S-equol, a Natural Metabolite of Soy Daidzein, for the Treatment of Menopausal Symptoms and Osteoporosis in Postmenopausal Women

Abstract

Key PointsS-equol is a potent, nonhormonal, nonsteroidal estrogen receptor • b agonist. S-equol is produced by the gut biotransformation of soy daidzein, an iso fl avone present in soy.• Individuals, particularly Asians, who are equol producers have fewer menopausal symptoms, • osteoporosis, diseases of the prostate, and cardiovascular diseases. A soy-derived dietary supplement containing 10 mg S-equol has been shown to reduce menopausal • symptoms and improve bone mineral density in postmenopausal women. A clinical study in men and women with doses of S-equol up to 320 mg/day demonstrated that the • compound has an excellent safety and pharmacokinetic pro fi le. IntroductionIn 2002 the results of the Women's Health Initiative (WHI) were published [ 1 ] . Surprisingly, postmenopausal women on hormone therapy (HT), Premarin ® (0.625 mg/day) plus medroxy-progesterone (2.5 mg/day), had signi fi cantly increased cardiovascular diseases, invasive breast cancer, stroke, and venous thromboembolism compared to the placebo group. The women on HT did have fewer hip fractures and there was a reduced incidence of colorectal cancer. Nonetheless, the fi ndings of WHI have had a major impact on women's health. Women do not want HT as re fl ected in the reduced prescriptions for products containing estrogens, and as a result, the incidence of hip fractures has increased by 55 % since 2002 [ 2 ] . As an alternative to HT, many women have resorted to nonhormonal therapies for the treatment of menopausal symptoms, including antidepressants, herbal extracts, soy extracts, and soy iso fl avones, also referred to as phytoestrogens [3][4][5][6] . It is well known that Japanese people consume large amounts of soy products and have fewer chronic diseases compared to Caucasians. Adlercreutz et al. [ 7 ] proposed that Japanese women have fewer menopausal symptoms based on their soy intake. The fi rst report on the consumption of soy products and the incidence of hot fl ashes was by Nagata et al., 2001 [ 8 ] . In this study, a questionnaire was used to measure an individual's intake of soy foods. The tertiles for soy intake were low (44.5 g/day), middle (75.2 g/day), and high (115.9 g/day); the intake of total iso fl avones was 20.5, 32.8, and 50.8 mg/day, respectively. A decrease in the hazard ratio for hot fl ashes was directly related to soy and total iso fl avone intake ( p < 0.005).Since these early fi ndings, many controlled clinical studies have been carried out with soy and soy iso fl avones to alleviate vasomotor symptoms (VMS) in menopausal women (for review, see [9][10][11] ). The results of meta-analysis are for the most part inconclusive as to the clinical bene fi t of soy and soy extracts. For many studies, the sample size was too small and the duration of the study was too short (<4-6 weeks) to show a statistical difference between the treated and placebo groups. If the frequency of hot fl ashes was the primary end point, there was little or no response to soy iso fl avone extracts in women who experienced four or fewer hot...

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“…As previously reported, 160 mg equol BID results in a −10 μM plasma equol concentration. 46 In rats, the equol concentration resulting from a 6 μM oral dose represents the daily intake of a 200 mg racemic equol/kg diet, which is a physiologically relevant level for dietary racemic equol. 47 …”