Transition From Estrogen–Progestin to Raloxifene in Postmenopausal Women: Effect on Vasomotor Symptoms

OBJECTIVE:To compare vasomotor symptoms after transition from estrogen–progestin therapy to raloxifene 60 mg/d with and without a placebo washout. METHODS:Postmenopausal women currently taking continuous combined estrogen–progestin therapy (conjugated equine estrogen, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5 mg) daily for 5 or more months were enrolled. Women were randomized to 1 of 4 blinded regimens1) 12 weeks estrogen–progestin; 2) 12 weeks placebo; 3) 4 weeks placebo, then 8 weeks raloxifene; or 4) 12 weeks raloxifene. For the final 36 weeks, all subjects received raloxifene. Vasomotor symptoms were assessed by patient diaries. RESULTS:A total of 266 women (mean age 57.5) were enrolled. Mean hot flush frequency at baseline was approximately 1 per week in the entire population, with 16% of women reporting hot flushes. Mean frequency and severity of hot flushes during the first 12 weeks of the study were statistically greater in the 3 groups transitioned off estrogen–progestin (range of hot flushes per week4 weeks, 11–12; 8 weeks, 18–24; 12 weeks, 13–16), as compared with those continuing estrogen–progestin, with no difference between these 3 groups (P ≥ .1). Approximately 50–70% of these women reported hot flushes, generally rated as mild to moderate by participants, after estrogen–progestin discontinuation. CONCLUSION:A large proportion of women discontinuing estrogen–progestin experience hot flushes. Raloxifene does not appear to increase the frequency or severity of vasomotor symptoms in women discontinuing estrogen–progestin more than that observed with placebo treatment after estrogen–progestin discontinuation. Transition from estrogen–progestin to raloxifene with no washout period therefore may be acceptable. LEVEL OF EVIDENCE:I