To the Editor.
—In focusing on the lipid effects of estrogen, Drs Barrett-Connor and Bush1 sharply restrict the scope of the debate on the sex difference in the risk of heart disease. An implicit assumption that sex is a nonmodifiable coronary risk factor further limits the discussion. The nature of the potent protective factor in menstruating women has not been established. We must take care not to overlook a mechanism that may also be protective in men and postmenopausal women.The suggestion that the effect of estrogen on lipid metabolism is the protective factor1 is not tenable in light of well-documented findings on heart disease expression in women with familial hypercholesterolemia (FH).2,3 Genetic lesions provide us with extreme cases that can clarify basic questions. In heterozygous FH, the sex difference in heart disease expression is preserved despite the lack of a corresponding sex difference in lipid phenotype.