Median prostate-specific antigen (PSA) levels are lower in transgender women receiving estrogen than comparable cisgender men without a prostate cancer diagnosis, researchers reported in study findings published in JAMA, possibly because of the gender-affirming therapy’s castrating effects. The finding raises questions about the utility of PSA testing for transgender women with intact prostates.

Of the 14,915 adult patients listed in Veterans Health Administration records from January 2000–August 2023 with at least one diagnostic code that was determined to be sensitive and specific for transgender identity, the researchers identified 210 patients aged 40 or older who met the following inclusion criteria:

  • Confirmed identity as a transgender woman
  • PSA testing was performed between ages 40 and 80
  • Received estrogen for six or more consecutive months at the time of their PSA test
  • No prostate cancer diagnosis

Only 2% of the patients were Black, whereas 86% were White. Their mean age was 60 (± 8) years. The median duration of estrogen therapy at the time of their PSA test was 4.7 years (range = 0.5–29.9).

Among the sample of transgender women receiving estrogen, the researchers found that their PSA was 0.02 (0–0.2) ng/ml and the 95th percentile was 0.6 ng/ml. PSAs were undetectable in 36% of patients (23% and 49% of PSAs in patients without and with orchiectomy, respectively). The highest PSA in the cohort was 2.21 ng/ml.

“[Our] study found the median PSA in transgender women receiving estrogen was 0.02 ng/ml,” the researchers reported. “In studies of similarly aged cisgender men, the median PSA was 0.6–1.9 ng/ml. Moreover, 36% of transgender women receiving estrogen had undetectable PSAs. Thus, PSA values in transgender women should be interpreted cautiously.”

Because of that, the researchers said that the utility of PSA screening for transgender women receiving gender-affirming hormones is unknown. Additionally, “for those who do undergo screening, the optimal cut point to define high risk is unknown. In this study, PSA values were very low among transgender women receiving estrogen, suggesting that the historic cut point of 4 ng/ml, often used as a threshold for further evaluation, is likely far too high a threshold for this population.”

For oncology nurses and other members of the cancer care team, the findings reinforce the essential need to consider each patient’s unique factors to best inform personalized, individual recommendations. Learn more about gender-inclusive care in the resources listed in the sidebar.