ABSTRACT
AIMS: The aim of this investigation was to study the effects of hormone replacement therapy (HRT) on left ventricular mass (LVM) and serum-angiotensin-converting enzyme (ACE) activity (S-ACE) in well controlled hypertensive postmenopausal women. METHODS: In this prospective, randomized, crossover, double-blind trial we studied 20 well controlled hypertensive postmenopausal women who received 6 months of HRT and 6 months of placebo on top of antihypertensive treatment. Two-dimensional M-mode, office blood pressure, 24-h ambulatory blood pressure (ABPM), S-estradiol and S-ACE activity were investigated at baseline, after 6 and 12 months. RESULTS: LVM was significantly influenced by HRT (analysis of variance, ANOVA, p<0.01). However, the order in randomization of HRT and placebo had an impact on the analysis of LVM reduction (baseline - HRT - placebo: ns; baseline - placebo - HRT: p<0.01 ANOVA). Only the women lacking blockade of the renin-angiotensin-aldosterone system (RAAS) as antihypertensive treatment (n=10) experienced a reduction in LVM and a tendency of decreased S-ACE activity in response to HRT compared with baseline (p< 0.05 and p= 0.06 respectively). CONCLUSIONS: Six months of HRT resulted in significant reduction of LVM without any change in ABPM. HRT may reduce LVM through interaction with the RAAS, since hypertensive women without RAAS blockade exhibited an effect of HRT on LVM and S-ACE activity, which was not seen in women on RAAS blockade.
Subject(s)
Hormone Replacement Therapy/methods , Hypertrophy, Left Ventricular/drug therapy , Peptidyl-Dipeptidase A/blood , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Cross-Over Studies , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Hypertension , Middle Aged , Postmenopause , Treatment OutcomeABSTRACT
AIMS: To investigate the medium-term effects of estrogen plus progesterone therapy (EPT) on vascular reactivity, endothelial function and hemodynamic responses in 20 hypertensive postmenopausal women. METHODS: This randomized, double-blind, cross-over, placebo-controlled study investigates the effect of 6 months of EPT (conjugated equine estrogen plus medroxyprogesterone). Blood pressure (office and ambulatory), heart rate and heart rate variability (HRV) were measured at baseline and following EPT/placebo treatment. In eight women, we used a wire-myograph to assess endothelial function and contractile response of subcutaneous arteries to transmural nerve stimulation (TNS) and exogenous noradrenaline. RESULTS: EPT decreased vascular reactivity to cumulative TNS compared with baseline (p<0.01) and placebo (p<0.05). Moreover, EPT diminished sensitivity to exogenous noradrenaline (p<0.05). Although EPT reinforced response to acetylcholine, we observed no difference in maximal relaxation induced by substance P or acetylcholine. EPT did not affect ambulatory blood pressure, heart rate or HRV. CONCLUSIONS: Oral combined medium-term EPT reduces adrenergic reactivity in subcutaneous arteries from treated hypertensive postmenopausal women. EPT might act postjunctionally at the adrenergic vascular receptor level. In the present study, EPT neither reduces sympathetic activity nor increases vagal tone, and thus does not support an effect on the central hemodynamic system.
Subject(s)
Estrogens, Conjugated (USP)/pharmacology , Hemodynamics/drug effects , Norepinephrine/pharmacology , Progesterone/pharmacology , Acetylcholine/pharmacology , Arteries/drug effects , Blood Pressure/drug effects , Cross-Over Studies , Double-Blind Method , Estrogens/administration & dosage , Estrogens/pharmacology , Estrogens, Conjugated (USP)/administration & dosage , Estrogens, Conjugated (USP)/therapeutic use , Female , Heart Rate/drug effects , Humans , Hypertension/drug therapy , Medroxyprogesterone/pharmacology , Middle AgedABSTRACT
OBJECTIVE: The acute effects of estrogen on hemodynamic responses were studied with emphasis on the sympathoadrenal system and peripheral circulation. DESIGN: Eleven healthy postmenopausal women recruited from the population-based study BEDA were included in this randomized, double-blind, cross-over, placebo-controlled hypothesis-generating pilot study, where the effect of transdermal estrogen (17 beta-estradiol, 100 microg/24 h) was tested. METHODS: Twenty-four hours after the patch with estrogen/placebo was attached, the blood pressure during rest and mental stress test was measured, together with blood samples for analysis of P-adrenaline and P-noradrenaline. Twenty-four-hour ambulatory registration of blood pressure and heart rate were recorded. Contractile properties and endothelial function of subcutaneous small arteries from gluteal biopsies were studied with the wire-myograph technique. RESULTS: Estrogen treatment reduced both ambulatory systolic blood pressure (5 mmHg, P = 0.05), diastolic blood pressure (3 mmHg, P < 0.05) and heart rate (6-8 beats/min during morning hours, P < 0.01). Diastolic blood pressure during and after mental stress was significantly reduced after estrogen treatment (p < 0.01). The levels of P-adrenaline and P-noradrenaline were similar in both treatment protocols. The contractile properties of the arteries were not significantly influenced by estrogen. Substance P induced nitric oxide-dependent relaxation in both estrogen-treated and placebo-treated precontracted arteries. Acetylcholine, on the other hand, induced a non-nitric oxide, non-prostanoid-dependent hyperpolarization, which was inhibited by potassium-induced depolarization after placebo but not after estrogen treatment. CONCLUSIONS: Acute administration of transdermal estrogen in clinically relevant doses modulates hemodynamics, probably by an altered parasympathetic balance, which might involve changes at the muscarinic receptor level.
Subject(s)
Estradiol/administration & dosage , Estrogen Replacement Therapy , Hemodynamics/drug effects , Postmenopause , Vasomotor System/drug effects , Administration, Cutaneous , Aged , Arteries/physiology , Blood Pressure/drug effects , Cross-Over Studies , Double-Blind Method , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Female , Heart Rate/drug effects , Humans , Pilot Projects , Postmenopause/blood , Reference Values , Skin/blood supply , Vasoconstriction/drug effectsABSTRACT
The aim of this study was to investigate the acute effects of transdermal 17beta-estradiol (Estraderm) on plasma levels of coagulatory and fibrinolytic factors in postmenopausal normotensive and hypertensive women. Eleven normotensive and 13 hypertensive women were included in this placebo-controlled crossover study. In a randomized order each subject was treated with a patch of 100 microg 17beta-estradiol or placebo for 24 hours. Serum levels of tissue type plasminogen activator (tPA) activity, plasminogen activator inhibitor-I (PAI-1) activity, tPA antigen, PAI-I antigen, FVII, FX, and fibrinogen were assayed after both treatments. There was no significant difference in serum levels of hemostatic variables after treatment with estrogen compared to levels after placebo treatment in either of the groups. Nor was there any measurable difference when comparing hypertensive and normotensive subjects.