FIBROTIC CHANGES IN TRANSGENDER OVARIES DUE TO TESTOSTERONE EXPOSURE

Abstract

Transgender men (TGM) undergo extensive testosterone (T) exposure as part of gender conformation therapy. Androgens have well known impacts on the HPG axis as well as direct effects on the ovary. Reports conflict on whether TGM ovaries have characteristics of PCOS, which can also heighten T levels in the patient. Elevated androgens and aging can both increase collagenization of the ovary. In this study, we evaluated ovarian morphologic differences in young and old TGM patients, examining fibrosis of the tissue. Ovarian fibrosis could impede ovulation, which may lead to problems with fertility. Ovarian fibrosis in TGM was compared to age-matched cisgender (CG) ovaries. All patients were divided into two age groups, young (≤35 yr) and old (>36 yr). Fibrosis was detected by histological quantitation of picrosirius red (PSR) staining. Ovaries from young and old TGM patients (n=5/3, respectively) were collected during gender confirming surgeries. Ovaries from young and old CG donors (n=3/4, respectively) were obtained from patients undergoing oophorectomy for benign reasons. All samples were collected following KUMC IRB approval. Ovaries were fixed in 4% formaldehyde, processed and embedded in paraffin. 7μm-thick histological sections were stained with 0.1% PSR/0.1% Fast Green. Four randomly selected cortical areas of each ovarian section were imaged at 10x using bright field microscopy. PSR staining intensities were quantified using ImageJ per NIH recommended methodology. One-Way AVOVA (p<0.05) followed by LSD means separation tests were completed using SPSS program. To correct for heterogeneity of variance, data was log transformed. Young (29±2.0yr) and old (40.0±0.7yr) TGM patients underwent 34.8±4.2mo and 40.6±39.2mo of T-therapy, respectively; note one old TGM patient was exposed for 119mo. Age matched young and old CG patients were 31±2.0 and 36±0.5yr of age. Ovarian PSR staining levels in young TGM patients were higher (292,184±122,991 p<0.05) compared to young CG donors (39,154±14,643). Ovaries from old TGM also showed increased PSR staining, (98,775±17,887) compared to old CG (34,359±5,540; p<0.05). TGM ovaries had few large follicles, which were atretic, whereas CG ovaries typically contained a few large healthy follicles. This study establishes quantitatively that long-term testosterone exposure increases collagen deposition within young and old TGM ovarian tissue compared to CG age matched tissues. Our findings indicate a lack of multiple follicles in TGM ovaries, which diverges from several prior observations that TGM ovaries exhibited a PCOS-like morphology. Increased number of subjects will clarify whether age of TGM and duration of T-therapy impacts the extent of ovarian fibrosis. By understanding the time frame of ovarian fibrosis, this may give TGM greater control over fertility as they transition.