Everyone in America, regardless of sex, is at risk for certain health problems. Cancer is always looming, with researchers investigating everything from cell phones to soda as potential causes. Alzheimer’s is a threat as you get older, and chronic conditions like diabetes and lower respiratory disease are never anything to disregard.

Some health care challenges, however, are unique to one sex or the other. Breast cancer is about 100 times more common in women, while men have to deal with higher chances of autism. Prostate cancer only threatens males; lupus disproportionately affects women. Regardless of these differences, one overarching health truth has held true: Women live longer than men.

We’ve known this for a long time, but we’ve never known exactly why. Dr. Steven Austad and Dr. Kathleen Fischer, both of the University of Alabama at Birmingham, wrote a perspective piece exploring the subtle differences between the sexes when it comes to health, published in Cell Metabolism. Before we find out, they said, we need to clean up the way we do our research.

“Humans are the only species in which one sex is known to have a ubiquitous advantage,” the paper reads. “Indeed, the sex difference in longevity may be one of the most robust features of human biology.”

Studies of longevity by sex in other species, many of which the researchers include in their analysis, have had mixed findings. Between different experiments, lifespan advantage shifts with diet, mating habits, and environmental conditions. For example, surveying 118 studies of laboratory mice revealed that 51 studies suggested females outlived males and 65 claimed it was the other way around. Carefully monitoring the variables, the authors argue, could turn the mice into a useful model to study for sex differences in molecular and cellular aspects of aging.

Getting a better grip on this physiology could help scientists develop age-related drugs, according to Austad. The researchers suggest that differences in hormones, which occur as early as male-female differentiation in the uterus, as a possible cause for the difference between the sexes.

“We may be able to develop better approaches,” he said in a statement. “There is some complicated biology underlying sex differences that we need to work on.”

Even without knowing the mechanics of these biological differences, researchers have a breadth of research supporting the female advantage. The Human Mortality Database offers lifespan data starting in 1751; female life expectancy has consistently been higher than males in all 38 countries involved with the database. This advantage is lifelong, meaning that from the moment they are born, women are set to outlive the opposite sex. Even in times of crisis, including famine, drought, or war, women come out on top.

“Every year, regardless of food availability or pestilence, women at the beginning of life and near its end survived better than men,” the researchers wrote.

Women show resistance even to the most lethal diseases: “Of the 15 top causes of death in the United States in 2013, women died at a lower age-adjusted rate of 13 of them, including all of the top six causes.”

As nice as a longer life may be, female longevity has a major caveat.

“One of the most puzzling aspects of human sex difference biology,” the researchers write, “something that has no known equivalent in other species, is that for all their robustness relative to men in terms of survival, women on average appear to be in poorer health than men through adult life.”

This observation holds true not only in western countries like the United States, but also in Bangladesh, China, Indonesia, Malaysia, Jamaica, India, and several other Eastern and Latin countries. The researchers suggest that since women are more prone to joint and bone problems like osteoporosis, sex differences in morbidity could be due to connective tissue problems in women — tissues that are known to respond to female sex hormones.

This theory is one of many proposed to explain the differences between men and women when it comes to health, but nothing so far has proven to be a definitive cause.

Source: Austad S, Fischer K. Sex Differences in Lifespan. Cell Metabolism. 2016.