Arterial Reactivity Is Enhanced in Genetic Males Taking High Dose Estrogens

McCrohon, Jane; Walters, William A. W.; Robinson, JH; McCredie, Robyn J.; Turner, Leo; Adams, Mark; Handelsman, David J.; Celermajer, David S.

doi:10.1016/s0735-1097(97)00063-6

Cited by 95 publications

(53 citation statements)

References 30 publications

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“…These observations are similar to those of others 24 who failed to observe any changes in epicardial coronary flow in postmenopausal women with CAD after long-term administration of estrogen, but differ from those of others who reported favorable effects of long-term administration of estrogen on vascular reactivity of atherosclerotic coronary arteries in both humans 19,20,25 and subhuman primates. 26,27 These differences could be due to the different types of estrogens used in the different studies or the different methods used to elicit and measure vasomotor changes (ie, acetylcholine versus CPT).…”

Section: Campisi Et Al Estrogen Replacement and Myocardial Blood Flowsupporting

confidence: 89%

Noninvasive Assessment of Coronary Microcirculatory Function in Postmenopausal Women and Effects of Short-Term and Long-Term Estrogen Administration

et al. 2002

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Background-Estrogen improves endothelial function in the coronary conduit vessels of animals; however, its effects on the coronary microcirculation have not been studied completely in humans. Methods and Results-We measured myocardial blood flow (MBF) with a PET scan at rest, during cold pressor testing (CPT), and during dipyridamole hyperemia in 54 postmenopausal women without coronary artery disease. Of these, 23 were not and 31 women were taking long-term hormone replacement therapy (HRT) using estrogen either alone or with a progestogen. Each group was subdivided by coronary risk factors (RFs). Twelve young healthy women served as controls. In women not taking HRT, MBF measurements were repeated after 25 mg of conjugated equine estrogens IV. Neither short estrogen nor long-term HRT affected MBF at rest in women with and without RFs. Dipyridamole MBF was attenuated only in the women with RF who were not taking HRT. Short-term estrogen and long-term HRT did not reverse the abnormal response. MBF responses to CPT were abnormal in women not taking HRT, regardless of RFs (20Ϯ15% versus 32Ϯ21%) and remained unchanged after short-term estrogen administration. Long-term HRT normalized the response to CPT only in women without RF (53Ϯ22% versus 59Ϯ36% in the young women; NS). MBFs were similar for women on estrogen alone or estrogen plus a progestogen, regardless of presence or absence of RFs. Conclusion-Menopause

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Section: Campisi Et Al Estrogen Replacement and Myocardial Blood Flowsupporting

confidence: 89%

Noninvasive Assessment of Coronary Microcirculatory Function in Postmenopausal Women and Effects of Short-Term and Long-Term Estrogen Administration

et al. 2002

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“…21 Furthermore, studies in male-to-female transsexuals have shown that both flow-mediated and nitroglycerininduced vasodilations in the brachial artery are enhanced compared with control men, suggesting that high-dose estrogen treatment enhances vascular reactivity in genetic males. 22,23 In healthy young men, single doses of sublingual estradiol or intravenous conjugated equine estrogens, at plasma concentrations within the physiological range for premenopausal women, have been shown to induce rapid onset, rapid offset, nongenomic effects on the endotheliummediated vasodilator response to acetylcholine, with no effect on the endothelium-independent action of sodium nitroprusside. 24 Not all studies have yielded positive results: for example, a study of short-term estrogen supplementation failed to show an effect on acetylcholine-induced coronary artery vasoconstriction in men, 25 and estrogens reportedly did not augment flow-mediated dilation in the brachial artery or influence serum levels of metabolites of NO in older male subjects.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Estrogen Supplementation Improves Vascular Function in Hypogonadal Men

et al. 2001

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Abstract-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 (meanϮSEM age, 68.7Ϯ2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; nϭ7) or placebo (nϭ5). 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 Ͻ30 to 308Ϯ65 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 mol/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 g/min) or to the endothelium-independent agent sodium nitroprusside (1.6 g/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. Many observational studies have suggested that estrogen treatment of postmenopausal women significantly reduces cardiovascular risk 1 ; however, the recently concluded Heart Estrogen/Progestin Replacement Study (HERS) found no significant evidence of a clinical benefit of hormonal therapy in women with established coronary artery disease. 2 In men, estrogens are produced in significant quantities by local tissue aromatization of androgenic precursors from the testes and adrenal glands. 3 There has been relatively limited study of the biological role of these hormones or their clinical implications in men.In human endothelial cells, which reportedly have a high density of estrogen receptors (20 to 80 000 per cell), the intensity of immunostaining for estrogen receptors is similar in male and female donor cells, and neither electrop...

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“…Despite the low circulating levels of estrogen found in men, a physiologic role for ER ␣ in males is supported by both animal and human studies. For example, estrogen administration improves vascular reactivity in some men (34)(35)(36), inhibits the response to carotid injury in castrated male rats (37), and reduces plaque formation in transgenic male mice which express high levels of apoE (38). Furthermore, disruption of the ER ␣ gene leads to an abnormal phenotype in male mice that includes both abnormal behavior and sterility (39-42).…”

Section: Introductionmentioning

confidence: 99%

Growth factor activation of the estrogen receptor in vascular cells occurs via a mitogen-activated protein kinase-independent pathway.

Karas¹,

Gauer²,

Bieber³

et al. 1998

J. Clin. Invest.

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Arterial Reactivity Is Enhanced in Genetic Males Taking High Dose Estrogens

Abstract: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.

Cited by 95 publications

References 30 publications

Noninvasive Assessment of Coronary Microcirculatory Function in Postmenopausal Women and Effects of Short-Term and Long-Term Estrogen Administration

Noninvasive Assessment of Coronary Microcirculatory Function in Postmenopausal Women and Effects of Short-Term and Long-Term Estrogen Administration

Low-Dose Estrogen Supplementation Improves Vascular Function in Hypogonadal Men

Growth factor activation of the estrogen receptor in vascular cells occurs via a mitogen-activated protein kinase-independent pathway.

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