Reproductive Health in Trans and Gender Diverse Patients: Effects of transmasculine gender-affirming hormone therapy on future reproductive capacity: clinical data, animal models, and gaps in knowledge.

In Brief: Animal studies are needed to inform clinical guidance on the effects of testosterone gender-affirming hormone therapy (T-GAHT) on fertility. This review summarizes current animal models of T-GAHT and identifies gaps in knowledge for future study.

Abstract: Testosterone gender affirming hormone therapy (T-GAHT) is frequently used by transgender and gender-diverse individuals assigned female at birth to establish masculinizing characteristics. Although many seek parenthood, particularly as a gestational parent or through surrogacy, the current standard guidance of fertility counseling for individuals on testosterone (T) lacks clarity. At this time, individuals are typically recommended to undergo fertility preservation or stop treatment, associating T-therapy with a loss of fertility; however, there is an absence of consistent information regarding the true fertility potential for transgender and gender-diverse adults and adolescents. This review evaluates recent studies that utilize animal models of T-GAHT to relate to findings from clinical studies, with a more specific focus on fertility. Relevant literature based on murine models in post- and pre-pubertal populations has suggested reversibility of the impacts of T-GAHT, alone or following gonadotropin-releasing hormone agonist (GnRHa), on reproduction. These studies reported changes in clitoral area and ovarian morphology, including corpora lutea, follicle counts, and ovarian weights from T-treated mice. Future studies should aim to determine the impact of the duration of T-treatment and cessation on fertility outcomes, as well as establish animal models that are clinically representative of these outcomes with respect to gender diverse populations.