Postmenopausal women tend to have higher blood pressure than premenopausal women; suggesting a protective role of the hormone estrogen on blood pressure regulation. This protective effect is in part due to the inhibition or regulatory effect of estrogen on the sympathetic nervous system. Heightened sympathetic nervous system stimulation constricts blood vessels by stimulating A-1 receptors located on the surface of vascular smooth muscles.
The route of estrogen administration is a major determinant of the effect of estrogen replacement therapy (ERT) on sympathetic discharge. The study noted below found that sympathetic nervous system discharge (stimulation) decreased significantly from baseline during transdermal ERT but not during oral ERT or placebo.
The decrease in sympathetic nerve discharge achieved only with transdermal administration is not thought to be a dose related because serum estradiol concentrations achieved with oral ERT were comparable to those with transdermal ERT. However, with oral administration the liver is exposed to a supraphysiological concentration of estrogen resulting in decreased hepatic synthesis of insulin-like growth factor-1 (IGF-1).
Administration of IGF-1 has been shown to decrease sympathetic nerve activity and blood pressure in rats. Deficiency of this growth factor is associated with sympathetic overactivity and elevated blood pressure in humans.
Of additional interest, reduction in IGF-1 induced by oral estrogen preparations is accompanied by reduced lean body mass and increased fat mass (adiposity), which is a powerful predictor of elevated sympathetic discharge and blood pressure.
Therefore, it seems plausible that during oral estrogen replacement, sympathetic overactivity related to IGF-1 deficiency and/or increased (fatty tissue) opposes the direct effect of estrogen to decrease sympathetic discharge.
Avoidance of first-pass hepatic (liver) metabolism with transdermal estrogen replacement allows the estrogen-induced sympathetic inhibition to be unopposed.
As such, the route of administration is an important consideration in optimizing the beneficial effects of estrogen replacement on blood presure and cardiovascular health.
Estrogen is also thought to act on the central nervous system by decreasing sympathetic nerve discharge, the neural stimulus for norepinephrine release from peripheral sympathetic nerve terminals. Estrogen replacement has been shown to both activate vasodilator mechanisms mediated by nitric oxide or prostacyclin and inhibit vasoconstrictor response to norepinephrine.
Sources:
Transdermal Estrogen Replacement Therapy Decreases Sympathetic Activity in Postmenopausal Women
Wanpen Vongpatanasin, MD; Meryem Tuncel, MD
Circulation. 2001;103:2903.
Estrogen Replacement, Vascular distensibility, and Blood Pressures in Postmenopausal women.
DeMeersman R, Zion AS, Giardina EGV, et al.
Am J Physiol. 1998;274:H1539–H1544.
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