Red Clover Same as Placebo for Hot Flashes?

SAN FRANCISCO--In a study published in the July 9 edition of The Journal of the American Medical Association (290:207-14, 2003) (www.jama.com), researchers found red clover may not be any better than placebo at reducing hot flashes in menopausal women. The study's authors--including researchers from the University of California, San Francisco, and the Kaiser Permanente Medical Care Program, Oakland, Calif.--compared the efficacy and safety of two red clover supplements against placebo in symptomatic menopausal women. In the double blind trial, 252 women aged 45 to 60 years who were experiencing at least 35 hot flashes per week were first administered a placebo for two weeks, followed by a random assignation to Promensil (82 mg/d of total isoflavones, from Stamford, Conn.-based Novogen), Rimostil (57 mg/d of total isoflavones, also Novogen's) or a placebo for 12 weeks. The study was conducted between three U.S. medical centers and included women who were recently postmenopausal and experiencing an average of 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.

Of the study's participants, 246 completed the 12-week protocol. The reductions in mean daily hot flash count at study's end 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 but not the Rimostil group reported an earlier reduction in hot flashes. Also, quality-of-life improvements and adverse events were comparable in the three groups.

"Although the study provides some evidence for a biological effect of Promensil," the study's authors concluded, "neither supplement had a clinically important effect on hot flashes or other symptoms of menopause."

Research out of The Netherlands last year released results to the contrary (Maturitas, 42, 3:187-93, 2002) (www.sciencedirect.com). They conducted a randomized, double blind, placebo-controlled trial using 30 menopausal women experiencing more than five flashes per day. All received single blind placebo tablets for four weeks before being randomized to either placebo or 80 mg/d of isoflavones for another 12 weeks. During the first four weeks of placebo, the frequency of hot flashes decreased by 16 percent. During the double blind phase of the trial, those on the supplement saw a further decrease of 44 percent, whereas no further reduction occurred within the placebo group.

Although questions remain as to the efficacy of red clover for hot flashes, Novogen (www.novogen.com) reported July 8 that a prospective, double blind, placebo-controlled trial using Promensil indicated the supplement may assuage vaginal dryness related to menopause. In a study out of King's College Hospital, London, Malcolm Whitehead, M.D., indicated 80 mg/d of Promensil significantly improved the vaginal maturation index, a measure of normal functioning of the epithelium lining the vagina, compared to placebo.

"The preliminary results of this study are encouraging news for women who want to manage menopause naturally," Whitehead said. "Unlike steroidal oestrogens, the natural isoflavone phytoestrogens [give] a welcome estrogenic effect in relieving vaginal dryness while showing no adverse thickening effect on the endometrium."