Do sex differences in chronic disease underpin the sex-frailty paradox?

The 'male-female health-survival paradox' is a well-described clinical phenomenon. More recently, it has been conceptualized as a 'sex-frailty paradox': females may be considered to be more frail (because they have poorer health status) but also less frail (because they are less vulnerable to death) than males of the same age. Here, we review potential biological, behavioral and social mechanisms underpinning sex differences in morbidity, mortality and frailty before considering the question at the center of the sex paradox - why is it that females are able to tolerate poor health better than males? We explore, in detail, a frequently cited explanation for the sex paradox that centers on sex differences in chronic disease and conclude by presenting a new approach to this old hypothesis.