Although rheumatoid arthritis (RA) is more predominant in women, the reasons for this are unclear. Many studies have examined the effects of estrogen on the risk and severity of RA, but the results are conflicting and controversial. A new study using data from the Women’s Health Initiative (WHI) clinical trials on hormone replacement therapy found that there were no significant differences in the risk of developing RA or the severity of RA between postmenopausal women who were on hormone replacement therapy and those who took placebos.

The WHI randomized controlled trials included over 27,000 postmenopausal women between the ages of 50 and 79 who took estrogen and progestin, estrogen alone or a placebo. Led by Brian Walitt of Washington Hospital Center in Washington, DC, the current study identified women who had RA based on whether they reported having it and were taking prescription medications to treat it. Self-reported information about whether women had RA was collected annually, and they were assessed for disease severity at the beginning of the study and after one year. Measures of self-reported joint pain/stiffness were also collected at that time and participants were asked to rate the severity of their symptoms.

The study is the only placebo-controlled trial to evaluate the effect of hormone replacement therapy on developing RA and the sixth study to evaluate the effects of hormone therapy on how women perceive disease severity. The results showed that there were 105 new cases and 63 existing cases of RA. There were no statistically significant differences on either new RA cases over an average of five to six years or on the severity of RA symptoms after one year. While earlier studies had suggested that hormones had a protective effect against developing RA, they were observational. The current study found no significant protective benefit from hormones in preventing RA.

Although the prevalence of RA in the study was about half of what is found in the general population, this may be due to the tendency of clinical trials to recruit healthier patients and the exclusion of participants taking prednisone, which is used to treat arthritis. Although the WHI methodology has many advantages over prior studies, the sample size for RA was much less than what would be required to observe the effect of hormone replacement therapy on developing RA. However, it is unlikely that larger studies will be carried out, due to the health risks of hormone replacement therapy. Also, the study relied on self-reported information, and even though it tried to minimize overreporting by including only women taking medications for RA, this approach is not as effective as performing chart reviews or physical exams.

The authors conclude that “the design of the WHI provided a unique opportunity to examine the effects of PHT [postmenopausal hormone therapy] on RA. Despite the participation of 27,347 women, there was no statistically significant evidence of a difference in the hazard of RA incidence or a difference in RA symptom severity between the PHT and placebo groups.”

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Article: “Effects of Postmenopausal Hormone Therapy on Rheumatoid Arthritis: The Women’s Health Initiative Randomized Controlled Trials,” Brian Walitt, Mary Pettinger, Arthur Weinstein, James Katz, James Torner, Mary Chester Wasko, Barbara V. Howard, Arthritis Care & Research, March 2008.

Contact: Amy Molnar
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Wiley-Blackwell