Context Clinical trials demonstrating increased risk of cardiovascular disease
and breast cancer among women randomized to hormone replacement therapy have
increased interest in other therapies for menopausal symptoms. Dietary supplements
containing isoflavones are widely used as alternatives to hormonal therapies
for hot flashes, but there is a paucity of data supporting their efficacy.
Objective To compare the efficacy and safety of 2 dietary supplements derived
from red clover with placebo in symptomatic menopausal women.
Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial of menopausal women,
aged 45 to 60 years, who were experiencing at least 35 hot flashes per week.
The study was conducted between November 1999 and March 2001 at 3 US medical
centers and included women who were recently postmenopausal (mean [SD], 3.3
[4.5] years since menopause) experiencing 8.1 hot flashes per day. Women were
exluded if they were vegetarians, consumed soy products more than once per
week, or took medications affecting isoflavone absorption.
Intervention After a 2-week placebo run-in, 252 participants were randomly assigned
to Promensil (82 mg of total isoflavones per day), Rimostil (57 mg of total
isoflavones per day), or an identical placebo, and followed-up for 12 weeks.
Main Outcome Measure The primary outcome measure was the change in frequency of hot flashes
measured by participant daily diaries. Secondary outcome measures included
changes in quality of life and adverse events.
Results Of 252 participants, 246 (98%) completed the 12-week protocol. The reductions
in mean daily hot flash count at 12 weeks were similar for the Promensil (5.1),
Rimostil (5.4), and placebo (5.0) groups. In comparison with the placebo group,
participants in the Promensil group (41%; 95% confidence interval [CI], 29%-51%; P = .03), but not in the Rimostil group (34%; 95% CI, 22%-46%; P = .74) reduced hot flashes more rapidly. Quality-of-life
improvements and adverse events were comparable in the 3 groups.
Conclusion Although the study provides some evidence for a biological effect of
Promensil, neither supplement had a clinically important effect on hot flashes
or other symptoms of menopause.