A population-level cohort study of 264.4 million deaths across 20 countries found that females born since the 1930s had higher cancer mortality than males between the ages of 35 and 60 years, largely due to breast and gynecologic cancers. Although females live longer than males on average, these cancers appear to reduce their total survival and advantage, according to findings published in JAMA Network Open by Canudas-Romo et al.
“These findings underscore the ongoing need for action on the prevention, early detection, and treatment of early-onset female reproductive cancers,” the investigators commented.
Inside the Analysis
The investigators focused on population-level mortality data from 20 countries with complete records from 1955 to 2020, obtained from the Human Mortality and World Health Organization Mortality Databases.
The analysis examined sex differences in survival by assessing the contributions of age, birth cohort, and cause of death, with particular focus on breast and gynecologic cancers.
Survival was measured using the truncated cross-sectional average length of life, which incorporates historical mortality information for all birth cohorts alive at a given time. For each country, the sex gap in survival—defined as the difference in truncated cross-sectional average length of life between females and males—was calculated, decomposed, and graphically illustrated by birth cohort, age, and calendar year.
Female Cancers Hamper Survival Advantage
The analysis included 264.4 million deaths from all causes (119.1 million among females [45.1%] and 145.2 million among males [54.9%]), including 11.5 million deaths due to female reproductive cancers. Differences between males and females in truncated cross-sectional average length of life ranged from 8.31 years (95% confidence interval [CI] = 8.28–8.34 years) in Hungary to 4.22 years (95% CI = 4.20–4.25 years) in the Netherlands.
In all countries, females appeared to have a survival advantage for major causes of death, with the exception of neoplasms at reproductive ages. The investigators found that females aged between 35 and 60 years in most populations had a consistent cross-cohort excess in cancer mortality compared with males, driven primarily by breast cancer and, to a lesser extent, gynecologic cancers.
Eliminating female reproductive cancers would increase female survival and widen the sex gap in truncated cross-sectional average length of life by an estimated mean of 0.77 years (95% CI = 0.75–0.78 years), varying from 0.96 years (95% CI = 0.92–1.00 years) in Ireland to 0.51 years (95% CI = 0.50–0.52) in Japan.
“In this population-level cohort study of 20 low-mortality countries, we found that, although females consistently outlived males, their survival advantage was hampered by the burden of female reproductive cancers, particularly in midlife,” the investigators concluded. They continued, “These findings shift attention from the well-established male mortality disadvantage to a less recognized, biologically rooted, female vulnerability associated with reproductive function. Framing this excess risk as the price of reproduction provides critical insight into gender differences in longevity and underscores the need for increased efforts in prevention, early detection, and equitable access to treatment of female reproductive cancers across the lifespan.”
Vladimir Canudas-Romo, PhD, of The Australian National University, Canberra, is the corresponding author of the article in JAMA Network Open.
Disclosure: The study was funded by grants from the Australian Research Council, European Research Council, Leverhulme Trust, and the Australian National Health and Medical Research Council Investigator Fellowship. The study authors reported no conflicts of interest.
