Vascular Effects of Phytoestrogens and Alternative Menopausal Hormone Therapy in Cardiovascular Disease

Abstract

Phytoestrogens are estrogenic compounds of plant origin classified into different groups including isoflavones, lignans, coumestans and stilbenes. Isoflavones such as genistein and daidzein are the most studied and most potent phytoestrogens, and are found mainly in soy based foods. The effects of phytoestrogens are partly mediated via estrogen receptors (ERs): ERα, ERβ and possibly GPER. The interaction of phytoestrogens with ERs is thought to induce both genomic and non-genomic effects in many tissues including the vasculature. Some phytoestrogens such as genistein have additional non-ER-mediated effects involving signaling pathways such as tyrosine kinase. Experimental studies have shown beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle, and extracellular matrix. Phytoestrogens may also affect other pathophysiologic vascular processes such as lipid profile, angiogenesis, inflammation, tissue damage by reactive oxygen species, and these effects could delay the progression of atherosclerosis. As recent clinical trials showed no vascular benefits or even increased risk of cardiovascular disease (CVD) and CV events with conventional menopausal hormone therapy (MHT), phytoestrogens are being considered as alternatives to pharmacologic MHT. Epidemiological studies in the Far East population suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal CVD and thromboembolic events. Also, the WHO-CARDIAC study supported that consumption of high soybean diet is associated with lower mortalities from coronary artery disease. However, as with estrogen, there has been some discrepancy between the experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials. This is likely because the phytoestrogens clinical trials have been limited in many aspects including the number of participants enrolled, the clinical end points investigated, and the lack of long-term follow-up. Further investigation of the cellular mechanisms underlying the vascular effects of phytoestrogens and careful evaluation of the epidemiological evidence and clinical trials of their potential vascular benefits would put forward the use of phytoestrogens as an alternative MHT for the relief of menopausal symptoms and amelioration of postmenopausal CVD.

Free radical scavenging actions of threeTrifoliumspecies in the protection of blood plasma antioxidant capacityin vitro

“…Due to the disputable effects of the conventional hormone replacement therapy (Rossouw et al, 2002), plant-derived supplements are of increasing interest as useful in alleviation of menopausal symptoms. Phytoestrogens may also delay the progression of atherosclerosis by reduction of pathological changes in the cardiovascular system, such as alterations in the lipid profile, inflammatory processes, and oxidative stress (Gencel et al, 2011). Isoflavonoid phytoestrogens significantly contribute to medicinal properties of Trifolium plants, however, it should be emphasized that in addition to isoflavones, clovers synthesize a wide range of other bioactive compounds.…”

Genistein enhances TRAIL-induced cancer cell death via inactivation of autophagic flux

“…of cancer and neurodegenerative diseases (37). It has been reported that genistein enhances the induction of apoptosis by chemotherapeutic agents in several types of cancer cells (38,39).…”

Fitoösztrogének a menopauza terápiájában

“…Kémiai szerkezetük alapján négy csoportba oszthatjuk őket (1. táblázat): izoflavonoidok, lignánok, kumesztá-nok, sztilbének [16].…”