Menopause is accompanied by a dramatic rise in the prevalence of hypertension in women, suggesting a protective role of endogenous estradiol on blood pressure (BP). Both animal experimental and human clinical investigations suggest that estrogen engages several mechanisms that protect against hypertension, such as activation of the vasodilator pathway mediated by nitric oxide and prostacyclin and inhibition of the vasoconstrictor pathway mediated by the sympathetic nervous system and angiotensin. However, emerging evidence from recent clinical trials indicates a small increase, rather than decrease, in systolic BP with oral estrogen administration in postmenopausal women, without any detectable effect on diastolic BP. Mechanisms underlying this selective rise in systolic BP in postmenopausal women and oral contraceptive-induced hypertension in premenopausal women remain unknown, but the rise may be related to supraphysiologic concentration of estrogen in the liver. To date, transdermal delivery of estrogen, which avoids the first-pass hepatic metabolism of estradiol, appears to have a small BP-lowering effect in postmenopausal women and may be a safer alternative in hypertensive women.
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Ashraf, M.S., Vongpatanasin, W. Estrogen and hypertension. Current Science Inc 8, 368–376 (2006). https://doi.org/10.1007/s11906-006-0080-1