Results from the Women's Health Initiative randomized trial in 16,608 healthy postmenopausal women have revealed more risks than benefits in terms of invasive breast cancer and cardiovascular disease rates in patients treated for more than 5 years with a combination of conjugated oestrogens and progestin compared with placebo. Hormone-replacement therapy (HRT) is more effective in healthy women (maintaining vascular health) than in older women with atherosclerosis (restoring endothelial dysfunction). The initiation of HRT in patients at risk of a cardiovascular event results in an increased rate of cardiovascular complications and has not been proven beneficial in the long term. The point at which HRT is started after menopause plays a crucial role in the effectiveness of hormones on the vascular system: it is uncertain whether HRT initiated shortly after menopause can delay clinical signs of atherosclerotic disease.