Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial
- PMID: 12117397
- DOI: 10.1001/jama.288.3.321
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial
Abstract
Context: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.
Objective: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.
Design: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.
Interventions: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).
Main outcomes measures: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.
Results: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.
Conclusions: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Comment in
-
Failure of estrogen plus progestin therapy for prevention.JAMA. 2002 Jul 17;288(3):366-8. doi: 10.1001/jama.288.3.366. JAMA. 2002. PMID: 12117403 No abstract available.
-
Postmenopausal hormone replacement therapy for chronic disease prevention: results from the Women's Health Initiative trial.CMAJ. 2002 Aug 20;167(4):377-8. CMAJ. 2002. PMID: 12197697 Free PMC article. No abstract available.
-
Estrogen plus progestin increased coronary heart disease and breast cancer events in postmenopausal women.ACP J Club. 2002 Sep-Oct;137(2):41. ACP J Club. 2002. PMID: 12207419 No abstract available.
-
Do the risks of estrogen plus progestin outweigh the benefits in healthy post-menopausal women?J Fam Pract. 2002 Oct;51(10):821. J Fam Pract. 2002. PMID: 12401147 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2819; author reply 2823-4. doi: 10.1001/jama.288.22.2819. JAMA. 2002. PMID: 12472311 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2822; author reply 2823-4. doi: 10.1001/jama.288.22.2822-jlt1211-1-10. JAMA. 2002. PMID: 12472312 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2822; author reply 2823-4. doi: 10.1001/jama.288.22.2822-jlt1211-1-9. JAMA. 2002. PMID: 12472313 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2821-2; author reply 2823-4. doi: 10.1001/jama.288.22.2821-jlt1211-1-8. JAMA. 2002. PMID: 12472314 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2821; author reply 2823-4. doi: 10.1001/jama.288.22.2821-jlt1211-1-7. JAMA. 2002. PMID: 12472315 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2822-3; author reply 2823-4. doi: 10.1001/jama.288.22.2822-jlt1211-1-11. JAMA. 2002. PMID: 12472316 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2821; author reply 2823-4. doi: 10.1001/jama.288.22.2821-jlt1211-1-6. JAMA. 2002. PMID: 12472317 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2820-1; author reply 2823-4. doi: 10.1001/jama.288.22.2820-jlt1211-1-5. JAMA. 2002. PMID: 12472318 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2820; author reply 2823-4. doi: 10.1001/jama.288.22.2820-jlt1211-1-4. JAMA. 2002. PMID: 12472319 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2820; author reply 2823-4. doi: 10.1001/jama.288.22.2820-jlt1211-1-3. JAMA. 2002. PMID: 12472320 No abstract available.
-
Risks of postmenopausal hormone replacement.JAMA. 2002 Dec 11;288(22):2819-20; author reply 2823-4. doi: 10.1001/jama.288.22.2819-jlt1211-1-2. JAMA. 2002. PMID: 12472321 No abstract available.
-
Hormone replacement following early menopause.JAMA. 2002 Dec 11;288(22):2824-5; author reply 2825. JAMA. 2002. PMID: 12472322 No abstract available.
-
Oestrogen plus progestin increased coronary heart disease and breast cancer in postmenopausal women.Evid Based Nurs. 2003 Jan;6(1):20. doi: 10.1136/ebn.6.1.20. Evid Based Nurs. 2003. PMID: 12546038 No abstract available.
-
Estrogen therapy in postmenopausal women.Curr Rheumatol Rep. 2003 Feb;5(1):43-4. doi: 10.1007/s11926-003-0082-9. Curr Rheumatol Rep. 2003. PMID: 12590884 No abstract available.
-
Hormone replacement therapy: the final frontier.Can Fam Physician. 2003 Feb;49:157-9. Can Fam Physician. 2003. PMID: 12619737 Free PMC article. No abstract available.
-
Prescriptions for estrogen replacement therapy in Ontario before and after publication of the Women's Health Initiative Study.JAMA. 2003 Jun 25;289(24):3241-2. doi: 10.1001/jama.289.24.3241. JAMA. 2003. PMID: 12824204 No abstract available.
-
Hormone replacement therapy.S Afr Med J. 2003 Aug;93(8):554-5. S Afr Med J. 2003. PMID: 14531100 No abstract available.
-
Exercise and risk of breast cancer.JAMA. 2003 Dec 24;290(24):3193; author reply 3193. doi: 10.1001/jama.290.24.3193-a. JAMA. 2003. PMID: 14693869 No abstract available.
-
Effects of estrogen-only treatment in postmenopausal women.JAMA. 2004 Aug 11;292(6):683-4; author reply 685-6. doi: 10.1001/jama.292.6.683-c. JAMA. 2004. PMID: 15304457 No abstract available.
-
Effects of estrogen-only treatment in postmenopausal women.JAMA. 2004 Aug 11;292(6):684-5; author reply 685-6. doi: 10.1001/jama.292.6.684-c. JAMA. 2004. PMID: 15304459 No abstract available.
-
Estrogen plus progestin and risk of venous thrombosis.JAMA. 2005 Mar 16;293(11):1322; author reply 1322-3. doi: 10.1001/jama.293.11.1322-b. JAMA. 2005. PMID: 15769960 No abstract available.
-
Low-fat diet and cardiovascular disease.JAMA. 2006 Jul 19;296(3):280; author reply 280-1. doi: 10.1001/jama.296.3.280-a. JAMA. 2006. PMID: 16849659 No abstract available.
-
Risk of cancer was still increased over 2 years after stopping hormone therapy.Evid Based Med. 2008 Oct;13(5):142. doi: 10.1136/ebm.13.5.142. Evid Based Med. 2008. PMID: 18836110 No abstract available.
-
Commentary on "menopausal hormone treatment in postmenopausal women: risks and benefits".South Med J. 2014 Nov;107(11):696-7. doi: 10.14423/SMJ.0000000000000191. South Med J. 2014. PMID: 25365436 No abstract available.
-
Effectiveness of transdermal oestradiol and natural micronised progesterone for menopausal symptoms.Br J Gen Pract. 2018 Oct;68(675):499-500. doi: 10.3399/bjgp18X699353. Br J Gen Pract. 2018. PMID: 30262631 Free PMC article. No abstract available.
-
The dangers of compounded bioidentical hormone replacement therapy.Br J Gen Pract. 2019 Oct 31;69(688):540-541. doi: 10.3399/bjgp19X706169. Print 2019 Nov. Br J Gen Pract. 2019. PMID: 31672802 Free PMC article. No abstract available.
Similar articles
-
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.JAMA. 2004 Apr 14;291(14):1701-12. doi: 10.1001/jama.291.14.1701. JAMA. 2004. PMID: 15082697 Clinical Trial.
-
Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials.JAMA. 2013 Oct 2;310(13):1353-68. doi: 10.1001/jama.2013.278040. JAMA. 2013. PMID: 24084921 Free PMC article. Clinical Trial.
-
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.JAMA. 1998 Aug 19;280(7):605-13. doi: 10.1001/jama.280.7.605. JAMA. 1998. PMID: 9718051 Clinical Trial.
-
The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.JAMA. 2024 May 28;331(20):1748-1760. doi: 10.1001/jama.2024.6542. JAMA. 2024. PMID: 38691368 Review.
-
Postmenopausal hormone therapy and the risks of coronary heart disease, breast cancer, and stroke.Semin Reprod Med. 2014 Nov;32(6):419-25. doi: 10.1055/s-0034-1384624. Epub 2014 Oct 16. Semin Reprod Med. 2014. PMID: 25321418 Free PMC article. Review.
Cited by
-
Estrogen Regulated Genes Compel Apoptosis in Breast Cancer Cells, Whilst Stimulate Antitumor Activity in Peritumoral Immune Cells in a Janus-Faced Manner.Curr Oncol. 2024 Aug 24;31(9):4885-4907. doi: 10.3390/curroncol31090362. Curr Oncol. 2024. PMID: 39329990 Free PMC article. Review.
-
Sex differences in survival outcomes of early-onset colorectal cancer.Sci Rep. 2024 Sep 26;14(1):22041. doi: 10.1038/s41598-024-71999-8. Sci Rep. 2024. PMID: 39327445 Free PMC article.
-
Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation.Adv Exp Med Biol. 2024;1460:767-819. doi: 10.1007/978-3-031-63657-8_26. Adv Exp Med Biol. 2024. PMID: 39287872 Review.
-
A sex-oriented analysis concerning skeletal muscle quantity and quality and associations to quality of life in hospitalized patients with cirrhosis.Health Qual Life Outcomes. 2024 Sep 12;22(1):78. doi: 10.1186/s12955-024-02295-2. Health Qual Life Outcomes. 2024. PMID: 39267044 Free PMC article.
-
Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biol Res. 2024 Sep 4;57(1):61. doi: 10.1186/s40659-024-00542-w. Biol Res. 2024. PMID: 39227995 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous