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 regimens: 1) 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 week: 4 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> or =.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