Observational studies indicate that oral hormone replacement therapy (HRT) in menopause is associated with a 20-40% reduction of coronary risk. Population risk/benefit analyses on mortality after large-scale HRT use indicate that excess deaths can be counted when coronary heart disease is relatively less frequent than breast cancer before age 60 (as occurs in Italy). The decline in mortality trends for coronary heart disease support a word for caution for a large scale use of HRT in the next years even in those populations for which a relative advantage is presently estimated.