A Mouse Model to Investigate the Impact of Gender Affirming Hormone Therapy with Estradiol on Reproduction

Abstract

Gender‐affirming hormone therapy (GAHT) can help transgender and/or gender diverse (TGD) individuals achieve emobidment goals that align with their transition needs. Clinical evidence from estradiol (E)‐GAHT patients indicate widespread changes in tissues sensitive to E and testosterone (T), particularly in the reproductive system. Notably, E‐GAHTs effects on hormones and reproduction vary greatly between patients. With the goal of informing clinical research and practice for TGD individuals taking E, this study examines intact male mice implanted with capsules containing one of three different E doses (low 1.25 mg; mid 2.5 mg; high 5 mg), or a blank control capsule. All E‐GAHT doses suppress T and follicle stimulating hormone levels while elevating E levels. Only the high E‐GAHT dose significantly supresses luteinizing hormone levels. All E‐GAHT doses affect epididymis tubule size similarly while seminiferous tubule morphology and bladder weight changes are dose‐dependent. E‐GAHT does not alter the presence of mature sperm, though E‐exposed sperm have altered motility. These data represent the first evidence that mouse models offer an effective tool to understand E‐GAHTs impact on reproductive health and the dose‐dependent effects of this model permit examinations of diverse patient outcomes.

Male animal sterilization: history, current practices, and potential methods for replacing castration

“…Estrogen treatment in the adult male also suppresses testosterone production by negative feedback on the HPG and is used in gender-affirming hormone therapy ( 429 ). While the negative feedback on the HPG did suppress LH, FSH, and testosterone and, in general, resulted in hypoplasia of germ cells, it has been surprising to find that estrogen treatment did not arrest spermatogenesis ( 430 ).…”

“…Overall, estrogen or androgen treatments in the adult male do not induce sterility consistently and could be problematic due to the adverse effects on other organs ( 429 , 432 ). However, a transient neonatal administration of sex steroids, prior to the onset of puberty, has shown potential for inducing sterilization.…”

A Review of Animal Models Investigating the Reproductive Effects of Gender-Affirming Hormone Therapy

“…They reported physiologic female levels of serum E2 with all three doses following 3 weeks of therapy and found that administration of E2 was associated with a significant reduction in testicular weight vs. controls (p < 0.001). Pfau et al utilized adult male C57BL/6NHsd mice who received subcutaneous implants containing either 1.25 mg, 2.5 mg, or 5 mg of estradiol powder or a control capsule [28]. All implanted capsules were left in place for 6 weeks.…”