TRT's role in prostate cancer risk may be overstated

December 1, 2007

Physicians who hesitate to prescribe testosterone replacement therapy for fear of promoting prostate cancer should re-examine the evidence.

Key Points

"The major concern with TRT is the risk of increased prostate cancer," Dr. Crawford, professor of surgery (urology) and radiation oncology at the University of Colorado Health Sciences Center, Denver, reminded the audience at the first annual Urology Congress here. "The reality is that there are no data to support testosterone substitution as a cause of prostate cancer. It is time to reevaluate this notion."

Hypogonadism is receiving increased attention as the population ages. Low testosterone is frequently seen in older men, as well as in those with erectile dysfunction, type 2 diabetes, HIV/AIDS, cancer, osteoporosis, depression, chronic pain treated with opioids, and several other conditions.

TRT can reverse some or all of those familiar problems, Dr. Crawford said, but many physicians and some patients reject treatment out of fear that TRT may elevate the risk of prostate cancer.

The argument linking TRT with increased risk of prostate cancer is familiar and compelling: If castration kills prostate cancer, then boosting testosterone should have the opposite effect of promoting prostate tumors. But the argument is fallacious: Castration does not kill prostate cancer; it slows progression of the disease. Men dying of prostate cancer have already been deprived of testosterone, yet androgen deprivation therapy is known to fail in virtually all patients, Dr. Crawford said.

The only investigational support for the idea that testosterone promotes prostate cancer is based on a single 1941 report of equivocal acid phosphatase results in a single patient, he explained. That one report has been repeated and amplified into a widely accepted and unsupported belief, Dr. Crawford said.

Data reported over the intervening decades show that falling rates of testosterone and rising rates of prostate cancer are associated with increasing age, he added. That raises the possibility that TRT could protect against prostate cancer, but there are no data to support or to refute any potential protective effect against the disease.

A 2004 Institute of Medicine report on testosterone and aging concluded, "...the influence of testosterone on prostate carcinogenesis and other prostate outcomes remains poorly defined." Data published since 2000 indicate that hypogonadism, defined as serum testosterone of 280 ng/dL or lower, is associated with a Gleason score of 8 or higher at prostate cancer diagnosis. Most authorities define hypogonadism as serum testosterone below 300 ng/dL, Dr. Crawford noted.

In men with localized prostate cancer, a low testosterone level before treatment is emerging as an independent predictor for extraprostatic disease, more aggressive disease, and a worse response to treatment.

In more recent testosterone treatment trials, investigators have found prostate cancer rates of about 1%, Dr. Crawford added. That figure is similar to the rate of prostate cancer found by routine screening of the general male population.

More recent TRT trials are encouraging, Dr. Crawford said, but they are not definitive. Sample sizes are small, selection bias is evident, follow-up periods are short, and trials have not been randomized or blinded. Further basic research is insufficient to support or refute claims that TRT promotes prostate cancer.

Trials of TRT following radical prostatectomy show no associated increase in PSA levels, Dr. Crawford added. At the same time, men who receive TRT after prostatectomy show all of the expected benefits: improved muscle mass and strength, less visceral fat, improved cognition, improved mood, better physical performance, fewer fractures, increased sexual interest, improved erectile function, and better quality of life.

"There is documentation that you can use TRT," Dr. Crawford said. "It is safe with appropriate medical monitoring."

He recommended biopsy before initiating TRT and quarterly PSA testing and digital rectal exams for the first year. PSA and DRE can be scaled back to semiannually after the first year on therapy, he said.

Dr. Crawford serves on the speakers bureaus of Andrx/Auxilium, Celgene, Merck, and sanofi-aventis.