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Transgender women retain their prostate even after gender-affirmation surgery and thus remain at risk of prostate cancer. Studies to date are limited to case reports.1 We describe a large case series of transgender women with prostate cancer within the Veterans Affairs (VA) health system.
After Durham VA institutional review board approval with a waiver of informed consent, VA records for all adults with an International Classification of Diseases code for prostate cancer and at least 1 code for transgender identity at any time from January 2000 to November 2022 were queried. Detailed chart review was performed to confirm transgender identity and prostate cancer diagnosis. The number of cases per year was approximated using previous estimates of the median year of transgender identity entry in VA records (2011), corresponding to approximately 11 years of follow-up (2011-2022).2 Data from community clinicians were included if available in VA notes. Data at diagnosis were collected, including gender-affirming hormone therapies used, prostate-specific antigen (PSA), PSA density (measure of prostate cancer aggressiveness [lower risk, <0.15 ng/mL/g]), bilateral orchiectomy status, biopsy grade group (grades 1-5, with 5 being most severe), and clinical stage (T1-T4, with T4 being most advanced; eMethods in Supplement 1). Because estrogen, which lowers testosterone and suppresses prostate cancer,3 was the most common feminization therapy, patients were grouped by never used estrogen, formerly used estrogen but stopped prior to prostate cancer diagnosis, or actively used estrogen at diagnosis. Due to limited sample sizes, analyses were only descriptive.
Among 449 patients with prostate cancer and transgender identity codes, 155 (35%, an estimated 14 cases per year) were confirmed transgender women with prostate cancer: 116 never used estrogen, 17 formerly used estrogen, and 22 actively used estrogen at diagnosis. All prostate cancer diagnoses were screen detected. At diagnosis, the median age was 61 years, 88% were White, median PSA was 6.8 ng/mL, the median duration of estrogen use was 32 months among former and active estrogen users, 43% (50 of 115) were biopsy grade group 1, and 45% (49 of 108) were clinical stage T1 (Table); 98% (152 of 155) had not undergone bilateral orchiectomy. Biopsy grade group 1 or 2 was found in 58 of 82 patients (71%) with no prior estrogen use, 9 of 16 (56%) with former estrogen use, and 9 of 17 (53%) with estrogen use at diagnosis.
The percentage of patients with biopsy grade group 4 or 5 was 23% (19 of 82) of patients who never used estrogen, 10 (12%) of whom were grade group 5; 25% (4 of 16) of former users, 1 (6%) of whom was grade group 5; and 35% (6 of 17) of active users, 5 (29%) of whom were grade group 5. The median PSA density was 0.21 ng/mL/g for never estrogen users, 0.26 ng/mL/g for former users, and 0.31 ng/mL/g for active users.
This case series demonstrated that prostate cancer occurs in transgender women and is not as rare as published case reports might suggest. However, rates were lower than expected based on prior prostate cancer incidence estimates in cisgender male veterans.4 Using data from 2005 to 2019,4 the age-weighted cisgender mean number of cases was 331 per 100 000 in 2011 (median year of transgender identity entry in the VA2). Given estimates of 10 000 transgender women in the VA,2 33 cases per year would be expected. Instead, only about 14 per year were observed. Lower rates may stem from less PSA screening owing to barriers including lack of prostate cancer risk awareness or stigma,5 the suppressive effects of estrogen on prostate cancer development, or prostate cancers being missed in transgender women because of misinterpretation of “normal” PSA levels among those receiving gender-affirming hormone therapies.
Although limited numbers precluded formal statistical comparisons, transgender women receiving estrogen at diagnosis had the most aggressive disease (highest PSA density and proportion of biopsy grade group 5), suggesting delayed diagnosis or early selection of cancer cells resistant to androgen deprivation, which tend to be more aggressive. Among transgender women, 25% overall and 35% receiving estrogen had biopsy grade group 4 or 5 vs only 16% among cisgender male veterans.6 Only 8% of transgender women with prostate cancer vs 29% of cisgender male veterans with prostate cancer were Black,6 suggesting additional disparities at the intersection of race and gender identity.
Limitations include being a case series without a formal comparison group, restriction to the VA population, and the inability to access records outside the VA unless documented in notes, which may have underestimated prostate cancer numbers. Associations between characteristics such as estrogen use and markers of disease severity may reflect selection on disease diagnosis (an index event). Future work is needed to optimize prostate cancer detection strategies in transgender women.
Accepted for Publication: March 28, 2023.
Published Online: April 29, 2023. doi:10.1001/jama.2023.6028
Concept and design: Nik-Ahd, Freedland.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Nik-Ahd, Freedland.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Nik-Ahd, Anger, Freedland.
Obtained funding: Carroll, Cooperberg.
Administrative, technical, or material support: De Hoedt, Butler, Carroll, Freedland.
Supervision: Butler, Anger, Carroll, Cooperberg, Freedland.
Conflict of Interest Disclosures: Dr Cooperberg reported serving as an advisor for Astellas, Astra Zeneca, Janssen, Merck, Veracyte, Bayer, Dendreon, Exact Sciences, Exosome, Verana Health, and ConcertAI outside the submitted work. No other disclosures were reported.
Data Sharing Statement: See Supplement 2.