麻豆传媒

PALM SPRINGS, Calif. -- Men who take long-acting opioids for chronic pain may have a higher risk of hypogonadism than those on short-acting formulations of the drugs, researchers said here.

Those on long-acting opioids, such as oxycodone (OxyContin), were nearly five times as likely to have low testosterone than men on short-acting versions such as hydrocodone (Vicodin) (P=0.008), reported Andrea Rubinstein, MD, of Kaiser Permanente in Santa Rosa, Calif., and colleagues, at the American Academy of Pain Medicine meeting here.

It's been well documented that opioid use is linked with hypogonadism in men, though much research has focused on long-acting opioids, particularly methadone, Rubinstein said. But less is known specifically about short-acting opioids and their ties to low testosterone.

So Rubinstein and colleagues conducted a retrospective cohort study of 81 men, ages 18 to 80, with hypogonadism, who were referred to a chronic pain clinic within Kaiser Permanente Northern California between January 2009 and June 2010.

All had been on stable, daily doses of daily opioids for chronic pain for at least three months. None had a previous diagnosis of hypogonadism.

The majority of the cohort (57%) had low morning testosterone levels, based on a cut-off of 250 ng/dL. As expected, Rubinstein said, testosterone levels differed in terms of body mass index (BMI) and Morphine Sulfate Equivalent dose.

She and colleagues found that a significantly larger proportion of men on long-acting opioids were hypogonadal compared with those on short-acting drugs (74% versus 34%, P<0.001).

Even when controlling for dose and BMI, those on long-acting opioids had a far higher risk of being hypogonadal than those on short-acting drugs (OR 4.78, 95% CI 1.51 to 15.07, P=0.008).

"It's easy to see that there's something going on there," Rubinstein told 麻豆传媒. "Duration of action appears to be the primary culprit."

She added that in those multivariate analyses, BMI was independently associated with low testosterone, but the effect was small. Dose, on the other hand, wasn't associated with hypogonadism and neither was age.

Rubinstein explained that opioids may interfere with the action of luteinizing hormone, which is involved in testosterone production. It has a pulsatile release, peaking every 90 minutes or so. Troughs in short-acting opioid release may allow time for testosterone synthesis. Long-acting opioids, which have a continuous release, don't offer this same kind of opportunity, she said.

Still, she cautioned that it's too early to tell for sure whether long-acting opioids have worse effects on testosterone than their short-acting counterparts, but she said that clinicians should "check for low testosterone regularly, regardless of what type of opioid patients are on."

She added that doctors currently don't look for low testosterone often enough in their chronic opioid patients, but doing so could stave off some of the complications of hypogonadism, including osteoporosis, low libido, insulin resistance, and obesity.

Steven Linder, MD, of the VA Hospital in Palo Alto, Calif., who was not involved in the study, said it's especially relevant to watch for this condition given the rising rate of young war veterans on chronic opioid therapy.

"It's one thing to have a 70-year-old patient on long-term opioids be hypogonadal," he said, "but it's another when you have 26-year-olds on long-term [opioid] therapy."

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