Estradiol With or Without Progesterone and Ambulatory Blood Pressure in Postmenopausal Women

Abstract

Abstract-The purpose of this study was to determine whether transdermal estradiol and intravaginal progesterone given in doses to mimic the premenopausal state would lower blood pressure (BP) in postmenopausal women. Fifteen healthy postmenopausal women were studied in each of 3 conditions: on placebo, after 8 weeks of transdermal estradiol 0.2 mg twice per week, and again 2 weeks after addition of intravaginal progesterone 300 mg/d. Women were studied at each point after 2 days of 100 mmol/d sodium intake. Twenty-four-hour ambulatory BP monitoring was performed, and blood was assayed for estradiol, progesterone, and hormones of the renin-angiotensin-aldosterone system (RAAS). ANOVA with pairwise comparisons was used for analysis. Urinary sodium excretion was similar at each time point. Levels of estrogen and progesterone similar to those in premenopausal women were achieved. On estradiol, nocturnal systolic BP (110Ϯ3 mm Hg), diastolic BP (63Ϯ2 mm Hg), and mean BP (77Ϯ2 mm Hg) fell significantly (PϽ0.02) compared with placebo systolic BP (116Ϯ2 mm Hg), diastolic BP (68Ϯ2 mm Hg), and mean BP (82Ϯ2 mm Hg). Daytime BP followed the same trend but was significantly lower only for mean BP. There was no activation of the RAAS. The addition of progesterone resulted in no further fall in BP but a significant activation of the RAAS. Thus, contrary to what is often assumed, administration of estradiol with or without progesterone not only did not raise BP but rather substantially lowered BP. This BP-lowering effect may be responsible for the lower incidence of hypertension in premenopausal than in postmenopausal women. (Hypertension. 1999;33:1190-1194.)Key Words: hypertension Ⅲ women Ⅲ blood pressure monitoring, ambulatory Ⅲ renin-angiotensin system P remenopausal women have a lower incidence of cardiovascular disease than age-matched men 1 ; however, after menopause the incidence of cardiovascular disease in women is similar to that in men. Much of the focus of investigation to explain this change in risk has been on estrogen-induced effects producing a more beneficial lipid profile in the premenopausal woman. However, beneficial changes in lipid profiles appear to account for only 25% to 50% of the cardiovascular benefit 2,3 seen in premenopausal women, thereby raising the question of other estrogeninduced cardiovascular benefits that may be lost at menopause.Hypertension is considered a major risk factor for cardiovascular disease. Of note, several studies have shown that the incidence of hypertension is lower in women than men until approximately the age of 51 years 1 . After this time, the incidence of hypertension in women exceeds that in men. Since 51 years is the average age of menopause in the United States, this observation raises the question of whether the loss of the gonadal sex steroids, estradiol and progesterone, contributes to the rise in blood pressure (BP). This possibility is contrary to the common belief in clinical practice that estrogens raise BP. In part, this belief stems from the observed hyperten...

Menopause and the characteristics of the large arteries in a population study

“…Journal of Human Hypertension in agreement with the hypothesis that oestrogen deprivation, either at the onset of menstruation 27 or in non-substituted postmenopausal normotensive [23][24][25] or hypertensive 22 women, may increase blood pressure. Oestrogens change the loading conditions on the elastin or collagen fibres or alter the structure of the vessel wall.…”

“…18 Other studies are in keeping with our findings, but did not correct for the level of blood pressure [19][20][21] or reported that withdrawal of hormonal replacement therapy for 4 weeks resulted in a decrease of systemic arterial compliance and an increase in pulse wave velocity in the femoralisdorsalis pedis region, but not in the aorto-femoral territory. 21 Recent studies using ambulatory monitoring [22][23][24][25][26] or automated blood pressure self-measurement 27 are…”

“…Initially, the sample had been stratified by sex and age (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59), у60 years), in an attempt to recruit the same number of subjects in each stratum. Households were identified from population registries as persons who shared the same address.…”

Dose response effect of cyclical medroxyprogesterone on blood pressure in postmenopausal women

“…The current study used a double-blind, randomised, placebocontrolled design with adequate power to detect small changes in clinic and ambulatory blood pressure produced by different doses of a C21 progestogen administered in a cyclical regimen in doses spanning the usual clinical dose range combined with a fixed daily dose of oral oestrogen. The results of the current study are consistent with those of previous studies, including the PEPI study, which have found no change [2][3][4][5][6][7][8][9][10]12 or a reduction [24][25][26]29 in blood pressure associated with the addition of a progestogen to 'replacement' doses of oestrogen.…”

“…Collectively, previous studies have variably shown no change, 1-12 a decrease 1,2,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] or an increase 4,9,11,21,[30][31][32][33][34][35] in blood pressure with various combinations of HRT. Unfortunately, few of the previous studies have been designed to differentiate between the effects on blood pressure of the individual oestrogen ('natural', conjugated equine or semisynthetic) and progestogen (C21 or C19 derivatives administered as cyclical or continuous therapy) components of the regimen when these preparations have been administered in combination.…”