Abstract
Objectives
At present the Women's Health Initiative trial is the only reported randomised controlled
trial studying the effects of hormone therapy among healthy postmenopausal women.
The Women's Health Initiative reports have been criticized for lacking in generalisability,
due to the characteristics of the trial population. We aimed to compare the health
effects of oral continuous combined hormone therapy with a placebo and non-treatment
among healthy Estonian women.
Methods
Eligible women were randomised into a blind group of hormone therapy versus placebo
and into a non-blind group of open label hormone therapy versus non-treatment. One
thousand seven hundred and seventy-eight postmenopausal women aged 50–64 at the time
of sampling were recruited in 1999–2001 at three clinical centers in Estonia. Participants
received conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 5 mg/d, if less than 3 years had passed since menopause at recruitment, or matched placebo
or non-treatment. Trial treatment was stopped gradually from 1 January 2004 to 31
May 2004.
Results
After a follow-up period from 2.0 to 5.0 years the combined hazard ratio, stratified
by blinding and adjusted for age at recruitment and former oral contraceptive use
was 1.12 (95% confidence interval [CI]: 0.90–1.40) for coronary heart disease, 1.24
(95% CI: 0.85–1.82) for cerebrovascular disease, 1.36 (95% CI: 0.73–2.52) for total
cancer, and 0.61 (95% CI: 0.42 to 0.89) for bone fractures.
Conclusions
The results from the Estonian Postmenopausal Hormone Therapy randomised trial are
consistent with the Women's Health Initiative findings.
Keywords
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References
- Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women.JAMA. 1998; 280: 605-613
- Cardiovascular disease outcomes during 6.8 years of hormone therapy. Heart and Estrogen/Progestin Replacement Study follow up (HERS II).JAMA. 2002; 288: 49-57
- Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial.Lancet. 2002; 360: 2001-2008
- A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT Atherosclerosis Study.Br J Obstet Gynaecol. 2002; 109: 1056-1062
- Effects of estrogen replacement on the progression of coronary–artery atherosclerosis.N Engl J Med. 2000; 343: 522-529
- Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women. A randomized controlled trial.JAMA. 2002; 288: 2432-2440
- Hormone therapy and the progression of coronary–artery atherosclerosis in postmenopausal women.N Engl J Med. 2003; 349: 535-545
- A clinical trial of estrogen-replacement therapy after ischemic stroke.N Engl J Med. 2001; 345: 1243-1249
- Increased risk of recurrent venous thromboembolism during hormone replacement therapy: results of the randomised, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET).Thromb Haemost. 2000; 84: 961-967
- Noncardiovascular disease outcomes during 6.8 years of hormone therapy. Heart and estrogen/progestin replacement study follow-up (HERS II).JAMA. 2002; 288: 58-66
- Postmenopausal hormone therapy increases risk for venous thromboembolic disease: the heart and estrogen/progestin replacement study.Ann Intern Med. 2000; 132: 689-696
- Glycemic effects of postmenopausal hormone therapy: the heart and estrogen/progestin replacement study: a randomized, double-blind, placebo-controlled trial.Ann Intern Med. 2003; 138: 1-9
- 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: 321-333
- Estrogen plus progestin and the risk of coronary heart disease.N Engl J Med. 2003; 349: 523-534
- Effects of estrogen plus progestin on stroke in postmenopausal women. The Women's Health Initiative: a randomized trial.JAMA. 2003; 289: 2673-2684
- Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. The Women's Health Initiative randomized trial.JAMA. 2003; 289: 3243-3253
- Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The Women's Health Initiative Memory Study: a randomized controlled trial.JAMA. 2003; 289: 2651-2662
- Effects of estrogen plus progestin on risk of fracture and bone mineral density. The Women's Health Initiative Randomized Trial.JAMA. 2003; 290: 1729-1738
- Estrogen plus progestin and colorectal cancer in postmenopausal women.N Engl J Med. 2004; 350: 991-1004
- Estrogen plus progestin and the risk of peripheral arterial disease. The Women's Health Initiative.Circulation. 2004; 109: 620-626
- The randomized world is not without its imperfections: reflections on the Women's Health Initiative Study.Fertil Steril. 2002; 78: 951-956
- The end of WISDOM.Climacteric. 2002; 5: 313-316
- Impact of blinding on recruitment—The Estonian Postmenopausal Hormone Therapy Trial.J Clin Epidemiol. 2004; 57: 1237-1243
- WISDOM: history and early demise—was it inevitable?.Climacteric. 2002; 5: 317-325
International Statistical Classification of Diseases and Related Health Problems, 1989 Revision. Geneva: World Health Organization; 1992.
- Breast cancer and hormone-replacement therapy in the Million Women Study.Lancet. 2003; 362: 419-427
- 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: 2663-2672
- Effects of estrogen plus progestin on health-related quality of life.N Engl J Med. 2003; 348: 1839-1854
- Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures. The Women's Health Initiative randomized trial.JAMA. 2003; 290: 1739-1748
- Study of completeness of registration at the Estonian cancer registry.Eur J Cancer Prev. 2003; 12: 153-156
Estonian Health Insurance Fund. Available at: http://www.haigekassa.ee/HK/in_english.htm. Accessed October 14, 2004.
The R Project for Statistical Computing. Available at: http://www.r-project.org. Accessed August 9, 2005.
- Postmenopausal hormone replacement therapy. Scientific review.JAMA. 2002; 288: 872-881
- Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials.JAMA. 2001; 285: 2891-2897
- Effects of hormone therapy on bone mineral density: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial.JAMA. 1996; 275: 1389-1396
- Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis.Am J Med. 1999; 106: 574-582
- Comparison of Estonian and Finnish physicians’ opinions of menopause and hormone therapy.Maturitas. 2004; 49: 107-113
- Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.Health Technol Assess. 2003; 7: 1-117
- Hormone replacement therapy in postmenopausal women: utilization of health care resources by new users.Am J Obstet Gynecol. 2001; 185: 318-326
- Treatment adherence in the Estonian postmenopausal hormone therapy (EPHT) trial [ISRCTN35338757].Maturitas. 2005; 52: 286-295
Article info
Publication history
Accepted:
January 30,
2006
Received in revised form:
January 26,
2006
Received:
October 3,
2005
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
