Friday, May 10, 2024
5/10/2024
SUMMARY Transgender (TG) men (assigned female at birth) and TG women (assigned male at birth) comprise a vulnerable population whose health is largely understudied. Approximately 75%–95% of TG individuals will use exogenous hormones as part of gender-affirming care. Gender-affirming hormone therapy is a community priority for TG people and can be a critical protective factor for improving general health and well-being. However, exogenous hormone use doubles the risk of breast cancer (BC) in cisgender (sex assigned at birth aligns with gender) women. Yet it is unknown whether gender-affirming hormone therapy modifies BC risk in TG individuals. Despite this lack of evidence, current BC screening guidelines state TG men and women should follow cisgender guidelines, especially if they are =50 years old and if TG women have used hormones for =5 years. We hypothesize that gender-affirming hormone therapy modifies BC cancer risk, and the steroid metabolome will reflect this. We will test our hypothesis with our SPECTRUM (Studying PRIDE to Enhance Cancer screening guidelines for TRansgender Users of gender- affirMing hormones) Study in response to the Notice of Special Interest NOT-MD-19-001. We will recruit individuals (aged 25-50 years) across the spectrum of gender identities with varying hormone use through an ancillary study of PRIDE, one of the largest nationwide cohorts of sexual and/or gender minority people, of whom 33% are TG. We will use this cohort to conduct the following aims: Aim 1) Quantify hormone use across the gender identity spectrum (n=5000) and examine the association between hormone use and the steroid metabolome in a subset (n=1200), Aim 2) Evaluate longitudinal changes in the steroid metabolome based on age, gender-affirming hormone use, and gonad inventory in TG men and women (n=600), Aim 3) Incorporate hormonal evidence into screening guidelines using the Delphi method with 10 experts. Until gender identity data are collected systematically, a TG-enhanced cohort provides a valuable resource to understand the role of gender-affirming hormone therapy and BC risk at the molecular level. Such knowledge is lacking yet could greatly improve screening recommendations, which now simply extrapolate cisgender guidelines to TG populations. Given the high prevalence of gender- affirming hormone therapy and the benefits it provides in terms of mental and general health, TG populations deserve to know what hormone use means in terms of their cancer risk. Practitioners who serve SGM people and screen for cancer also need guidelines that are evidence-based and gender-affirming.
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