OBJECTIVES: To synthesize findings from studies reporting sex-related differences in terms of clinical, economic, and/or humanistic outcomes in patients who used opioids in pain clinical trials.

METHODS: A literature review was conducted in PubMed/MEDLINE and Embase to identify all evidence related to the study objectives. The scope was defined using the Population, Intervention Comparators, Outcomes, and Study design (PICOS) criteria, based on which the citations were reviewed for inclusion and exclusion criteria. Studies were included if they were of clinical trial design, reported outcomes by male and female groups, and published in English. Information from selected studies was extracted into a pre-defined template. Synthesis of findings included qualitative summaries and quantitative descriptive statistics.

RESULTS: Of the 72 studies reviewed, a total of 6 met the criteria for inclusion. The therapeutic areas included general dentistry, endodontics, temporomandibular disorder with myofascial pain, lumbar decompressive surgery, thoracotomy, and transabdominal preperitoneal hernia repair. Opioids used in included studies were nalbuphine, morphine, oxycodone, and pentazocine. Most studies reported a sex-related difference (83%; n=5) in efficacy, analgesic response, pain experience, or utilization. Some studies reported better analgesic response among women, while another reported women feeling greater pain and using more opioids than men.

CONCLUSIONS: This literature review demonstrates that there is a lack of studies reporting sex-related differences in patients taking opioids in pain clinical trials, and the consensus within these limited studies is elusive. Published studies suggest that there is a difference between men and women taking opioids for their pain. Pain and particularly use of opioids for pain management are leading public health issues and pose significant burden to the individual and society. It is important to understand sex-related differences in use of opioids for pain and the extent to which sex must be a consideration for treatment in clinical settings.