Cardiovascular disease (CVD) is more common in postmenopausal than premenopausal women, suggesting vascular protective effects of
estrogen. Vascular
estrogen receptors ERalpha,
ERbeta and a transmembrane
estrogen-
binding protein GPR30 have been described. Also, experimental studies have demonstrated
vasodilator effects of
estrogen on the endothelium, vascular smooth muscle and extracellular matrix. However, randomized clinical trials have not supported vascular benefits of menopausal
hormone therapy (
MHT), possibly due to the subjects' advanced age and age-related changes in
estrogen synthesis and metabolic pathways, the vascular ERs number, distribution and integrity, and the post-ER vascular signaling pathways. Current
MHT includes natural
estrogens such as
conjugated equine estrogen, as well as synthetic and semi-
synthetic estrogens. New estrogenic formulations and
hormone combinations have been developed.
Phytoestrogens is being promoted as an alternative
MHT. Specific ER modulators (
SERMs), and selective agonists for
ERalpha such as PPT,
ERbeta such as
DPN, and GPR30 such as G1 are being evaluated. In order to enhance the vascular effectiveness of
MHT, its type, dose, route of administration and timing may need to be customized depending on the subject's age and pre-existing CVD. Also, the potential interaction of
estrogen with
progesterone and
testosterone on vascular function may need to be considered in order to maximize the vascular benefits of
MHT on senescent blood vessels and postmenopausal CVD.