The ovaries of transgender men indicate effects of testosterone treatment on the ovarian stroma without changes in non-growing follicle density

The ovarian stroma surrounds ovarian follicles and provides a supportive microenvironment during follicle quiescence and subsequent growth. In this study, we investigated the effect of testosterone exposure on human ovarian stromal composition, specifically collagen and elastin content and stromal cell density (SCD), and its relationship with non-growing follicle density (NGFD). Whole ovaries were obtained from transgender men receiving long-term testosterone therapy (mean age 27.6 ± 1.7 years, n = 8) at oophorectomy and compared with ovarian cortical biopsies from age-matched healthy women obtained at caesarean section (mean age 31.8 ± 1.5 years, n = 8). Testosterone-exposed ovarian tissue demonstrated a more fibrotic stromal composition, characterised by increased collagen and reduced elastin, resulting in a higher collagen–elastin ratio indicative of increased intrinsic tissue rigidity. SCD was significantly higher in testosterone-exposed tissue, consistent with stromal cell hyperplasia, whereas NGFD was comparable to controls. These findings indicate that elevated circulating testosterone alters ovarian stromal composition and cellularity without reducing the non-growing follicle pool. Although interpretation is limited by the use of pregnancy-derived control tissue, these findings provide insight into the effects of testosterone on the ovarian microenvironment and warrant further investigation of their functional significance for transgender men considering pregnancy or fertility preservation.