Do Men and Women Have Different Pain Relief Response to Opioids? Interview with:
Roberta Agabio, M.D.
Dpt. Biomedical Sciences
University of Cagliari
Cittadella Universitaria Monserrato
Monserrato (CA) – ITALY  What is the background for this study?

Response: Pain is the leading cause for seeking medical care worldwide, and opioids are the most frequently prescribed drugs for pain relief. Differences and similarities between men and women in both effectiveness and side effects to opioids used for pain relief have been described. In addition, individuals may respond differently to these medications for other reasons for example: the intensity of pain experienced, amount and type of administration of opioids (e.g. fixed doses established by physicians or flexible doses decided by patients), mental condition, age, body weight, and use of alcohol, tobacco and/or cannabis.

However, the role of these factors in influencing sex differences and similarities in the response to opioids used for pain control has not been thoroughly investigated. What are the main findings?

Response: We included data from all published clinical studies in which the response to opioids for pain relief was broken down for men and women. We used a meta-analysis approach. We found that, in the treatment of acute pain, men and women were not statistically significant different when the response was measured 30 minutes after opioid administration while women obtained a better response than men when patients self-administered opioids for pain relief. No sex difference was found in the response to opioids in the treatment of chronic cancer pain, while women showed better responses than men in the treatment of chronic non-cancer pain.

These findings are also affected by several factors like age, comorbid mental disorders, type of administration, and body weight. In other words, compared to men, women may self-administer lower doses of opioids to achieve relief from acute pain as well as receive lower doses of opioids to treat chronic non-cancer pain (. However, several factors may influence the response to opioids. Unfortunately, we were not able to evaluate all the factors because information on most of them was not provided or was not broken down based on sex. What should readers take away from your report?

Response: Despite the extensive use of opioids to treat chronic and acute pain, knowledge about potential sex differences is limited in the literature, especially as it relates to their effectiveness, safety and doses needed. What recommendations do you have for future research as a result of this work?

Response: Future studies on the effectiveness and safety of opioids in the treatment of chronic and acute pain should collect and provide information broken down for men and women on all possible influencing factors described above. Is there anything else you would like to add?

Response: The results of our study suggest that women may require lower doses of opioids than men to treat acute and chronic pain. Accordingly, it may be reasonable for clinicians to consider starting pain treatment with opioids for women at lower doses compared to men and then evaluate whether the doses should be increased, according to individual experience with pain and side effects. Influencing factors of the response to opioids in the treatment of pain should always be investigated in order to personalize the dose for each subject. This approach may contribute to the important ongoing efforts aimed at combatting the current opioid crisis.


Pharmacol Res. 2019 Sep 6:104447. doi: 10.1016/j.phrs.2019.104447. [Epub ahead of print]

Sex differences in the response to opioids for pain relief: A systematic review and meta-analysis.

Pisanu C1, Franconi F2, Gessa GL3, Mameli S4, Pisanu GM5, Campesi I6, Leggio L7, Agabio R8.

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