Testosterone suppression in opioid users: a systematic review and meta-analysis

Drug Alcohol Depend. 2015 Apr 1;149:1-9. doi: 10.1016/j.drugalcdep.2015.01.038. Epub 2015 Feb 8.


Background: Whether used for pain management or recreation, opioids have a number of adverse effects including hormonal imbalances. These imbalances have been reported to primarily involve testosterone and affect both males and females to the point of interfering with successful treatment and recovery. We conducted a systematic review and meta-analysis to determine the extent that opioids affect testosterone levels in both men and women, which may be relevant to improved treatment outcomes for opioid dependence and for pain management.

Methods: We searched PubMed, EMBASE, PsycINFO, and CINAHL for relevant articles and included studies that examined testosterone levels in men and women while on opioids. Data collection was completed in duplicate.

Results: Seventeen studies with 2769 participants (800 opioid users and 1969 controls) fulfilled the review inclusion criteria; 10 studies were cross-sectional and seven were cohort studies. Results showed a significant difference in mean testosterone level in men with opioid use compared to controls (MD=-164.78; 95% CI: -245.47, -84.08; p<0.0001). Methadone did not affect testosterone differently than other opioids. Testosterone levels in women were not affected by opioids. Generalizability of results was limited due to high heterogeneity among studies and overall low quality of evidence.

Conclusions: Our findings demonstrated that testosterone level is suppressed in men with regular opioid use regardless of opioid type. We found that opioids affect testosterone levels differently in men than women. This suggests that opioids, including methadone, may have different endocrine disruption mechanisms in men and women, which should be considered when treating opioid dependence.

Keywords: Methadone; Opiates; Prescription opioids; Sex hormones; Testosterone.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Methadone / adverse effects
  • Narcotics / adverse effects
  • Opioid-Related Disorders / metabolism*
  • Sex Characteristics
  • Testosterone / antagonists & inhibitors*


  • Narcotics
  • Testosterone
  • Methadone