Perimenopausal women in estrogen vasomotor trials: contribution to placebo effect and efficacy outcome.

OBJECTIVE: To determine the difference, if any, in the placebo response when both perimenopausal and postmenopausal women are enrolled, compared with postmenopausal women alone, in a study assessing the efficacy of synthetic conjugated estrogen tablets on moderate-to-severe vasomotor symptoms (MSVS).

METHODS: A total of 120 healthy women (72 active; 48 placebo) complaining of moderate-to-severe vasomotor symptoms were enrolled in a randomized, placebo-controlled, double-blind, multicenter clinical trial. In all, 109 patients completed treatment to week 12. Women were enrolled using minimal inclusion and exclusion criteria, and included perimenopausal women (n = 34; 0 to 6 months since last menses) as well as menopausal women (n = 79; > 12 months since last menses).

RESULTS: Changes in MSVS in the intent-to-treat (ITT) population showed differences between the active and placebo treatments at weeks 4 (p < 0.022), 8 (p < 0.010) and 12 (p < 0.010). At week 12, the mean percentage reduction in MSVS was 81% for the active treatment group and 58% in the placebo treatment group. To examine the placebo response, the ITT population was broken down into groups defined by the time since their last menses. The perimenopausal group (0 to 6 months since last menses) demonstrated a consistently higher placebo response than that of the postmenopausal groups (> 12 months since last menses).

CONCLUSIONS: Perimenopausal women contributed to a higher placebo response, compared with the rate of response previously reported in clinical studies of estrogen replacement in postmenopausal women. Including perimenopausal women in future vasomotor symptom trials will require study populations of sufficient size to maintain the statistical power to demonstrate a difference between therapeutic response to active or placebo treatment.