Discussion and conclusion
Because the mental and physical conditions of women in menopause are complicated, health care in this life stage has to be done holistically. By the systemic evaluation of these conditions, the personal management for each woman should be selected. Lifestyle improvements, including diet habits, exercise, and relaxation, should be conducted before medical treatment.
Among the health problems in menopause, menopausal symptoms, especially vasomotor symptoms like hot flashes and sweating, disturb daily activities and quality of life seriously in the great portion of women in Western societies and also for a certain number of Japanese women. In the majority of such women, the symptoms cannot be controlled by nonmedical management and need to be treated by some medical interventions.
Although the mechanism underlying vasomotor symptom has not been fully clarified, the results of various basic and clinical studies have indicated that dramatic changes in the hormonal environment, especially the sharp decline of estrogen, during menopause play key roles. Hormone replacement therapy (HRT) has been widely adapted as a potent evidence-based medicine for menopausal symptoms. The report of a large-scaled study in the United States, the Women's Health Initiative published in 2002 (19), indicated increasing risks associated with a kind of HRT regimen after long-term use. It is, however, still convincing that the first choice of medical treatment for severe vasomotor symptom is tailor-made HRT under appropriate diagnostic and follow-up medical care.
At the same time, the development of medical treatments for the women suffering from health problems caused by estrogen deficiency including severe menopausal symptoms who cannot use HRT has been a great issue in clinical practice. It is also expected in menopausal health care that a medical intervention will improve the quality of life in the majority of menopausal Japanese menopausal women who complain of moderate- to mild-grade menopausal symptoms that are not severe enough to be treated by HRT.
In the clinical trial in which a subjective score is used as the end point of evaluation, how to obtain solid data showing the efficacy of a product is particularly critical. The severity of menopausal symptoms is one of the typical cases, which is easily influenced by nonspecific factors inducing placebo effects.
The series of studies described in this paper were attempts to investigate whether natural S-equol supplementation can be a new alternative. To confirm the efficacy of the compound strictly in clinical trials, the confirmation study was designed to include 3 periods. The screening period aimed to exclude the placebo effects of the intervention. At the same time, equol nonproducers were selected by the results of 3 separate measurements of urinary equol contents. Furthermore, special attention was paid to minimizing the bias caused by evaluation methods of interviewers who assessed changes of symptoms. In the follow-up period, it was predicted that a rebound response should appear if the ingested natural S-equol supplement had actual biological effects suppressing menopausal symptoms. As the result, such rebound patterns were observed in the responses of hot flashes and neck or shoulder stiffness. It is indicative that these procedures for standardizing the enrolled population and arrangements adapted in the study made certain contributions to clarifying the importance of equol's effects on certain menopausal symptoms.
This study confirmed the positive effects of equol on menopausal symptoms and was the first report, to our knowledge, based on a prospective randomized, double-blind, placebo-controlled study. Thus, natural S-equol, a novel soybean-derived functional component, has a promising role in the management of menopausal symptoms as an alternative remedy.