Histopathological Changes in the Uterus, Ovaries, and Fallopian Tubes Following Testosterone Therapy in Transgender...

Background: Gender-affirming testosterone therapy is an essential component of medical transition for transgender men. Despite its widespread use, the histopathological effects of testosterone exposure on the uterus, ovaries, and fallopian tubes remain incompletely characterized. This study aimed to characterize histopathological findings in the gynecologic organs of transgender men receiving testosterone therapy before gender-affirming hysterectomy with bilateral salpingo-oophorectomy. Methods: This retrospective cohort study included transgender men who underwent laparoscopic hysterectomy with bilateral salpingo-oophorectomy at a tertiary referral center between 2015 and 2019. Demographic characteristics, duration of testosterone therapy, operative findings, and histopathological results were reviewed. Estrogen receptor (ER) and progesterone receptor (PR) expression in uterine tissues was assessed immunohistochemically. Results: Fifty-two transgender men were included. The median age was 25.5 years (range, 19-46 years), the median body mass index was 24.8 kg/m², and the mean duration of testosterone therapy was 16.1 ± 7.8 months. Proliferative endometrium was the predominant pattern (78.8%), followed by inactive (17.3%) and atrophic (3.8%) endometrium. Endometrial polyps were identified in 13.5% of patients. Multifollicular ovarian morphology was observed in 90.4%, and paratubal cysts in 63.5%. No premalignant or malignant lesions were detected. ER expression was positive in all endometrial samples and in 92% of myometrial specimens, while PR expression was preserved in all evaluated uterine tissues. Conclusions: In this cohort, proliferative endometrium and multifollicular ovarian morphology were common despite testosterone therapy, and uterine ER and PR expression remained detectable. The absence of premalignant or malignant lesions was reassuring within the observed exposure period; however, the retrospective design, modest sample size, absence of a control group, limited characterization of hormone exposure, and lack of longitudinal follow-up preclude conclusions regarding long-term oncologic safety or malignancy risk.