Re: Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial
To the editor,
Schierbeck et al(1) reported that, after 10 years of an open randomized study, women receiving hormone replacement therapy (HRT) early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke. In our opinion, this study results warrant caution.
In this trial, the open label design with a “no treatment” group of comparison creates important risks of bias. The awareness of the treated group about the intervention may affect the behavior of patients and staff in favor of the outcome, reduction of cardiac events. The trial largely took place when HRT was widely believed to reduce cardiovascular events prior to the reporting of the Heart and Estrogen∕ Progestin Replacement Study (HERS).(2) Also, the use of composite outcomes in this trial is problematic. Composite outcomes work often as an exaggerated perception of how well interventions work.(3)
Furthermore, the present study was not designed to evaluate cardiovascular outcomes a priori. The cardiovascular outcomes were not standardized, or monitored by the researchers, but based on individual clinicians’ inclusion of data in a national database.
1. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, Kober L, Jensen JE. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomized trial. BMJ 2012;345:e6409.
2. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998;280:605-13.
3. Cordoba G, Schwartz L, Woloshin S, Bae H, Gotzsche PC. Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review. BMJ 2010;341:c3920.
Competing interests: No competing interests