Prostate-Specific Antigen and Prostate Cancer in Gender-Affirming Hormone Therapy for Transgender or Nonbinary Individuals.

PURPOSE

The effects of gender-affirming hormone therapy on prostate-specific antigen (PSA) and prostate cancer incidence in transgender or nonbinary individuals (TGNB) born with prostate glands remain uncharacterized.

METHODS AND MATERIALS

The cohort included 1024 self-identified TGNB individuals assigned male at birth who received PSA testing in the Veterans Affairs Healthcare System, matched by birth year to cisgender men. PSA changes were measured using linear-mixed effects modeling accounting for repeated measures and matching.

RESULTS

Non-gonadotrophin releasing hormone (GnRH) agonist or antagonist therapy was associated with 1.30 ng/mL lower PSA (95% confidence interval [CI], 1.14-1.46; P < .001) and GnRH therapy was associated with 1.08 ng/mL lower PSA (95% CI, 0.60-1.55; P < .001) compared with cisgender men. Among 450 TGNB individuals who had undergone PSA testing before and after initiation of hormone therapy, non-GnRH and GnRH therapies resulted in 0.49 ng/mL decrease (95% CI, 0.35-0.62; P < .001) and 0.73 ng/mL decrease (95% CI, 0.43-1.02; P < .001), respectively, from a median baseline of 0.70 ng/mL. From time of age 50 years, TGNB prostate cancer incidence was 1.79 per 1000 patient-years versus 4.02 per 1000 patient-years in cisgender men.

CONCLUSIONS

Gender-affirming hormone therapies are associated with significant decreases in PSA, and TGNB individuals assigned male at birth remain at risk of prostate cancer. Future work should establish if a lower threshold for biopsy should be used in these contexts and if the decreased incidence is a result of ascertainment bias or hormone therapy resulting in a true decrease in the incidence of prostate cancer.