One of the main concerns from the large secondary and primary prevention cardiovascular trials such as the Heart and Estrogen/progestin Replacement Study and the Women's Health Initiative (WHI) study was that there appeared to be an increased risk of coronary events in the first years of usage. These findings were initially surprising bearing in mind that observational trials had previously shown benefit. Subsequent analyses have confirmed that the risks were primarily in the over-seventies age group. In the younger age groups (50-59 years), there was a trend towards reduction of risk and a significant reduction in all-cause mortality. Why did this occur? There are a number of possible reasons but, in the opinion of the author, the dose of estrogen was the overriding factor. Although 0.625 mg of conjugated equine estrogens is a standard dose for women in their early fifties, this was a relative overdose for women with an average age of initiation of 63 years (WHI). Inappropriately high doses of estrogen could have caused cardiovascular harm due to disturbances in thrombogenesis and vascular remodelling. Lower doses of hormone replacement therapy, or more accurately, more appropriately targeted doses for each age group, could avoid initial harm, thus allowing for long-term benefits to predominate.