BMJ 1994;308:1268-1269 (14 May)

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Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased?

W F M Potshuma, R G J Westendorp, J P Vandenbroucke 

Department of Clinical Epidemiology, Leiden University Hospital, PO Box 9600, 2300 RC Leiden, Netherlands Correspondence and requests for reprints to: Dr Westendorp.

Abstract

Objective : To quantify the effect of selection of relatively healthy women in studies reporting reduced relative risk for cardiovascular disease in postmenopausal women taking hormone replacement therapy. Design - Review of the follow up studies reported in three recent meta- analyses to determine the effect of oestrogen therapy on both total cancer and cardiovascular disease. The same standard statistical methods as in the original analyses were used.
Main outcome measures : Relative risks of total cancer and cardiovascular disease.
Results : In most of the follow up studies the relative risk for total cancer was below 1. The studies that showed the largest reduction in cardiovascular disease also showed the largest reduction in cancer, indicating a healthy cohort effect. Although heterogeneity within the studies prevented pooling, the best estimate for the protective effect on total cancer was a relative risk of 0.83 among women taking oestrogen (95% confidence interval 0.71 to 0.96), while in the same studies the relative risk for cardiovascular disease was 0.57 (0.50 to 0.64).
Conclusions : Unintended selection of relatively healthy women for oestrogen therapy may have influenced the reported beneficial effect of oestrogen therapy on cardiovascular disease. It is unclear how much of the cardioprotection is due to this selection. Universal preventive hormonal replacement therapy for postmenopausal women is unwarranted at present.

Clinical implications

  • Clinical implications

  • Hormone replacement therapy has been recommended for all postmenopausal women to prevent cardiovascular disease

  • This recommendation is based on meta-analyses of observational studies

  • Further analysis of the results fron these observational studies also showed a reduced risk of cancer in women taking hormone replacement therapy

  • As oetrogen increases the risk of or has no effect on cancer, the results suggest a healthy cohort bias

  • Current evidence is insufficient to justify giving hormone replacement therapy to all postmenopausal women


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Relevant Article

Cardioprotective effect of hormone replacement therapy Is not due to a selection bias
M Stampfer, F Grodstein, D Spiers, W F M Posthuma, R G J Westendorp, and J P Vandenbroucke
BMJ 1994 309: 808-809. [Extract] [Full Text]

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