Number of women needed in a prospective trial to prove potential cardiovascular benefit of hormone replacement therapy

Abstract

Introduction Hormonal replacement therapy (HRT) may be beneficial for the cardiovascular system if hormones are given shortly after the onset of menopause. So far, no randomized trial has provided conclusive results.

Materials and methods Based on Belgian population data, we calculated the number of women that should be included in a prospective double-blinded study to prove a potential cardiovascular benefit of HRT. Sample size calculations were based on the extrapolation of empirical observations made in three large databases from epidemiological studies carried out in Belgium during the past 20 years.

Results The 10-year mortality varies with the age at which women are included in the observation. In the normal Belgian female population, the cardiovascular mortality risk is 0.85% and 1.58% for women aged 50–54 and 55–59 years, respectively. To prove that HRT induces a decrease of 10-year mortality of 30% in a normal population of 50–54-year-old women, 34 630 subjects would have to be included; for reductions of 20% and 10%, the numbers would be, respectively, 82 468 and 348 056. To prove a significant decrease in 10-year mortality starting with a normal population with an average age of 55–59 years, the numbers needed for hypothetical reductions of 30%, 20% and 10% would be, respectively, 18 514, 44 072 and 185 936.

Conclusion If cardiovascular mortality is the study end-point, it is obvious that such a study will be a gigantic task. Taking cardiovascular morbidity as the end-point, such a study would be feasible.

Key words:

• HORMONE REPLACEMENT THERAPY
• CARDIOVASCULAR BENEFIT
• PROSPECTIVE TRIAL