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Prostate Cancer Outcomes Worse With Higher Periprostatic vs Serum Testosterone

Men with increased periprostatic testosterone exposure have worse clinical outcomes after radical prostatectomy for prostate cancer, a new study finds.

In a study of 266 men undergoing radical prostatectomy, 20% had testosterone levels in the prostatic dorsal venous complex that were at least twice as high as peripheral testosterone concentrations measured in serum, including 5% of men with 10 times the serum concentration, Nima Sharifi, MD, scientific director of the Desai Sethi Urology Institute at the University of Miami Miller School of Medicine in Miami, Florida, and colleagues reported in The Journal of Clinical Investigation.

“Together, these data suggest that, in a subset of men, there exists an alternative local androgen physiology we have termed “sneaky” [testosterone] physiology that exposes the prostate to enriched gonadal [testosterone] and is associated with poor clinical outcomes in men with prostate cancer,” according to Dr Sharifi’s team.

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The investigators found indicators of testicular shunting of testosterone directly to the prostatic venous plexus in a subset of men. Isocaproic acid, a byproduct of androgen biosynthesis, and 17-OH-progesterone, a marker of intratesticular testosterone, were enriched in the dorsal vein of these men, as evidenced by a higher dorsal to peripheral testosterone ratio. Men with varicoceles also have 17-OH-progesterone enrichment due to testicular blood backflow, the investigators noted.

Patients with a dorsal to peripheral testosterone ratio greater than 2 (compared with less than 2) had significantly lower progression-free survival rates, defined as biochemical recurrence or initiation of radiation therapy after prostatectomy, Dr Sharifi and colleagues reported. In multivariable analyses, the dorsal to peripheral testosterone ratio more strongly predicted the outcome than preoperative PSA, extraprostatic extension (pT3), pathologic Gleason score, age, or race.

“The potential implications for this finding are broad and profound,” Dr Sharifi’s team wrote. “In men who already have androgen-dependent prostatic diseases such as benign prostatic hyperplasia or prostate cancer, knowledge of the absence, presence, and extent of this ‘sneaky’ [testosterone] physiology and total prostatic androgen exposure may further clarify an individual’s distinct natural history of the disease.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Alyamani M, Michael P, Hettel D, et al. Elevated periprostatic venous testosterone correlates with prostate cancer progression after radical prostatectomy. J Clin Invest. Published online September 1, 2023. doi:10.1172/JCI171117