Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study
Introduction
Classical hormone replacement therapy (HRT) may be contraindicated or not advisable in some postmenopausal women. The need to alleviate menopausal symptoms in these women is widely recognized and alternative treatments to HRT are desirable. Soy isoflavones have been investigated as a natural alternative to HRT, but results of clinical trials are controversial [1], [2], [3], [4], [5], [6], [7], [8], [9]. The neuro-hormone melatonin is another potentially useful substance for contrasting some menopausal symptoms, such as sleep disturbances, depression and attenuated cognitive capacities [10], [11], [12], [13], [14].
The association of soy isoflavones and melatonin has never been tested before. We argued that joint administration of both these substances could be effective in alleviating menopausal symptoms of patients with breast cancer, women at increased risk of the disease or those for whom, for any reason, classic HRT cannot be recommended. To verify the feasibility of a randomized trial, we tested the combination of isoflavones and melatonin in a pilot study on 20 women and observed a considerable improvement in psychological, somatic and vasomotor symptoms. Subsequently, we planned the present randomized trial to confirm the efficacy of the association, jointly with that of soy isoflavones and melatonin when singly administered.
Section snippets
Material and methods
The study was a before-and-after, double-blind, randomized, multicenter trial performed according to a 2×2 factorial design and carried out in three Italian Centers: Bari (III Clinic of Obstetrics and Gynecology of the University of Bari), Forlı̀ (Departments of Obstetrics and Gynecology and Medical Oncology, Pierantoni Hospital), and Milan (National Cancer Institute, INT), which was the reference center.
The institutional review boards and ethic committees of the involved centers approved the
Results
Fig. 1 shows the trial profile. Three hundred and eighty-eight consecutive postmenopausal women were screened between April and October 2000; 126 women were not randomized of whom 98 were not eligible and 28 refused to sign the informed consent. The remaining 262 women were randomized in the participating Centers: 60 in Bari, 80 in Forlı̀, and 122 in Milan. Thirty of the 262 (11.5%) randomized subjects dropped out of the study. In particular, melatonin was not supplied to one woman who decided
Discussion
In the last few years, soy isoflavones have been regarded as a possible alternative to HRT for the treatment of menopausal symptoms, without the undesirable side effects of steroid hormones. Several papers have reported the beneficial properties of soy-enriched foods or soy extract on hot flushes and night sweats of postmenopausal women [2], [3], [4], [5], [6], [7], but the clear-cut effectiveness of soy isoflavones is still controversial [1], [8], [9]. A decrease in symptoms of about 30% in
Acknowledgements
The study was supported by a grant from the Associazione Italiana Ricerca Cancro (AIRC). The Italian League Against Cancer (Milan Section) also contributed by favoring recruitment of subjects. At the National Cancer Institute (INT) of Milan, the study was performed in the ambit of the Me.Te.C.O. Group (Medicina delle Terapie non Convenzionali in Oncologia). The Authors are grateful to Dr Edoardo Berselli, Dr Paola Ballerini, Dr Lucio Ascani, Dr Mara Cambiè and Dr Jose Minut for their
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