Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception
Condition: Pain; Hypogonadism
MeSH terms: Hypogonadism
Intervention: AndroGel; Placebo
Intervention description: 5g gel, applied once daily to the upper arms, upper back or shoulders.; 5g gel, applied once daily to the upper arms, upper back or shoulders.
Intervention MeSH terms: Testosterone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 84.0
Sex: Male
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Testosterone; Pain; Opioid; Hypogonadism

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men

          -  Age 18 years and older

          -  Non-cancer chronic pain

          -  Serum total testosterone level <350 ng/dl

          -  Consumption of at least 20 mg of hydrocodone (or analgesic equivalent of another
             opioid) for at least 4 weeks

          -  Absence of hospitalization in the past 2 months

          -  No acute illness in the past 2 months

          -  No current anabolic therapy (growth hormone, DHEA, etc)

          -  No current use or consumption in the past 2 months of melatonin

          -  Normal prostate exam

          -  Normal PSA level

        Exclusion Criteria:

          -  Cancer-related chronic pain

          -  Liver enzymes > 3 times upper limit of normal

          -  Serum creatinine > 2 times upper limit of normal

          -  Neurological disease

          -  Active psychiatric illness

          -  Any addictive drug use

          -  Alcoholism (>3 drinks/day)

          -  Patients currently receiving melatonin or anabolic agents

          -  Hospitalization in the past 2 months

          -  Acute illness in the past 2 months

          -  Consumption of < 20 mg of hydrocodone (or analgesic equivalent of another opioid)

          -  Severe BPH

          -  PSA > 4.0 ng/ml

          -  Prostate cancer

          -  Breast cancer