Transmasculine and gender diverse (TMGD) individuals are assigned female at birth and may undergo gender affirming hormone treatment (GAHT) using exogenous testosterone to produce masculinisation and align physical traits with their gender identity. An increasing number of TMGD individuals are choosing to postpone or avoid surgery to remove internal gynecological organs. However, the safety of using exogenous testosterone in the presence of the reproductive system remains unknown. This study aimed to investigate the incidence of gynaecological (pre-)malignancies in a nationally representative cohort study of TMGD patients receiving testosterone.
The retrospective cohort study examined transgender patients who visited the Amsterdam University Medical Centre (UMC) gender identity clinic from February 1972 to December 2018. The study included individuals assigned female at birth who had used testosterone for at least one year. Patients who received systemic oestrogens were excluded. Transgender people get testosterone treatment as a standard hormonal treatment, which is followed by a gonadotropin-releasing hormone agonist. Various formulations of testosterone were prescribed, and some participants also received progesterone treatment or hormonal contraceptives.
This study followed EQUATOR Network’s Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, which were evaluated by VU UMC’s ethical board, and informed consent was declined because of the retrospective design. All the data were processed anonymously.
Medical data on vulvar, vaginal, endometrial and ovarian premalignancies were analyzed. Information included age at initiation of GAHT, medical history, hormone treatment details, and endocrine laboratory results extracted from medical records. Gynaecological histopathology data were collected from the PALGA database. Statistical analysis was conducted using STATA statistical software and OpenEpi version 3. Data were included up to the date of the latest biopsy or surgery, and the mean oestradiol and testosterone levels were calculated. The duration of testosterone use prior to pathological findings was evaluated separately for each organ. Age-adjusted standardized incidence ratios (SIRs) were calculated based on total cohort follow-up per organ. Multiple logistic regression analysis was used to evaluate the associated factors linked with endometrial activity.
The cohort consisted of 1955 TMGD individuals. The median age at the start of GAHT was 21 years (interquartile range [IQR] 18 to 29). Before the testosterone therapy, 21.1% (413/1955) used puberty suppression. The median duration of testosterone use was 1.7 years (IQR 1.4 to 2.4) before oophorectomy and hysterectomy and 3.1 (2.3 to 5.4) before vulvar or vaginal biopsy or surgery. The median age at the time of biopsy or surgery was 24 years (IQR 20 to 33) for ovarian and uterine histopathology acquisition and 29 (IQR 22 to 39) for vulvar and vaginal histopathology acquisition. There were no gynaecological malignancies found, so SIR was not calculated. The expected incidence was 0.26 or less for all types of cancer. One ovarian borderline tumour, one case of simple endometrial hyperplasia, and one case of vulvar intraepithelial neoplasia III (VIN3) Â were identified. The age-adjusted SIR for cases of VIN greater than grade II was 0.23 (95% confidence interval [CI]: 0.01 to 1.12).
This is the largest study to date that reports on the gynaecological histopathological findings in individuals with TMGD who underwent testosterone. Based on these results, it is concluded that the short-term use of testosterone does not appear to increase the risk of gynecological malignancies in TMGD individuals compared to the general female population assigned at birth. To know the long-term effects of testosterone on gynaecological organs and counsel properly, further studies are needed for the follow-up to retain these organs.
Reference: Vestering A, van Vugt WLJ, Berner AM, et al. Incidence of gynaecological (pre-)malignancies and endometrial activity in transmasculine and gender diverse individuals using testosterone: a retrospective, single-centre cohort study. eClinicalMedicine. 2025:103248. doi:10.1016/j.eclinm.2025.103248
