Gender Differences in Analgesic Responses to Opioids for Acute, Chronic Pain

Men and women may respond differently to opioids prescribed for pain relief.

Men and women may respond differently to opioids prescribed for pain relief, and these responses may be influenced by factors that include comorbid mental health disorders and age, according to the results of a systematic review and meta-analysis published in Pharmacological Research.

In this systematic review and meta-analysis conducted according to PRISMA guidelines, the investigators searched the Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed (MEDLINE) databases with no date limitation for randomized controlled trials, controlled clinical trials, and observational clinical studies in which opioids were used for the management of acute or chronic pain, and responses to opioids were examined based on gender. The final search for publications was performed in January 2019. ROBINS-I was used to evaluate risk for bias, and the GRADE system was used to evaluate the overall quality of evidence.

A total of 40 comparisons (n=6794) were included. For studies in which opioids were used for acute pain, evidence considered to be of moderate quality indicated that men and women have comparable responses to opioids 30 minutes after administration, and that women self-administer lower amounts of opioids daily (n=3598; P <.0001; high risk for bias). For studies in which opioids were used to manage chronic pain, low-quality evidence indicates that women may be prescribed lower daily doses of opioids for noncancer pain (n=1952; P =.0009), and very low-quality evidence indicates that men and women do not differ in daily doses of morphine for cancer pain (n=708; P =.19). These results were significantly modified by patients’ age, type of opioids, type of administration, comorbid mental disorders, and body weight.

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 “The results of the present meta-analysis suggest an urgent need to conduct large clinical and observational trials in which information about all possible influencing factors are properly reported for men and women. Appropriate clinical research would help to reduce fatalities caused by opioid overdose (more than 33,000 deaths in 2015, in the US alone), especially since the use of prescription opioid pain relievers account for approximately half of opioid-overdose deaths,” concluded the study authors.

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Pisanu C, Franconi F, Gessa GL, et al. Sex differences in the response to opioids for pain relief: A systematic review and meta-analysis [published online September 6, 2019]. Pharmacol Res. doi: 10.1016/j.phrs.2019.104447