Sex differences in pain and analgesia: the role of gonadal hormones

Eur J Pain. 2004 Oct;8(5):397-411. doi: 10.1016/j.ejpain.2004.01.003.


There is now strong evidence for sex differences in pain and analgesia. These differences imply that gonadal steroid hormones such as estradiol and testosterone modulate sensitivity to pain and analgesia. The goal of this review is to present an overview of gonadal steroid modulation of pain and analgesia in animals and humans, and to describe mechanisms by which males' and females' biology may differentially predispose them to pain and to analgesic effects of drugs and stress. Evidence is presented to demonstrate that sex differences in pain and analgesia may be both quantitative and qualitative in nature. Current research suggests that sex-specific management of clinical pain will be a reality in the not-so-distant future.

Publication types

  • Review

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Drug Resistance / genetics
  • Female
  • Gonadal Steroid Hormones / metabolism*
  • Gonadal Steroid Hormones / pharmacology
  • Humans
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Opioid Peptides / metabolism
  • Pain / drug therapy
  • Pain / genetics
  • Pain / metabolism*
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism
  • Sex Characteristics*
  • Stress, Physiological / genetics
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology


  • Analgesics
  • Gonadal Steroid Hormones
  • Opioid Peptides
  • Receptors, Opioid