Uterine and Ovarian Histopathology After Testosterone for Gender Affirmation: A Systematic Review

The objective of this systematic review was to evaluate the effects of testosterone on uterine and ovarian pathology in transmasculine patients at the time of gender-affirming surgery.

Searches were conducted using MEDLINE, CINAHL with Full Text, Cochrane Library, Scopus, and Europe PMC for articles published before April 5, 2021, containing concepts of testosterone use, uterine histopathology, and transgender population. The initial search yielded a total of 658 abstracts. Studies were analyzed in full text if they reported one or more uterine or ovarian histopathological findings in a noncisgender population receiving testosterone for gender affirmation. Rayyan software was used for the abstract review.

This review was registered with PROSPERO. Twenty-eight full-text articles were reviewed, of which 17 met the inclusion criteria. Two reviewers performed data extraction and risk of bias assessment. Thirteen studies included endometrial histopathology results, representing 522 patients. Endometrial findings demonstrated that 254 patients (48.7%) were atrophic, 243 (46.6%) were proliferative, and 16 (3.0%) were secretory. Twelve patients (2.3%) had endometrial intraepithelial neoplasia (EIN), including one (0.2%) with focal adenocarcinoma. Eleven studies reported ovarian histopathology in 410 patients and 765 ovaries. A total of 143 (34.9%) patients had polycystic-appearing ovaries. Three (0.7%) patients had benign ovarian neoplasms. No ovarian malignancies were reported.

The endometrium was predominately found to be atrophic or proliferative, with low rates of EIN and carcinoma. No ovarian malignancy was observed. Based on this review, patients on testosterone do not have an increased risk of precancerous endometrial lesions due to unopposed hormones in the setting of amenorrhea.