Supplementary Files
Keywords
Female
Male
Pain
Sex hormones
Abstract
Introduction: Pain is a complex phenomenon shaped by multiple factors. Among these, sex differences are increasingly recognized due to the higher prevalence of chronic pain in women and their greater sensitivity to nociceptive stimuli. Sex hormones have been proposed as key, though not exclusive, contributors to these differences. This review aimed to explore the evidence on the factors that determine sex differences in pain perception.
Methods: A review was conducted using PubMed/MEDLINE (January 1, 2024). Following assessment, 50 articles met eligibility criteria and were included.
Results: Women experience more experimental pain and show higher prevalence of chronic pain conditions such as migraine, temporomandibular disorder, and osteoarthritis. Hormonal influences, including the dual effects of estrogen and progesterone and the potentially protective role of testosterone, appear to be context-dependent and insufficient to fully explain these differences. Neurobiological mechanisms, as well as differences in opioid system responses, contribute to sex-specific pain perception. Clinically, women exhibit greater sensitivity to opioids but also a higher incidence of adverse effects. Psychosocial factors further modulate pain experience through bidirectional interactions with biological mechanisms.
Conclusions: Sex hormones appear to account only partially for sex differences in pain perception, as their effects depend on interactions with neurobiological and psychosocial mechanisms. Understanding these determinants may contribute to a more comprehensive, sex-informed approach to pain assessment and management. Future research should prioritise standardised reporting of sex and gender variables, rigorous assessment of hormonal status, and longitudinal designs capturing hormonal transitions, in line with current international recommendations.
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Copyright (c) 2026 Juan Camayo Zorilla, Juan David Peláez Martínez, Valentina Morales Arias, Manuela Rodríguez Giraldo, David Alejandro Ríos Pineda, Rafael Ordoñez Lizarralde, Fredy Ariza Cadena (Autor/a)