Top

Drugs

Published in:

01-04-2007 | Current Opinion

Drospirenone for Oral Contraception and Hormone Replacement Therapy

Are its Cardiovascular Risks and Benefits the Same as Other Progestogens?

Authors: Apurva Motivala, Dr Bertram Pitt

Published in: Drugs | Issue 5/2007

Abstract

The use of combined estrogen/progesterone has been shown to result in an increased cardiovascular risk in randomised double-blinded trials. However, these studies used oral progestogen (progestin) preparations, which lack anti-mineralocorticoid activity and have suboptimal anti-androgenic activity compared with progesterone. Drospirenone is a unique progestogen that has clinically been shown to have anti-mineralocorticoid/anti-androgenic effects. Drospirenone in combination with estrogen is currently being used for oral contraception and hormone replacement therapy, and has been shown to have favourable effects on a number of cardiovascular risk factors. Our review of the literature suggests that because of its anti-mineralocorticoid effects, drospirenone in conjunction with estrogen may prevent the development of cardiovascular disease in both pre- and post-menopausal women.

The use of trade names is for product identification purposes only and does not imply endorsement.

Belchetz PE. Hormonal treatment of postmenopausal women. N Engl J Med 1994; 330: 1062–71PubMedCrossRef

Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA 2004; 291: 47–53PubMedCrossRef

Mosca L, Collins P, Herrington DM, et al. Hormone replacement therapy and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 2001; 104: 499–503PubMedCrossRef

Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709–17PubMedCrossRef

Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309–21PubMedCrossRef

Conn JW, Knopf RF, Nesbit RM. Clinical characteristics of primary aldosteronism from an analysis of 145 cases. Am J Surg 1964; 107: 159–72PubMedCrossRef

Okubo S, Niimura F, Nishimura H, et al. Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion. J Clin Invest 1997; 99: 855–60PubMedCrossRef

Struthers AD, MacDonald TM. Review of aldosterone- and angiotensin II-induced target organ damage and prevention. Cardiovasc Res 2004; 61: 663–70PubMedCrossRef

Harada E, Yoshimura M, Yasue H, et al. Aldosterone induces angiotensin-converting-enzyme gene expression in cultured neonatal rat cardiocytes. Circulation 2001; 104: 137–9PubMedCrossRef

10.

Park JB, Schiffrin EL. ET(A) receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats. Hypertension 2001; 37: 1444–9PubMedCrossRef

11.

Barr CS, Lang CC, Hanson J, et al. Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol 1995; 76: 1259–65PubMedCrossRef

12.

Rocha R, Chander PN, Khanna K, et al. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 1998; 31: 451–8PubMedCrossRef

13.

Rocha R, Chander PN, Zuckerman A, et al. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 1999; 33: 232–7PubMedCrossRef

14.

Luft FC. Workshop: mechanisms and cardiovascular damage in hypertension. Hypertension 2001; 37: 594–8PubMedCrossRef

15.

Rajagopalan S, Duquaine D, King S, et al. Mineralocorticoid receptor antagonism in experimental atherosclerosis. Circulation 2002; 105: 2212–6PubMedCrossRef

16.

Staessen J, Lijnen P, Fagard R, et al. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol 1981; 91: 457–65PubMedCrossRef

17.

Borghi C, Boschi S, Ambrosioni E, et al. Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors. J Clin Pharmacol 1993; 33: 40–5PubMed

18.

Tang WH, Vagelos RH, Yee YG, et al. Neurohormonal and clinical responses to high-versus low-dose enalapril therapy in chronic heart failure. J Am Coll Cardiol 2002; 39: 70–8PubMedCrossRef

19.

McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999; 100: 1056–64PubMedCrossRef

20.

Silvestre JS, Robert V, Heymes C, et al. Myocardial production of aldosterone and corticosterone in the rat: physiological regulation. J Biol Chem 1998; 273: 4883–91PubMedCrossRef

21.

Gomez-Sanchez CE, Zhou MY, Cozza EN, et al. Aldosterone biosynthesis in the rat brain. Endocrinology 1997; 138: 3369–73PubMedCrossRef

22.

Takeda Y, Miyamori I, Inaba S, et al. Vascular aldosterone in genetically hypertensive rats. Hypertension 1997; 29: 45–8PubMedCrossRef

23.

Rossi GP, Andreis PG, Neri G, et al. Endothelin-1 stimulates aldosterone synthesis in Conn’s adenomas via both A and B receptors coupled with the protein kinase C- and cyclooxygenase-dependent signaling pathways. J Investig Med 2000; 48: 343–50PubMed

24.

Urata H, Nishimura H, Ganten D, et al. Angiotensin-converting enzyme-independent pathways of angiotensin II formation in human tissues and cardiovascular diseases. Blood Press Suppl 1996; 2: 22–8PubMed

25.

Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 2003; 108: 1831–8PubMedCrossRef

26.

Preston RA, White WB, Pitt B, et al. Effects of drospirenone/17-beta estradiol on blood pressure and potassium balance in hypertensive postmenopausal women. Am J Hypertens 2005; 18: 797–804PubMedCrossRef

27.

White WB, Pitt B, Preston RA, et al. Antihypertensive effects of drospirenone with 17beta-estradiol, a novel hormone treatment in postmenopausal women with stage 1 hypertension. Circulation 2005; 112: 1979–84PubMedCrossRef

28.

White WB, Hanes V, Chauhan V, et al. Effects of a new hormone therapy, drospirenone and 17-beta-estradiol, in postmenopausal women with hypertension. Hypertension 2006; 48: 246–53PubMedCrossRef

29.

Lim PO, Farquharson CA, Shiels P, et al. Adverse cardiac effects of salt with fludrocortisone in hypertension. Hypertension 2001; 37: 856–61PubMedCrossRef

30.

Korkmaz ME, Muderrisoglu H, Ulucam M, et al. Effects of spironolactone on heart rate variability and left ventricular systolic function in severe ischemic heart failure. Am J Cardiol 2000; 86: 649–53PubMedCrossRef

31.

Ramires FJ, Mansur A, Coelho O, et al. Effect of spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy. Am J Cardiol 2000; 85: 1207–11PubMedCrossRef

32.

Yee KM, Pringle SD, Struthers AD. Circadian variation in the effects of aldosterone blockade on heart rate variability and QT dispersion in congestive heart failure. J Am Coll Cardiol 2001; 37: 1800–7PubMedCrossRef

33.

Kasama S, Toyama T, Kumakura H, et al. Spironolactone improves cardiac sympathetic nerve activity and symptoms in patients with congestive heart failure. J Nucl Med 2002; 43: 1279–85PubMed

34.

Chowdhary S, Vaile JC, Fletcher J, et al. Nitric oxide and cardiac autonomie control in humans. Hypertension 2000; 36: 264–9PubMedCrossRef

35.

Farquharson CA, Struthers AD. Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 2000; 101: 594–7PubMedCrossRef

36.

Ahokas RA, Warrington KJ, Gerling IC, et al. Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface. Circ Res 2003; 93: e124–35PubMedCrossRef

37.

Flack JM, Oparil S, Pratt JH, et al. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol 2003; 41: 1148–55PubMedCrossRef

38.

White WB, Duprez D, St Hillaire R, et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003; 41: 1021–6PubMedCrossRef

39.

Elstein M, Furniss HA. Advances in oral hormonal contraception. Zentralbl Gynakol 1995; 117: 559–65PubMed

40.

Parsey KS, Pong A. An open-label, multicenter study to evaluate Yasmin, a low-dose combination oral contraceptive containing drospirenone, a new progestogen. Contraception 2000; 61: 105–11PubMedCrossRef

41.

Fotherby K, Caldwell AD. New progestogens in oral contraception. Contraception 1994; 49: 1–32PubMedCrossRef

42.

Darney PD. The androgenicity of progestins. Am J Med 1995; 98: 104-SCrossRef

43.

Fuhrmann U, Krattenmacher R, Slater EP, et al. The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception 1996; 54: 243–51PubMedCrossRef

44.

Laurent H, Bittier D, Hofmeister H, et al. Synthesis and activities of anti-aldosterones. J Steroid Biochem 1983; 19: 771–6PubMedCrossRef

45.

Oelkers W, Foidart JM, Dombrovicz N, et al. Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism. J Clin Endocrinol Metab 1995; 80: 1816–21PubMedCrossRef

46.

Muhn P, Krattenmacher R, Beier S, et al. Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Pharmacological characterization in animal models. Contraception 1995; 51: 99–110PubMedCrossRef

47.

Muhn P, Fuhrmann U, Fritzemeier KH, et al. Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci 1995; 761: 311–35PubMedCrossRef

48.

Oelkers W, Berger V, Bolik A, et al. Dihydrospirorenone, a new progestogen with antimineralocorticoid activity: effects on ovulation, electrolyte excretion, and the renin-aldosterone system in normal women. J Clin Endocrinol Metab 1991; 73: 837–42PubMedCrossRef

49.

Berger V, Beier S, Elger W, et al. Influence of different progestogens on blood pressure of non-anaesthetized male spontaneously hypertensive rats. Contraception 1992; 46: 83–97PubMedCrossRef

50.

Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks: US population data. Arch Intern Med 1993; 153: 598–615PubMedCrossRef

51.

Wassertheil-Smoller S, Anderson G, Psaty BM, et al. Hypertension and its treatment in postmenopausal women: baseline data from the Women’s Health Initiative. Hypertension 2000; 36: 780–9PubMedCrossRef

52.

Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349: 523–34PubMedCrossRef

53.

Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001; 345: 1291–7PubMedCrossRef

54.

Julius S, Nesbitt SD, Egan BM, et al. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 2006; 354: 1685–97PubMedCrossRef

55.

Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich) 2002; 4: 393–404CrossRef

56.

Lloyd-Jones DM, Evans JC, Larson MG, et al. Treatment and control of hypertension in the community: a prospective analysis. Hypertension 2002; 40: 640–6PubMedCrossRef

57.

White WB, Prisant LM, Wright JT Jr, et al. Management of patients with hypertension and diabetes mellitus: advances in the evidence for intensive treatment. Am J Med 2000; 108: 238–45PubMedCrossRef

58.

Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens 2003; 16: 925–30PubMedCrossRef

59.

Preston RA, Alonso A, Panzitta D, et al. Additive effect of drospirenone/17-beta-estradiol in hypertensive postmenopausal women receiving enalapril. Am J Hypertens 2002; 15: 816–22PubMedCrossRef

Title: Drospirenone for Oral Contraception and Hormone Replacement Therapy
Are its Cardiovascular Risks and Benefits the Same as Other Progestogens?
Authors: Apurva Motivala
Dr Bertram Pitt
Publication date: 01-04-2007
Publisher: Springer International Publishing
Published in: Drugs / Issue 5/2007
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200767050-00001

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Drospirenone for Oral Contraception and Hormone Replacement Therapy

Are its Cardiovascular Risks and Benefits the Same as Other Progestogens?

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2007

Azithromycin Extended Release

Botulinum Neurotoxin Type A Free of Complexing Proteins (XEOMIN®) in Focal Dystonia

Induction of Anaesthesia

Imatinib

Sitaxentan in Pulmonary Arterial Hypertension

Oral Vinorelbine