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Basic biology may explain higher death rates for boys

(Reuters Health) - It's known that women, as a group, outlive men, but the female survival advantage begins at birth and may stem from some fundamental vulnerability of boys, according to a new study.

Researchers looking at U.S. national data on both boys and girls from infancy up to age 20 found boys more likely to experience a range of illnesses, and to die of them, than girls.

"What is surprising is that the pattern of excess male mortality exists across such a broad range of diseases and at all ages," said the study's senior author Dr. Chris Feudtner of The Children's Hospital of Philadelphia.

Less surprising is that boys were also at greater risk for death from accidental or violent injuries, especially as teenagers, which is when the difference in risk between boys and girls is largest, Feudtner told Reuters Health.

But the pattern of disease-linked deaths, extending from birth through young adulthood, suggests there may be a genetic, hormonal or other explanation for female robustness or male vulnerability, the authors write in Pediatrics.

Previous research has found a disparity in deaths between boys and girls, and shown that it begins at an early age (see Reuters story of March 24, 2008 here: reut.rs/le797B).

That has prompted debate about whether the difference results from behavior, biology or both.

Feudtner and his coauthors used data from the Centers for Disease Control and Prevention for diseases and deaths between 1999 and 2008 among all individuals in the U.S. younger than 20 years old, and compared it to the estimated number of boys and girls nationwide based on the 2000 census.

In all age groups, boys were 1.44 times more likely to die than girls, in general, and were more likely than girls to die from diseases in 17 out of 19 categories.

That 44 percent greater risk is important, said Alexander Kulminski, a senior research scientist at the Duke University Population Research Institute's Center for Population Health and Aging in Durham, North Carolina.

"This is a big difference," Kulminski told Reuters Health. "Put it in this way, for two dying girls we have almost three dying boys."

Among infants, males were more likely to die than females at every week of age, and overall 1.12 times more likely to die.

As previous studies have shown, the biggest gender gap in mortality occurs between 15 and 19 years old, when boys are nearly two and a half times more likely than girls to die.

"The infant mortality rate is due to a wide variety of congenital malformations and genetic or metabolic conditions, as well as problems that occur during the process of being born, and then the risk of death goes down until it starts to rise again, mostly due to rising risk of external causes of death like car accidents and violent injuries," Feudtner told Reuters Health via email.

In all age groups, however, males were 13 percent more likely than girls to develop one of the seven types of pediatric cancer. And, when girls and boys with the same cancers were compared, boys were 10 percent more likely to die from the disease.

Only in two disease categories - disorders of the muscles, bones or connective tissue and of the skin - girls were at greater risk, and the difference was almost entirely accounted for by cases of lupus, which is more common in females.

This provides good evidence that the differences in risk of dying between females and males in childhood, and perhaps even in adulthood, might be traced to their different biology, according to Kulminski.

Among adult men and women, cardiovascular risk factors, exposure to alcohol and tobacco and risky behaviors are often cited as the main reasons for mortality differences, Feudtner said.

But in this study, the differences cannot be attributed to alcohol or tobacco and are unlikely due to behavior, he said. That makes genetics or a gene-environment interaction the most likely explanation, he said.

For example, Feudtner and his coauthors point out in their report, the X chromosome "has 836 active protein-coding genes" and women have two copies of it whereas men only have one. That raises men's vulnerability to diseases caused by recessive genes and makes DNA repairs in that chromosome more difficult.

In addition, Kulminski noted, the same gene sometimes acts differently in a man compared to a woman and can sometimes have a protective effect against a disease for one person while increasing the risk of that disease for another.

Understanding what causes the 44 percent increased risk of death for boys could have important implications in the future for prevention or therapy, Feudtner said.

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