Elucidating risk factors for androgen deficiency associated with daily opioid use

Am J Med. 2014 Dec;127(12):1195-201. doi: 10.1016/j.amjmed.2014.07.015. Epub 2014 Jul 22.


Background: Opioids can suppress testosterone in men, which can lead to extensive morbidity. Identifying risk factors for androgen deficiency in men using daily opioids could improve monitoring and safety.

Methods: In a retrospective cohort study, we used Kaiser Permanente Northern California databases to identify men on stable doses of opioids. These subjects had no diagnoses of cancer or endocrine disorders except treated primary hypothyroidism. Subjects were divided into those using long-acting opioids and short-acting opioids. Total testosterone was measured in blood drawn in the morning while the subjects were on their regular dose of opioid. The association between opioid duration of action and androgen deficiency, controlling for dose, body mass index, age, diabetes, hyperlipidemia, and hypertension, was assessed using logistic regression.

Results: The study included 1585 men. Men on long-acting opioids were more likely to be androgen deficient than men on short-acting opioids (57% vs 35%, P < 0.001; odds ratio [OR] 3.39; 95% confidence interval [CI], 2.39-4.77). As dose increased, the odds of androgen deficiency increased; however, dose was more strongly associated with androgen deficiency in men on short-acting opioids (OR 1.16; 95% CI, 1.09-1.23, for each 10-mg increase in dose) than in men on long-acting opioids (OR 1.01; 95% CI, 1.01-1.02).

Conclusion: Use of long-acting opioids is a key risk factor in the development of androgen deficiency. Dose was significantly associated with androgen deficiency, but more so for men on short-acting than on long-acting opioids.

Keywords: Androgen deficiency; Chronic pain; Hypogonadism; Long-acting opioid; OPIAD; Opioid; Opioid risk; Short-acting opioid; Testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Delayed-Action Preparations / adverse effects
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Middle Aged
  • Statistics as Topic
  • Testosterone / blood
  • Testosterone / deficiency*


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Testosterone