Men taking daily long-acting opioids were nearly five times more likely to become hypogonadal than were men on short-acting opioids, researchers have found.

Although opioids are known to cause low testosterone in men, a study by Andrea L. Rubinstein, MD, and colleagues in The Clinical Journal of Pain is reportedly the first study to show a significant difference in risk between agents that are short-acting (immediate release, taken every four to six hours) and those that are long-acting (slow release, taken every eight to 12 hours).

The researchers studied 81 men who were aged 26 to 79 years (median age: 51 years) seen in a chronic-pain clinic between January 2009 and June 2010. None of the men had a previous diagnosis of hypogonadism and all had been on a stable daily dose of an opioid for at least three months. Hypogonadism was defined as morning total serum testosterone levels below 250 ng/dL.

Continue Reading

They found 53% of all the men taking daily opioids were hypogonadal. Of the 46 men receiving long-acting formulations, 34 (74%) were hypogonadal, compared with 12 of 35 men (34%) using short-acting opioids (hydrocodone or oxycodone) exclusively.

After controlling for daily dosage and BMI, men on long-acting opioids had 4.78 times greater odds of becoming hypogonadal than did men on the short-acting agents. BMI was also significantly associated with hypogonadism, but daily dose was not. 


  1. Rubinstein AL et al. Clin J Pain. 2013; doi: 10.1097/AJP.0b013e31827c7b5d.