Spectrum of Histopathologic Findings in Transgender Men Undergoing Gender-Affirming Gynecologic Surgery Following Preoperative Androgen Therapy: A Tertiary Care Center Study

Abstract

Introduction

Transgender men are assigned female sex at birth, but identify with a masculine gender identity, prompting them to undergo gender-affirming surgery, usually following androgen therapy, which induces changes in histology of hormone sensitive gynecologic organs.

Methods

Transgender men undergoing gender-affirming gynecologic surgery, following testosterone therapy (September 2019 to April 2025) were retrospectively included. Histopathology slides were reviewed for features associated with androgen exposure.

Results

Twenty patients (aged 16-35 years) underwent hysterectomy, following androgen therapy (mean duration 21.7 ± 17.8 [4-63] months). Endometrium was histologically inactive (15 of 20; 75%), with prominent ciliated cell metaplasia (n = 11; 55%), stromal expansion and decidua-like change (n = 13; 65%). Cervix (55% and 60%) and vagina (100% and 50%) revealed transitional and prostatic-type metaplasia. NK3 homeobox 1 (NKX3.1)-positive basal keratinocytes were present in all the patients (n = 20; 100%), in a focal to diffuse distribution along the basal squamous epithelium. Bilateral ovaries showed numerous cystic follicles (n = 14; 70%), with evidence of follicular maturation (n = 12; 60%). Cervix specimens from 25 benign cisgender hysterectomies (in reproductive age group) revealed focal NKX3.1-positive basal keratinocytes in 2 patients (8%), but no transitional metaplasia or prostatic-type metaplastic glands. Ovaries in the transgender group were frequently multicystic, and one patient each showed ovarian endometriosis and mucinous cyst adenofibroma. Fallopian tubes show paratubal mesonephric remnants, but no hypertrophy of these remnants was present.

Conclusions

Distinctive histologic alterations are seen in gender-affirming gynecologic surgery samples from transmasculine patients receiving preoperative androgen therapy. Awareness of these changes is vital for pathologists to avoid diagnostic errors and facilitate better patient management.