Why males are more likely to die from conception to old age

Sexual inequality begins in the womb, but not in the way you might think. In a study of more than 574,000 births in South Australia between 1981 and 2011, we found boys are more likely to be born preterm and the risk is greater for boys the earlier the birth.

Mothers expecting boys are also more likely than mothers of girls to suffer pre-eclampsia (a serious disorder of pregnancy characterised by high blood pressure, fluid retention and protein in the urine), gestational high blood pressure or gestational diabetes late in pregnancy.

Many more boys are conceived than girls. Despite this the sex ratio at birth is only slightly in boys’ favour. For every 100 girls born in Australia 106 boys are born, a statistic that holds across most human populations. But males are more likely to die before females at all ages from conception to old age, which we think explains why Australia is around 51% female despite fewer girls being born.

Miscarriages and stillbirths are more likely to involve males. After birth, male babies are also more likely to die or suffer major illness. Australian Institute of Health and Welfare data show boys make up 75% of SIDS deaths, 54% of cancer diagnoses, 60% of infant deaths and are more likely to be disabled (often associated with preterm birth).

As males and females age, disparities in the burden of diseases are prevalent in Australia. Greater numbers of men suffer heart disease (59%), endocrine disorders including type 2 diabetes (57%) and cancer (56%).

Some conditions, however, are more likely in women. These include blood and metabolic disorders (59%), neurological disorders including dementia (58%) and musculoskeletal conditions including arthritis (56%). There is also a female predominance in many auto-immune diseases.

Why are men more likely to die earlier?

We don’t know for sure why there are differences in disease prevalence, severity, age of onset and even symptoms between the sexes, but our research suggests genetic differences between males and females could contribute to differences in the uterus.

Males have XY sex chromosomes and females have XX sex chromosomes. We found 142 genes are expressed differently between normal male and female placentas delivered at term. About a third of the genes are on the sex chromosomes, but two-thirds are on the autosomes (non-sex chromosomes) and only a small number are associated with hormones.

The greatest sex differences are in the brain, specifically in the anterior cingulate cortex, which controls things such as heart rate and blood pressure as well as some emotion and decision-making (1,818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes) and thyroid (163 genes). In other organs, sex differences were mostly confined to genes on the sex chromosomes and those involved in hormone production.

Since defects in how the placenta develops and functions are associated with pregnancy complications, it is likely the placenta is a key contributor to the different outcomes we see between pregnancies carrying boys versus girls. These probably hark back to our evolution.

Evolution and the battle of the sexes

In the animal kingdom, males are somewhat dispensable, with the dominant male the most likely to breed with multiple females each season. Thus, in many species, it is only the biggest, strongest and fittest males who reproduce.

Bigger babies are more likely to survive birth and infancy and grow up to reproduce. So maintaining fetal and post-natal growth makes the male more likely to pass on his genes.

Females, conversely, will almost always reproduce and pass on their genes – assuming they survive to adulthood. So the growth strategies of the male and female fetus focus on passing on their genes to the next generation.

Research has found sex differences in how the fetus responds to maternal asthma. Asthma attacks in pregnancy, which are akin to an inflammatory storm, cause the female fetus to taper her growth in response. In so doing, the female fetus is more likely to survive.

However, a maternal asthma exacerbation does not affect the growth of the male fetus. He keeps growing at the same rate but places himself at risk of preterm birth and stillbirth should another asthma attack occur.

The developmental origins of health and disease thesis links the growth and development of the fetus to the health of the infant, child and adult. How well we grow in utero strongly influences our propensity for adult onset diseases. The fetus is said to be programmed in utero for health or disease across the life course.

So how well you grow in the uterus is influenced by your genetics but also by environmental factors. Together these shape your health for life and sex matters.

Claire Roberts receives funding from the National Health and Medical Research Council (NHMRC), the Channel 7 Children's Research Council and the University of Adelaide.