Special Topics in Pain: Opioids

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Effects of Testosterone Replacement on Pain Catastrophizing and Sleep Quality in Men With Opioid-Induced Androgen Deficiency.

Author(s): Huang, G et al.
Journal: Pain Medicine. 2017; 18: 1070-1076. 29 references.
Reprint: Grace Huang, MD, Section on Men's Health, Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, BLl-541, Boston, MA 02115, USA. E-mail: ghaung7@partners.org
Faculty Disclosure: Abstracted by N Walea, who has nothing to disclose. Please see original article for disclosures.
Objective: Review and evaluate the latest advances and newest information in the area of Opioids; Review and evaluate the latest advances and newest information in the area of Steroids; Review and evaluate the latest advances and newest information in the area of other (unspecified) systems

Editor’s Note: This was a good study looking at the effects of testosterone on pain catastrophizing and sleep quality – essentially more biopsychosocial variables.  By treating a laboratory value in the treatment group and confirming its improvement over placebo, one can clearly say that the treatment “worked” and replaced testosterone; the results, therefore, are meaningful in that the treatment group was appropriately treated for their condition.  A prior study had already determined an improvement in pain perception and tolerance when androgen deficiency was treated in this population, but it appears that this effect was not mediated by the biopsychosocial variables mentioned above.  Therefore, a different mechanism is likely involved and will hopefully be determined in future studies.

Class: Opioids; Steroids; Opioid induced androgen deficiency

Recent studies reported that testosterone replacement in men using opiates for chronic pain who have opioid-induced androgen deficiency improved pain perception and pain tolerance. Low testosterone levels have also been associated with poor sleep efficiency, increased nocturnal waking and reduced slow wave sleep.  

This study evaluates whether testosterone administration could reduce pain catastrophizing and improve sleep quality in men with opioid-induced androgen deficiency. The participants were 62 community-dwelling men with a mean (standard deviation; SD) age at baseline of 48 (8) years. Participants were required to have been taking at least 20 mg of hydrocodone (or morphine equivalent dose of another opioid) daily for at least 4 weeks and have a morning total testosterone less than 350 ng/dL as measured by liquid chromatography-tandem mass spectrometry  (LC-MS/MS). The participants were randomized into one of 2 groups, the testosterone group (n = 33) or the placebo group (n = 29).

 Serum total testosterone levels were measured by LC-MS/MS with sensitivity of 2 ng/dl. Self-assessment of pain catastrophizing was measured using the pain catastrophizing scale (PCS) questionnaire before and after 14 weeks of intervention. Self-assessment of insomnia was measured using the insomnia severity index before and after 14 weeks of intervention.  

 Daily the participants applied transdermal gel containing either placebo or 5 g of transdermal testosterone gel for 14 weeks. The aim was to raise serum testosterone levels into the mid-normal range for healthy young men (500-1000 ng/dl). Two weeks after randomization, the dose of testosterone gel was adjusted if the serum total testosterone level was < 500 ng/dl, in which case the dose was increased to 7.5 g daily. The mean (SD) total testosterone concentrations were 223 (86) ng/dl and 237 (97) in the testosterone and placebo group, respectively at baseline. The mean (SD) free testosterone levels were 44(23) pg/ml and 44 (19) pg/ml in the testosterone and placebo groups respectively. The mean ISI scores, which were consistent with subclinical sleep disturbance, were similar between the two groups.

Mean (SD) serum total testosterone concentrations increased from 223 (86) to 775 (555) ng/dl in the testosterone group, but did not change significantly in the placebo group. Similarly, mean free testosterone concentrations increased from 44 (23) to 184 (154) pg/ml in the testosterone group. Of the 33 men in this group, 23 required a testosterone dose increase from 5 g to 7.5 g daily to achieve the target range of serum testosterone between 500 to 1000 ng/dl.

Both groups had moderate improvements in their scores on all of the domains of pain-catastrophizing. However, when compared with placebo, the testosterone group evidenced no significant effect on either the total score or subscale scores on the PCS questionnaire from baseline to the end of treatment. Changes in PCS were not significantly related to changes in serum testosterone concentrations among the testosterone treatment group.

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