Drospirenone; hormone replacement therapy; progestogen; body weight; antialdosterone; renin-angiotensin-aldosterone system
Résumé :
[en] Hormone replacement therapy (HRT) remains the most effective treatment for menopausal symptom relief, and may provide cardiovascular benefits in younger women initiating treatment soon after menopause. However, large surveys indicate that many symptomatic women refuse or discontinue HRT prematurely owing to fear of weight gain. A continuous combined HRT containing 17beta-estradiol (E(2)) 1 mg plus drospirenone (DRSP) 2 mg is effective in relieving menopausal symptoms and preventing postmenopausal osteoporosis. DRSP is a unique synthetic progestogen with a pharmacological profile similar to that of natural progesterone, including antialdosterone activity, a property not exhibited by other synthetic progestogens. DRSP can therefore reduce estrogen-related sodium and water retention in postmenopausal women receiving HRT via the renin-angiotensin-aldosterone system, which regulates sodium and water balance. This may translate into weight benefits. Pooled data from two placebo-controlled clinical trials (n = 333) indicated statistically significant weight loss of -1.5 kg at 6 and 12 months in postmenopausal women receiving E(2)/DRSP vs. placebo (p < 0.001). In a third randomized controlled trial (n = 1147), women receiving E(2)/DRSP maintained or lost weight, whereas weight increases were observed in women receiving E(2) monotherapy (p < 0.0125). E(2)/DRSP could help maintain or even slightly decrease body weight during treatment, potentially improving HRT acceptance and compliance.
Menopause practice: A clinician's guide [Internet]. Cleveland (OH): North American Menopause Society; date unknown [cited 2007 June 7]. Available from: http://www.menopause.org/edumaterials/cliniciansguide/cliniciansguidetoc.htm
Hill K. The demography of menopause. Maturitas 1996;23:113-127.
Consensus conference on hormone replacement therapy - Final consensus statement [Internet]. Edinburgh: Royal College of Physicians of Edinburgh; October 2003 [cited 2007 June 7]. Available from: http://www.rcpe.ac.uk/ education/standards/consensus/hrt_03.php
National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med 2005;142:1003-1013.
Skouby SO, Al-Azzawi F, Barlow D, Calaf-Alsina Erdogan Ertungealp J, Gompel A, Graziottin A, Hudita D, Pines A, Rozenberg S, et al. European Menopause and Andropause Society. Climacteric medicine: European Menopause and Andropause Society (EMAS) 2004/2005 position statements on peri- and postmenopausal hormone replacement therapy. Maturitas 2005;51:8-14.
MacLennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev 2004;(4):CD002978.
North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause 2007;14:168-182.
Recommendations on postmenopausal hormone therapy. Update to the original IMS Position Statement in Climacteric 2004;7:8-11 [Internet]. Lancaster (UK): International Menopause Society; 2007 Feb 27 [cited 2007 June 7]. Available from: http://www.imsociety.org/pdf_files/comments_and_press_statements/ ims_press_statement_27_02_07.pdf?SESSID=jbtblkcosb1roa118msar3c220
Managing the menopause. British Menopause Society Council consensus statement on hormone replacement therapy [Internet], Marlow, (UK): British Menopause Society; 2006 Jun 10 [cited 2007 June 7]. Available from: http://www.thebms.org.uk/statementcontent.php?id=1#
Center for Drug Evaluation and Research. Guidance for industry: Estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms - recommendations for clinical evaluation. Rockville, (MD): US Department of Health and Human Services, Food and Drug Administration; January 2003.
Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes 2005;3:47.
Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. J Am Med Assoc 2001;285:2891-2897.
Grady D, Ruben SB, Petitti DB, Fox CS, Black D, Ettinger B, Ernster VL, Cummings SR. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992;117:1016-1037.
Stampfer MJ, Colditz G. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 1991;20:47-63.
Hsia J, Criqui MH, Herrington DM, Manson JE, Wu L, Heckbert SR, Allison M, McDermott MM, Robinson J, Masaki K; Women's Health Initiative Research Group. Conjugated equine estrogens and coronary heart disease. Arch Intern Med 2006;166:357-365.
Grodstein F, Manson JE, Stampfer M. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health 2006;15:35-44.
Salpeter SR, Walsh JM, Greyber E, Ormiston TM, Salpeter EE. Mortality associated with hormone replacement therapy in younger and older women: a meta-analysis. J Gen Intern Med 2004;19:791-804.
Alexandersen P, Tankó LB, Bagger YZ, Qin G, Christiansen C. The long-term impact of 2-3 years of hormone replacement therapy on cardiovascular mortality and atherosclerosis in healthy women. Climacteric 2006;9:108-118.
LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: systematic review and meta-analysis. J Am Med Assoc 2001;285:1489-1499.
Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. J Am Med Assoc 1998;279:688-695.
Gambacciani M, Ciaponi M, Cappagli B, Monteleone P, Benussi C, Bevilacqua G, Genazzani AR. Effects of low-dose, continuous combined estradiol and norethisterone acetate on menopausal quality of life in early postmenopausal women. Maturitas 2003;44:157-163.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, et al. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. J Am Med Assoc 2002;288:321-333.
Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, et al. Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. J Am Med Assoc 2004;291:1701-1712.
Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, Trevisan M, Black HR, Heckbert SR, Detrano R, et al. Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003;349:523-534.
Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, Hsia J, Hulley S, Herd A, Khan S, et al. HERS Research Group. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). J Am Med Assoc 2002;288:49-57.
Hoffmann M, Hammar M, Kjellgren, Lindh-Astrand L, Brynhildsen J. Changes in women's attitudes towards and use of hormone therapy after HERS and WHI. Maturitas 2005;52:11-17.
Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. J Am Med Assoc 2004;291:47-53.
Ettinger B, Grady D, Tosteson AN, Pressman A, Macer JL. Effect of the Women's Health Initiative on women's decisions to discontinue postmenopausal hormone therapy. Obstet Gynecol 2003;102:1225-1232.
Breslau ES, Davis WW, Doner L, Eisner EJ, Goodman NR, Meissner HI, Rimer BK, Rossouw JE. The hormone therapy dilemma: women respond. J Am Med Womens Assoc 2003;58:33-43.
Rolnick SJ, Kopher RA, DeFor TA, Kelley ME. Hormone use and patient concerns after the findings of the Women's Health Initiative. Menopause 2005;12:399-404.
Strothmann A, Schneider HP. Hormone therapy: the European women's perspective. Climacteric 2003;6:337-346.
Genazzani AR, Schneider HP, Panay N, Nijland EA. The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy. Gynecol Endocrinol 2006;22:369-375.
Strothmann A, Schneider HPG, Schaefer M. Hormone therapy: the US women's perspective. Poster presented at the 16th Annual Meeting of the North American Menopause Society, San Diego, California, September 28-October 1, 2005.
Bakken K, Eggen AE, Lund E. Side-effects of hormone replacement therapy and influence on pattern of use among women aged 45-64 years. The Norwegian Women and Cancer (NOWAC) study 1997. Acta Obstet Gynecol Scand 2004;83:850-856.
van Seumeren I. Weight gain and hormone replacement therapy: are women's fears justified? Maturitas 2000;34(Suppl 1):S3-S8.
Clinkingbeard C, Minton BA, Davis J, McDermott K. Women's knowledge about menopause, hormone replacement therapy (HRT), and interactions with healthcare providers: an exploratory study. J Womens Health Gend Based Med 1999;8:1097-1102.
Schneider HP. Cross-national study of women's use of hormone replacement therapy (HRT) in Europe. Int J Fertil Womens Med 1997;42(Suppl 2):365-375.
Lewin KJ, Sinclair HK, Bond CM. Women's knowledge of and attitudes towards hormone replacement therapy. Fam Pract 2003;20:112-119.
Reynolds RF, Obermeyer CM, Walker AM, Guilbert D. The role of treatment intentions and concerns about side effects in women's decision to discontinue postmenopausal hormone therapy. Maturitas 2002;43:183-194.
Faulkner DL, Young C, Hutchins D, McCollam JS. Patient noncompliance with hormone replacement therapy: a nationwide estimate using a large prescription claims database. Menopause 1998;5:226-229.
Wing RR, Matthews KA, Kuller LH, Meilahn EN, Plantinga P. Weight gain at the time of menopause. Arch Intern Med 1991;151:97-102.
Pasquali R, Casimirri F, Labate AM, Tortelli O, Pascal G, Anconetani B, Gatto MR, Flamia R, Capelli M, Barbara L. Body weight, fat distribution and the menopausal status in women. Int J Obes Relat Metab Disord 1994;18:614-621.
Poehlman ET, Goran MI, Gardner AW, Ades PA, Arciero PJ, Katzman-Rooks SM, Montgomery SM, Toth MJ, Sutherland PT. Determinants of decline in resting metabolic rate in aging females. Am J Physiol 1993;264:E450-E455.
Björkelund C, Lissner L, Andersson S, Lapidus L, Bengtsson C. Reproductive history in relation to relative weight and fat distribution. Int J Obes Relat Metab Disord 1996;20:213-219.
Ley CJ, Lees B, Stevenson JC. Sex- and menopause-associated changes in body-fat distribution. Am J Clin Nutr 1992;55:950-954.
Augoulea A, Mastorakos G, Lambrinoudaki I, Christodoulakos G, Creatsas G. Role of postmenopausal hormone replacement therapy on body fat gain and leptin levels. Gynecol Endocrinol 2005;20:227-235.
Arabi A, Garnero P, Porcher R, Pelissier C, Benhamou CL, Roux C. Changes in body composition during post-menopausal hormone therapy: a 2 year prospective study. Hum Reprod 2003;18:1747-1752.
Meeuwsen IB, Samson MM, Duursma SA, Verhaar HJ. The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women. Endocrinology 2001;142:481-487.
Shadoan MK, Anthony MS, Rankin SE, Clarkson TB, Wagner JD. Effects of tibolone and conjugated equine estrogens with or without medroxyprogesterone acetate on body composition and fasting carbohydrate measures in surgically postmenopausal monkeys. Metabolism 2003;52:1085-1091.
Norman RJ, Flight IH, Rees MC. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and postmenopausal women: weight and body fat distribution. Cochrane Database Syst Rev 2000;(2):CD001018.
Genazzani AR, Gambacciani M. Effect of climacteric transition and hormone replacement therapy on body weight and body fat distribution. Gynecol Endocrinol 2006;22:145-150.
Espeland MA, Stefanick ML, Kritz-Silverstein D, Fineberg SE, Waclawiw MA, James MK, Greendale GA. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators. J Clin Endocrinol Metab 1997;82:1549-1556.
Oelkers W, Foidart JM, Dombrovics N, Welter A, Heithecker R. Effects of new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-angiotensin system, body weight, blood pressure, glucose tolerance and lipid metabolism. J Clin Endocrinol Metab 1995;80:1816-1821.
Oelkers W. Drospirenone, a progesterone with antimineralocorticoid properties: a short review. Mol Cell Endocrinol 2004;217:255-261.
Elger W, Schwarz S, Hedden A, Reddersen G, Schneider B. Sulfamates of various estrogens are prodrugs with increased systemic and reduced hepatic estrogenicity at oral application. J Steroid Biochem Mol Biol 1995;55:395-403.
Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005;8(Suppl 1):3-63.
Muhn P, Fuhrmann U, Fritzemeier KH, Krattenmacher R, Schillinger E. Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Ann N Y Acad Sci 1995;761:311-335.
Pollow K, Juchem M, Elger W, Jacobi N, Hoffman G, Mobus Y. Dihydrospirorenone (ZK30595): a novel synthetic progesterone - characterization of binding to different receptor proteins. Contraception 1992;46:561-574.
Krattenmacher R. Drospirenone: pharmacology and pharmacokinetics of a unique progesterone. Contraception 2000;62:29-38.
Borenstein J, Yu HT, Wade S, Chiou CF, Rapkin A. Effect of an oral contraceptive containing ethinyl estradiol and drospirenone on premenstrual symptomatology and health-related quality of life. J Reprod Med 2003;48:79-85.
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;61:105-111.
Apter D, Borsos A, Baumgärtner W, Melis GB, Vexiau-Robert D, Colligs-Hakert A, Palmer M, Kelly S. Effect of an oral contraceptive containing drospirenone and ethinylestradiol on general well-being and fluid-related symptoms. Eur J Contracept Reprod Health Care 2003;8:37-51.
Pearlstein TB, Bachmann GA, Zacur HA, Yonkers KA. Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation. Contraception 2005;72:414-421.
Yonkers KA, Brown C, Pearlstein TB, Foegh M, Sampson-Landers C, Rapkin A. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol 2005;106:492-501.
Archer DF, Thorneycroft IH, Foegh M, Hanes V, Glant MD, Bitterman P, Kempson RL. Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial. Menopause 2005;12:716-727.
Rubig A. Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties. Climacteric 2003;6(Suppl 3):49-54.
Warming L, Ravn P, Nielsen T, Christiansen C. Safety and efficacy of drospirenone used in a continuous combination with 17β-estradiol for prevention of postmenopausal osteoporosis. Climacteric 2004;7:103-111.
Tanko LB, Christiansen C. Effects of 17β-oestradiol plus different doses of drospirenone on adipose tissue, adiponectin and atherogenic metabolites in postmenopausal women. J Intern Med 2005;258:544-553.
Foidart JM, Wuttke W, Bouw GM, Gerlinger C, Heithecker R. A comparative investigation of contraceptive reliability, cycle control and tolerance of two monophasic oral contraceptives containing either drospirenone or desogestrel. Eur J Contracept Reprod Health Care 2000;5:124-134.
Huber J, Foidart JM, Wuttke W, Merki-Feld GS, The HS, Gerlinger C, Schellschmidt I, Heithecker R. Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone. Eur J Contracept Reprod Health Care 2000;5:25-34.
Schürmann R, Holler T, Benda N. Estradiol and drospirenone for climacteric symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled study of the safety and efficacy of three dose regimens. Climacteric 2004;7:189-196.
Preston RA, White WB, Pitt B, Bakris G, Norris PM, Hanes V. Effects of drospirenone/17-β estradiol on blood pressure and potassium balance in hypertensive postmenopausal women. Am J Hypertens 2005;18:797-804.
White WB, Pitt B, Preston RA, Hanes V. Antihypertensive effects of drospirenone with 17β-estradiol, a novel hormone treatment in postmenopausal women with stage 1 hypertension. Circulation 2005;112:1979-1984.
White WB, Hanes V, Chauhan V, Pitt B. Effects of a new hormone therapy, drospirenone and 17-β-estradiol, in postmenopausal women with hypertension. Hypertension 2006;48:246-253.
