It is widely accepted that in women,
estrogens provide protection against the development of
cardiovascular disease. However, the cardiovascular role of
estrogens in men remains uncertain, despite preliminary evidence that endogenous
estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating
estrogen. We studied the responsiveness of forearm resistance arteries to
vasoconstrictor and
vasodilator agents in 12 men (mean+/-SEM age, 68.7+/-2.6 years) rendered hypogonadal as a result of treatment for
prostatic cancer, before and after 8 weeks of
estrogen supplementation (
estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery
cannula in doses that did not affect blood pressure or heart rate.
Estrogen supplementation was well tolerated, with no adverse effects. After
estrogen treatment, mean
estradiol levels increased from <30 to 308+/-65 pmol/L, and both systolic and diastolic blood pressures were reduced.
HDL cholesterol levels increased significantly, and
vasoconstrictor responses to the
NO synthase inhibitor N(G)-monomethyl-
L-arginine (1, 2, 4 micromol/min) were enhanced.
Vasoconstrictor responses to
angiotensin II (8, 16, 32 ng/min) were markedly attenuated by
estrogen treatment, as were
vasoconstrictor responses to
norepinephrine (25, 50, 100 ng/min).
Estrogen did not alter the
vasodilator responses to
acetylcholine (9.25, 18.5, 37 microgram/min) or to the endothelium-independent agent
sodium nitroprusside (1.6 microgram/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose
estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of
vasoconstrictor responses to
angiotensin II and
norepinephrine. These findings suggest the need to consider a possible clinical role for
estrogenic compounds in cardiovascular risk reduction in some groups of men.