GENETICS: GENDER

Most of the differences between human males and females are based on the chromosomal mechanism of sex determination—two X-chromosomes in females and one X chromosome and one Y chromosome in males. There is a gene on the Y chromosome (called Sry) that encodes a protein (called testis differention factor (TDF)) that is required for testicular development. The testes secrete male sex hormones (androgens), which set in motion a cascade that affects both biology and behavior and makes men and women very different creatures.

These differences affect aging, beginning by the fifth decade of life. The death rate, which increases exponentially with age, was 1.7 times higher in males of the fifty-five to fifty-nine age group in 1998 than in females. This difference is largely because of diseases of the circulatory system, in which the male death rate was 2.3 times the female rate in this age group. The estrogenic hormones secreted by the ovaries modulate circulating cholesterol levels, with higher levels of low-density lipoprotein (LDL) cholesterol and lower levels of high-density lipoprotein (HDL) cholesterol in males on the average. The male pattern is associated with greater risk of death from heart disease. At reproductive senescence, with involution of the gonads, the protective effects of estrogens are lost, and eventually the death rate from heart disease in females catches up with that of males. Another consequence of the cessation of estrogen production at reproductive senescence is the gradual demineralization of bone, resulting in osteoporosis, with its attendant fractures. This, plus a likely effect on cholesterol, provide the rationale for taking post-menopausal estrogens.

Another disease contributing in a major way to the higher male death rate is lung cancer, in which the death rate of males in the fifty-five to fifty-nine age group is 1.7 times the female death rate. The difference is related to the greater rate of smoking among males.

A consequence of the differing death rates is a difference in the life expectancies at birth of males and females, with a greater life expectancy seen in females in all developed countries. This gender gap in longevities was 6.7 years in 1998 in the United States (73.5 years vs. 80.2 years). It ranges from 6.5 years to 8.5 years in other developed countries. A social consequence of the gender gap is that the sex ratio, which is 1.05 (males/ females) at birth is about 0.33 at age eighty-five. Widows greatly outnumber widowers. In general, men die quickly of catastrophic illnesses while women become older and suffer from more chronic diseases. An important example is Alzheimer's disease. A major part of its greater incidence in women is that they live longer, but there is a greater female prevalence even after adjustment or stratification for age.

Interestingly, those males who survive to an advanced age are, on the average, in better condition than females of the same age.

David W. E. Smith

BIBLIOGRAPHY

Fratiglioni, L.; Viitanin, M.; von Strauss, E.; Tontodonati, V.; Herlitz, A.; and Winblad, B. "Very Old Women at Risk of Dementia and Alzheimer's Disease." Neurology 48 (1997): 132–138.

Koopman, P. "Sry and Sox 9: Mammalian Testisdetermining Genes." Cellular and Molecular Sciences 55 (1999): 839–856.

National Center for Health Statistics. "Vital Statistics of the United States: Mortality 1979–1998." Tables 292a. Available on the Internet at www.cdc/nchs/

Smith, D. W. E. "Women Live Longer than Men." In Human Longevity. Oxford, U.K., and New York: Oxford University Press, 1993. Pages 71–98.

Smith, D. W. E. "Centenarians: Longevity Outliers." The Gerontologist 37 (1997): 200–207.