Prostate Cancer Test Ineffective for Early Detection in Trans Women

A test used to detect prostate cancer may not be effective at identifying early stages of the disease in transgender women, a new study has found.

A common screening method for prostate cancer involves testing for prostate-specific antigens (PSAs), but trans women often have lower levels of PSAs — potentially delaying diagnosis and resulting in more advanced disease, according to new research.

The study, published in JAMA Network, suggests that typical prostate screening tests may not effectively detect early-stage prostate cancer in trans women, which could explain why trans women are more likely to present with high-grade disease compared with cisgender men.

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The prostate is a small gland that makes semen, and trans women keep their prostates following gender-affirming surgery — so they remain at risk for prostate cancer. The prostate also produces a protein called PSA, and elevated levels of PSAs in the blood are typically found in those with prostate cancer. That’s why testing for PSA levels is a common screening method for the disease.

But PSA production is regulated by androgens, or male hormones, and trans women often receive gender-affirming hormones such as estrogen, which results in reduced PSA levels. As a result, researchers suggest that PSA thresholds considered to be “normal” for cis men are set too high for trans women, potentially resulting in missed disease.

The researchers conducted the study by analyzing Veterans Health Administration records between January 2000 and August 2023. They examined data from 210 patients who were 40 and older, on estrogen, and had no history of prostate cancer.

Ultimately, they found that PSA levels were much lower in trans patients on estrogen.

The median PSA level in trans women receiving estrogen was 0.02 ng/mL, while similarly aged cisgender men without known prostate cancer typically have a median PSA level of 1 (0.6-1.9) ng/mL. Additionally, 36% of transgender women receiving estrogen had undetectable PSAs.

The standard PSA threshold for further evaluation is 4 ng/mL, and the authors suggest this is likely far too high a threshold for this population.

The researchers also found that trans patients were unlikely to get additional prostate cancer screening until their PSA levels eventually increased, suggesting that any prostate cancer they experienced was likely only detected at a far more advanced state.

There are no PSA ranges set specifically for trans women at this time, and the researchers say their findings suggest that more tailored, targeted prostate cancer screening practices are needed for this demographic.

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“As more and more trans women have appropriate access to gender-affirming care, it’s critical not to lose sight of long-term cancer risks in retained organs,” said co-senior author Matthew R. Cooperberg, M.D., MPH, a UCSF urology professor and co-leader of the prostate cancer program at the UCSF Helen Diller Family Comprehensive Cancer Center, in a statement. “We are just starting to understand how estrogen and related treatments modulate prostate cancer risk, and how to interpret PSA values in this population, so we can evolve a rational and evidence-based screening policy.”

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