REPRODUCTIVE HEALTH IN TRANS AND GENDER DIVERSE PATIENTS: Effects of feminizing gender-affirming hormone therapy on testicular function and reproductive capacity: review of data from clinical and experimental studies.

Feminizing gender-affirming hormone therapy (E-GAHT) is expected to negatively impact reproductive ability in transgender, non-binary, and gender-diverse individuals with testes by disrupting biological pathways involved in spermatogenesis.

• E-GAHT may include combined estrogen, progesterone and/or antiandrogens collectively aimed at achieving individualized embodiment goals.
• The primary mechanism of reproductive impact is disruption of the biological pathways involved in spermatogenesis.
• Current clinical approaches to reduced fertility include fertility preservation and treatment cessation.

Some clinical studies indicated that sperm quality may be reduced in E-GAHT patients before initiating E-GAHT.

• Baseline sperm quality reduction prior to treatment initiation is a finding that cannot be studied using GAHT-treated animal models.
• This pre-treatment reduction in sperm quality represents a gap between clinical populations and translational animal research.
• This finding highlights that reproductive impairment in TNG individuals may not be solely attributable to hormone therapy itself.

Large variability exists in clinical populations using E-GAHT that has not been fully replicated in translational animal research.

• A literature search was performed to identify both clinical and experimental studies using rodent models applicable to the reproductive needs of E-GAHT users.
• The variability in clinical populations includes differences in hormone regimens, dosages, duration of treatment, and patient characteristics.
• Animal GAHT models have yet to be capitalized to examine fertility preservation strategies.

There is little research on the impact of E-GAHT on testicular function or on the potential recovery of spermatogenesis after stopping GAHT.

• The review identified a gap in knowledge regarding both the severity and duration of testicular function impairment from E-GAHT.
• Recovery of spermatogenesis following treatment cessation is not well characterized in either clinical or experimental literature.
• Experimental research with animal models is described as a novel promising method to help identify the reproductive pathways affected by GAHT and the degree of those effects.

Animal models receiving GAHT represent a novel and promising method to identify reproductive pathways affected by E-GAHT and the degree of those effects.

• Rodent models were specifically identified through the literature search as applicable to the reproductive needs of E-GAHT users.
• Experimental research with animal models may identify mechanisms involved in testicular function impairment, their severity, and duration.
• Animal models could potentially help inform patients about reproductive health decisions, but this potential has not yet been fully utilized for fertility preservation research.

Increasing knowledge to inform and improve fertility preservation outcomes and reproductive health for E-GAHT patients is identified as an important clinical and research priority.

• Many TNG people of reproductive age may have the wish to create a future family.
• Current fertility preservation approaches include both preservation strategies and treatment cessation.
• The paper calls for improved translational research to bridge gaps between animal models and the clinical variability observed in TNG populations.