Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women.

BACKGROUND There is apparently compelling evidence, from observational studies, that hormone replacement therapy (HRT) may have benefits in reducing cardiovascular events in post-menopausal women. However, these observational data are subject to biases and confounding and require support from formally designed randomised controlled trials of the effects of HRT on cardiovascular disease risk. OBJECTIVES To assess the effects of HRT for the primary and secondary prevention of cardiovascular diseases in post-menopausal women. SEARCH STRATEGY We searched MEDLINE (1998 to December 2002)), EMBASE (1998 to December 2002), the Cochrane Controlled Trials Register (CCTR) (Issue 4 2002), the National Research Register (1998 to present), Clinical Trials.gov (1998 to present), and the database of Spanish Clinical Trials (1998 to present) and reference lists of articles. SELECTION CRITERIA Randomised controlled trials comparing HRT with controls (placebo or no treatment) with a minimum follow up of 6 months for treating or preventing cardiovascular disease in postmenopausal women with or without cardiovascular disease. DATA COLLECTION AND ANALYSIS Three independent reviewers extracted information from the articles, solving discrepancies by consensus. All outcomes studied were dichotomous. Risk ratios and 95% confidence intervals (CI) were calculated for each study and plotted. Random effects meta-analysis was used in efficacy outcomes (cardiovascular events) and fixed-effects meta-analysis in variables regarding side effects (deep venous thrombosis). MAIN RESULTS No protective effect of HRT was seen for any of the cardiovascular outcomes assessed: all cause mortality, cardiovascular death, non-fatal MI, venous thromboemboli or stroke. Higher risks of venous thromboembolic events (Relative risk (RR) 2.15, 95% CI 1.61 to 2.86), pulmonary embolus (RR 2.15, 95% CI 1.41 to 3.28), and stroke (RR 1.44, 95% CI 1.10 to 1.89) was found in those randomised to HRT compared with placebo. No substantial heterogeneity (p <0.1) was detected in any of the outcomes studied. AUTHORS' CONCLUSIONS At present, a recommendation for initiating HRT for the reason of preventing cardiovascular events in post-menopausal women (with or without cardiovascular disease) should not be made. Women with other risk factors for venous thromboembolic events should be discouraged from using HRT if the sole goal is to prevent cardiovascular events.

[1]  Shah Ebrahim,et al.  Socioeconomic position and hormone replacement therapy use: explaining the discrepancy in evidence from observational and randomized controlled trials. , 2004, American journal of public health.

[2]  N. Cherry,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[3]  J. Hsia,et al.  Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: A randomized controlled trial , 2002 .

[4]  C. White.  Second long term HRT trial stopped early , 2002, British medical journal.

[5]  V. Beral,et al.  Evidence from randomised trials on the long-term effects of hormone replacement therapy , 2002, The Lancet.

[6]  P. Schofield,et al.  A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT Atherosclerosis Study , 2002, BJOG : an international journal of obstetrics and gynaecology.

[7]  H. Sox,et al.  Postmenopausal Hormone Replacement Therapy and the Primary Prevention of Cardiovascular Disease , 2002, Annals of Internal Medicine.

[8]  Graham A Colditz,et al.  Failure of estrogen plus progestin therapy for prevention. , 2002, JAMA.

[9]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[10]  D. Petitti.  Hormone replacement therapy for prevention: more evidence, more pessimism. , 2002, JAMA.

[11]  Deborah Grady,et al.  Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). , 2002, JAMA.

[12]  D. Grady.  A 60-year-old woman trying to discontinue hormone replacement therapy. , 2002, JAMA.

[13]  B. Vastag.  Hormone replacement therapy falls out of favor with expert committee. , 2002, JAMA.

[14]  E. Barrett-Connor,et al.  Raloxifene and Cardiovascular Events in Osteoporotic Postmenopausal Women: Four-Year Results From the MORE (Multiple Outcomes of Raloxifene Evaluation) Randomized Trial , 2002 .

[15]  A. Verbeek,et al.  Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. , 2002, American journal of epidemiology.

[16]  S. Reis,et al.  Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina. , 2002, Journal of the American College of Cardiology.

[17]  Robert Selzer,et al.  Estrogen in the Prevention of Atherosclerosis , 2001, Annals of Internal Medicine.

[18]  C. Viscoli,et al.  A clinical trial of estrogen-replacement therapy after ischemic stroke. , 2001, The New England journal of medicine.

[19]  J. Hsia,et al.  Postmenopausal Hormone Therapy and Risk of Stroke: The Heart and Estrogen-progestin Replacement Study (HERS) , 2001, Circulation.

[20]  S. Störk,et al.  Effect of Oral Postmenopausal Hormone Replacement on Progression of Atherosclerosis: A Randomized, Controlled Trial , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[21]  H. Arnesen,et al.  Increased Risk of Recurrent Venous Thromboembolism during Hormone Replacement Therapy , 2000, Thrombosis and Haemostasis.

[22]  N. Cherry,et al.  Oestrogen and women's heart disease: ESPRIT-UK. , 2000, QJM : monthly journal of the Association of Physicians.

[23]  D. Reboussin,et al.  Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. , 2000, The New England journal of medicine.

[24]  N. Wenger.  Hormonal and Nonhormonal Therapies for the Postmenopausal Woman: What is the Evidence for Cardioprotection? , 2000, The American journal of geriatric cardiology.

[25]  D. Reboussin,et al.  The estrogen replacement and atherosclerosis (ERA) study: study design and baseline characteristics of the cohort. , 2000, Controlled clinical trials.

[26]  K. McPherson,et al.  Value of drug-licensing documents in studying the effect of postmenopausal hormone therapy on cardiovascular disease , 2000, The Lancet.

[27]  Paul Cleary,et al.  Use of Hormone Replacement Therapy by Postmenopausal Women in the United States , 1999, Annals of Internal Medicine.

[28]  L. Speroff,et al.  The heart and estrogen/progestin replacement study (HERS). , 1998, Maturitas.

[29]  E. Vittinghoff,et al.  Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. , 1998, JAMA.

[30]  K. Schenck-Gustafsson,et al.  Longterm effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease , 1998 .

[31]  JoAnn E. Manson,et al.  Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group. , 1998, Controlled clinical trials.

[32]  E. Barrett-Connor,et al.  Hormone replacement therapy, heart disease, and other considerations. , 1998, Annual review of public health.

[33]  K. McPherson,et al.  Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials , 1997, BMJ.

[34]  B. Psaty,et al.  Duration of estrogen replacement therapy in relation to the risk of incident myocardial infarction in postmenopausal women. , 1997, Archives of internal medicine.

[35]  H. Genant,et al.  The comparative effect on bone density, endometrium, and lipids of continuous hormones as replacement therapy (CHART study). A randomized controlled trial. , 1996, JAMA.

[36]  J. Manson,et al.  Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. , 1996, The New England journal of medicine.

[37]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[38]  S. Wimalawansa.  Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae: four-year randomized study. , 1995, The American journal of medicine.

[39]  S. Tonstad,et al.  Efficacy of sequential hormone replacement therapy in the treatment of hypercholesterolemia among postmenopausal women , 1995, Journal of internal medicine.

[40]  M. Clarke,et al.  Identifying relevant studies for systematic reviews , 1995, BMJ.

[41]  M. Sheehan,et al.  The influence of menopause and hormonal replacement therapy on body cell mass and body fat mass. , 1995, American journal of obstetrics and gynecology.

[42]  Susan R. Johnson,et al.  Effects of Estrogen or Estrogen/ Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial , 1995 .

[43]  T. Meade,et al.  Hormone replacement therapy and cardiovascular disease: the case for a randomized controlled trial. , 1995, Ciba Foundation symposium.

[44]  K. Dickersin,et al.  Systematic Reviews: Identifying relevant studies for systematic reviews , 1994 .

[45]  D. Edwards,et al.  Continuous combined and sequential estradiol and norethindrone acetate treatment of postmenopausal women: effect of plasma lipoproteins in a two-year placebo-controlled trial. , 1994, American journal of obstetrics and gynecology.

[46]  D. Petitti.  Coronary heart disease and estrogen replacement therapy. Can compliance bias explain the results of observational studies? , 1994, Annals of epidemiology.

[47]  J. Aloia,et al.  Calcium Supplementation with and without Hormone Replacement Therapy To Prevent Postmenopausal Bone Loss , 1994, Annals of Internal Medicine.

[48]  S. P. Nielsen,et al.  A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment. , 1993, Maturitas.

[49]  Caroline S. Fox,et al.  Hormone Therapy To Prevent Disease and Prolong Life in Postmenopausal Women , 1992, Annals of Internal Medicine.

[50]  A. Lane,et al.  Treatment of Postmenopausal Osteoporosis with Transdermal Estrogen , 1992, Annals of Internal Medicine.

[51]  C. Christiansen,et al.  Changes in calcanean bone mineral occurring spontaneously and during hormone replacement therapy in early post-menopausal women. , 1992, Scandinavian journal of clinical and laboratory investigation.

[52]  J. Gallagher,et al.  Clinical studiesEffect of progestin therapy on cortical and trabecular bone: Comparison with estrogen* , 1991 .

[53]  G. Colditz,et al.  Estrogen replacement therapy and coronary heart disease: A quantitative assessment of the epidemiologic evidence☆☆☆ , 1991 .

[54]  C. Christiansen,et al.  17 Beta-estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women. , 1990, The Journal of clinical endocrinology and metabolism.

[55]  P. Pietschmann,et al.  Effects of one-year hormone replacement therapy on peripheral bone mineral content in patients with osteoporotic spine fractures. , 1990, Acta endocrinologica.

[56]  D. Mellström,et al.  Effect of oral oestriol on vaginal flora and cytology and urogenital symptoms in the post-menopause. , 1990, Maturitas.

[57]  C. Christiansen,et al.  Estrogen/gestagen therapy changes soft tissue body composition in postmenopausal women. , 1989, Metabolism: clinical and experimental.

[58]  C. Christiansen,et al.  Long-term and withdrawal effects of two different oestrogen-progestogen combinations on lipid and lipoprotein profiles in post-menopausal women. , 1989, Maturitas.

[59]  S. P. Nielsen,et al.  Reversal of postmenopausal vertebral bone loss by oestrogen and progestogen: a double blind placebo controlled study , 1988, British medical journal.

[60]  C. Christiansen,et al.  The long-term effect of oral and percutaneous estradiol on plasma renin substrate and blood pressure. , 1987, Circulation.

[61]  C. Christiansen,et al.  The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss. , 1987, American journal of obstetrics and gynecology.

[62]  C. Christiansen,et al.  Dose-response evaluation of cyclic estrogen/gestagen in postmenopausal women: placebo-controlled trial of its gynecologic and metabolic actions. , 1982, American journal of obstetrics and gynecology.

[63]  W. O'Fallon,et al.  Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis. Comparison with conventional therapy. , 1982, The New England journal of medicine.

[64]  C. Christiansen,et al.  Effect of 1,25‐dihydroxy ‐ vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis , 1981, European journal of clinical investigation.

[65]  J. Coope.  Is oestrogen therapy effective in the treatment of menopausal depression? , 1981, The Journal of the Royal College of General Practitioners.

[66]  C. Christiansen,et al.  Prevention of early postmenopausal bone loss: controlled 2‐year study in 315 normal females , 1971, European journal of clinical investigation.

[67]  E. Beckman,et al.  Estrogen replacement therapy II: a prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. , 1979, Obstetrics and gynecology.

[68]  R. Lindsay,et al.  Oestrogen Replacement Therapy for Prevention of Osteoporosis after Oophorectomy , 1973, British medical journal.