Endocrine Abstracts

JOINT404

Background: Gender incongruence is a marked and persistent incongruence between an individual’s experienced gender and their sex registered at birth. This may lead to a desire to medical transition. For adolescents, this usually includes puberty suppressing drugs and subsequent gender affirming hormone therapy (GAHT). For trans girls, pubertal hormones can be suppressed with GnRH analogues (GnRHa) or cyproterone acetate (CA), and subsequent feminisation induced with 17β-estradiol (E2). It is currently not known if long-term use of these medications may cause testicular damage or irreversibly affect gamete number and quality hampering evidence-based fertility preservation counselling.

Aim of this study: To assess the effect of puberty suppression and subsequent GAHT on markers of testicular health and fertility in trans girls via histological analysis of testicular tissue obtained at orchidectomy. Differences in outcomes between those who received GnRHa versus CA are explored.

Methods: The primary outcome was the developmental stage of the most mature germ cell visible by routine histological examination and overall advancement of spermatogenesis, expressed as a modified Johnsen score (MJS). Secondary outcomes were basal membrane thickness (BMT), open lumen, peritubular myoid cell pattern (α-SMA staining), edema, fibrosis, Leydig cell presence and Sertoli cell maturity (podoplanin staining). Serum levels of E2, follicle stimulating hormone, luteinizing hormone and Inhibin B at the last pre-operative follow-up consultation were obtained from the patient files.

Participants

Sixty-seven participants were identified; 21 had received GnRHa and 46 CA. GnRHa were generally started at Tanner stage II-III, while CA was started at Tanner stage IV-V. The median total treatment duration for those who had GnRHa+E2 was 67 (IQR: 57-73) months and for those who had CA+E2 33 (IQR: 28-44) months. All participants had received E2 for a median duration of 27 (IQR: 20-34) months. All treatments were interrupted 2 weeks prior to orchidectomy.

Results: As expected, most participants showed spermatogenic arrest at orchidectomy, although full spermatogenesis was observed in a small minority, all treated with CA. All but one had spermatogonial stem cells. A disconnected α-SMA staining pattern and (moderately or severely) increased BMT, both likely indicating testicular damage, were observed in 49,3% and 55,2%, respectively. MJS inversely correlated with BMT. GnRHa were associated with a more immature testicular morphology when compared to CA.

Conclusion: Long-term puberty suppression and subsequent GAHT induces testicular immaturity and spermatogenic arrest in most trans girls. It may in addition cause testicular damage, visible as increased BMT, which adversely correlates with MJS.