Sperling Prostate Center

Low Testosterone Linked with High Grade Prostate Cancer

UPDATE: 2/15/2023
Originally published 5/23/2017

Here’s a suggestion you don’t hear every day: if you’re diagnosed with low-risk prostate cancer (PCa), get your testosterone (T) checked.

If you’re wondering what your male hormone levels have to do with PCa, you’re asking an important question. It was long believed that high T levels could lead to the development of PCa and faster growth of the malignancy. Therefore, the standard of care for men diagnosed with advanced PCa has been drastically reduce T levels by cutting off or blocking T from the tumor—a treatment called “chemical castration.” More recently, however there is increasing evidence that connects low T levels at the time of diagnosis with dangerously aggressive PCa.

A very recent (2022) review of five studies (for a total of 1,203 prostatectomy cases) correlated patients’ pre-surgical T levels, diagnosis at biopsy, and gland pathology after surgery; the authors found that low T levels were linked with a high rate of worse cancer than originally diagnosed. In fact, the lower the level of T, the higher the chances of having intermediate-risk, high-risk, and metastatic PCa, and even PCa-specific mortality.[i]

No one knows why this seemingly paradoxical situation exists, because the biological mechanisms aren’t yet understood. However, T level may offer an additional biomarker, after MRI and biopsy, to confirm a patient’s PCa aggression level in order to make the best treatment plan. A simple blood test to evaluate T level does not seem like too much to ask, when so much is at stake.


A recent study by Ferro, et al. (2016)[ii] suggests that Active Surveillance patients with low testosterone (low T) may be harboring hidden aggressive prostate cancer (PCa). The Ferro team’s research sprang from previous reports of patients with high-grade, high-stage PCa who had low T at the same time. Ferro’s team wondered if testing for low circulating T levels in Active Surveillance (AS) patients might predict which patients were not truly suitable for AS.

The team enrolled 388 men who were eligible for AS but who chose instead to undergo radical prostatectomy. Initially, they all met the low-risk criteria for AS: clinical stage T2a or less, PSA less than 10ng/ml, two or fewer positive biopsy cores, Gleason score less than or equal to 3+3, and PSA density less than 0.2 ng/mL/cc. Just based on those clinical factors, it would seem like all the patients could safely go on AS. Prior to surgery, all patients had their blood tested to measure levels of circulating testosterone. Low T was defined as less than 300 ng/dL.

Following surgery, all whole gland specimens could be analyzed and compared with the initial biopsy findings and other clinical factors.  Those who were found to have a higher stage than T2a and who were upgraded to Gleason 4+3 were reclassified (not eligible for AS). In fact, Ferro’s group defined such patients as having “unfavorable disease,” suggesting that they had high probability of recurrence after surgery.

The researchers found a significant correlation between unfavorable disease, positive surgical margins, and presurgical low T blood test results. Thus, a simple blood test for low T added an independent predictor regarding the safety or not of going on AS even when all other clinical factors indicated safety for AS. The team concluded that “…our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor” if the doctor and patient are leaning toward AS.

It seems, therefore, that when patients are diagnosed with low-risk prostate cancer, a testosterone test is a reasonable screening method. Detecting circulating levels below 300 ng/dL may indicate a need for further diagnostic tests. Multiparametric MRI would be a superb way to obtain a visual evaluation of the size, shape, extent and aggression level that would assure proper patient selection for AS – as well as provide a baseline image for future AS monitoring. Part of our mission at the Sperling Prostate Center is to assure that those with indolent disease are not overtreated – and just as important, those with aggressive disease are not mistakenly placed on AS.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] Tu, H, Gu J, Meng Q, Kim J et al. Low serum testosterone is associated with tumor aggressiveness and poor prognosis in prostate cancer. Oncology Letters 13, no. 3 (2017): 1949-1957.
[ii] Ferro M, Lucarelli G, Bruzzese D, Di Lorenzo G et al. Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance. Oncotarget. 2016 Oct 25. doi: 10.18632/oncotarget.12906. [Epub ahead of print]


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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