Prostate Cancer Incidence under Androgen Deprivation: Nationwide Cohort Study in Trans Women Receiving Hormone Treatment

Abstract

Context Trans women (male sex assigned at birth, female gender identity) mostly use anti-androgens combined with estrogens and can subsequently undergo vaginoplasty including orchiectomy. Because the prostate remains in situ after this procedure, trans women are still at risk for prostate cancer. Objective The incidence of prostate cancer in trans women using hormone treatment. Design In this nationwide retrospective cohort study, data of participants were linked to the Dutch national pathology database (PALGA) and to Statistics Netherlands, to obtain data on prostate cancer diagnosis and mortality.
 Setting Gender identity clinic. Participants Trans women who visited our clinic between 1972 and 2016 and received hormone treatment were included. Main Outcome Measures Standardized incidence ratios (SIRs) were calculated using the number of observed prostate cancer cases in our cohort and the number of expected cases based on age-specific incidence numbers from the Netherlands Comprehensive Cancer Organization. Results The study population consisted of 2,281 trans women with a median follow-up time of 14 years (interquartile range 7-24), and a total follow-up time of 37,117 years. Six prostate cancer cases were identified after median 17 years of hormone treatment. This resulted in a lower prostate cancer risk in trans women compared to Dutch reference males (SIR 0.20, 95CI 0.08 to 0.42). Conclusions Trans women receiving androgen deprivation therapy and estrogens have a substantially lower risk for prostate cancer compared to the general male population. Our results support the hypothesis that androgen deprivation has a preventive effect on the initiation and development of prostate cancer.

Approach to Interpreting Common Laboratory Pathology Tests in Transgender Individuals

“…It is known that androgen deprivation as part of feminizing hormone therapy is associated with a substantially lower risk for prostate cancer than the general male population ( 40 ). All published case reports of prostate cancer in trans people using feminizing hormone therapy have had histology showing high risk adenocarcinoma with PSA concentrations at diagnosis ranging from 5 to 1722 ng/mL (ng/mL equivalent to ug/L) ( 40 , 41 ). Physiologically, in the setting of androgen deprivation in people with a prostate gland, it would be expected that PSA should be lower than the age-specific reference interval.…”

Cancer Stage, Treatment, and Survival Among Transgender Patients in the United States

“…In transwomen, the prostate is not removed as part of gender-affirming surgery because of possible complications, such as incontinence ( 28 ). Previous research suggests prostate cancer is rare among transfeminine patients because of treatment with antiandrogen and estrogen therapy, possibly followed by bilateral orchiectomy ( 15 , 29 , 30 ). Yet, although the incidence of prostate cancer may be lower in transwomen than cismen, a growing body of research indicates that prostate cancer could be more aggressive among transwomen, which may explain our finding of increased mortality among transgender patients with prostate cancer ( 29 ).…”

Prostate cancer in transgender women: what does a urologist need to know?

“…The cancer-specific data available in each case report was not standardised making it difficult to extrapolate relevant information. However, most patients were in their seventh decade of life and had been receiving GAHT for ≥10 years (mean [interquartile range, IQR] 25.1 [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] years). It is not possible to ascertain from these reports whether patients had been screened previously for prostate cancer, whether they had risk factors such as ethnicity or family history or received self-prescribed or clinicianinitiated hormone therapy.…”

“…This message is upheld by a more recent systematic review of incidence of all reproductive cancers in the transgender population in which there is a clear message that very little is known in this population and that future research should focus on this topic. 20 Recently, de Nie et al 21 Transgender women should be made aware that they have a prostate (regardless of transition status including after GAS) and are therefore at risk of benign prostate diseases (not discussed here) as well prostate cancer. All published cohort studies have described a lower incidence of prostate cancer in transgender women compared to cisgender males.…”

“…All published cohort studies have described a lower incidence of prostate cancer in transgender women compared to cisgender males. Whilst some suggestion exists from the Nie et al 21 cohort that those who did develop prostate cancer had high-grade disease, without further information about each individual patient and larger numbers, no statistical conclusion can be drawn as to whether transgender women on GAHT will have more aggressive disease. This possibility certainly warrants further investigation.…”