Testosterone Can Improve Pain Tolerance in Men on Opioids

A Boston University study shows for the first time that testosterone gel can decrease discomfort in men with pain syndromes and low testosterone levels who are chronic users of opioids.

The men in the trial had pain conditions that ranged from headaches to backaches and had all become deficient in testosterone, which is a side effect of opioid use. During the study they used a transdermal testosterone gel or a placebo for three months, lead author Shehzad Basaria, MD, associate professor and director of the androgen clinical research unit at Boston University, Massachusetts, explained at ENDO 2013: the Endocrine Society 95th Annual Meeting last week.

The research is the first to show that testosterone can have an effect on pain in humans, commented Stanley Korenman, MD, professor of medicine and endocrinology at the University of California, Los Angeles, who was not involved with the study.

"It is a terrific paper that opens up a new avenue of scientific exploration," he told Medscape Medical News. "In the category of hypogonadal men who take opioids regularly, using testosterone could be a way to get them off narcotics," he added.

But both Drs. Basaria and Korenman emphasized that before testosterone can be used clinically to reduce pain or to wean men off opioids, it will need to be tested in diverse populations in larger studies.

Improvements in Perception and Tolerance of Pain Come First

Dr. Basaria explained rodent studies have shown that rats that become androgen deficient experience pain more acutely, and when their testosterone is restored, their tolerance for pain increases.

In their trial, 84 men (age, 18 to 64 years) with opioid-induced androgen deficiency were randomly assigned to 5 g of transdermal testosterone gel or placebo for 14 weeks. Two weeks after randomization, dose titration was performed to achieve serum testosterone concentrations between 500 and 1000 ng/dL.

The primary outcome was a measure of the overall level of pain on the brief pain inventory (BPI) questionnaire. Secondary outcomes included quantitative sensory testing of pain threshold and tolerance and measures of quality of life using the SF-36 questionnaire.

Sixty-five men completed the trial, 36 taking testosterone and 29 on placebo. Both total and free serum testosterone levels significantly increased in the testosterone group.

At 12 weeks, men randomized to testosterone showed nominal mean improvements on the pain interference subscale of BPI, but neither this nor overall changes in composite BPI scores were significantly different between the 2 groups.

However, the men assigned to testosterone were more able than those on placebo to withstand pain caused by application of pressure with mechanical tools ( P < .031), and they could also endure more intense pain caused by pressure than those on placebo (P = .049). They also showed a trend toward greater tolerance for discomfort caused by continued exposure of their skin to ice water (P = .08).

Those on the transdermal gel also reported decreased emotional symptoms that limited their daily activity, as measured by the SF-36 questionnaire.

Dr. Basaria said the reason they may not have seen a significant change in the primary end point could be that, "usually, we see improvement in pain perception and pain tolerance in laboratory tests before patients themselves report a decrease in their symptoms."

ENDO 2013: the Endocrine Society's 95th Annual Meeting. Abstract LB-FP-6, presented June 15, 2013.

Barbara Boughton • Medscape Medical News © 2013 WebMD, LLC

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