Hypogonadism associated with long-term opioid therapy: A systematic review

J Opioid Manag. May-Jun 2015;11(3):255-78. doi: 10.5055/jom.2015.0274.


Background: Sexual dysfunction and Opioid-Induced Sexual Hormone Deficiency (OPISHD) have been associated with patients on long-term opioid pain therapy. There have been few comprehensive reviews to establish a relation between hypogonadism with chronic opioid pain management. The OPISHD is often not treated and literature guiding this topic is scarce.

Objective: To investigate hypogonadism associated with long-term opioid therapy based on qualitative data analysis of the available literature.

Study design: Systematic review.

Interventions: The review included relevant literature identified through searches of PubMed, Cochrane, Clinical Trials, US National Guideline Clearinghouse, and EMBASE, for the years 1960 to September 2013. The quality assessment and clinical relevance criteria used were the Cochrane Musculoskeletal Review Group Criteria for randomized control trials and the Newcastle-Ottawa Scale Criteria for observational studies. The level of evidence was classified as good, fair, and poor, based on the quality of evidence.

Main outcome measures: The primary outcome measures were clinical symptoms and laboratory markers of hypogonadism. Secondary outcome measure was management of OPISHD.

Results: Thirty-one studies were identified, of which 14 studies met inclusion criteria. There were no randomized control trials and eight of 14 studies were of moderate quality. The remaining studies were of poor quality. Four studies report most patients on long-term oral opioid therapy have associated hypogonadism and three studies of patients receiving intrathecal opioid therapy suggest that hypogonadism is common.

Conclusions: There is lack of high-quality studies to associate chronic opioid pain management with hypogonadism. At present, there is fair evidence to associate hypogonadism with chronic opioid pain management, and only limited evidence for treatment of OPISHD.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Chronic Pain / diagnosis
  • Chronic Pain / drug therapy*
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypogonadism / chemically induced*
  • Hypogonadism / diagnosis
  • Male
  • Narcotic Antagonists / administration & dosage
  • Narcotic Antagonists / adverse effects*
  • Risk Assessment
  • Risk Factors
  • Time Factors


  • Narcotic Antagonists