Twenty years of prospective follow up in the US Nurses' Health Study shows that daily HRT containing oestrogen doses of 0.625 mg or higher plus progestin may increase the risk of stroke by up to 1.45 times.

While data from the on going study show that HRT may prevent major coronary events in women with previous heart disease, the greatly increased risk of stroke means that women who take hormone replacement to prevent cardiovascular problems may be facing a double edged sword.

Based on data from completed questionnaires and medical records for 70,533 nurses, the study showed that, while there was little overall difference in the relative risk of stroke among users and non users of HRT, stroke risk varied according to the daily oestrogen dose.

Women taking 0.625 mg every day of oestrogen only HRT were 1.35 times more likely to experience a stroke. This risk rose to 1.63 times in women taking doses higher than 1.25 mg per day. Women taking combined pills had an intermediate risk of stroke of 1.45.

While this study found a decreased risk of coronary events with HRT, the authors suggest caution since these data contradict those of earlier randomised trials. Instead, they suggest that oestrogen could be associated with an early risk of coronary events followed by a later protective effect. The authors do stress, however, that this is not proven (Ann Intern Med, 2000; 133: 933-41).