A search for sex differences in response to analgesia

It is generally accepted that males and females respond differently to painful conditions. With few exceptions, according to the published literature, females demonstrate a lower pain threshold and a lower tolerance of painful stimuli. There is some support in the literature that females experience greater analgesic efficacy than do males after the administration of narcotic analgesics. We compared the analgesic response of females and males to ibuprofen in a post-third-molar extraction dental pain model.

We performed a meta-analysis of 314 subjects included in the ibuprofen treatment arm of 7 double-blind, post-third-molar extraction dental pain (moderate to severe) studies, which were submitted to the agency electronically. The inclusion and exclusion criteria were practically identical in all studies. Pain relief and pain intensity measurements used the same metrics in all studies and were recorded just before and at least at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, and 6. 0 hours after drug administration.

The study included 195 female subjects and 119 male subjects (mean age, 21 years). Other than requiring dental extractions, the subjects were all healthy. Postoperative baseline pain was greater in females than in males to a statistically significant degree (P =.006). Both pain intensity and pain relief scores demonstrated the well-established analgesic effect of ibuprofen in the pooled data set as well as in all the individual studies. Moreover, the mean pain intensity and pain relief scores over time for the female and male treatment groups were not noticeably different at any time point after drug administration, with no imputation for missing values. Analysis of the data using the "baseline observation carried-forward" technique for remedicated subjects (the technique recommended by the Food and Drug Administration for efficacy analysis of acute analgesic medications) produced the same results, which were confirmed by analysis of variance and t tests at each time point of the study.

Our results demonstrated no sex effect on the analgesic response to ibuprofen. These results were obtained under the post-third-molar extraction setting, in which the least possible confounding factors are present. To fully establish the generality of this phenomenon, studies should be carried out in other pain models and using analgesic medications with different mechanisms of action. Arch Intern Med. 2000;160:3424-3428.