Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

Phase 2

Completed

Conditions: Pain
Hypogonadism

Interventions: Drug: AndroGel
Other: Placebo

Registration Number: NCT00351819

Lead Sponsor: Boston University

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 84

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Androgel (testosterone gel)	AndroGel	Testosterone replacement therapy
Placebo	Placebo	Placebo gel

Primary Outcome Measures

Name	Time	Method
Brief Pain Inventory (BPI) at Week 14	Week14 after intervention	BPI is a self-administered questionnaire that measuring chronic pain. BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score assesses the severity of pain on a continuous scale from 0 (no pain) to 10 (severe pain). The pain interference score corresponds to the item on pain interference, ranging from 0 (does not interfere) to 10(completely interferes). The total score is the sum of the pain severity score and pain interference score, ranging from 0(no pain) to 20 (severe and completely interfered pain).
Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14	Week 14 after intervention	Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.
Algometer-induced Pressure Pain at Week 14	Week 14 after intervention	A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.
Ice Water-induced Cold Pain and Its After-sensation at Week 14	Week 14 after intervention	Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.

Secondary Outcome Measures

Name	Time	Method
Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) at Week 14	Week 14 after intervention	The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL.
Pain Catastrophizing Scale (PCS) at Week 14	Values at week 14 after intervention	PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.
Sexual Functioning as Assessed by International Index of Erectile Function (IIEF) at Week 14	Week14 after intervention	IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.