The effect of estrogen therapy on spermatogenesis in transgender women

To describe the histopathologic parameters of orchiectomy specimens obtained after gender-affirming surgery from transgender women who used gender-affirming hormone therapy (GAHT), which included estrogen and spironolactone. Our hypothesis was that an increasing duration of GAHT affects testicular health.

Retrospective cohort study.

Tertiary referral center.

All transgender women (individuals assigned male at birth who identified as female) who underwent orchiectomy with or without vaginoplasty between December 2015 and March 2020.

GAHT (estrogen and spironolactone) in the setting of patients with orchiectomy with or without vaginoplasty.

Demographic and perioperative data and pathology records were reviewed. The following pathology parameters were recorded: testicular volume, testicular weight, presence of spermatogenesis (active vs. reduced), maturation arrest, testicular atrophy, hyalinization, scarring/fibrosis, and Sertoli cell and Leydig cell phenotypes. The patients were grouped into one of three categories describing the duration of GAHT use: 0-36 months, 37-60 months, and >60 months years. Descriptive statistics were performed and comparisons between outcomes (demographic data and pathology parameters) were made among the GAHT groups.

Eighty-five (N = 85) patients underwent orchiectomy during the study period with 85.9% (n = 73) undergoing concurrent vaginoplasty. The mean (SD) age and body mass index of the cohort were 39 ±16 years and 28.4 ± 5.4 kg/m², respectively. In addition, although this was not statistically significant, patients in the 37-60 and >60-month groups were more likely to smoke marijuana than those in the 0-36-month group (26.3% and 21.2% vs. 4.2%, respectively). Mean testicular weight and volume across the cohort were 60.1 ± 24.9 grams and 65.5 ± 41.1 cm³, respectively. Spermatogenesis was present in 28.2% (n = 24) of specimens with active spermatogenesis noted in 8.2% (n = 7). Hyalinization, scarring/fibrosis, and atrophy were present in 28.2% (n = 24), 20.0% (n = 17), and 25.9% (n = 22) of specimens, respectively. There were no differences in pathology parameters across the GAHT groups. Testicular weight and volume were not associated with any differences in pathology parameters. Additionally, age was not associated with testicular weight, volume, or pathology parameters with the exception of the following: when patients were categorized as either ≤40 years of age (n = 48) vs. > 40 years of age (n = 37), patients who were older were more likely to have hyalinization (43.2% vs. 16.7%) as well as atrophy (40.5% vs. 14.6%).

The duration of GAHT use was not associated with any differences in orchiectomy pathology parameters in patients undergoing gender-affirming surgery, and some patients may still have some spermatogenesis based on the parameters observed in this study.