Emerging and accumulating safety signals for the use of estrogen among transgender women

Abstract Efforts to alleviate the psychological distress of gender dysphoria have included the use of exogenous estrogen (often with anti-androgens) to alter secondary sex characteristics of natal males. In response to the rapid increase in presenting cases among young people, extensive scrutiny has...

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Main Authors: Lauren Schwartz, M. Lal, J. Cohn, Carrie D. Mendoza, Leslie MacMillan
Format: Article
Language:English
Published: Springer 2025-06-01
Series:Discover Mental Health
Online Access:https://doi.org/10.1007/s44192-025-00216-3
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author Lauren Schwartz
M. Lal
J. Cohn
Carrie D. Mendoza
Leslie MacMillan
author_facet Lauren Schwartz
M. Lal
J. Cohn
Carrie D. Mendoza
Leslie MacMillan
author_sort Lauren Schwartz
collection DOAJ
description Abstract Efforts to alleviate the psychological distress of gender dysphoria have included the use of exogenous estrogen (often with anti-androgens) to alter secondary sex characteristics of natal males. In response to the rapid increase in presenting cases among young people, extensive scrutiny has now been brought to bear on these medical interventions for minors, with ESCAP reporting “an urgent need for safeguarding clinical, scientific, and ethical standards.” However, due to the lack of systematic outcome data, the associated risk–benefit profile is unknown. Several recent systematic reviews have found the evidence of benefit to be of low or very low certainty, while some risks, such as infertility, have been long recognized. This paper compiles several emerging and accumulating safety signals in the medical literature. These range from increased rates of previously associated adverse outcomes with long-term estrogen use (e.g., acute cardiovascular events) to associations of estrogen use with newly identified adverse outcomes. Estrogen also induces changes in the brain, raising concerns for negative impacts on mood (e.g., depression) and cognition. These safety signals indicate the need for further investigation and a thorough systematic search for others, which may now be more evident due to the increased number of young people receiving these treatments. There is an urgent need for the evidence base to be improved with more studies, especially those with systematic long-term follow-up and those that can disentangle possible confounders, as well as systematic reviews to help interpret their reliability.
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spelling doaj-art-fa2c23ffa0b54cd483a5716ab5bfa48c2025-08-20T02:39:43ZengSpringerDiscover Mental Health2731-43832025-06-015111710.1007/s44192-025-00216-3Emerging and accumulating safety signals for the use of estrogen among transgender womenLauren Schwartz0M. Lal1J. Cohn2Carrie D. MendozaLeslie MacMillanOklahoma City Psychiatry: Lauren H. Schwartz MD PLLCThe Killarney Group, GenspectSociety for Evidence-Based Gender MedicineAbstract Efforts to alleviate the psychological distress of gender dysphoria have included the use of exogenous estrogen (often with anti-androgens) to alter secondary sex characteristics of natal males. In response to the rapid increase in presenting cases among young people, extensive scrutiny has now been brought to bear on these medical interventions for minors, with ESCAP reporting “an urgent need for safeguarding clinical, scientific, and ethical standards.” However, due to the lack of systematic outcome data, the associated risk–benefit profile is unknown. Several recent systematic reviews have found the evidence of benefit to be of low or very low certainty, while some risks, such as infertility, have been long recognized. This paper compiles several emerging and accumulating safety signals in the medical literature. These range from increased rates of previously associated adverse outcomes with long-term estrogen use (e.g., acute cardiovascular events) to associations of estrogen use with newly identified adverse outcomes. Estrogen also induces changes in the brain, raising concerns for negative impacts on mood (e.g., depression) and cognition. These safety signals indicate the need for further investigation and a thorough systematic search for others, which may now be more evident due to the increased number of young people receiving these treatments. There is an urgent need for the evidence base to be improved with more studies, especially those with systematic long-term follow-up and those that can disentangle possible confounders, as well as systematic reviews to help interpret their reliability.https://doi.org/10.1007/s44192-025-00216-3
spellingShingle Lauren Schwartz
M. Lal
J. Cohn
Carrie D. Mendoza
Leslie MacMillan
Emerging and accumulating safety signals for the use of estrogen among transgender women
Discover Mental Health
title Emerging and accumulating safety signals for the use of estrogen among transgender women
title_full Emerging and accumulating safety signals for the use of estrogen among transgender women
title_fullStr Emerging and accumulating safety signals for the use of estrogen among transgender women
title_full_unstemmed Emerging and accumulating safety signals for the use of estrogen among transgender women
title_short Emerging and accumulating safety signals for the use of estrogen among transgender women
title_sort emerging and accumulating safety signals for the use of estrogen among transgender women
url https://doi.org/10.1007/s44192-025-00216-3
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AT carriedmendoza emergingandaccumulatingsafetysignalsfortheuseofestrogenamongtransgenderwomen
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