Effects of Drugs, Phytoestrogens, Nutrients and Probiotics on Endothelial Dysfunction in the Estrogen-Deficient State

Background: Endothelial dysfunction is commonly present in estrogen-deficient states, e.g., after menopause. In the search for alternatives to hormone replacement therapy (HRT), treatments based on phytoestrogens or in non-hormonal mechanisms have been under evaluation. Objective: Here we aim to present an overview of innovative potential treatments for endothelial dysfunction in estrogen-deficient states, introducing our own preliminary data about the probiotic kefir. Methods: We conducted a review based on a PubMed database search for keywords of interest (Menopause, Ovariectomy, Vascular dysfunction, Hot flashes, Metformin, Statins, Phytoestrogens, Omega-3, Vitamin D, Probiotics). Results: Vascular parameters were found to be improved by both metformin and statins through pleiotropic effects, being related to a decrease in oxidative stress and restoration of the nitric oxide pathway. Phytoestrogens such as genistein and resveratrol have also been shown to improve vascular dysfunction, which seems to involve their estrogenic-like actions. Omega-3, vitamin D and its analogues, as well as probiotics, have shown similar vascular beneficial effects in both postmenopausal women and an animal model of ovariectomy (OVX), which could be related to antioxidant and/or anti-inflammatory effects. Moreover, our preliminary data on the probiotic kefir treatment in OVX rats suggested a vascular antioxidant effect. In particular, some evidence points to statins and vitamin D having anti-atherogenic effects. Conclusion: Pleiotropic effects of common medications and natural compounds could have therapeutic potential for endothelial dysfunction in estrogen-deficient states. They could, therefore, work as future complementary or alternative treatments to HRT.