Sperling Prostate Center

Testosterone Replacement Therapy is Safe for Prostate Cancer Patients

I have previously written on the safety of testosterone replacement therapy (TRT) as well as the use of multiparametric MRI to monitor TRT use during active surveillance. Both of those articles are backed up by published research because I believe it’s important for patients to have access to scientifically tested information.

Ever since the 1940s, mainstream medical practice has firmly discouraged TRT for men at risk of prostate cancer, or already diagnosed with it. It was believed that testosterone “fuels” prostate cancer. Yet numerous studies in the past decade have shown that administering TRT to patients with low testosterone (low T) who also had prostate cancer made no difference whatsoever with their cancer! Their testosterone levels increased, but had no detectable effect on their cancer. While these studies concluded that testosterone supplementation does not drive prostate cancer, they don’t answer the question, “Why not?”

Answering the question

I found a 2009 paper by Gat et al.[i] that offers a credible answer. First, it’s important to understand a few basics. Testosterone is a male hormone produced by the testicles. It is supplied to the body by blood circulation, where “much of it is transported bound to a specific plasma (blood) protein, sex hormone-binding globulin (SHBG).”[ii] Another circulating portion of it is bound to another blood protein called albumin. A third amount, the least, is called free testosterone because it is not bound to anything. Free testosterone is also called bioavailable testosterone, because not being bound to a protein, it easily picked up by tissues. Thus, a blood draw to evaluate total testosterone actually measures the levels of both bound and free testosterone that are circulating in the blood.

Gat et al. discovered a condition – actually, a flaw in Mother Nature’s design – that causes a certain amount of free testosterone to detour directly to the prostate gland instead of dispersing into the bloodstream. They call it a “back-door” entry to the prostate. The flaw has to do with standing upright, which means that venous blood (blood in veins) returning to the heart from the lower part of the body has to fight against gravity. In order to do so, the veins have one-way valves that prevent venous blood from flowing backward and pooling low in the body. According to Gat’s research, those valves tend to wear out as men age. In particular, the vein heading upward from the testicles (Internal Spermatic Vein or ISV) is prone to this.

When the valves wear out

If the ISV malfunctions, blood pools in the veins directly above the testicle. The veins begin to bulge with extra blood, and the pressure of the pooled blood is greater than the flow pressure from the prostate. While the majority of ISV blood will still make its way to the rest of the body, some of it is forced upward (backflow) into the prostate gland. The blood that heads to the rest of the body will carry the majority of testosterone produced by the testicles, since it is bound with blood proteins. However, the majority of free testosterone – the kind most readily available for tissue absorption – is not traveling with those proteins. Instead, the blood that backflows to the prostate is saturated with free testosterone, reaching concentrations up to 130 times greater than free testosterone in circulating blood![iii] This means the gland is literally bathing in free testosterone. It also means that free testosterone levels will be lower when a testosterone blood draw is taken.

The effect of the free testosterone “bath”

Now we circle back to the connection between testosterone and prostate cancer. According to Gat’s publication, when the abnormal valves lead to a concentration of free testosterone in the prostate, this hormone places constant stress on the genes that respond to it. (Remember: hormones are chemical messengers.) This stress pushes cell mutations, as an increasing number of genetic errors occurs – and the cell’s mechanism for detecting copy errors is increasingly damaged. The authors theorize that rapid proliferation of prostate cells results, leading to the condition known as benign prostatic hyperplasia (BPH), and eventually to prostate cancer in many cases. So yes, there is a causal link between testosterone and prostate cancer – but it’s not found on the path decades of research has followed.

Gat’s work illuminates the problem of two different testosterone effects: total testosterone circulating in the blood vs. a localized saturation of free testosterone affecting the prostate gland. The results of studies showing that testosterone supplementation to treat low T did not affect prostate cancer were puzzling to those who expected the cancer to run wild. However, if Gat is correct, it’s not serum blood levels that are cancer-causing. It’s the pooling and backflow of testicular venous blood saturating the gland that’s the source. No wonder the efforts to find a correlation between serum levels of testosterone and prostate cancer ended up with frustration.

To be clear, Gat et al. are not claiming that every case of prostate cancer is due to the weak ISV valves. There are many factors that can stimulate genetic changes in prostate cells such that they become malignant. However, high serum testosterone is not the culprit, and since TRT is a treatment that affects blood levels, using it therapeutically to benefit low T patients should not be a source of worry

What is needed now is verification of Gat’s (and his colleagues’) work, and that must come from replicating their methodologies. Science is only as good as repeated research results. It is hoped that the will and means will be found to validate this discovery, since TRT can be beneficial to low T patients regardless of their risk or history of prostate cancer.

[i] Gat Y, Joshua S, Gornish MG. Prostate cancer: a newly discovered route for testosterone to reach the prostate : Treatment by super-selective intraprostatic androgen deprivation. Andrologia. 2009 Oct;41(5):305-15.

[ii] https://en.wikipedia.org/wiki/Testosterone

[iii] Gat, Y & Gornish, M. (2009). Reversal of benign prostate hyperplasia by super-selective intraprostatic androgen deprivation therapy. European Urological Review. 4. 10-14.


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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