Male-female Health-survival Paradox Research Articles

Sex and gender differences in health and disease. Part II. Clinical and medical-social

An important condition for providing quality and safe care is to understand the differences between men and women in epidemiology, pathophysiology, risk factors, clinical performance of diseases, response to treatment and use of medical care. The first part of the review was devoted to the evolutionary mechanisms of differences in life expectancy and potential strategies for increasing life expectancy in men. The second part of the review examines sex and gender differences using the example of 3 groups of diseases, which, according to the World Health Organization, are the main causes of death in the European Region, in the programming of health and disease, as well as the reasons for the male-female health-survival paradox.

Genetic associations with longevity are on average stronger in females than in males

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that “one-size-fits-all” for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

Analyzing the demographic coherence of selected US, Australian and Chinese biometric data sets used to price long-term care insurance and life care annuities

This paper examines the implicit healthy life expectancy used for actuarial calculations in some selected biometric data sets from the US, Australia and China. We are interested in checking the demographic/epidemiological coherence of these data sets because this health indicator is rarely presented when authors build their biometric data sets, nor when they are used to calculate long-term care insurance (LTCI) and life care annuity (LCAs) premiums, nor when they are employed in research articles to estimate the future demand for LTC services. We follow a methodology based on multistate life table methods that enables us to obtain a life expectancy matrix for individuals on the basis of their initial health state. We also present some additional indicators of longevity, mortality and morbidity, these being the median age at death, the interquartile range, the weighted modal age at death, the mortality ratio and the implicit LTC prevalence rates broken down by health state. We find several weaknesses that highlight the difficulty involved in building the biometric data sets needed to make an actuarially fair valuation of the premiums for LTCI and LCAs. We also verify the existence of the so-called “male–female health-survival paradox”. From the perspective of a potential purchaser of this type of insurance products, disclosing and explaining the summary measures of health and longevity would make it easier for them to understand the need to protect themselves against the cost of possible LTC services and also make the computation of the premiums more transparent.

Secular trends of life expectancy and disability-free life expectancy at age 65 and associated gender and area-level socioeconomic inequalities in Hong Kong: a serial cross-sectional study between 2007 and 2020

Despite Hong Kong's world leading longevity, little is known about its associated disability burden and social patterning. Hence, this study assessed the gender-specific secular trends and area-level inequalities in life expectancy (LE) and disability-free life expectancy (DFLE) at age 65 in Hong Kong. Population structure, death records, and disability data in 2007, 2013, and 2020 were retrieved from the Census and Statistics Department to estimate LE and DFLE using the Sullivan Method. District-based sociodemographic indicators were used to compare LE and DFLE across 18 districts of Hong Kong in2013. Between 2007 and 2020, LE at age 65 increased by 3.7 years (from 18.3 to 22.0) in men and by 2.1 years (from 22.7 to 24.8) in women. By contrast, DFLE increased more slowly, by 1.8 years (from 14.6 to 16.3) in men and by only 0.1 year (from 16.4 to 16.5) in women, leading to a substantial increase in proportion of life spent with disability. Results from multiple linear regression using district-based data in 2013 showed a similar extent of associations of education with LE and DFLE (mean year difference: 0.81 [95% CI: 0.14, 1.48] and 0.68 [0.10, 1.27], respectively, per 10% increase in average education level), while female gender was more strongly associated with LE (4.44 [3.56, 5.31]) than with DFLE (2.00 [1.18, 2.82]). Expansion of disability burden and male-female health-survival paradox hold true in Hong Kong. Unlike Western countries with a stronger socioeconomic patterning of DFLE, the extent of area-level socioeconomic inequalities in LE and DFLE appears to be more comparable in Hong Kong. Health and Medical Research Fund (Ref.no.: 19202031) by the Health Bureau of Hong Kong.

The Sensitivity of the Healthy Life Years Indicator: Approaches for Dealing with Age-Specific Prevalence Data

The Healthy Life Years (HLY) indicator is the official European Union indicator and a cornerstone of many health policies used in over 15 countries in the EU region to set national health plans and monitor targets. It is also used to investigate trends over time in the proportion of total life years spent in good or poor health, socioeconomic inequalities in health and mortality and the male-female health survival paradox. Based on the Global Activity Limitation Indicator (GALI) included in the European Union Statistics on Income and Living Conditions (EU-SILC), a great amount of effort has been directed at harmonising and making HLY comparable across countries. Nonetheless, the characteristics of the age-specific prevalence distribution are still rarely accounted for, regardless of the fact that patterns of prevalence often fluctuate considerably by age. In addition, the impact of assumptions used at very young ages on HLY estimates are seldom discussed, despite the fact that the majority of policies and initiatives at the EU level use HLY at birth, while data on health is only available after age 16. In this paper, we assess whether smoothing the age-specific prevalence distributions by different methods, extrapolating to older ages and changing assumptions at younger ages affect HLY estimates. Overall, assumptions made before age 15 are the most important and affect women and men differently, thus affecting HLY at birth for some countries. Estimates at age 65 are very slightly impacted. Generalised linear models (GAMs) seem promising for harmonising and extrapolating to older ages, while using polynomials or aggregating into 5-year age groups seem best for younger ages. As most EU policies use HLY at birth and by sex for developing and monitoring health policies, caution is needed when estimating HLY at birth.
 * This article belongs to a special issue on “Levels and Trends of Health Expectancy: Understanding its Measurement and Estimation Sensitivity”.

Sex hormones and physical function among the Chinese oldest-old and centenarian women

BackgroundPhysical independence is crucial for overall health in the elderly individuals. The life expectancy of women has been shown to be higher than that of men, which is also known as the “male–female health-survival paradox”. Sex hormones may be one of the explanations. However, the relationships between sex hormones and physical function remain unclear in the elderly females. This study was designed to explore these relationships among the Chinese oldest-old and centenarian women.MethodsData from 1226 women were obtained from the China Hainan Centenarian Cohort Study. Home interviews, physical examinations and blood analyses were conducted using standardized procedures. Variables including age, Han ethnicity, illiteracy, smoker, drinker, estradiol (E2), testosterone (T), follicle-stimulating hormone, and luteinizing hormone were used in the multivariate logistic and linear regression analyses.ResultsIn all the participants, age [beta (95% confidence interval): − 0.84 (− 0.98, − 0.71)] and E2 levels [beta (95% confidence interval): − 0.22 (− 0.28, − 0.17)] were negatively associated with activities of daily living (ADLs) in the multivariate linear regression analyses (P < 0.05 for all). We also observed significantly negative associations of age [odds ratio (95% confidence interval): 0.90 (0.88, 0.91)] and E2 levels [odds ratio (95% confidence interval): 0.98 (0.98, 0.99)] with physical normality in the multivariate logistic regression analyses (P < 0.05 for all). Age and E2 levels gradually decreased with increases in the ADL quartiles across all the participants (P < 0.05 for all).ConclusionsThis study demonstrated that E2 levels were negatively associated with physical function among the Chinese oldest-old and centenarian women.

The Effects of "Diet-Smoking-Gender" Three-Way Interactions on Cognitive Impairment among Chinese Older Adults.

Investigations on gender variations in the risk factors of cognitive impairment are required to promote future precision medicine among older adults, as well as to contribute to a better understanding of the “male–female health-survival paradox”. With this study, we aimed to investigate the effects of “diet–smoking–gender” three-way interactions on cognitive impairments among Chinese older adults. We conducted a 16-year prospective cohort study among 15,953, 15,555, 16,849, 9716, 7116, and 13,165 older adults from the 2002, 2005, 2008–2009, 2011–2012, 2014, and 2017–2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), respectively. Cognitive impairment was measured by the Mini-Mental State Examination (MMSE). The dietary diversity score (DDS) was calculated using the CLHLS food frequency questionnaire. Generalized estimating equations (GEE) were used to assess the “diet–smoking–gender” three-way interaction effects on cognitive impairment across the six waves of CLHLS. We found that higher dietary diversity was associated with lower probability of cognitive impairment among older adults (OR = 0.92; 95%CI = 0.90, 0.98). However, smoking behavior may negatively influence the protective effect of higher dietary diversity on cognitive function among females (OR = 1.26; 95%CI = 1.07, 1.49). Our findings imply that we should take gender differences and lifestyle behaviors into consideration in implementing dietary interventions to improve cognitive function among older adults.

Sex differences in quality of life and depressive symptoms among middle-aged and elderly Europeans: results from the SHARE survey

Objectives We examine sex differences in quality of life (QoL) and depressive symptoms across age and European regions. Methods We performed a large cross-sectional study based on 64,552 women and 53,647 men aged 50+ who participated in the Survey of Health, Ageing and Retirement in Europe (SHARE) from 2004-2020. Linear and logistic regression models were used to examine associations with QoL (CASP-12) and depressive symptoms (EURO-D). Results Women reported slightly lower QoL (coefficient −0.78, 95% CI −0.92; −0.65) and more depressive symptoms (odds ratio (OR) 2.23, 95% CI 2.13; 2.34) than men. Sex differences in QoL increased with advancing age, whereas sex differences in depressive symptoms were stable across age groups. No overall sex difference in QoL was found in Northern Europe, but women had lower QoL than men in Western (coefficient −0.49, 95% CI −0.69; −0.29), Southern (coefficient −1.35, 95% CI −1.61; −1.09) and Eastern (coefficient −0.72, 95% CI −1.05; −0.39) Europe. However, sex differences varied within the specific CASP-12 items, with women having overall lower control and autonomy, but more self-realisation, than men. Women reported more depressive symptoms than men in all regions, with the largest overall sex difference in Southern Europe (OR 2.62, 95% CI 2.40; 2.86). A female disadvantage was found for most of the EURO-D items, with the largest sex differences for ‘tearfulness’, ‘depression’ and ‘sleep’. Conclusion Middle-aged and elderly European women report lower QoL and more depressive symptoms than European men, lending support for the male-female health survival paradox.

Gynecological aspects as a component of comprehensive geriatric assessment: A study of self-rated symptoms of pelvic organ prolapse among community-dwelling elderly women in Japan

ObjectivesDespite the reported ‘male-female health-survival paradox’, no components of the comprehensive geriatric assessment (CGA) routinely used in the field of geriatrics focus on female-specific symptoms. To investigate the impact of gynecological factors among elderly women, we noted the gynecological history and examined the association between self-rated symptoms of pelvic organ prolapse (POP) and CGA. Study designThis community-based, cross-sectional study in Japan included 164 community-dwelling women aged ≥75 years. Main outcome measuresThe main outcome measures were the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), activities of daily living (ADL), and Timed Up and Go (TUG) test. Self-rated symptoms of POP were assessed using POPDI-6, and the participants were dichotomized into POPDI-6 >0 (symptom group) and POPDI-6 = 0 (no-symptom group). Several components of the CGA were compared between the groups with and without symptoms of POP and the association with POPDI-6 score was analyzed by multiple logistic regression analysis. ResultsCompared with the no-symptom group, the symptom group had significantly longer TUG test time (≥13.5 s) (P = 0.024) and difficulty in basic ADL (score <21) (P = 0.02). In multiple logistic regression analysis, basic ADL <21 and TUG time ≥13.5 s were significantly associated with POPDI-6 >0 (odds ratio [OR] = 2.78; 95% confidence interval [CI] = 1.10–7.06 and OR = 3.45; 95% CI = 1.01–1.24). ConclusionsSelf-rated POP symptoms were associated with CGA components among community-dwelling elderly women. Evaluating POP symptoms as part of the CGA could be meaningful for improving physical and psychological health in elderly women.

Sex differences in activity and health changes following COVID-19 in Europe-results from the SHARE COVID-19 survey.

While a female advantage in the overall survival from the coronavirus disease 2019 (COVID-19) has been demonstrated, potential sex differences in health changes are not investigated. In a sample of 21 395 men and 29 139 women aged 50+ from the SHARE COVID-19 survey, we investigated sex differences in social activities, self-rated health and mental health following the COVID-19 outbreak. We found considerable sex differences in all European regions with women experiencing larger negative changes across all social activities and health measures than men lending support for the male–female health-survival paradox.

Decomposition of gender differences in cognitive functioning: National Survey of the Japanese elderly

BackgroundIt is well known that females generally live longer than males, but women tend to suffer from more illnesses and limitations than men do, also for dementia. However, limited empirical evidence is available why this ‘male-female health-survival paradox’ is observed. This study aimed to investigate factors which account for gender differences in health, particularly cognitive functioning and decline among older adults.MethodsData were retrieved from the National Survey of the Japanese Elderly, which is a longitudinal survey of a nationwide representative sample of Japanese adults aged 60 or over. Gender differences in cognitive functioning and decline in three-year follow-ups were decomposed using Blinder–Oaxaca decomposition analysis, regarding demographic, socioeconomic, and health-related factors into the ‘explained’ component, by differences in individual attributes listed above, and the ‘unexplained’ component.ResultsEmpirical analyses showed that women’s lower cognitive functioning was partly explained by the endowment effect. Moreover, a shorter duration of formal education and a larger proportion with their longest occupation being domestic worker accounted for steeper cognitive decline and more prevalent mild cognitive impairment in women than in men.ConclusionThis empirical study suggested that gender differences in cognitive functioning and decline account for different individual attributes of social determinants among men and women. Particularly, men seem to be more engaged in activities which accumulate intellectual experiences through education and occupation, as suggested by the cognitive reserve hypothesis.

COVID-19: when, along with aging, sex matters

Older persons are more susceptible to infection due to the age-related immunologic changes and the state of constitutive lowgrade inflammation. The rate of complications from the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and its related coronavirus disease 2019 (COVID-19), is significantly higher in the elderly, with men as the most affected. It is known that women, in general, are less susceptible to viral infections complications thanks to three main differences in sex chromosomes, innate immunity, and steroid hormones. COVID-19 epidemiology in Italy further support that older women, even if frailer, may experience lower mortality than men, which extends the ‘male-female health-survival paradox’ to acutely ill patient groups.

Living longer but less healthy: The female disadvantage in health expectancy. Results from the KORA-Age study.

We explored the male-female health-survival paradox in the context of health expectancy (HE) at age 65 and thereafter, using three different morbidity measures and different severity cut-offs with and without adjustments for the share of nursing home residents. HE at ages 65, 70, 75, 80, and 85 was estimated with the Sullivan method, linking morbidity prevalence from the KORA (Cooperative Health Research in the Region of Augsburg)-Age study to 2016 Bavarian mortality data. Morbidity measures comprised deficit accumulation (Frailty Index, FI, cut-offs 0.08 and 0.25), disability (Health Assessment Questionnaire-Disability Index, HAQ-DI, cut-off >0) and participation (Global Activity Limitation Indicator, GALI, "limited" vs "not limited"). Morbidity data were available for 4083 participants (52.7% female). HE was lower in women than in men at all ages. Differences in morbidity prevalence, absolute HE, and health proportions of life expectancy (relative HE) increased with age for FI≥0.25 and GALI, but not for HAQ-DI>0 and FI>0.08. Accounting for the share of nursing home residents resulted in a slight reduction of HE estimates but had no impact on estimated sex differences. In HE at age 65 and thereafter, women's health disadvantage was larger than their life expectancy advantage over men.

Vitamin D Receptor Polymorphisms in Sex-Frailty Paradox

The “male-female health-survival paradox” evidences that the survival advantage observed in women is linked to higher rates of disability and poor health status compared to men, a phenomenon also called the “sex-frailty paradox”. The depletion of vitamin D seems to play a role in the fragilization of old persons, and genetic polymorphisms of the vitamin D receptor (VDR) gene seem to be involved in regulating the vitamin D pathway. This study correlated the VDR gene polymorphisms (FokI, ApaI, BsmiI, and TaqI) with frailty, computed by frailty index (FI), in 202 persons (127 women and 75 men, aged from 60 to 116 years), aiming to capture the involvement of vitamin D in the sex-frailty paradox. The results showed slightly higher FI (p = 0.05), lower levels of 25(OH)D (p = 0.04), and higher levels of parathyroid hormone PTH (p = 0.002) and phosphorus (p < 0.001) in women than in men. Interestingly, the ApaI minor allele (Aa + aa) showed a significant positive association with FI (p = 0.03) and a negative association with inorganic phosphorus values (p = 0.04) compared to AA genotype only in women, regardless of age. The exact mechanism and the causal role that, in old women, links ApaI polymorphism with frailty are still unclear. However, we could speculate that a specific genetic profiling, other than 25(OH)D levels, play a role in the sex-frailty paradox.

Differences in frailty in older men and women.

Frailty describes an individual's vulnerability to adverse health outcomes and is a useful construct that assists health professionals to understand the heterogeneity of the ageing population. While the pathophysiological pathways that lead to frailty are not well defined, an individual's sex appears to be a key factor influencing the ageing trajectory. Compared with age-matched men, women tend to have poorer health status (ie, they are more frail) but longer life expectancy (ie, they are more resilient). It seems likely that a combination of biological, behavioural and social factors underpin this male-female health-survival paradox. Randomised controlled trial data for frailty interventions in older adults are emerging, with multicomponent programs incorporating exercise and nutrition-based strategies showing promise. Pharmaceutical and other innovative therapeutic strategies for frailty are highly anticipated. Sex differences in the effectiveness of frailty interventions have not been addressed in the research literature to date. In the future, successful interventions may target many (if not all) biopsychosocial domains, with careful consideration of issues relevant to each sex.

Adolescence and Gender Equality in Health

Adolescence and Gender Equality in Health

A study of health status in Hainan centenarians

Objective To evaluate the health status of Hainan centenarians and compare the gender disparity, and to determine whether the'male-female health-survival paradox’is present among them. Methods A cross-sectional study was conducted on the health status and gender disparity of individuals aged 100 and over in Hainan province from June 2014 to December 2016.Data of sociodemographics, lifestyles as well as health-related parameters were collected.The multi-dimensional health assessment of centenarians was conducted based on the recognition of standard on Chinese healthy elderly in 2013. Results A total of 940 centenarians(men 18.6%, women 81.4%)were included.The prevalences of hypertension, diabetes and dyslipidemia were 66.1%, 9.8%, and 21.2%, respectively, while no significant gender difference was found.Male centenarians were more independent in activity of daily living than did female centenarians(41.1% vs.25.9%, P<0.001). The prevalences of dementia(7.7% vs.4.0%)and depression(33.6% vs.18.9%)were more dominant in females than in males.Multivariate logistic regression showed that the proportions of functional disability, depression and sleep disorders were higher in female centenarians than in male centenarians(P<0.05)after adjusting for general demographic characteristics, lifestyle and other health indicators. Conclusions Although the female proportion dominates the centenarian population, female general health states are worse than male centenarians.More attentions on physical and mental health should be paid to the female centenarians. Key words: Centenarians; Health assessment

Cross-national comparison of sex differences in ADL and IADL in Europe: findings from SHARE.

Women experience greater longevity than men, but have poorer health, although sex differences vary across health measures and geographical regions. We aim to examine sex differences in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) over age across European regions in a cross-sectional setting including 51,292 men and 62,007 women aged 50+ from a pooled sample of waves 1 (2004-2005) to 6 (2015) in the Survey of Health, Ageing and Retirement in Europe. ADL and IADL were dichotomised into no limitations and at least one limitation. Binomial regression models were used to estimate absolute and relative sex differences. Women had higher risk than men of ADL limitations (RR = 1.21, 95% CI 1.16; 1.27) and IADL limitations (RR = 1.54, 95% CI 1.48; 1.60), corresponding to risk differences of 1.3% and 5.7%, respectively. When we stratified by age groups and regions, sex differences in ADL were found in all age groups in Southern Europe, in the age groups 65-79years and 80+ years in Western and Eastern Europe, and from the age of 80 in Northern Europe. For IADL, sex differences were found in all age groups in the four European regions, except from ages 50-64 in Eastern Europe. The absolute sex differences increased with age in all European regions. In conclusion, our results lend support for the male-female health survival paradox by showing that European women have higher risk of ADL and IADL limitations than European men and that sex differences increase with advancing age.

Older women are frailer, but less often die than men: a prospective study of older hospitalized people

ObjectivesThe association between frailty, mortality and sex is complex, but a limited literature is available on this topic, particularly for older hospitalized patients. Therefore, the objective of our study was to prospectively evaluate sex differences in frailty, assessed by the Multidimensional Prognostic Index (MPI) and mortality, institutionalization, and re-hospitalization in an international cohort of older people admitted to hospital. Study designWe used data from nine public hospitals in Europe and Australia, to evaluate sex differences in mortality, frailty and the risk of institutionalization and re-hospitalization, during one year of follow-up. Main outcome measuresPeople aged 65 years or more admitted to hospital for an acute medical condition or for a relapse of a chronic disease were included. A standardized comprehensive geriatric assessment, which evaluated functional, nutritional, and cognitive status, risk of pressure sores, comorbidities, medications and co-habitation status, was used to calculate the MPI to measure frailty in all hospitalized older people. Data regarding mortality, institutionalization and re-hospitalization were also recorded for one year. ResultsAltogether, 1140 hospitalized patients (mean age = 84.2 years; 694 women = 60.9%) were included. The one-year mortality rate was 33.2%. In multivariate analysis, adjusted for age, MPI score, centre and diagnosis at baseline, although women had higher MPI scores than men, the latter had higher in-hospital (odds ratio, OR = 2.26; 95% confidence intervals, CI = 1.27–4.01) and one-year post-discharge mortality (OR = 2.04; 95%CI = 1.50–2.79). Furthermore, men were less frequently institutionalized in a care home than female patients (OR = 0.55; 95%CI: 0.34–0.91), but they were also more frequently re-hospitalized (OR = 1.42; 95%CI: 1.06–1.91) during the year after hospital discharge. ConclusionOlder hospitalized men were less frail, but experienced higher in-hospital and one-year mortality than women. Women were admitted more frequently to nursing homes and experienced a lower risk of re-hospitalization. These findings suggest important differences between the sexes and extends the ‘male-female health-survival paradox’ to acutely ill patient groups.

Sex Differences in Comorbidity and Frailty in Europe.

To examine sex differences in prevalent comorbidity and frailty across age and European regions. This is a cross-sectional study based on 113,299 Europeans aged 50+ participating in the Survey of Health, Ageing and Retirement in Europe from 2004-2005 to 2015. Sex differences in the Comorbidity Index and the Frailty Phenotype were investigated using ordinal logistic regressions. European women had generally higher odds of prevalent comorbidity (OR 1.11, 95% CI 1.07-1.15) and frailty (OR 1.56, 95% CI 1.51-1.62). Sex differences increased with advancing age. No overall sex difference in comorbidity was found in Western Europe, but women had more comorbidity than men in Eastern (OR 1.30, 95% CI 1.18-1.44), Southern (OR 1.23, 95% CI 1.15-1.30), and Northern (OR 1.08, 95% CI 1.01-1.16) Europe. Women were frailer than men in all regions, with the largest sex difference in Southern Europe (OR 1.84, 95% CI 1.72-1.96). European women are frailer and have slightly more comorbidity than European men lending support for the male-female health survival paradox.