Long-term treatment of ovariectomized mice with estradiol or phytoestrogens as a new model to study the role of estrogenic substances in the heart.

Epidemiological data reveal that the overall risk for heart disease is lower for premenopausal women compared to age-matched men. However, the beneficial effect for the female sex is lost upon menopause. Thus, it has been suggested that estrogens convey the protective effect for the female sex against heart disease. Numerous natural plant products, i.e., phytoestrogens (PE), interfere with or alter the development or function of the endocrine system. Although PEs have been studied intensively with regard to the effects on the reproductive organs, such as the uterus or mammary gland, surprisingly little data are available about the effects of PEs on the heart. Here, we conducted a long-term study with ovariectomized mice to examine putative estrogenic effects of the PEs genistein (GEN), resveratrol (RES), and equol (EQ), using estradiol (E2) as a reference compound on heart size, morphology, and cardiac gene expression. We report for the first time significant changes in these parameters by GEN and E2. Changes in the size of cardiomyocytes were observed by GEN and E2. In line with these observations, cardiac expression of insulin-like growth factor 1 (Igf1) was significantly induced by both GEN and E2. Thus, we speculate that endocrine active compounds, like the isoflavone GEN, which is used as a food additive or as a drug for the treatment of menopausal symptoms, may directly affect heart function.