Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial.
BACKGROUND
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.


METHODS
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 excluded if they were vegetarians, consumed soy products more than once per week, or took medications affecting isoflavone absorption.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Tice
Jeffrey A
JA
Division of General Internal Medicine, Department of Medicine, University of California, San Francisco 94143, USA. jtice@medicine.ucsf.edu
Ettinger
Bruce
B
Ensrud
Kris
K
Wallace
Robert
R
Blackwell
Terri
T
Cummings
Steven R
SR
D019587:Dietary Supplements; D004311:Double-Blind Method; D004968:Estrogens, Non-Steroidal / Q000627:therapeutic use*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D007529:Isoflavones / Q000627:therapeutic use*; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D048789:Phytoestrogens; D010936:Plant Extracts / Q000627:therapeutic use; D028321:Plant Preparations; D017698:Postmenopause / Q000187:drug effects; D011788:Quality of Life; D029921:Trifolium
D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D028321:Plant Preparations