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Hypogonadism in Men With Chronic Pain Linked to the Use of Long-acting Rather Than Short-acting Opioids

Rubinstein, Andrea L. MD*; Carpenter, Diane M. MPH; Minkoff, Jerome R. MD

doi: 10.1097/AJP.0b013e31827c7b5d
Original Articles

Aim: There is a need to elucidate the variables associated with testosterone suppression among men on daily opioid therapy for chronic pain.

Objective: The objective of this study was to examine several variables related to opioid use including daily dose, duration of action (long acting vs. short acting), and specific opioid to ascertain specific influences on total serum testosterone levels in men with chronic pain who use opioids daily.

Setting: This is a retrospective cohort study of men within the Kaiser Permanente, Northern California (KPNC) health care system on some form of daily opioid use for chronic pain.

Participants: Eighty-one men between the age of 26 and 79 years were seen in a chronic pain clinic between January 2009 and June 2010. All men were on stable dose of an opioid for at least 3 months, none with a previous diagnosis of hypogonadism.

Main Outcome Measures: Total serum AM testosterone levels were measured at KPNC Regional Laboratory.

Results: Average total serum AM testosterone levels for this population showed 53% of all men receiving daily opioids were hypogonadal (AM total serum testosterone <250 ng/dL). In men receiving long-acting opioids, 74% (34/46) were hypogonadal compared with 34% (12/35) in men using short-acting opioids (hydrocodone or oxycodone) exclusively [AM total testosterone: median, 126 ng/dL; mean, 169 ng/dL (SD, 128 ng/dL) vs. median, 283 ng/dL; mean, 315 ng/dL (SD, 142 ng/dL); P<0.001]. After controlling for daily dosage and body mass index, men on long-acting opioids had 4.78 times greater odds of becoming hypogonadal than did men on short-acting opioids [95% confidence interval (CI), 1.51-15.07; P=0.008]. Body mass index was also significantly associated with hypogonadism (odds ratio, 1.13; 95% CI, 1.03-1.24; P=0.006), whereas daily dose was not (odds ratio, 1.02; 95% CI, 0.99-1.05; P=0.29).

Conclusions: Among a contemporary sample of men receiving chronic daily opioids, we found a high prevalence of hypogonadism associated with duration of action, but not with total daily dose of the opioid.

Departments of *Chronic Pain

Endocrinology, Kaiser Permanente, Santa Rosa

Division of Research, Kaiser Permanente, Oakland, CA

The authors declare no conflict of interest. Supported by Kaiser Permanente Community Benefit Program, Kaiser Permanente Division of Research, Oakland, CA.

Reprints: Andrea L. Rubinstein, MD, Department of Chronic Pain, Kaiser Permanente, 3559 Round Barn Blvd, Santa Rosa, CA 95403 (e-mail:

Received December 12, 2011

Accepted November 4, 2012

© 2013 by Lippincott Williams & Wilkins