Testosterone Replacement Therapy (TRT) and Prostate

At my clinic in Tulsa we do a lot of testosterone replacement therapy (TRT). Low testosterone is associated with a number of medical concerns and many of our male patients complain of fatigue and decreased performance when their testosterone levels are low.

There are a number of ways to manage ‘Low T’ including supplementing with testosterone. When we offer testosterone replacement one of the first questions many patients ask is “Well, what about prostate cancer? Doesn’t testosterone replacement cause prostate cancer?”

There is a lot of evidence suggesting that testosterone replacement therapy (TRT) does not increase risk of prostate cancer or other problems. Here, I present several studies validating this position.

How it all began…

The question of an association between higher levels of testosterone fueling prostate cancer and low levels reducing prostate cancer dates back to a study by Dr Huggins in 1941.[1] In his study, he castrated one patient and noted an improvement in prostate cancer. He also noted advancement of prostate cancer with the administration of testosterone injections.

However, “more recent data have shown no apparent increase in pCA rates in clinical trials of T supplementation in normal men or men at increased risk for pCA, no relationship of pCA risk with serum T levels in multiple longitudinal studies, and no reduced risk of pCA in men with low T. The apparent paradox in which castration causes prostate cancer to regress yet higher T fails to cause pCA to grow is resolved by a saturation model, in which maximal stimulation of pCA is reached at relatively low levels of T.”[2] In that same article, Morgentaler concludes “there is not now-nor has there ever been-a scientific basis for the belief that T causes pCA to grow.”

Hormone levels and prostate cancer

In a study published in 2008, the investigators evaluated 3886 men with a history of prostate cancer and compared them to 6438 men without prostate cancer. They measured testosterone, free testosterone, DHEA-S, androstenedione, androstenediol, estradiol, and calculated free estradiol and found no correlations between the levels of these hormones and risk of prostate cancer.[3]

Testosterone Replacement & Prostate Cancer

Gould published a review of 16 studies evaluating various testosterone formulations. He found no risk of increased prostate cancer over the baseline prevalence. Some studies went as long as 15 years.[4]

There was another study evaluating 1365 men on testosterone replacement therapy (TRT) for 20 years. These men were screened with a digital rectal exam (DRE) and prostate specific antigen (PSA) at baseline and then every 6 months. Any abnormal changes were evaluated with an ultrasound and prostate biopsy. Their conclusion was that there was no difference in PSA, free PSA, or prostate cancer compared to baseline risk. All cancers in the treatment group were localized and curative. They felt that testosterone treatment and monitoring may be safer than no treatment.[5]

13 men with testosterone deficiency and untreated prostate cancer received testosterone replacement therapy (TRT) for a median of 2.5 years. Testosterone levels increased from an average of 238 ng/dL to 664 ng/dL. There was no increase in any of the patient’s PSA nor their prostate volume during the study. 54% of follow up prostate biopsies showed no cancer. There was no local progression or metastasis.[9]

Testosterone Replacement after Radical Prostatectomy (for Prostate Cancer)

10 patients with organ confined prostate cancer had their prostates removed (radical prostatectomy). They were treated with testosterone and their PSAs were followed. After 19 months they had no detectible increase in their PSA levels (PSA <0.1) and there was no recurrence of their prostate cancer. They concluded that testosterone replacement therapy was safe in a highly select group of patients. [6]

Testosterone Replacement after Prostate Brachytherapy (for Prostate Cancer)

31 men received testosterone replacement therapy (TRT) for low testosterone after having brachytherapy. They were followed from 0.5-8.5 years (median 4.5 years). Their testosterone levels rose to 365-1373 ng/dL after starting TRT. One patient noted a transient elevation in PSA. The PSA levels were <1 in all patients. No patients stopped their TRT due to cancer recurrence or progression. The authors concluded that TRT may be used with caution and close followup after brachytherapy for prostate cancer.[7]

What does it all mean?

There does not appear to be a link to higher levels of testosterone and increased risk of prostate cancer. The proposed ‘saturation model’ appears to be an appropriate explanation for the benefit of castration explained by Huggins yet contradicted by the later studies.

Caution should be exercised when considering testosterone replacement therapy (TRT) for any patient much less in those with other risks.