Long-term Opioid Use in Men Linked to Hypogonadism

Fran Lowry

March 09, 2020

NATIONAL HARBOR, Maryland ― Long-term opioid use in men is linked to a significantly increased risk for hypogonadism, new research suggests.

Findings from a retrospective case-control study show that men who used long-acting opioids on a long-term basis had close to a 1.5-fold increased risk of developing the condition. Moreover, for every increase in 100 maximum morphine equivalent daily dose (MEDD), there was a 44% increase in risk.

Dr Natalie Hanks

Hypogonadism, a condition in which little or no testosterone is produced by the testes, puts men at risk for infertility and osteoporosis, but such adverse endocrine effects of long-term opioid use are frequently unrecognized, study investigator Natalie Hanks, MD, Ochsner Clinical School, University of Queensland University Medical Center, New Orleans, Louisiana, told Medscape Medical News.

The findings were presented here at the American Academy of Pain Medicine (AAPM) 2020 Annual Meeting.

Frequently Overlooked Side Effect

The investigators note that opioid-induced androgen deficiency (OPIAD) can be detrimental to patients' quality of life as well as to the healthcare system.

The investigators examined the dose-response relationship between opioids and hypogonadism to shed more light on future diagnosis and management of OPIAD.

The researchers analyzed data from 357 men aged 18–80 years with long-term opioid use, defined as using opioids continuously for longer than 3 months.

Exclusion criteria included the following: a diagnosis of hypogonadism prior to initiation of long-term opioid use; a history of Klinefelter syndrome, a rare genetic condition in which a male is born with an extra copy of the X chromosome; other chromosomal abnormalities; cryptorchidism; varicocele; myotonic dystrophy; mumps; radiotherapy to the testes; testicular torsion; long-term corticosteroid use; prostate cancer; or an endocrine disorder.

In total, 95 long-term opioid users had hypogonadism and served as case patients; 263 long-term opioid users did not have hypogonadism and served as control patients.

Case patients were matched to control patients by age, race, and body mass index in a 1:4 ratio. MEDD data were collected from electronic health records.

The prevalence of hypogonadism varied with MEDD dose. It was 15.6% for MEDD <100; 27.1% for MEDD 100–199; 41.5% for MEDD 200–299, 35.7% for MEDD 300–499; and 50% for MEDD 500–800.

Interestingly, for 14 patients, the estimated probability of hypogonadism plateaued in the MEDD 500–800 range.

The results also showed a significant linear association between maximum MEDD and the odds of developing hypogonadism with long-term use of long-acting opioids (odds ratio, 1.44; 95% confidence interval, 1.16 – 1.78) by 100 units' difference in maximum MEDD.

"I feel as if hypogonadism is often overlooked or forgotten among all of the other side effects that go along with opioid use," Hanks said. "Our findings require replication in other clinical settings, but our results do suggest that we should start to look for signs of hypogonadism and opioid-induced androgen deficiency in this population and try to diagnose and treat it promptly."

An Important Reminder

Commenting on the findings for Medscape Medical News, Robert Bolash, MD, Cleveland Clinic, in Ohio, said the study provides important information about an often ignored side effect of long-term opioid use.

Dr Robert Bolash

This "well-matched control trial was conducted in a sizeable cohort and shows a thought-provoking dose-response curve," said Bolash.

"The relationship appears to be nonlinear, with particular hazard at low and moderate doses, then a plateau at high-dose therapy ranges. It would be interesting to see if duration of therapy was similarly hazardous or if dose was the primary driver of this endocrine dysfunction," he added.

Bolash also said the study is an important reminder about this important side effect of long-term opioid used.

"Contemporary pain physicians often consider the respiratory depressant and gastrointestinal side effects of this class of therapy, and may need to revisit the notable challenges that opioids can impart on the endocrine side effects as well," he noted.

Hanks and Bolash report no relevant financial relationships.

American Academy of Pain Medicine (AAPM) 2020 Annual Meeting: Abstract LB015. Presented February 27, 2020.

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