It has been well documented that the frequency of vasomotor menopausal symptoms, such as hot flashes and night sweats, of Japanese menopausal women is less than that of Western women. High intake of soy isoflavones in the traditional Japanese diet has been postulated as the possible explanation of the difference. Epidemiological studies have reported that the content of equol, which is a biologically active metabolite of the isoflavone, daidzein, is lower in the women who complain of severe vasomotor symptoms. To investigate the involvement of equol in the manifestation of menopausal symptoms, especially vasomotor symptoms, and the possible therapeutic role of a supplement containing equol (natural S-equol developed by Otsuka Pharmaceutical) on the menopausal symptoms of Japanese women, 3 randomized clinical trials were conducted. The studies indicated that a daily dose of 10 mg of natural S-equol improved menopausal symptoms. In the confirmation study, menopausal women who were equol nonproducers who consumed 10 mg/d of natural S-equol for 12 wk had significantly reduced severity and frequency of hot flashes as well as a significant reduction in the severity of neck or shoulder stiffness. The equol-ingesting group also showed trends of improvement in sweating and irritability and a significant improvement in the somatic category symptoms. Thus, it is concluded that the supplement containing natural S-equol, a novel soybean-derived functional component, has a promising role as an alternative remedy in the management of menopausal symptoms.