estradiol-drospirenone-combination and Hypertension

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.

Topics: Androstenes; Antihypertensive Agents; Blood Pressure; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Female; Humans; Hypertension; Postmenopause

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.

Topics: Androstenes; Blood Pressure; Cardiovascular Diseases; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Female; Humans; Hypertension; Postmenopause; Renin-Angiotensin System; Risk Factors

Progesterone has a high affinity for the mineralocorticoid receptor and is an antagonist of aldosterone. Almost all synthetic progestogens are devoid of an antimineralocorticoid effect, and are unable to antagonize the salt-retaining effect of estrogens. This property could be one cause of the weight gain and increase in blood pressure associated with the use of combined oral contraceptives and, in some susceptible women, with postmenopausal hormone replacement therapy (HRT). This review illustrates the results of clinical studies with drospirenone, a new progestogen with antialdosterone activity. In normally menstruating women, 3 mg drospirenone per day, taken from day 5 to day 25 of the cycle, inhibits ovulation. A combination of 3 mg drospirenone with 30 microg ethinylestradiol (Yasmin, Schering AG, Berlin, Germany) is a highly effective and well-tolerated oral contraceptive, with an overall Pearl Index of 0.57 and an adjusted Pearl Index of 0.09. In addition, this combination leads to mild natriuresis and a slight compensatory activation of the renin-aldosterone system. This effect hasbeen clinically demonstrated: compared with an oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, 30 microg ethinylestradiol/3 mg drospirenone, given over 6 months, led to slight decreases in body weight and blood pressure. For postmenopausal HRT, 2 mg drospirenone was combined with 1 mg 17beta-estradiol (Angeliq, Schering AG, Berlin, Germany) for continuous treatment. To evaluate the endometrial safety of this combination, data were assessed from 520 postmenopausal women receiving 1 mg 17beta-estradiol and drospirenone (1, 2 or 3 mg per day) for at least 100 weeks. There were no cases of hyperplasia or carcinoma during the entire study period, and 85-92% of women had an atrophic/inactive endometrium. Data from two studies, with a treatment duration of at least 6 months, demonstrated a decrease in mean systolic blood pressure of 1.8 mmHg and a decrease in mean diastolic blood pressure of 3.8 mmHg, after treatment with 1 mg 17beta-estradiol/2 mg drospirenonefor 28 weeks. However, in a subgroup of slightly hypertensive women (initial blood pressure of more than 140/90 mmHg), the mean decrease in systolic blood pressure after 28 weeks of treatment with 1 mg 17beta-estradiol/2 mg drospirenone was 12.5 mmHg, and the mean decrease in diastolic blood pressure was 9.4 mmHg. Since high blood pressure is a cardiovascular risk factor, the use of

Topics: Androstenes; Contraceptives, Oral; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Progesterone Congeners; Renin-Angiotensin System

Topics: Adult; Aldosterone; Androstenes; Antihypertensive Agents; Computed Tomography Angiography; Contraceptives, Oral, Hormonal; Diagnosis, Differential; Drug Combinations; Estradiol; Female; Humans; Hypertension; Patient Selection; Polycystic Ovary Syndrome; Renin; Renin-Angiotensin System; Spironolactone