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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progesterone is more than a progestin. Beyond functions in cycle and pregnancy, progesterone binds with high affinity to the mineralocorticoid receptor (MR) acting as an antagonist, with obvious significance for electrolyte homeostasis, an array of MR-related functions in the circulation as well as in the CNS. Progesterone induces natriuresis at physiological concentrations. Lack of antimineralocorticoid activity with conventional progestins may account for sodium and water retention, minor elevation of blood pressure and "pill hypertension" in susceptible women on oral contraceptives. Ethinylestradiol (EE) contributes to this problem by distinct activation of the renin-angiotensin-aldosterone (RAAS) system. Drospirenone (DRSP: 6beta,7beta,15beta,16beta-dimethylene-3-oxo 17alpha-pregn-4-ene-21,17 carbolactone) is the first synthetic progestin with antialdosterone activity. DRSP and progesterone bind to PR in uterine (affinity of both is about 30% of R5020) and MR in kidney cytosol (affinity about 230 and 100% of aldosterone, respectively). Intrauterine administration of DRSP in silastic tubes induced maximum local progestational effects in rabbits. At systemic subcutaneous (s.c.) administration (McPhail-assay) full endometrial transformation was obtained at 1mg per animal per day. At 1-3mg DRSP per animal per day subcutaneously, pregnancy maintenance after ovariectomy, antiovulatory activity, and antimineralocorticoid activity were seen in the respective assays in rats. The latter activity indicates about eight-fold higher potency than spironolactone. DRSP decreased blood pressure in male hypertensive rats, whereas an increase was noted under conventional progestins. DRSP also prevented hypertension and fetal growth retardation in pregnant rats after L-NAME, an inhibitor of nitric oxide synthase. DRSP has antiandrogenic activity. Feminizing effects were recorded during sexual differentiation in male fetuses at high doses. Powerful antiandrogenic effects were also seen in gonad intact and testosterone substituted castrated male rats. The antiandrogenic potency of DRSP is superior to that of spironolactone but below that of cyproterone acetate. Endometrial transformation, inhibition of ovulation, and antimineralocorticoid, i.e. natriuretic effects and mild antiandrogenic effects were recorded at the same range of oral doses (0.5-4 mg per day) in humans. Combined with EE (3 mg DRSP+30 microg EE), DRSP provides effective inhibition of ovulation and cycle control. Body weight compared to conventional oral contraceptives was reduced. DRSP (3 mg per day+15, 20, or 30 microg ethinyl estradiol per day) prevented the mild increase of blood pressure seen under a conventional levonorgestrel-containing contraceptive and even tended to reduce pretreatment blood pressure. Studies on modulation (i.e. inhibition) of glucocorticoid effects at the MR in the CNS remain an unexplored and interesting area for research.
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PMID:Conception and pharmacodynamic profile of drospirenone. 1466 81

Drospirenone is a new progestogen in hormone replacement therapy, with anti-mineralocorticoid activity. This anti-mineralocorticoid activity counteracts water and sodium retention, helping to reduce the likelihood of fluid retention that some women experience with hormone replacement therapy. In a post hoc analysis of women with mild hypertension, estradiol (1 mg) plus drospirenone (2 mg) was found to lower blood pressure in mildly hypertensive women. The introduction of estradiol plus drospirenone may offer the opportunity to re-evaluate the contribution of the progestogen component of hormone replacement therapy.
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PMID:A new hormone replacement therapy containing a progestogen with anti-mineralocorticoid activity. 1651 13

Drospirenone (DRSP), a progestin with antialdosterone activity, has been developed for hormone therapy in combination with 17-beta-estradiol (E2) in postmenopausal women. We evaluated the antihypertensive efficacy and safety of various doses of DRSP and E2 and estradiol alone in postmenopausal women with hypertension using ambulatory and clinic blood pressure (BP) monitoring. This was a randomized, double-blind clinical trial of 3 doses of DRSP combined with estradiol, estradiol alone, and placebo in 750 postmenopausal women with stage 1 to 2 hypertension between 45 to 75 years. Ambulatory and clinic BPs, potassium, aldosterone, and lipid measurements and adverse events were evaluated in postmenopausal women with stages 1 to 2 hypertension during 8 weeks of double-blind therapy. DRSP and E2 induced dose-related reductions in the ambulatory and clinic systolic BP with physiological increases in serum aldosterone. Significant decreases in 24-hour systolic pressure were observed at doses of 2 and 3 mg of DRSP combined with estradiol but not by estradiol alone or 1 mg of DRSP with estradiol. There were no significant changes from baseline in potassium in any treatment group. Small, significant reductions in total and low-density lipoprotein cholesterol occurred on all of the active treatments, and serum triglycerides did not change. Adverse event rates were low and similar across treatment groups. In conclusion, these data show that DRSP combined with E2 significantly reduces BP in postmenopausal women with hypertension and did not induce significant increases in serum potassium. These characteristics may lead to a new benefit for this novel hormone therapy in postmenopausal women with hypertension.
Hypertension 2006 Aug
PMID:Effects of a new hormone therapy, drospirenone and 17-beta-estradiol, in postmenopausal women with hypertension. 1751 26

Menopause is a risk factor for cardiovascular disease (CVD) because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism. The menopause compounds many traditional CVD risk factors, including changes in body fat distribution from a gynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction and vascular inflammation. Many CVD risk factors have different impacts in men and women. In postmenopausal women, treatment of arterial hypertension and glucose intolerance should be priorities. Observational studies and randomized clinical trials suggest that hormone replacement therapy (HRT) started soon after the menopause may confer cardiovascular benefit. In contrast to other synthetic progestogens used in continuous combined HRTs, the unique progestogen drospirenone has antialdosterone properties. Drospirenone can therefore counteract the water- and sodium-retaining effects of the estrogen component of HRT via the renin-angiotensin-aldosterone system, which may otherwise result in weight gain and raised blood pressure. As a continuous combined HRT with 17beta-estradiol, drospirenone has been shown to significantly reduce blood pressure in postmenopausal women with elevated blood pressure, but not in normotensive women. Therefore, in addition to relieving climacteric symptoms, drospirenone/17beta-estradiol may offer further benefits in postmenopausal women, such as improved CVD risk profile.
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PMID:Menopause and cardiovascular disease: the evidence. 1736 94

Hypertension is one of the most important risk factors for the development of cardiovascular disease. The prevalence of hypertension increases with age and also after the menopause; therefore, blood pressure monitoring and effective control of elevated blood pressure are very important in postmenopausal women. The knowledge that aldosterone is a dual cardiovascular and endocrine hormone has blurred the once distinct boundary between gynecology and cardiovascular medicine. Aldosterone plays a major role in salt and water homeostasis, but also binds to mineralocorticoid receptors in the cardiovascular system, leading to structural and functional changes and consequent organ damage. Highly selective aldosterone blockade via the mineralocorticoid receptor has long-term antihypertensive effects. Drospirenone is a novel progestogen with aldosterone receptor antagonism (PARA), and therefore has antihypertensive effects through reduced salt and water retention. A new hormone therapy that combines 17beta-estradiol with drospirenone has been shown in several clinical studies to have a blood pressure-lowering effect in postmenopausal women with elevated blood pressure, in addition to effectively relieving symptoms of the menopause. These findings suggest a potential additional benefit on the cardiovascular system for the drospirenone/17beta-estradiol combination in the treatment of women with menopausal symptoms and elevated blood pressure.
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PMID:Drospirenone with 17beta-estradiol in the postmenopausal woman with hypertension. 2208 36

Menopause is accompanied by an increased prevalence of hypertension, which may partially explain the corresponding cardiovascular risk observed in postmenopausal women. The relationship between blood pressure and cardiovascular risk is continuous, consistent and independent of other risk factors. There are profound benefits of treating hypertension: antihypertensive therapy has been associated with large reductions in stroke, myocardial infarction and heart failure. Despite these proven benefits, hypertension is inadequately treated, or not treated at all, in the majority of patients. There has been concern regarding the use of hormone therapy in hypertensive postmenopausal women. Drospirenone/17beta-estradiol, a hormone therapy, has been demonstrated to lower blood pressure in hypertensive postmenopausal women either alone or when administered simultaneously with antihypertensive drugs. This might offer a potential advantage in patients with elevated blood pressure. It is also known that the risk for target organ events extends to levels well below the established definition of 140/90 mmHg. High-normal blood pressure carries an increased cardiovascular risk when compared to lower levels of blood pressure. Identification and management of elevated blood pressure are an important component of the successful management of the postmenopausal woman and can help prevent the untoward consequences of elevated blood pressure.
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PMID:Effects of blood pressure reduction on cardiovascular risk estimates in hypertensive postmenopausal women. 1736 96

The prevalence of hypertension increases in women after the menopause. Associated with the rise in postmenopausal blood pressure (BP) are increased salt sensitivity and imbalance between the renin-angiotensin-aldosterone system and nitric oxide pathways that lead to sodium and water retention. Drospirenone is the first synthetic progestogen with antialdosterone activity similar to natural progesterone. Drospirenone counteracts the salt- and water-retaining effects of estrogen and causes natriuresis, which leads to a reduction in BP. In preclinical studies as well as early efficacy studies (for menopausal symptoms), drospirenone exhibited antihypertensive and natriuretic effects. Subsequent clinical trials in postmenopausal women proved that drospirenone with 17beta-estradiol has a significant BP-lowering effect in untreated hypertension and has additive effects when coadministered with ACE inhibitors, angiotensin II type 1 receptor antagonists and thiazide diuretics. The lowest effective dose of drospirenone for reduction in BP is 2mg, a dose that is also protective of the uterus in women treated with estrogen therapy. Additionally, clinical trials have shown that drospirenone up to 3 mg/day has an acceptable safety profile with no clinically significant elevations in plasma potassium in patients with concomitant NSAID use, diabetes mellitus or mild to moderate renal insufficiency. In addition to effectively relieving menopausal symptoms and lowering BP, drospirenone reduces bodyweight and lipoprotein concentrations. Thus, drospirenone is a unique progestogen that confers the additional benefit of BP reduction, an effect that could lead to potential benefit with respect to some cardiovascular risk concerns in women taking hormone therapy.
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PMID:Drospirenone, a new progestogen, for postmenopausal women with hypertension. 1757 11

Menopause is commonly characterized by an increase in blood pressure. Higher blood pressure may partially explain the elevated risk for cardiovascular events observed in postmenopausal women. There is a graded relationship between blood pressure and cardiovascular risk which extends to levels of blood pressure well below 140/90 mmHg, the classical established blood pressure limit for the diagnosis of hypertension. Despite this knowledge and the wide availability of consensus treatment guidelines for hypertension, high blood pressure remains untreated or poorly treated in many postmenopausal patients. It is clear that novel and innovative population strategies for lowering blood pressure in postmenopausal women are warranted. Clinical trials suggest that oral estrogen administration may produce either a neutral effect or a small increase in blood pressure in postmenopausal women. Transdermal estrogen administration has not been studied as extensively but may produce a decrease in blood pressure. The mechanisms for the differences observed between oral and transdermal estrogen have not been completely elucidated. Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity that has been developed for hormone therapy as DRSP/17beta-estradiol (DRSP/E2). In several clinical trials, DRSP/E2 has demonstrated a significant antihypertensive effect as well an additive effect when combined with existing antihypertensive therapy. Despite the wide availability of treatment guidelines, a wide array of antihypertensive agents, and the introduction of hormone replacement therapy that can lower blood pressure, optimizing blood pressure control remains a serious issue confronting the physician who cares for the postmenopausal woman.
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PMID:Comparative effects of conventional vs. novel hormone replacement therapy on blood pressure in postmenopausal women. 1981 Dec 45

Drospirenone (DRSP), is a unique progestin with antimineralocorticoid activity that has been combined with 17-beta estradiol (E2) for the treatment of symptoms of the menopause in women with hypertension. We assessed the effects of DRSP/E2, E2 alone, and placebo on early morning systolic blood pressure (BP) as well as the rate of rise in systolic BP in 748 postmenopausal women with stage 1 and 2 hypertension at baseline and after 8 weeks of double-blind therapy. Patient characteristics (mean age, 56.5 years, 73% to 77% Caucasian; 13% to 17% African-American) and the clinic (152/95 mm Hg) and 24-hour BP (139/83 mm Hg) measurements were similar at baseline. The early morning systolic BP was reduced significantly on DRSP at 3 mg, 2 mg, and 1 mg with E2 compared with placebo, while E2 alone was similar to placebo. The reductions in early morning systolic BP were larger with increasing dose. Changes in the rate of rise in systolic BP between the lowest values during sleep and following a plateau period post-awakening was significant for the 3 mg DRSP group. In conclusion, DRSP/E2 induced significant reductions in early morning systolic BP in post-menopausal women. This attribute could play a potential role in reducing some of the untoward cardiac and cerebrovascular events that have been observed in studies of other progestins/estrogens in postmenopausal women.
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PMID:Effects of the hormone therapy, drospirenone and 17-beta estradiol, on early morning blood pressure in postmenopausal women with hypertension. 2040 81