Abstract

Isoflavones, lignans, and coumestans are three classes of phytoestrogens– plant constituents with a chemical structure similar to 17β-estradiol. Phytoestrogens exert weak estrogenic and anti-estrogenic effects that vary according to the target tissue, and are mediated through binding to estrogen receptors α (ERα) and β (ERβ). Phytoestrogens, therefore, fall into the category of natural selective estrogen receptor modulators (SERMs). Although their potency is a small fraction of 17β-estradiol, in sufficiently large doses the biologic effects may be significant. A single plant may contain more than one type of phytoestrogen, any one of which may enhance or diminish the tissue-specific effects of another. Most phytoestrogen products that have been studied in randomized controlled trials (RCTs) are composed of a mixture of isoflavones and perhaps other ingredients. Isoflavones such as genistein, daidzein, and glycitein are derived from plant sources that include soy and red clover. In a systematic review of 11 RCTs investigating the skeletal effects of phytoestrogens, only 4 studies showed clear skeletal benefit, with several others demonstrating attenuation of bone mineral density (BMD) loss compared with placebo.¹ Only 1 of these trials used a single purified isoflavone, genistein 54 mg. In this study,² an increase in BMD similar to that of estrogen was observed. Other studies with genistein have not shown consistent skeletal benefit. It is uncertain whether the variability of findings in the investigations of genistein is due to differences in study design, dosage, purity of the formulation, variation in calcium and vitamin D intake, or other factors. Ipraflavone, a synthetic isoflavone derivative, did not prevent bone loss or reduce bone turnover in a 4-year RCT of 474 postmenopausal women, and was found to induce lymphocytosis in a significant number of them.³