What is a normal PSA level for transgender women on estrogen therapy?

According to data from the Veterans Health Administration (VHA), a prostate-specific antigen (PSA) test cannot accurately determine the level at which transgender women on estrogen therapy are at risk for prostate cancer.

In a group of more than 200 transgender women taking estrogen who did not have prostate cancer, the mean PSA level was 0.02 ng/ml – 50 times lower than the level found in studies of cisgender men of similar age without known prostate cancer, Dr. Farnoosh Nik-Ahd of the University of California San Francisco and colleagues reported in a research letter published in JAMA.

In addition, PSA levels were undetectable in more than a third of these trans women who received estrogen.

The extremely low PSA levels of these transgender women receiving estrogen indicate “that the historical cutoff of 4 ng/mL, often used as a threshold for further investigation, is likely far too high a cutoff for this population,” Nik-Ahd and colleagues wrote.

They therefore suggested that PSA levels in transgender women should be interpreted with caution. “Further studies are needed to understand the risks and benefits of PSA screening in this population and to establish ideal prostate cancer screening practices,” they noted.

In a press release, co-author Dr. Stephen Freedland of Cedars-Sinai Medical Center in Los Angeles said: “Many transgender women take estrogen as part of their gender reassignment treatment. This dramatically lowers PSA levels, which may mean that the cutoff we use as ‘normal’ is too high to detect early-stage cancer in these patients.”

He added that while a PSA test is the best way to detect prostate cancer early, transgender women “should keep in mind that the test values ​​are not tailored to them” and that results should be interpreted by a urologist.

The same research team published a study last year in JAMA suggesting that the risk of prostate cancer in transgender women is higher than previously estimated.

Furthermore, this study showed that disease was most aggressive in trans women who were receiving estrogen at diagnosis: 25% of all trans women, 35% of whom were receiving estrogen, had biopsy group 4 or 5 disease, compared to only 16% of cisgender men who were veterans, suggesting a possible delayed diagnosis.

“One possible reason for the delayed diagnosis may be the lack of specific PSA reference ranges for transgender women receiving gender-affirming hormones,” wrote Nik-Ahd and colleagues. “Due to the castrating effect of gender-affirming hormones, PSA levels, whose production is regulated by androgens, would be expected to decrease.”

Therefore, researchers sought to determine PSA levels in a nationwide cohort of transgender women receiving estrogen.

Using VHA records from January 2000 to August 2023, Nik-Ahd and colleagues identified 210 patients who met study criteria: confirmed identity as a transgender woman, no diagnosis of prostate cancer, estrogen treatment (regardless of orchiectomy status/use of other gender-affirming hormones), and a PSA test between the ages of 40 and 80 while on estrogen treatment for 6 or more consecutive months.

Of this group, 86% were white and only 2% were black or African American. The average age was 60 years and the median estrogen duration at the time of PSA determination was 4.7 years.

At the time of PSA measurement, 89% of the patients had received spironolactone, 39% progesterone, 30% finasteride, 3% goserelin and 5% leuprolide. Approximately half of the patients underwent bilateral orchiectomy before PSA measurement.

The authors noted that the low percentage of black patients in the study is consistent with previous studies that showed fewer black transgender women had prostate cancer. “More studies are needed examining the experiences of minority transgender women and disparities in prostate cancer screening,” they suggested.