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Low Testosterone Risk Greater with Longer-Acting Opioids

August 07, 2014

By Anne Harding

NEW YORK - Men on long-acting opioids are more likely to develop androgen deficiency than are men on the shorter-acting form of the drug, new findings show.

"There is a distinct risk difference between long-acting opiates and short-acting opiates in terms of androgen deficiency," said lead author Dr. Andrea Rubinstein of Kaiser Permanente Medical Group in Santa Rosa, California.

"What's unusual about this is that the central belief around the use of opioids for chronic pain has been that long-acting opiates are safer than short-acting opiates, although there hasn't been any evidence for that," she told Reuters Health.

Opioids were first linked to testosterone deficiency in men in the 1970s, but risk factors for developing this deficiency have not been investigated, Dr. Rubinstein and her Kaiser colleague Diane Carpenter note in their report, online July 22 in American Journal of Medicine.

In an earlier study of 81 men treated for chronic pain with opioids, the researchers found that the risk of androgen deficiency was nearly five-fold higher with the long-acting form of the drug.

In the current study, the researchers looked at 1,585 men treated at Kaiser Permanente Northern California, who had all had at least one testosterone measurement and were taking a single opioid drug, either short- or long-acting, continuously, or were taking one long-acting opioid plus one short-acting opioid. A total of 616 were using a long-acting opioid, while 969 used short-acting opioids only.

Fifty-seven percent of the men on long-acting opioids were androgen deficient, versus 35% of the men on short-acting opioids (p<0.001). After the researchers controlled for dose, body mass index, age, diabetes, hyperlipidemia, and hypertension, they found that patients on long-acting opioids had 3.39 times higher odds of having androgen deficiency.

The effect of dose was greater with short-acting opioids, with an odds ratio of androgen deficiency of 1.16 for every 10 milligram increase in morphine standard equivalent dose, versus 1.01 for men on long-acting opioids.

The dose effect may be stronger with the shorter-acting opioids because a higher dose may mean a patient is taking the drug more frequently, and so is less likely to have low levels of the medication in their blood, Dr. Rubinstein said. "Those short-acting opiates start to approximate being a long-acting opiate," she explained.

"The incidence of this is common enough that it warrants screening," Dr. Rubinstein added. "We recommend checking testosterone levels in everyone on opioids, and then I think you also need to check it periodically when you change from a short- to a long-acting opiate or if you significantly change the dose."

Low testosterone carries risks beyond loss of libido, including loss of bone density, depression and weight gain, the researcher added.

"If you do have somebody who has low testosterone, it's relatively easy to treat that," she said. "You can give supplemental testosterone or manipulate their opiate dose."

Also, according to Dr. Rubinstein, patients being put on chronic opioid therapy should be told about the risk of androgen deficiency.


Am J Med 2014.


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