The effect of methadone on the hypothalamic pituitary gonadal axis and sexual function: A systematic review

Drug Alcohol Depend. 2020 Feb 1:207:107823. doi: 10.1016/j.drugalcdep.2019.107823. Epub 2019 Dec 23.

Abstract

Background: Opioid abuse is a public health crisis. As opioid misuse worsens, efforts are being made to increase access to medication-assisted treatments. Methadone is a medication-assisted treatment used to treat opioid dependence and chronic pain. While methadone is beneficial in the treatment of opiate abuse and chronic pain, side effects of the medication include hormonal and sexual function changes. The purpose of this report is to review the effects of methadone on the hypothalamic pituitary gonadal axis hormones and sexual functioning in males and females.

Methods: A search of PubMed was conducted using pre-defined criteria, resulting in the evaluation of 295 articles. A total of 72 articles, including 52 human studies and 20 animal studies, met the selection criteria and were reviewed. The included studies examined the effects of methadone on the hypothalamic pituitary gonadal axis and/or sexual function.

Results: There was evidence of methadone-induced hormonal changes, disruptions in the hypothalamic pituitary gonadal axis, and sexual dysfunction, although there was some variability in the results of the reviewed studies. Differences in methadone dose and length of exposure to treatment appears to influence the variability in the results. Much of the literature examines the effects of methadone in males, with very limited research examining the effects in females.

Conclusions: Despite its effectiveness for opiate abuse and chronic pain treatment, methadone has disruptive effects on the hypothalamic pituitary gonadal axis and sexual function. Further research is warranted to better define potential methadone-induced endocrine consequences and to further examine the effects of methadone in females.

Keywords: Estrogens; HPG axis; Methadone; Opioids; Sexual function; Testosterone.

Publication types

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

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Animals
  • Chronic Pain / drug therapy
  • Female
  • Gonadal Disorders / chemically induced*
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects*
  • Male
  • Methadone / adverse effects*
  • Opiate Substitution Treatment / adverse effects
  • Opioid-Related Disorders / drug therapy
  • Sexual Dysfunction, Physiological / chemically induced*

Substances

  • Analgesics, Opioid
  • Methadone