et al. Lesbian, gay, bisexual, and transgender-related content in undergraduate medical education. JAMA. 2011;306(9):971–977.
- Feldman J. Medical and surgical management of the transgender patient: what the primary care clinician needs to know. In: Makadon H, Mayer K, Potter J, Goldhammer H, eds. Fenway Guide to Lesbian, Gay, Bisexual, and Transgender Health. Philadelphia, PA: American College of Physicians; 2008:365–392.
- Hickok LR, Toomey C, Speroff L. A comparison of esterified estrogens with and without methyltestosterone: effects on endometrial histology and serum lipoproteins in postmenopausal women. Obstet Gynecol. 1993;82(6):919–924.
- Loverro G, Resta L, Dellino M, et al. Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals. Taiwan J Obstet Gynecol. 2016;55(5):686–691.
- Mertens HJ, Heineman MJ, Koudstaal J, Theunissen P, Evers JL. Androgen receptor content in human endometrium. Eur J Obstet Gynecol Reprod Biol. 1996;70(1):11–13.
- Urban RR, Teng NN, Kapp DS. Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance. Am J Obstet Gynecol. 2011;204(5):e9–e12.
- Mueller A, Gooren L. Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2008;159(3):197–202.
- Allen NE, Key TJ, Dossus L, et al. Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2008;15(2):485–497.
- Hage JJ, Dekker JJ, Karim RB, Verheijen RH, Bloemena E. Ovarian cancer in female-to-male transsexuals: report of two cases. Gynecol Oncol. 2000;76(3):413–415.
- Dizon DS, Tejada-Berges T, Keolliker S, Steinhoff M, Grania CO. Ovarian cancer associated with testosterone supplementation in a female-to-male transsexual patient. Gynecol Oncol Invest. 2006;62(4):226–228.
- Schenck TL, Holzbach T, Zantl N, et al. Vaginal carcinoma in a female-to-male transsexual. J Sex Med. 2010;7(8):2899–2902.
- Peitzmeier SM, Reisner SL, Harigopal P, Potter J. Female-to-male patients have high prevalence of unsatisfactory Paps compared to non-transgender females: implications for cervical cancer screening. J Gen Intern Med. 2014;29(5):778–784.
- Potter J, Peitzmeier SM, Bernstein I, et al. Cervical cancer screening for patients on the female-to-male spectrum: a narrative review and guide for clinicians. J Gen Intern Med. 2015;30(12):1857–1864.
- Coleman E, Bockting W, Botzer M, et al; World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, Version 7. https://s3.amazonaws.com/amo_hub_content/Association140/files/Standards_of_Care_V7_2011_WPATH(2)(1).pdf. Published 2011. Accessed January 21, 2017.
- Obedin-Maliver J, Light A, de Haan G, Jackson RA. Feasibility of vaginal hysterectomy for female-to-male transgender men. Obstet Gynecol. 2017;129(3):457–463.
- American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 444: Choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156–1158.
- Van Caenegem E, T’Sjoen G. Bone in trans persons. Curr Opin Endocrinol Diabetes Obes. 2015;22(6):459–466.
- Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014;124(6):1120–1127.
- Stephens SC, Bernstein KT, Philip SS. Male to female and female to male transgender persons have different sexual risk behaviors yet similar rates of STDs and HIV. AIDS Behav. 2011;15(3):683–686.
- Wierckx K, Van Caenegem E, Pennings G, et al. Reproductive wish in transsexual men. Hum Reprod. 2012;27(2):483–487.
- Ethics Committee of the American Society for Reproductive Medicine. Access to fertility services by transgender persons: an Ethics Committee opinion. Fertil Steril. 2015;104(5):1111–1115.
- Wallace SA, Blough KL, Kondapalli LA. Fertility preservation in the transgender patient: expanding oncofertility care beyond cancer. Gynecol Endocrinol. 2014;30(12):868–871.
- Cipres D, Seidman D, Cloniger C 3rd, Nova C, O’Shea A, Obedin-Maliver J. Contraceptive use and pregnancy intentions among transgender men presenting to a clinic for sex workers and their families in San Francisco. Contraception. 2016;95(2):186–189.
- Xavier JM, Simmons R. The Washington Transgender Needs Assessment Survey, 2000. http://www.glaa.org/archive/2000/tgneedsassessment1112.shtml. Accessed January 2, 2017.
- Jaffee KD, Shires DA, Stroumsa D. Discrimination and delayed health care among transgender women and men: implications for improving medical education and health care delivery. Med Care. 2016;54(11):1010–1016.
- Unger CA. Care of the transgender patient: a survey of gynecologists’ current knowledge and practice. J Womens Health. 2015;24(2):114–118.
- Obedin-Maliver J, Goldsmith ES, Stewart L, et al. Lesbian, gay, bisexual, and transgender-related content in undergraduate medical education. JAMA. 2011;306(9):971–977.
- Feldman J. Medical and surgical management of the transgender patient: what the primary care clinician needs to know. In: Makadon H, Mayer K, Potter J, Goldhammer H, eds. Fenway Guide to Lesbian, Gay, Bisexual, and Transgender Health. Philadelphia, PA: American College of Physicians; 2008:365–392.
- Hickok LR, Toomey C, Speroff L. A comparison of esterified estrogens with and without methyltestosterone: effects on endometrial histology and serum lipoproteins in postmenopausal women. Obstet Gynecol. 1993;82(6):919–924.
- Loverro G, Resta L, Dellino M, et al. Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals. Taiwan J Obstet Gynecol. 2016;55(5):686–691.
- Mertens HJ, Heineman MJ, Koudstaal J, Theunissen P, Evers JL. Androgen receptor content in human endometrium. Eur J Obstet Gynecol Reprod Biol. 1996;70(1):11–13.
- Urban RR, Teng NN, Kapp DS. Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance. Am J Obstet Gynecol. 2011;204(5):e9–e12.
- Mueller A, Gooren L. Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2008;159(3):197–202.
- Allen NE, Key TJ, Dossus L, et al. Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2008;15(2):485–497.
- Hage JJ, Dekker JJ, Karim RB, Verheijen RH, Bloemena E. Ovarian cancer in female-to-male transsexuals: report of two cases. Gynecol Oncol. 2000;76(3):413–415.
- Dizon DS, Tejada-Berges T, Keolliker S, Steinhoff M, Grania CO. Ovarian cancer associated with testosterone supplementation in a female-to-male transsexual patient. Gynecol Oncol Invest. 2006;62(4):226–228.
- Schenck TL, Holzbach T, Zantl N, et al. Vaginal carcinoma in a female-to-male transsexual. J Sex Med. 2010;7(8):2899–2902.
- Peitzmeier SM, Reisner SL, Harigopal P, Potter J. Female-to-male patients have high prevalence of unsatisfactory Paps compared to non-transgender females: implications for cervical cancer screening. J Gen Intern Med. 2014;29(5):778–784.
- Potter J, Peitzmeier SM, Bernstein I, et al. Cervical cancer screening for patients on the female-to-male spectrum: a narrative review and guide for clinicians. J Gen Intern Med. 2015;30(12):1857–1864.
- Coleman E, Bockting W, Botzer M, et al; World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, Version 7. https://s3.amazonaws.com/amo_hub_content/Association140/files/Standards_of_Care_V7_2011_WPATH(2)(1).pdf. Published 2011. Accessed January 21, 2017.
- Obedin-Maliver J, Light A, de Haan G, Jackson RA. Feasibility of vaginal hysterectomy for female-to-male transgender men. Obstet Gynecol. 2017;129(3):457–463.
- American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 444: Choosing the route of hysterectomy for benign disease. Obstet Gynecol. 2009;114(5):1156–1158.
- Van Caenegem E, T’Sjoen G. Bone in trans persons. Curr Opin Endocrinol Diabetes Obes. 2015;22(6):459–466.
- Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014;124(6):1120–1127.
- Stephens SC, Bernstein KT, Philip SS. Male to female and female to male transgender persons have different sexual risk behaviors yet similar rates of STDs and HIV. AIDS Behav. 2011;15(3):683–686.
- Wierckx K, Van Caenegem E, Pennings G, et al. Reproductive wish in transsexual men. Hum Reprod. 2012;27(2):483–487.
- Ethics Committee of the American Society for Reproductive Medicine. Access to fertility services by transgender persons: an Ethics Committee opinion. Fertil Steril. 2015;104(5):1111–1115.
- Wallace SA, Blough KL, Kondapalli LA. Fertility preservation in the transgender patient: expanding oncofertility care beyond cancer. Gynecol Endocrinol. 2014;30(12):868–871.
- Cipres D, Seidman D, Cloniger C 3rd, Nova C, O’Shea A, Obedin-Maliver J. Contraceptive use and pregnancy intentions among transgender men presenting to a clinic for sex workers and their families in San Francisco. Contraception. 2016;95(2):186–189.
