The long-term effect of oral and percutaneous estradiol on plasma renin substrate and blood pressure.

Hassager, Christian; Riis, Bente Juel; Strøm, Verner; Guyene, Thanh‐Tam; Christiansen, Claus

doi:10.1161/01.cir.76.4.753

Cited by 107 publications

(42 citation statements)

References 28 publications

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“…Thus, we suggest that oral therapy causes high hepatic exposure to estrogens leading to excessive angiotensinogen production, activation of the renin-angiotensin system, and systemic hypertension: an effect avoided by transdermal estrogen preparations. 32 It is interesting to note the increase in serum creatinine in this study. This may be a consequence of alterations in renal blood flow secondary to renin-angiotensin system activation.…”

Section: This Latter Observation Awaits Prospective Confirmation In Tmentioning

confidence: 51%

Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure

et al. 2009

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Abstract-Current hormone replacement therapy may not optimize cardiovascular health in women with premature ovarian failure. We compared the effects of physiological and standard sex steroid replacement regimens on cardiovascular health in these women. In an open-label, randomized, controlled crossover trial, 34 women with premature ovarian failure were randomly assigned to 4-week cycles of physiological (transdermal estradiol and vaginal progesterone) and standard (oral ethinylestradiol and norethisterone) therapy for 12 months. Cardiovascular health was assessed by 24-hour ambulatory blood pressure, arterial stiffness, and renal and humoral factors. Eighteen women (19 to 39 years of age) completed the 28-month protocol. Both regimens caused similar suppression of luteinizing hormone and follicle-stimulating hormone and provided symptom relief. In comparison with the standard regimen, physiological sex steroid replacement caused lower mean 24-hour systolic and diastolic blood pressures throughout the 12-month treatment period (ANOVA; PՅ0.0001 for both): systolic blood pressure was 7.3 mm Hg (95% CI: 2.5 to 12.0 mm Hg) and diastolic was 7.4 mm Hg (95% CI: 3.9 to 11.0 mm Hg) lower at 12 months. Although there were no differences in arterial stiffness, physiological sex steroid replacement reduced plasma angiotensin II (ANOVA; Pϭ0.007) and serum creatinine (ANOVA; Pϭ0.015) concentrations without altering plasma aldosterone concentrations. In comparison with a standard regimen, physiological sex steroid replacement in women with premature ovarian failure results in lower blood pressure, better renal function, and less activation of the renin-angiotensin system. These findings have major implications for the future cardiovascular health of young women who require long-term sex steroid replacement therapy. Key Words: ovarian failure Ⅲ premature Ⅲ hypertension Ⅲ hormone replacement therapy Ⅲ renin-angiotensin system Ⅲ ambulatory blood pressure monitoring P remature ovarian failure, the onset of the menopause before the age of 40 years, is a relatively common problem, affecting 1% of women. 1 Sufferers are exposed to prolonged estrogen deficiency and have an increased risk of premature death, 2 mainly from cardiovascular disease. 3,4 In an attempt to reduce this risk, sex steroid replacement is usually offered in the convenient form of the combined oral contraceptive pill 5 or hormone replacement therapy (HRT) designed for postmenopausal women. These standard regimens often use nonphysiological synthetic hormones and do not restore normal serum sex steroid hormone concentrations. 6 The use of the oral contraceptive pill in healthy young women and HRT in postmenopausal women has been linked to increases in blood pressure 7 and the associated outcomes of stroke and subarachnoid hemorrhage. 8,9 Although hormone replacement will frequently be prescribed until the age of normal menopause, 10 there has been no formal assessment of these therapies in younger women with premature ovarian failure. In these women, the combined c...

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Section: This Latter Observation Awaits Prospective Confirmation In Tmentioning

confidence: 51%

Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure

et al. 2009

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“…Among others, beneficial influence on classic risk factors, 4,5 scavenging of free radicals, 22 and interference with the RAS have been reported. In this context, enhanced production of angiotensinogen 10,11 and reduced levels of ACE 13,23 have been observed, whereas the effect of estrogens on renin are the subject of ongoing controversy. 10,13,23 In ovariectomized rats, estrogen deficiency causes vascular overexpression of the AT 1 receptor.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Modulates AT ₁ Receptor Gene Expression In Vitro and In Vivo

et al. 1998

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Background-The AT 1 receptor has been implicated in the pathogenesis of hypertension and atherosclerosis. Estrogen deficiency is also associated with cardiovascular diseases. Therefore, we examined the AT 1 receptor gene expression in ovariectomized rats with and without estrogen replacement therapy and the influence of estrogen on AT 1 receptor expression in cultured vascular smooth muscle cells. Methods and Results-Rat aortic tissue was examined 5 weeks after ovariectomy. In one group, estrogen (1.7 mg estradiol) was administered during the 5-week period. Functional experiments assessed angiotensin II-induced contraction of aortic rings. AT 1 receptor mRNA levels were measured by quantitative polymerase chain reaction and Northern blotting. AT 1 receptor density was assessed by radioligand binding assays. These techniques were also applied in cultured vascular smooth muscle cells. The efficacy of angiotensin II on vasoconstriction was significantly increased in aortas from ovariectomized rats. As assessed by radioligand binding assays, AT 1 receptor density was increased to 160% without changes in receptor affinity during estrogen deficiency. AT 1 receptor mRNA levels were consistently increased to 187% in ovariectomized rats compared with sham-operated animals. Estrogen substitution therapy in ovariectomized rats reversed this AT 1 receptor overexpression. To explore the underlying mechanisms, the direct influence of estradiol on AT 1 receptor expression was investigated in VSMCs. Estradiol (1 mol/L) led to a time-dependent downregulation of AT 1 receptor mRNA, with a maximum of 33.3% at 12 hours. There was a correlative decrease in AT 1 receptor density. Conclusions-This novel observation of estrogen-induced downregulation of AT 1 receptor expression could explain the association of estrogen deficiency with hypertension and atherosclerosis, because activation of the AT 1 receptor plays a key role in the regulation of blood pressure, fluid homeostasis, and vascular cell growth. (Circulation. 1998;97:2197-2201.)Key Words: angiotensin Ⅲ hypertension Ⅲ hormones Ⅲ genes Ⅲ muscle, smooth Ⅲ atherosclerosis T he low incidence of vascular diseases in premenopausal women and the rapid increase of the risk of cardiovascular events after menopause as well as the beneficial effects of estrogen replacement therapy on cardiac and vascular morbidity have suggested a important role of estrogens in the pathogenesis of atherosclerosis. [1][2][3] In addition to its effects on classic cardiovascular risk factors, eg, in the sense of a decrease of cholesterol plasma levels, 4,5 estrogen has been recognized to directly influence vascular as well as myocardial cells. Indeed, VSMCs, myocytes, and cardiac fibroblasts have been shown to contain functional estrogen receptors. [6][7][8] Moreover, there is increasing evidence that estrogen interferes with the RAS. The production of angiotensinogen is enhanced, whereas ACE levels are decreased, by estrogens. According to a recent report, plasma renin levels are also reduced during estroge...

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“…Oestrogen clearly elevates angiotensinogen gene expression and serum levels of angiotensinogen. 22 The effect on renin levels is less clear, largely because of difficulties in measuring renin protein levels directly. 23 Shunkert et al 24 used an immunoradiometric assay with a monoclonal antibody to assess renin levels in postmenopausal women with and without hormone replacement therapy.…”

Section: Pathophysiologymentioning

confidence: 99%

Hypertension in women

Rosenthal

Oparil

2000

J Hum Hypertens

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Hypertension in women has received less attention than hypertension in men, and the major controlled trials of antihypertensive therapy have been carried out in populations made up predominantly of and have emphasised outcomes in men. Recently it has been recognised that women develop high blood pressure, particularly systolic hypertension, at an increased rate as they age, and that this age-related blood pressure increase is exaggerated by the menopause. The age-related rise in blood pressure, particularly systolic blood pressure and pulse pressure, contributes substantially to the age-related increase in risk of heart attack, heart failure, and stroke in middle-aged and elderly women. This article reviews

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The long-term effect of oral and percutaneous estradiol on plasma renin substrate and blood pressure.

Abstract: The long-term effect of percutaneous and oral estrogen replacement therapy on blood pressure, plasma renin substrate, and serum estrogens was examined in a 2 year placebo-controlled study with

Cited by 107 publications

References 28 publications

Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure

Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure

Estrogen Modulates AT ₁ Receptor Gene Expression In Vitro and In Vivo

Hypertension in women

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The long-term effect of oral and percutaneous estradiol on plasma renin substrate and blood pressure.

Abstract: The long-term effect of percutaneous and oral estrogen replacement therapy on blood pressure, plasma renin substrate, and serum estrogens was examined in a 2 year placebo-controlled study with

Cited by 107 publications

References 28 publications

Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure

Cardiovascular Effects of Physiological and Standard Sex Steroid Replacement Regimens in Premature Ovarian Failure

Estrogen Modulates AT 1 Receptor Gene Expression In Vitro and In Vivo

Hypertension in women

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Product

Resources

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Estrogen Modulates AT ₁ Receptor Gene Expression In Vitro and In Vivo