Authors
Karen Schiwon, Florian Sieg, Florian Schneider, Jochen Hess, Sabine Kliesch, Stefan Schlatt, Sara Di Persio, Nina Neuhaus
Published in
Reproduction & fertility. Aug 10, 2026. Epub Aug 10, 2026.
Abstract
Gender affirming hormone therapy (GAHT) facilitates the desired phenotypic changes consistent with the individual's gender identity. However, inter-individual variability in treatment effects have been reported at endocrine and testicular tissue level. To address the hypothesis that treatment effects are not homogeneous, we selected 24 persons from a cohort of 453 persons assigned male at birth, based on a similar dose of cyproterone acetate (Androcur, 10 or 12.5 mg/day). Principal component analysis and hierarchical clustering on principal components was performed considering clinical parameters and identified four distinct clusters. Cluster 1 (n=3) was characterized by the presence of tubules with round or elongated spermatids, highest numbers of reserve spermatogonia (Adark) and cells positive for UTF1, PIWIL4, NANOS3, and KIT. Persons in Cluster 2 (n=4) showed a high percentage of tubules with spermatogonia as the most advanced germ cell type, and high testosterone levels, which were not suppressed to the desired female values. Persons in Cluster 3 (n=10) had low testosterone but elevated AMH levels and suppressed spermatogenesis to the spermatogonial level. Finally, persons in Cluster 4 (n=7) had the highest number of Sertoli cell only tubules and tubular shadows as well as highest person age. Despite homogenous inclusion criteria we observed heterogenous treatment effects. Consultation regarding contraceptives as well as fertility preservation therefore has to be considered in counselling ideally prior to initiation of GAHT.
Hormonal therapy can help to align one's physical appearance with gender identity. However, the hormonal therapy does not work the same for everyone. The effects on testis function, including hormone and sperm production, can vary considerably. In this study we characterized persons who received comparable therapies to transition to their desired female gender. We found four subgroups: In Group 1 sperm was still produced by testicular tissues. In Group 2 only precursors of sperm were present but male, rather than the desired female hormone levels were observed. In Group 3 only precursors of sperm were present and desired hormone levels were reached. Finally, Group 4 largely showed loss of germ cells and included the oldest people in the study. These results are relevant for counselling, as individuals need to be informed of the different effects that hormonal therapy can have with regard to sperm production and thereby fertility.
PMID:
42572996
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.
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