Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial

10,739 post-menopausal women (50-79 years) who have had a hysterectomy and no prior history of breast cancer were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or an equivalent placebo for a mean period of 7.1 years to determine the effectiveness of estrogen alone on joint symptoms. Results at 1 year, including data from all participants, indicated that estrogen significantly improved joint pain; however, the frequency and severity of joint swelling was significantly higher in this group. These findings were replicated at 3 years and 6 years (a lack of significance in joint pain at 6 years was an exception) in a random 9.9% subset of the population. However, when only adherent patients were considered, it was found that estrogen significantly decreased joint pain, but did not significantly affect joint swelling at the 3-year follow-up.