Effects of feminizing gender-affirming hormone therapy on testicular function and reproductive capacity

Feminizing gender affirming hormone therapy (GAHT) may include combined estrogen, progesterone and/or antiandrogens (collectively referred to as E-GAHT) aiming to achieve individualized embodiment goals. This kind of treatment is expected to negatively impact the reproductive ability of transgender, nonbinary and/or gender diverse (TNG) individuals having testes, mainly by disrupting the biological pathways involved in spermatogenesis. There is little research on the impact of E-GAHT in the testis, or on the potential recovery of spermatogenesis by stopping GAHT. Studies using animal models receiving GAHT are a novel promising method to help identify the reproductive pathways affected by GAHT and the degree of those effects. A literature search was performed to identify both clinical and experimental studies using rodent models applicable to the reproductive needs of E-GAHT users. We found large variability in clinical populations that has not been fully replicated in translational research. Further, animal GAHT models have yet to be capitalized to examine fertility preservation. Some clinical studies indicated sperm quality may be reduced in E-GAHT patients prior to initiating E-GAHT, which cannot be studied using GAHT-treated animals. As many TNG people of reproductive age may have the wish to create a future family, it is important to increase the knowledge that will inform and improve E-GAHT patients’ fertility preservation outcomes and reproductive health.