RESEARCH – July 2007

The impact of hormone therapy on cardiovascular disease, bone fractures and cancer: The Estonian Postmenopausal Hormone Therapy randomised trial [ISRCTN35338757]


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Context: The US Women’s Health Initiative (WHI) trial was the only reported randomised controlled trial studying the effects of hormone therapy among healthy postmenopausal women before the Estonian Postmenopausal Hormone Therapy (EPHT) randomised trial was set up. It has been criticized as being, in part, a secondary cardiovascular prevention trial which could not test the hypothesis that hormone therapy may be cardioprotective when started around menopause.
Objectives: To compare the health effects of oral continuous combined hormone therapy versus placebo and non-treatment among healthy Estonian women.
Design: Population-based randomised controlled trial with a blind group of hormone therapy versus placebo and a non-blind group of open label hormone therapy versus non-treatment.
Setting: Three clinical centres in Estonia.
Participants: 1778 postmenopausal women aged 50–64 at the time of sampling recruited in 1999–2001.
Intervention: The participants received conjugated equine oestrogens, 625 g/d, plus medroxyprogesterone acetate, 2.5 mg/d, or conjugated equine oestrogens, 625 g/d, plus medroxyprogesterone  acetate, 5 mg/d, if less than 3 years had passed since menopause at the time of recruitment, or a matched placebo or non-treatment.
Main outcome measures: The incidence and the hazard ratio for coronary heart disease (ICD-10 I20-I25), cerebrovascular disease (ICD-10 I60-I69), total cancer (ICD-10 C00-C97), and bone fractures (ICD-10 S12, S22, S32, S42, S52, S62, S72, S82, S92).
Results: Trial treatment was stopped prematurely because of the WHI results from January 1, 2004 to May 31, 2004. After a follow-up period of 2.0 to 5.0 years the combined hazard ratio, adjusted for blinding, age group at recruitment and former oral contraceptive use was 1.12 (95% CI 0.90–1.40) for coronary heart disease, 1.24 (0.85–1.82) for cerebrovascular disease, 1.36 (0.73–2.52) for total cancer, and 0.61 (0.42–0.89) for bone fractures.
Conclusions: The results of the EPHT randomised trial showed a non-significant increase in cardiovascular diseases and total cancer, and a significant decrease in bone fractures among the healthy users of hormone therapy. These findings are consistent with the results of the WHI trial.