Incidence of gynaecological (pre-)malignancies and endometrial activity in transmasculine and gender diverse individuals using testosterone: a retrospective, single-centre cohort study.

BACKGROUND

The number of transmasculine and gender diverse (TMGD) individuals that choose to postpone or refrain from surgical intervention to remove their internal gynaecological organs has been increasing. However, the safety of exogenous testosterone use in the presence of the reproductive organs, i.e. the risk of gynaecological malignancies remains unclear. This study aims to evaluate the incidence of gynaecological (pre-)malignancies in a nationwide cohort of TMGD individuals using testosterone treatment.

METHODS

This retrospective cohort study conducted at the Amsterdam University Medical Centre in the Netherlands, included transmasculine and gender diverse (TMGD) individuals receiving testosterone at our clinic between February 17, 1972 and December 3, 2018. Data from medical records were linked to the national pathology database to acquire diagnoses related to gynaecological cancer or gynaecological pathologies with malignant potential. TMGD individuals assigned female at birth who received testosterone were included, excluding those last seen before 1991. Based on observed and expected cases, age-adjusted standardised incidence ratios (SIR) were calculated to assess relative risk compared to the general population assigned female at birth.

FINDINGS

The cohort comprised 1955 TMGD individuals. Median age at start of gender-affirming hormone therapy was 21 years (interquartile range [IQR] 18-29). Prior to testosterone treatment 21·1% (413/1955) had used puberty suppression. Median duration of testosterone usage was 1·7 years (IQR 1·4-2·4) before hysterectomy and oophorectomy and 3·1 (2·3-5·4) before vaginal and/or vulvar surgery or biopsy. Median age at time of surgery or biopsy was 24 years (IQR 20-33) for uterine and ovarian histopathology acquisition and 29 (IQR 22-39) for vaginal and vulvar histopathology acquisition. No gynaecological malignancies were found, precluding SIR calculation. Expected incidence was 0·26 or less for all cancer types. One ovarian borderline tumour, one case of simple endometrial hyperplasia and one case of vulvar intraepithelial neoplasia III (VIN3) were detected. Based on the expected number of >VIN2 cases in our cohort (4·4) the age-adjusted standardised incidence ratio for > VIN2 was 0·23 (95% CI: 0·01-1·12).

INTERPRETATION

This is the largest cohort to date reporting on gynaecological histopathologic findings in TMGD individuals using testosterone. Based on these findings we can conclude that the risk of gynaecological malignancies is not increased in TMGD individuals using testosterone for a relatively short period of time compared to the general population assigned female at birth. However, to determine the long-term effects of testosterone on gynaecological organs, and counsel patients appropriately, studies with longer follow-up of individuals retaining these organs are needed.

FUNDING

None.