Andrology of male‐to‐female transsexuals: influence of cross‐sex hormone therapy on testicular function

Abstract

Patients with gender dysphoria are offered cross-sex hormone therapy and sex reassignment surgery to achieve the transition between the sex assigned at birth and gender identity. According to international guidelines, cross-sex hormone therapy in trans-women should lead to a psychologically and physiologically healthy body with feminized serum hormone levels, resulting in suppression of spermatogenesis. However, in a recently published multi-center study, we discovered a high proportion of patients with male serum hormone levels and qualitatively intact spermatogenesis on the day of sex reassignment surgery. The objective of this study was to review the content of 11 publications that focus on the influence of cross-sex hormone therapy on testicular morphology. These publications were identified based on a PubMed search for the key words transgender/transsexual/gender dysphoria in male-to-female persons, cross-sex hormone therapy, and testicular tissues. Whereas three publications described a marked reduction of the spermatogenic level in all patients examined, eight publications reported inconsistent results. Histological analyses showed highly variable outcomes from qualitatively normal spermatogenesis and undisturbed Leydig/Sertoli cell morphology to full testicular regression with severe cellular damage and hyalinization. Explanations for these heterogeneous findings include insufficient cross-sex hormone therapy regarding dosage or duration. As complete spermatogenesis is associated with virilized serum hormone levels, these patients may face challenges especially after sex reassignment surgery in adjusting to the abruptly established hypogonadal state following removal of the testes. These findings also suggest that contraception should be discussed, and fertility preservation should be offered during/prior to cross-sex hormone therapy. There is a need for more individualized and better-controlled cross-sex hormone therapy and post-treatment regimens. Evidence-based guidelines for attending clinicians need to be established in order to deliver the most appropriate care.

The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty

“…Furthermore, our results from juveniles and the transfemale testes strongly suggest that States 0 and 1 are indeed reserve (undifferentiated, quiescent, or slow-cycling) spermatogonia that persist from infancy to adulthood even in the absence/suppression of T. For example, in the T-suppressed testes, while spermatogenesis is severely impaired, we observed a population of spermatogonia with the same transcriptional profile as the State 0-1 population identified in untreated adult testes (Guo et al, 2018). This likely accounts for the ability of spermatogonia in some transfemales to resume gametogenesis when T suppression is halted (Kohn et al, 2017;Schneider et al, 2017).…”

Understudied and Under-Reported: Fertility Issues in Transgender Youth—A Narrative Review

“…20 The few available studies of transgender women on estrogen therapy rely on small sample sizes (n = 1 to n = 11) and heterogeneous treatment protocols (low or high dose estrogen, estrogen + anti-androgens, oral vs transdermal) resulting in incomplete and often conflicting results. 21 Prolonged estrogen exposure has been reported to result in atrophy and absent or impaired spermatogenesis, 22,23 while normal spermatogenic activity and complete reversibility have also been reported. [24][25][26] One recent study reported heterogeneous results among 108 transgender women presenting for gender-affirming surgery after gender-affirming hormone treatment ranging from normal spermatogenesis (24%) to tubular shadows/atrophy (1.85%).…”

Transwomen in elite sport: scientific and ethical considerations

“…A transwoman who has had full gender affirmation surgery (including testes removal) will have very low testosterone levels below 1 nmol/L 14. These transwomen will have much less opportunity for a performance advantage in comparison to elite cis-women athletes.…”