Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

Naturally occurring opiates (endorphins) decrease testosterone levels by inhibiting the
synthesis of gonadotropin releasing hormone (GnRH) and also inhibiting testosterone
synthesis by the testes. Similarly, men with addiction to narcotics and those on exogenous
opioids for pain control have decreased serum testosterone levels. Indeed, these men
complain of decreased libido, erectile dysfunction and impaired quality of life. Animal
studies have shown that gonadectomy results in a decrease in pain threshold in rats and
repletion of testosterone elevates that threshold. These observations suggest that
testosterone may possess analgesic properties. Hence, the investigators hypothesize that
hypogonadism developing in men on opioids results in an increased sensitivity to pain and
requirement of higher doses of opioids. In this study, the investigators plan to administer
testosterone to men with opioid-induced hypogonadism and evaluate their pain perception,
pain sensitivity in response to noxious stimuli and changes in the requirement of opioids in
response to testosterone administration.

Hypothesis:

Testosterone replacement in men with opioid-induced hypogonadism will improve pain
tolerance, pain perception and quality of life.

Specific aims:

1. To evaluate the effects of testosterone replacement on pain sensitivity, pain
tolerance, and pain modulation in men with opioid-induced hypogonadism.

2. To determine the effects of testosterone replacement on health-related quality of life.

3. To determine whether testosterone replacement in hypogonadal men induces changes in the
dosage requirements of opioid medications for pain control.

To accomplish our specific aims, the investigators propose a randomized, double blind,
placebo-controlled, parallel arm study in which hypogonadal men with non-cancer chronic back
pain syndrome on chronic opioids and low testosterone levels (<300 ng/dl) will be randomized
to exogenous testosterone replacement therapy vs placebo. Our primary outcome is change in
pain tolerance using various external painful stimuli. Secondary outcomes are change in pain
sensitivity and modulation, quality of life and opioid requirements.