Abstract
OBJECTIVE: To assess the effect of hormone therapy (HT) on coronary heart disease (CHD) events in younger and older postmenopausal women.
DESIGN: A comprehensive database search identified randomized-controlled trials of HT of at least 6 months’ duration that reported CHD events, defined as myocardial infarction or cardiac death.
MEASUREMENTS: The pooled odds ratios (ORs) for CHD events were reported separately for younger and older women, defined as participants with mean time from menopause of less than or greater than 10 years, or mean age less than or greater than 60 years.
MAIN RESULTS: Pooled data from 23 trials, with 39,049 participants followed for 191,340 patient-years, showed that HT significantly reduced CHD events in younger women (OR 0.68 [confidence interval (C I), 0.48 to 0.96]), but not in older women (OR 1.03 [CI, 0.91 to 1.16]). Hormone therapy reduced events in younger women compared with older women (OR 0.66 [CI, 0.46 to 0.95]). In older women, HT increased events in the first year (OR 1.47 [CI, 1.12 to 1.92]), then reduced events after 2 years (OR 0.79 [CI, 0.67 to 0.93]).
CONCLUSIONS: Hormone therapy reduces the risk of CHD events in younger postmenopausal women. In older women, HT increases, then decreases risk over time.
References
Grodstein F, Stampfer MJ, Manson JE, et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med. 1996;335:453–61.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–33.
Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291:1701–12.
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.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.
Cochrane Collaboration. Cochrane Reviewer’s Handbook 4.2.2. Section 8. Analysing and presenting results. 2004. Accessed at http://www.cochrane.org/resources/handbook/section8.pdf on November 4, 2005.
Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326:219.
Komulainen M, Kroger H, Tuppurainen MT, et al. Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial. J Clin Endocrinol Metab. 1999;84:546–52.
Mosekilde L, Beck-Nielsen H, Sorensen OH, et al. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women—results of the Danish Osteoporosis Prevention Study. Maturitas. 2000;36:181–93.
Nachtigall LE, Nachtigall RH, Nachtigall RD, Beckman EM. Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. Obstet Gynecol. 1979;54:74–9.
Ravn P, Bidstrup M, Wasnich RD, et al. Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the early postmenopausal intervention cohort study. A randomized, controlled trial. Ann Intern Med. 1999;131:935–42.
Samaras K, Hayward CS, Sullivan D, Kelly RP, Campbell LV. Effects of postmenopausal hormone replacement therapy on central abdominal fat, glycemic control, lipid metabolism, and vascular factors in type 2 diabetes: a prospective study. Diabetes Care. 1999;22:1401–7.
Westendorp IC, de Kleijn MJ, Bots ML, et al. The effect of hormone replacement therapy on arterial distensibility and compliance in perimenopausal women: a 2-year randomised trial. Atherosclerosis. 2000;152:149–57.
Gallagher JC, Kable WT, Goldgar D. Effect of progestin therapy on cortical and trabecular bone: comparison with estrogen. Am J Med. 1991;90:171–8.
Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993;329:753–6.
Recker RR, Davies KM, Dowd RM, Heaney RP. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial. Ann Intern Med. 1999;130:897–904.
Herrington DM, Reboussin DM, Brosnihan KB, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med. 2000;343:522–9.
Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA. 1998;280:605–13.
Maheux R, Naud F, Rioux M, et al. A randomized, double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness. Am J Obstet Gynecol. 1994;170:642–9.
Os I, Hofstad AE, Brekke M, et al. The EWA (estrogen in women with atherosclerosis) study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins. J Intern Med. 2000;247:433–41.
Hall G, Pripp U, Schenck-Gustafsson K, Landgren BM. Long-term effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease. Maturitas. 1998;28:235–42.
Cherry N, Gilmour K, Hannaford P, et al. Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial. Lancet. 2002;360:2001–8.
Gallagher JC, Fowler SE, Detter JR, Sherman SS. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab. 2001;86:3618–28.
Hall GM, Daniels M, Doyle DV, Spector TD. Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids. Arthritis Rheum. 1994;37:1499–505.
Hodis HN, Mack WJ, Lobo RA, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001;135:939–53.
PEPI Trial Writing Group. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. 1995;273:199–208.
Utian WH, Shoupe D, Bachmann G, Pinkerton JV, Pickar JH. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril. 2001;75:1065–79.
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;345:1243–9.
Waters D, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women. JAMA. 2002;288:2432–40.
Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523–34.
Grodstein F, Stampfer MJ, Colditz GA, et al. Postmenopausal hormone therapy and mortality. N Engl J Med. 1997;336:1769–75.
Kannel WB, Wilson PW. Risk factors that attenuate the female coronary disease advantage. Arch Intern Med. 1995;155:57–61.
Hsia J, Langer RD, Manson JE, et al. Conjugated equine estrogens and coronary heart disease. The Women’s Health Initiative. Arch Intern Med. 2006;166:357–65.
Mikkola TS, Clarkson TB, Notelovitz M. Postmenopausal hormone therapy before and after the women’s health initiative study: what consequences? Ann Med. 2004;36:402–13.
Salpeter SR, Walsh JME, Ormiston TM, Greyber E, Buckley NS, Salpeter EE. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab. 2005; epub ahead of print.
Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998;279:1477–82.
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The institutions had no role in the design, conduct, or reporting of the study. No sponsorship from industry was provided to conduct this analysis.
The funding for this analysis came from salary support for Drs. Salpeter, Greyber, and Walsh.
An erratum to this article is available at http://dx.doi.org/10.1007/s11606-008-0762-2.
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Salpeter, S.R., Walsh, J.M.E., Greyber, E. et al. Brief report: Coronary heart disease events associated with hormone therapy in younger and older women. J Gen Intern Med 21, 363–366 (2006). https://doi.org/10.1111/j.1525-1497.2006.00389.x
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DOI: https://doi.org/10.1111/j.1525-1497.2006.00389.x