Factors responsible for the gender difference in life-span being 4-5 years in favor of women were investigated. Cardiovascular risks are responsible for a five times higher mortality and three times higher morbidity in men compared with women. Genetics demonstrate marked gender differences in chromosomal constitution and female preponderance of the life-guard telomeres on chromosomes during mitotic cell division. This difference, however, cannot explain the gender gap fully. Endogenous estradiol - acting in picomoles - provokes marked cardiovascular changes. Cardiac output increases around 20% during the second half of the menstrual cycle and in pregnancy. This continuous biological challenge during the reproductive years creates optimal cardiovascular compliance comparable to the effects of exercise. The "jogging female heart" may explain the lower incidence of cardiovascular disease before menopause and the equalization after the menopause.