La terapia hormonal en la posmenopausia y las promesas incumplidas
Resumen
El uso de la hormonoterapia de reemplazo en la posmenopausia fue una práctica extendida a lo largo del último cuarto de siglo. Su prescripción se basaba en los beneficios a nivel cardiovascular, óseo y sobre la función cognitiva, que justificaban el mayor riesgo de cáncer de mama de la misma. Sin embargo, el desarrollo en los últimos años de estudios clínicos aleatorizados para evaluar los reales beneficios de la hormonoterapia han dado por tierra con las promesas de prevención cardiovascular y de la función cognitiva que se le atribuía a esta terapia, confirmando además el mayor riesgo de cáncer mamario. Esto llevó a la inversión de la relación riesgo-beneficio de su uso prolongado en la mayoría de las pacientes y a una drástica reducción de su prescripción y comercialización en todo el mundo. El presente artículo busca revisar las razones de estos cambios, divulgar sus repercusiones y reflexionar sobre las lecciones a aprender antes de instaurar una nueva intervención farmacológica.
Citas
2) Barret-Connor E. Postmenopausal estrogen and prevention bias. Ann Inter Med 1991; 115(6): 455-6.
3) Influence of adherence to treatment and response of cholesterol on mortality in the coronary drug project. N Engl J Med 1980; 303(18): 1038-41.
4) Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280(7): 605-13.
5) Grady D, Herrington D, Bittner V, Blumenthal R, Davison M, Hlatky M, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002 Jul 3; 288(1):49-57. Erratum in: JAMA 2002 Sep 4; 288(9):1064.
6) Mosca L, Collins P, Herrington DM, Mendelsohn ME, Pasternak RC, Robertson RM, et al. Hormone replacement therapy and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 2001; 104(4): 499-503.
7) Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med 2001; 345(17): 1243-9.
8) Hodis HM, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med 2003; 349(6): 535-45.
9) Herrington DM, Reboussin DM, Brosnihan KB, Sharp PC, Shumaker SA, Snyder TE, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med 2000; 343(8): 522-9.
10) Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Writing Group for the Woman Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal woman: principal results From the Women’s Health Initiative randomized controlled trial. Jama 2002; 288(3): 321-33.
11) Hodis HN, Mack WJ, Lobo RA, Shoupe D, Sevanian A, Mahrer PR, et al. Estrogen in the prevention of atherosclerosis. Ann Inter Med 2001; 135(11): 939-53.
12) International Agency for Research on Cancer. Sex hormones (II). In: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Lyon: IARC, 1979: v.21
13) Clemons M, Goss P. Estrogen and the risk of breast cancer. N Engl J Med 2001; 344(4): 276-85.
14) Fuchs-Young R, Glasebrook AL, Short LL, Draper MW, Rippy MK, Cole HW, et al. Raloxifene is a tissue-selective agonist/antagonist that functions through the estrogen receptor. Ann N Y Acad Sci 1995; (761): 355-60.
15) Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997 Oct 11; 350(9084):1047-59. Erratum in: Lancet 1997 Nov 15; 350(9089):1484.
16) Chlebowski RT, Susan LH, Langer RD, Stefanick ML, Gass M, Lane D, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA 2003; 289(24): 3243-53.
17) Beral V, Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003; 362(9382): 419-27.
18) Carlson MC, Zandi PP, Plassman BL, Tschanz JT, Welsh-Bohmer KA, Steffens DC, et al. Hormone replacement therapy and reduced cognitive decline in older women: the Cache County Study. Neurology 2001; 57(12): 2210-6.
19) Hogervorst E, Williams J, Budge M, Riedel W, Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis. Neuroscience 2000; 101(3): 485-512.
20) Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA 1998; 279(9): 688-95.
21) Henderson VW, Paganini-Hill A, Miller BL, Elble RJ, Reyes PF, Shoupe D, et al. Estrogen for Alzheimer’s disease in women: randomized, double-blind, placebo-controlled trial. Neurology 2000; 54(2): 295-301.
22) Mulnard RA, Cotman CW, Kawas C, Van Dick CH, Sano M, Doody R, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. JAMA 2000; 283(8): 1007-15.
23) Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289(20): 2663-72.
24) Grodstein F, Clarkson TB, Manson JE. Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med 2003; 348(7): 645-50.
25) Petitti DB. Coronary heart disease and estrogen replacement therapy: can compliance bias explain the results of observational studies? Ann Epidemiol 1994; 4(2): 115-8.
26) Chalmers I. Underreporting research in scientific misconduct. JAMA 1990; 263(10): 1405-8.
27) Cohen W, Florida R, Goe WR. University-industry research centers in the United States. Pittsburgh: Carnegie-Mellon University, 1994
28) North American Menopause Society. Amended report from the NAMS Advisory Panel on Postmenopausal Hormone Therapy. Menopause 2003; 10(1): 6-12.
29) White C. Second long term HRT trial stopped early. BMJ 2002; 325(7371): 987.
30) Austin PC, Mamdani MM, Tu K, Jaakkimainen L. Prescriptions for estrogen replacement therapy in Ontario before and after publication of the Women’s Health Initiative Study. JAMA 2003; 289(24): 3241-2.