Drospirenone, a New Progestogen, for Postmenopausal Women with Hypertension
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REVIEW ARTICLE
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Drospirenone, a New Progestogen, for Postmenopausal Women with Hypertension Madhavi Mallareddy,1 Vladimir Hanes2 and William B. White1 1 2
Division of Hypertension and Clinical Pharmacology, Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut, USA Bayer HealthCare, Inc., Montville, New Jersey, USA
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 1. Hypertension during the Menopause . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454 2. Pathogenesis of Postmenopausal Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454 3. Co-Morbidities with Hypertension that May Affect Development of Cardiovascular Disease during Menopause . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455 4. Cardiovascular Effects of Hormone Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455 5. Drospirenone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457 5.1 Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457 5.2 Early Studies Demonstrating Antihypertensive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458 5.2.1 Studies in Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458 5.2.2 Studies in Healthy Human Controls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 5.3 Clinical Trials in Postmenopausal Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 5.4 Safety and Tolerability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463 6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
Abstract
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 re
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