Long-term estrogen therapy abolishes acute estrogen-induced coronary flow augmentation in postmenopausal women

Blumenthal, Roger S.; Brinker, Jeffrey A.; Resar, Jon R.; Gloth, Sean T.; Zacur, Howard A.; Coombs, Vicki J.; Gerstenblith, Gary; Reis, Steven E.

doi:10.1016/s0002-8703(97)70227-8

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…In view of several short-term clinical studies that found vasodilatory effects of estradiol in postmenopausal women (314), this observation is surprising at first sight. However, it is in agreement with several long-term studies that did not verify the vasodilatory effect of estradiol (351)(352)(353). Two observations also indicate that T, especially in supraphysiological doses, modulates vascular tone via nongenomic modes of action.…”

Section: B Effects Of T On Vascular Reactivitysupporting

confidence: 90%

Androgens and Coronary Artery Disease

Eckardstein

2003

Endocrine Reviews

517

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A significant and independent association between endogenous testosterone (T) levels and coronary events in men and women has not been confirmed in large prospective studies, although cross-sectional data have suggested coronary heart disease can be associated with low T in men. Hypoandrogenemia in men and hyperandrogenemia in women are associated with visceral obesity; insulin resistance; low high-density lipoprotein (HDL) cholesterol (HDL-C); and elevated triglycerides, low-density lipoprotein cholesterol, and plasminogen activator type 1. These gender differences and confounders render the precise role of endogenous T in atherosclerosis unclear. Observational studies do not support the hypothesis that dehydroepiandrosterone sulfate deficiency is a risk factor for coronary artery disease. The effects of exogenous T on cardiovascular mortality or morbidity have not been extensively investigated in prospective controlled studies; preliminary data suggest there may be short-term improvements in electrocardiographic changes in men with coronary artery disease. In the majority of animal experiments, exogenous T exerts either neutral or beneficial effects on the development of atherosclerosis. Exogenous androgens induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, plasminogen activator type 1 (apparently deleterious), lipoprotein (a), fibrinogen, insulin, leptin, and visceral fat mass (apparently beneficial) in men as well as women. However, androgen-induced declines in circulating HDL-C should not automatically be assumed to be proatherogenic, because these declines may instead reflect accelerated reverse cholesterol transport. Supraphysiological concentrations of T stimulate vasorelaxation; but at physiological concentrations, beneficial, neutral, and detrimental effects on vascular reactivity have been observed. T exerts proatherogenic effects on macrophage function by facilitating the uptake of modified lipoproteins and an antiatherogenic effect by stimulating efflux of cellular cholesterol to HDL. In conclusion, the inconsistent data, which can only be partly explained by differences in dose and source of androgens, militate against a meaningful assessment of the net effect of T on atherosclerosis. Based on current evidence, the therapeutic use of T in men need not be restricted by concerns regarding cardiovascular side effects. Available data also do not justify the uncontrolled use of T or dehydroepiandrosterone for the prevention or treatment of coronary heart disease.

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Section: B Effects Of T On Vascular Reactivitysupporting

confidence: 90%

Androgens and Coronary Artery Disease

Eckardstein

2003

Endocrine Reviews

517

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“…For instance, it has previously been shown that the acute administration of ethinyl oestradiol and 17â-oestradiol increased coronary blood flow in women (Blumenthal et al 1997) and in anaesthetized pigs (Vacca et al 1999). These findings are consistent with reports involving coronary blood vessels showing that 17â-oestradiol relaxed isolated human coronary arteries (Barton et al 1998), precontracted pig coronary artery rings and strips with (Teoh & Man, 1999) and without functioning endothelium (Crews & Khalil, 1999).…”

supporting

confidence: 84%

The Effect of Progesterone on Coronary Blood Flow in Anaesthetized Pigs

Molinari

Battaglia

Grossini

et al. 2001

Experimental Physiology

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The present study was designed to investigate the effect of progesterone on the coronary circulation and to determine the mechanisms involved. In pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous infusion of progesterone at constant heart rate and arterial blood pressure were assessed using an electromagnetic flowmeter. In 14 pigs, infusion of 1 mg h−1 of progesterone caused an increase in coronary blood flow without affecting left ventricular dP/dtmax (rate of change of left ventricular systolic pressure) and filling pressures of the heart. In a further four pigs, this vasodilatory coronary effect was enhanced by graded increases in the dose of the hormone of between 1, 2 and 3 mg h−1. The mechanisms of the above response were studied in the 14 pigs by repeating the experiment after haemodynamic variables had returned to the control values observed before infusion. In six pigs, blockade of muscarinic cholinoceptors and adrenoceptors with atropine, propranolol and phentolamine did not affect the coronary vasodilatation caused by progesterone. In the remaining eight pigs, this response was abolished by intracoronary injection of Nω‐nitro‐L‐arginine methyl ester (L‐NAME) even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L‐NAME with continuous intravenous infusion of papaverine. The present study showed that intravenous infusion of progesterone primarily caused coronary vasodilatation. The mechanism of this response was shown to involve the endothelial release of nitric oxide.

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“…Impaired vascular endothelial function, which is well documented to occur in postmenopausal women, may increase vascular resistance (30–34). Postmenopausal impairment of endothelial function may be due to the decline in estrogen-potentiated vasodilation (35–37). Estrogen appears to increase blood flow by enhancing nitric oxide bioavailability, thus improving endothelium-dependent vasodilation (38–40).…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular hemodynamics during stress in premenopausal versus postmenopausal women

et al. 2010

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Objective Following menopause, women are at increased risk for cardiovascular disease. The present study assessed cardiovascular hemodynamics in pre- versus postmenopausal women, with a focus on systemic vascular resistance (SVR) at rest and during stress. Sympathetic nervous system (SNS) activity, and cardiovascular adrenergic receptor (AR) function were also examined. Methods A total of 90 women (N = 45 premenopausal; N=45 postmenopausal) completed a laboratory protocol comprised of a resting baseline and 4 mental stress tasks. Measurements included blood pressure (BP), cardiac output (CO), SVR, and plasma catecholamines. In addition, α and β AR responsiveness to the infusion of selective pharmacological agonists were assessed. Results Compared to premenopausal women, postmenopausal women were characterized by similar BP, but lower CO and higher SVR, both at rest and during stress (p’s < 0.05). Postmenopausal women also had higher baseline plasma norepinephrine levels (p=.007) and reduced β AR responsiveness (p=.02), although β AR differences may have been confounded by aging effects. Conclusions After menopause, women exhibit altered SNS activity and a sustained increase in hemodynamic load that may contribute to pathological structural and functional changes in the heart and blood vessels.

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Long-term estrogen therapy abolishes acute estrogen-induced coronary flow augmentation in postmenopausal women

Cited by 15 publications

References 29 publications

Androgens and Coronary Artery Disease

Androgens and Coronary Artery Disease

The Effect of Progesterone on Coronary Blood Flow in Anaesthetized Pigs

Cardiovascular hemodynamics during stress in premenopausal versus postmenopausal women

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