Saturday, January 28, 2012

Do Women Feel Greater Pain Than Men?

Male vs Female A preponderance of research evidence suggests that there are profound differences between men and women in the prevalence, perception, reporting, and treatment of pain. A newly published study adds to that, finding at the least that women seem less shy than men about reporting their level of pain on standard assessment measures. Whether or not women actually feel greater pain and over a broad range of medical conditions, as suggested by this research, may be uncertain. Many aspects of the study, which relied on analyses of an electronic medical records database, are questionable in terms of clinical significance and external validity.

For their study, a team of researchers from Stanford University led by David Ruau, PhD, accessed electronic medical records for more than 72,000 patients who visited the Stanford Hospital and Clinics during a 4-year period; 2007 to 2010 [Ruau et al. 2012]. Culling the records, they narrowed the reports to 11,000 adult patients with 47 common diagnostic categories for which there was an initial pain-intensity score on an 11-point numeric rating scale (NRS: 0=no pain, 10=worst imaginable pain).

Importantly, the researchers only selected NRS scores from first encounters with healthcare personnel, before a diagnosis was made or treatment was started. They further condensed the 47 categories into 14 disease diagnoses for analysis: eg, disorders of the back, osteoarthritis and related disorders, disorders of the cervical region, and so forth. Of the total subjects represented, 56% of patients were women and 51% were white.

Writing in an early, online edition of the Journal of Pain, Ruau and colleagues report that significant differences in pain ratings, with women scoring higher than men on the NRS, occurred in patients with disorders of the musculoskeletal, circulatory, respiratory, and digestive systems, followed by infectious diseases, injury, and poisoning. NRS ratings for women patients were higher than men’s for all 14 disease diagnoses and statistically significant; at least P<0.05. However, absolute mean differences in NRS scores between females and males generally were less than 1 point on the 11-point scale, which the researchers claim was clinically significant, but this might be debatable.

Effect sizes for the differences in NRS scores between females and males — calculated as standardized mean differences, or Cohen’s d scores — ranged from very low to moderate. For 12 of the disease diagnoses there were small effect sizes between 0.21 and 0.49, while the 2 remaining categories had medium effect sizes of 0.50 and 0.51. [Effect sizes and their interpretation were discussed in an UPDATE here.]

The researchers observe that their results appear to confirm previous clinical findings — for example, that women with fibromyalgia or migraine tend to report more pain than their male counterparts — and the study also unearthed previously unreported gender differences in pain intensity for particular diseases; for example, acute sinusitis and cervical disorders (neck pain). However, the study does not shed light on why pain responses were at a higher level in females, such as whether women actually felt more pain or if there were confounding factors in pain measurement. It also should be noted that just because women reported more pain does not mean that they necessarily had less tolerance for pain than men.

COMMENTARY: Ruau et al. claim that this is the largest data-driven study documenting sex differences of disease-associated pain, and that it highlights the utility of using retrospective electronic medical record data to corroborate and expand on the outcomes of smaller clinical studies. However, we have previously cautioned [here] that there are many limitations of data-mining research and that the results may be misleading and biased by many uncontrolled or unknown variables.

For one thing, this study demonstrates how using very large sample sizes allows for relatively small absolute mean differences to achieve statistical significance (small P-values). However, as noted above, the overall mean differences in NRS-scores between women and men of much less than 1 point predominantly represented very small effect sizes that might not be of clinical importance. There also are some statistical anomalies in the study report, for example:

  1. The mean difference in NRS pain-intensity ratings of women over men for back disorders was only 0.50 points, which was highly statistically significant (P=0.00003) but represented the smallest effect size among the 14 diagnoses assessed (Cohen’s d = 0.21). This category also had the largest number of NRS data for women (N=1,146 scores).

  2. In contrast, the HIV disease category had the largest effect size (d = 0.51), according to presented data, and was statistically significant (P=0.007), but the mean difference in women’s over men’s NRS ratings was merely 0.23 points. This category also had the smallest number of NRS scores for women (N=41), which only provides 70% statistical power. Actually, these statistics probably reflect some sort of error in data extraction, calculation, and/or reporting.

Ruau and his team are to be commended for providing adequate data in their published report to facilitate detection of these deficiencies; however, it does not inspire great confidence in data-mining for reaching accurate and definitive conclusions regarding research questions. Rather, data-mining might be of most value in developing hypotheses for further study via better controlled, prospective trials.

Other limitations and caveats regarding this current research study should be noted….

  • No information was available in the database from this single medical center regarding prior treatments for pain or the use of over-the-counter medications at the time initial NRS-scores were recorded.

  • There could be differences in the way women use pain-rating scales, and psychosocial factors could affect how men rate their pain (eg, male stoicism or other cultural influences). Clinical setting also might be important, such as men being more inclined to downplay pain intensity to a female nurse or physician.

  • The researchers also observe that women are more likely than men to suffer from depression and anxiety, which were not assessed in this study and are psychological conditions that can increase susceptibility to pain. However, whether this means that women actually feel more pain or merely report more pain in these circumstances is unclear.

All of this is not to deny that there are stark differences between the sexes when it comes to pain, its perception, and its treatment. In prior UPDATES we discussed a greater prevalence of chronic pain in women [here], disparities of pain treatment in women [here] and how this seems to result in a greater incidence rate of suicide attempts by women [here]. Some research has found that women may have less effective skills for actively coping with pain, which was uniquely measured as “John Henryism” [discussed here].

IOM Report Of particular importance, the Institution of Medicine report on “Relieving Pain in America,” released last summer [and discussed in an UPDATE here], observes that “women consistently report a higher prevalence of chronic pain than men and are at greater risk for many pain conditions.” Women are likely to suffer from and have more pain from certain diseases; for example, fibromyalgia, interstitial cystitis, temporomandibular disorders, chronic fatigue syndrome, and others.

Why are there such differences? The IOM report notes that genetic factors may play a role in nociceptive sensitivity, affecting differences in women’s pain perception, tolerance, and analgesic response. Additionally, experimental studies have demonstrated both lower thresholds and less tolerance for pain in women linked in part to hormone levels. The report states, “Differences in chronic pain rates may occur because of hormonal fluctuation, criterion effects, differences in body size, skin thickness, blood pressure, social expectations, cognitive variation, method of stimulation, and differences in psychological traits such as anxiety and depression.”

The IOM report also describes disturbing disparities in pain care that women endure. Many of the sex-linked conditions are not well understood, and “women with these conditions have faced not only severe pain, but also misdiagnoses, delays in correct diagnosis, improper and unproved treatments, gender bias, stigma, and neglect, dismissal and discrimination from the health care system.”

So, while the research by Ruau and his team, described above, suggests that differences between women and men in pain reporting may encompass many more disease conditions than previously suspected, further data-mining approaches would probably contribute little to resolving the very serious concerns raised by the IOM report. Hopefully, more targeted research and more effective education will better address the special needs of women with pain in the near future.

REFERENCE: Ruau D, Liu LY, Clark JD, et al. Sex Differences in Reported Pain Across 11,000 Patients Captured in Electronic Medical Records. J Pain. 2012(Jan 16); online ahead of print [abstract here].

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