Opioids and the Hypothalamic-Pituitary-Gonadal (HPG) Axis

Leen Wehbeh, Adrian S. Dobs

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Context: Hypogonadism is a well-established consequence of opioid use. It has been reported in both men and women, although more widely studied in men. Evidence Acquisition: PubMed was searched for articles in English until December 2019 for opioids and hypogonadism. Bibliography of retrieved articles was searched for relevant articles. Evidence Synthesis: The prevalence of opioid-induced hypogonadism (OIH) varies between studies but was reported to be 69% in a recent systematic review. There is large heterogeneity in the studies, with different factors shown to have stronger association with hypogonadism such as specific types of opioids, higher doses, and longer durations of use. The consequences of OIH include sexual dysfunction, depression, decreased quality of life, and low bone density. There is paucity of randomized controlled trials assessing the efficacy of testosterone replacement therapy (TRT) for OIH in men, and even less studies on treating OIH in women. TRT studies in men reported varying outcomes with some studies favoring and others showing no clear benefit of TRT on different measures. Conclusions: Despite the high prevalence of OIH, it remains underrecognized and undertreated with multiple endocrine and metabolic consequences. A reasonable approach in patients using opioids includes informing them of this complication and its potential consequences, screening for signs and symptoms of hypogonadism then sex hormone levels if prolonged opioid use > 3 months, and treating patients diagnosed with hypogonadism, if and when clinically indicated, with sex hormones if chronic opioids are planned to be continued for ≥ 6 months.

Original languageEnglish (US)
Pages (from-to)E3105-E3113
JournalJournal of Clinical Endocrinology and Metabolism
Issue number9
StatePublished - Sep 1 2020


  • Estradiol
  • Hypogonadism
  • Opioids
  • Testosterone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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