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Estrogen receptor &bgr;-selective phytoestrogenic formulation prevents physical and neurological changes in a preclinical model of human menopause

Objective:As an alternative to estrogen therapy, the efficacy of an estrogen receptor &bgr;-selective phytoestrogenic (phyto-&bgr;-SERM) formulation to regulate climacteric symptoms and decline in brain responses associated with ovarian hormone loss in menopause was assessed. Methods:A phyto-&bgr;-SERM formulation-containing diet was compared with a commercial soy extract diet and a phytoestrogen-free base/control diet in an ovariectomized (OVX) mouse model of human menopause. Two treatment studies were conducted: (1) a 2-month study assessed the effects of experimental diets on tail skin temperature as a model of menopausal hot flashes, and (2) a 9-month study assessed the long-term impact of the diets on overall health, hair thinning/loss, spatial working memory, and associated protein expression in the hippocampus. Results:The phyto-&bgr;-SERM diet prevented OVX-induced menopause-like changes including the rise in skin temperature, hair thinning/loss, deficit in spatial memory function, and reversed OVX-induced decline in the expression of hippocampal proteins involved in neural plasticity and &bgr;-amyloid degradation/clearance. The soy extract diet had no effect or exacerbated OVX-induced changes. Conclusions:Overall, the phyto-&bgr;-SERM diet induced physical and neurological responses comparable with ovary-intact mice, suggesting the therapeutic potential of the phyto-&bgr;-SERM formulation for the prevention/alleviation of climacteric symptoms and decline in brain responses induced by ovarian hormone loss, which provides the basis for further work in postmenopausal women.