Female Resistance to Hypoxia: Does It Explain the Sex Difference in Mortality Rates?

There is currently no accepted explanation in the medical literature for the lower female total mortality rate in infancy, childhood and adulthood. We review the pediatric mortality data provided by Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) and show that for causes of respiratory infant death that are apparently independent of gender (e.g., suffocation from inhalation of food or other object), there is a consistently one-third lower rate of mortality in the female than in the male. This one-third lower mortality for causes of death with a respiratory terminal event is hypothesized to be due to an X-linked dominant allele that occurs with frequency 1/3. It appears as if a second X chromosome provides the one-third extra probability of protection afforded for an XX female compared with an XY male. It is suggested that the allele's function is unmasked during transient periods of cerebral anoxia, requiring a mechanism for anaerobic oxidation to prevent the death of respiratory control neurons in the brain stem. Examples of the female one-third extra chance of resistance to hypoxia are given for causes of death in infancy, such as infant respiratory distress syndrome (IRDS) and sudden infant death syndrome (SIDS), and for causes of suffocation in childhood and asphyxiation in adulthood. DNA testing of the X chromosome of probands from causes of respiratory death, such as SIDS and IRDS, where there is a one-third lower female than male death rate, is a future direction that can verify the existence of the proposed allele.