INTRODUCTION AND OBJECTIVES: Endometrial cancer is the 4th most common cancer in people assigned female at birth in the UK, affecting 9300 people per year. This may be preceded by the development of endometrial hyperplasia with atypia as a pre-malignant lesion. The literature suggests that up to 20% of endometrial carcinomas express the androgen receptor while others concluded that circulating blood levels of estrogens and testosterone are positively associated with an increased risk of endometrial cancer in postmenopausal women, although there is no evidence of causality. Given the prolonged exposure of trans men and non-binary people with a uterus to testosterone, historically there has been a concern that this may lead to development of hyperplasia and malignancy. Several studies have reported an increased incidence of endometrial hyperplasia in these patients but also report high rates of proliferative endometrium, which is unexpected in the context of testosterone therapy. Therefore the current recommendation for these patients is to undergo hysterectomy within two years of starting testosterone or 3-yearly ultrasound (US) scans for endometrial thickness. METHODS: We retrospectively reviewed the histology of 53 trans men and non-binary patients undergoing hysterectomy and bilateral salpingo-oophorectomy between January 2008 and December 2015 who had received prior testosterone therapy at the Gender Identity Clinic (GIC), London, UK. Haematoxilin and eosin slides from formalin-fixed paraffin embedded tissues were reviewed by two pathologists with blinding for demographics, clinical characteristics and original pathology reports. For each patient the duration of testosterone exposure was collected from commencement at the GIC to the time at hysterectomy RESULTS: Patients had a mean age of 39 years (range 20-61 years). Detailed prescribing information was available for 49 patients with median duration of testosterone exposure prior to surgery of 48.5 months (range 16-360 months). Patients had received between 1 and 5 different dosing regimens, with the 3 most common being nebido 1000mg 12-weekly (n=26), sustanon 250mg 3-weekly (n=26), and sustanon 250mg 4-weekly (n=30). Mean endometrial thickness was 1.7mm and mean myometrial thickness was 13.7mm. 19 cases had atrophic endometrium and 34 had inactive endometrium. One case had focal simple hyperplasia with no evidence of atypia arising in a background of atrophic endometrium. Tubal metaplasia was seen in 31 cases and eosinophilic metaplasia was present in two cases. No specimens contained evidence of endometrial carcinoma, cytological atypia, or any other recognised pre-malignant change. CONCLUSIONS: In summary, we found no evidence of malignant or pre-malignant changes in the endometrium of trans men and non-binary people with a uterus in response to long-term testosterone therapy. Early hysterectomy or regular US scanning is therefore unlikely to be necessary (though surgery may still be desirable as part of their transition). This has important implications for both patients, for whom US scans may cause significant distress and dysphoria, and for the NHS, as these interventions have cost implication Source of Funding: None