Daily Use of Long- vs. Short-Acting Opioids Increases Risk of Hypogonadism

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PALM SPRINGS, CA — Daily use of long-acting opioids — vs. daily use of short-acting opioids — increases the risk of hypogonadism in men, one of the first studies to evaluate this association, presented during the 2012 American Academy of Pain Medicine Annual Meeting, has found.

Andrea L. Rubinstein, MD, of Kaiser Permanente, Santa Rosa, CA, and colleagues noted that although opioid use in men has been linked to hypogonadism since the 1970s, whether this risk was linked to specific opioids, duration of action, or total daily opioid dose remained unknown.

Between January 2009 and June 2010, they enrolled 81 men who were 18–80 years of age and drew total testosterone. All were using an opioid daily at a stable dose for at least three months and none had been previously diagnosed with hypogonadism (total AM testosterone <250ng/dL).

The study found that 57% of the men were hypogonadal. When stratified by opioid administered, the percentage of hypogonadal patients was: 87.5% oxycodone CR, 83.3% morphine CR, 78.6% methadone, 75% fentanyl, and 37.5% buprenorphine for long-acting opioids, and 50% oxycodone IR and 28% hydrocodone for short-acting opioids. Overall, of the 46 men on long-acting opioids, 34 (75%) were hypogonadal, compared with 12 of 43 (34%) on short-acting opioids; this difference was statistically significant (P<0.001). 

When controlling for morphine sulfate equivalent dosage and body mass index, logistic regression analysis demonstrated patients on a long-acting opioid had a 4.78 greater risk of becoming hypogonadal than those on short-acting opioids (95% CI 1.51–15.07; P=0.008). Multivariate analysis, however, failed to show a significant association between dose and hypogonadism.

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