AIM: Affective and behavioural disorders possibly concomitant to the vasomotor menopausal symptoms worsen quality of life. A rational formulation containing soy isoflavones (60 mg), lactobacilli (500 millions spores), calcium (141 mg) and vitamin D3 (5 microg) was added of Magnolia bark extract (60 mg) and magnesium (50 mg) (Estromineral serena, ES). The Magnolia extract active principles interact with GABA system and exhibit a sedative central action. Magnesium intervenes in enzymatic reactions of the energetic metabolism and protects the bone integrity. Aim of this controlled study was to compare the clinical activity and safety of ES versus calcium+vitamin D3 (Ca+D) in menopause. METHODS: A controlled, randomised, multicentre study was carried out in symptomatic menopausal women with sleep or mood alterations. Women received 1 tablet/day of ES or Ca+D for 24 weeks. Symptoms during the treatment and final judgements on efficacy and acceptability were evaluated. RESULTS: Eighty-nine women (44 ES and 45 Ca+D, mean age 53.8 years, in menopause since 56.6 months) participated to the study. Flushing, nocturnal sweating, palpitations, insomnia, asthenia, anxiety, mood depression, irritability, vaginal dryness, dyspareunia, and libido loss, significantly decreased in severity and frequency during ES versus Ca+D treatment even since the fourth week. Woman wellbeing (good/very good 66.7% vs 20%) judgement on efficacy (72.7% vs 17.1%) and acceptability (93.9% vs 31.4%) were significantly better for ES. CONCLUSIONS: The controlled study showed the efficacy of Magnolia extract and magnesium on psycho-affective and sleep disturbances in menopause, in addition to the effects of isoflavones on vasomotor symptoms. A global natural approach to menopause with ES evidenced its therapeutic usefulness and safety.