Female Survival Advantage Relates to Male Inferiority Rather Than Female Superiority: A Hypothesis Based on the Impact of Age and Stroke Severity on 1-Week to 1-Year Case Fatality in 40,155 Men and Women

Background: It is generally believed that differences in age, stroke characteristics, and cardiovascular risk factors account for observed sex-specific differences in stroke survival. Objectives: We aimed to study female stroke survival advantage before and after the average age of menopause, and whether female survival advantage applies only to patients for whom stroke is the most likely cause of death.

Methods: The Danish National Indicator Project, a registry designed to list all hospitalized stroke patients in Denmark beginning in March 2001, had 40,155 registered patients as of February 2007. All registered patients had undergone evaluation including stroke severity (as measured by the Scandinavian Stroke Scale [SSS], using a total score of 0-58, in which lower scores indicate more severe strokes), computed tomography, and cardiovascular risk factors.

Patients were followed from admission until death or censoring. Case fatality (stratified by 1 week, 1 month, 3 months, and 1 year) in men and women was correlated with age and stroke severity. Adjustment for cardiovascular risk factors was performed by means of multivariate regression analysis. Results: A total of 20,854 (51.9%) men and 19,301 (48.1%) women were registered.

Women were significantly older than men at the time of stroke (74.5 vs 69.7 years, respectively; P <0.001) and had signficantly more severe strokes, as expressed by the mean SSS score (39.6 vs 43.3; P <0.001). Stratification of 1-week to 1-year case fatality according to age and stroke severity indicated that women survived significantly better than men from the mid-fifties onward, when controlling for age, stroke severity, and cardiovascular risk factor profile.

The observed female survival advantage increased with age. The female survival advantage was seen in patients with severe as well as mild strokes, but not in those younger than age 50 years. Conclusions: Our findings dispute the effects of female sex hormones as the underlying cause of female survival superiority over men.

Instead, we propose the hypothesis that the progressive deficiency of male sex hormones (testosterone), beginning in men in middle age, is the underlying cause of the gap in survival rates between men and women. Accordingly, the female survival advantage is rooted in male inferiority rather than innate female superiority. (Gend Med. 2010;7:284-295)