Role of sex hormones in lung cancer

Lung cancer represents the world’s leading cause of cancer deaths. Sex differences in the incidence and mortality rates for various types of lung cancers have been identified, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined. While some cancers such as lung adenocarcinoma are more commonly found among women than men, others like squamous cell carcinoma display the opposite pattern or show no sex differences. Associations of tobacco product use rates, susceptibility to carcinogens, occupational exposures, and indoor and outdoor air pollution have also been linked to differential rates of lung cancer occurrence and mortality between sexes. While roles for sex hormones in other types of cancers affecting women or men have been identified and described, little is known about the influence of sex hormones in lung cancer. One potential mechanism identified to date is the synergism between estrogen and some tobacco compounds, and oncogene mutations, in inducing the expression of metabolic enzymes, leading to enhanced formation of reactive oxygen species and DNA adducts, and subsequent lung carcinogenesis. In this review, we present the literature available regarding sex differences in cancer rates, associations of male and female sex hormones with lung cancer, the influence of exogenous hormone therapy in women, and potential mechanisms mediated by male and female sex hormone receptors in lung carcinogenesis. The influence of biological sex on lung disease has recently been established, thus new research incorporating this variable will shed light on the mechanisms behind the observed disparities in lung cancer rates, and potentially lead to the development of new therapeutics to treat this devastating disease.     

Estrogens and the diabetic kidney

Background: Across all ages, the incidence and rate of progression of most nondiabetic renal diseases are markedly higher in men compared with age-matched women. These observations suggest that female sex may be renoprotective. In the setting of diabetes, however, this female protection against the development and progression of renal disease is diminished.Objective: This review aimed to summarize our current understanding of sex differences in the development and progression of diabetic renal disease, and of the contribution of sex hormones, particularly estrogens, to the pathophysiology of this disease. We also attempted to answer why female sex does not protect the diabetic kidney.Methods: Using terms such as gender, sex, diabetes, diabetic nephropathy, estrogens, and sex hormones, the PubMed database was searched for English-language articles; targeted searches were conducted using terms such as gender/sex differences in diabetic renal disease. No restrictions were imposed on publication dates.Results: Although the existing data regarding the sex differences in the incidence and progression of diabetic renal disease are inconclusive, the undisputed fact is that women with either type 1 or type 2 diabetes mellitus exhibit a much higher incidence of renal disease compared with nondiabetic women. It is conceivable that the loss of female sex as a renoprotective factor in diabetes may be related to the abnormal regulation of sex hormone concentrations. Both clinical and experimental data suggest that diabetes may be associated with an imbalance in estradiol concentrations. Supplementation with 17β-estradiol or administration of selective estrogen receptor modulators reduces the incidence of diabetes and attenuates the progression of diabetic renal disease.Conclusions: Serum concentrations of ovarian hormones may provide a new means for predicting future risk of renal complications in diabetes. Exogenous steroid hormones may be an effective treatment for attenuating the progression of diabetic nephropathy.     

A varied pattern of change of the sex differential in survival in the G7 countries

Over the course of the 20th century the sex differential in life expectancy at birth in the industrialized countries has widened considerably in favour of women. Starting in the early 1970s, the beginning of a reversal in the long-term pattern of this differential has been noted in some high-income countries. This study documents a sustained pattern of narrowing of this measure into the later part of the 1990s for six of the populations that comprise the G7 countries: Canada, France, Germany, Italy, England and Wales (as representative of the United Kingdom) and USA. For Japan, a persistence of widening sex differences in survival is noted. The sex differences in life expectancy are decomposed over roughly three decades (early 1970s to late 1990s) from the point of view of four major cause-of-death categories: circulatory diseases, cancers, accidents/violence/suicide, and 'other' (residual) causes. In the six countries where the sex gap has narrowed, this has resulted primarily from reduced sex differences in circulatory disease mortality, and secondarily from reduced differences in male and female death rates due to accidents, violence and suicide combined. In some of the countries sex differentials in cancer mortality have been converging lately, and this has also contributed to a narrowing of the difference in life expectancy. In Japan, males have been less successful in reducing their survival disadvantage in relation to Japanese women with regard to circulatory disease and cancer; and in the case of accidents/violence/suicide, male death rates increased during the 1990s. These trends explain the divergent pattern of the sex difference in life expectation in Japan as compared with the other G7 nations.     

Tobacco smoking and sex ratios in the United States

Results of an investigation into the effect of smoking on U.S. age-specific sex ratios indicate that the contribution of smoking to imablances in these ratios in substantial. 1st, the mathematics of the stationary population model is used to analyze the overall trend in age-specific stationary population sex ratios for 1910 and 1962, without reference to smoking. As age-specific and sex-specific mortality rates at the younger ages declined to nearly zero during this period, most male-female differences between those rates also declined. As a result, sex ratios at the younger ages decreased more slowly with age in 1962 than in 1910. Average U.S. annual cigarette consumption per person for ages 15 and over increased from 49 in 1910 to 3958 in 1962. Splitting overall age-specific and sex-specific mortality rates into smoking and nonsmoking components, the analysis is extended to examine the effects of smoking, utilizing age-specific mortality rates derived by linearly interpolating and extrapolating American Cancer Society mortality data. Percent reductions in age-specific sex ratios due to smoking probably represent fairly accurately the true values in the U.S. population in 1962. Reductions in sex ratios at each age from what they would have been if the total population had been nonsmoking varies from 0% at age 35 to 20% at age 85. It is apparent that smoking has a cumulative effect on the sex ratio with increased age.     

Sex differences in telomeres and lifespan in Soay sheep: From the beginning to the end

There is tremendous diversity in ageing rates and lifespan not only among taxa but within species, and particularly between the sexes. Women often live longer than men, and considerable research on this topic has revealed some of the potential biological, psychological and cultural causes of sex differences in human ageing and lifespan. However, sex differences in lifespan are widespread in nonhuman animals suggesting biology plays a prominent role in variation in ageing and lifespan. Recently, evolutionary biologists have borrowed techniques from biomedicine to identify whether similar mechanisms causing or contributing to variation in ageing and lifespan in humans and laboratory animals also operate in wild animals. Telomeres are repetitive noncoding DNA sequences capping the ends of chromosomes that are important for chromosomal stability but that can shorten during normal cell division and exposure to stress. Telomere shortening is hypothesized to directly contribute to the ageing process as once telomeres shorten to some length, the cells stop dividing and die. Men tend to have shorter telomeres and faster rates of telomere attrition with age than women, suggesting one possible biological cause of sex differences in lifespan. In this issue of Molecular Ecology, Watson et al. ( 2017 ) show that telomere lengths in wild Soay sheep are similar between females and males near the beginning of life but quickly diverge with age because males but not females showed reduced telomere lengths at older ages. The authors further show that some of the observed sex difference in telomere lengths in old age may be due to male investment in horn growth earlier in life, suggesting that sexually dimorphic allocation to traits involved in sexual selection might underlie sex differences in telomere attrition. This study provides a rare example of how biological mechanisms potentially contributing to sex differences in lifespan in humans may also operate in free‐living animals. However, future studies using a longitudinal approach are necessary to confirm these observations and identify the ultimate and proximate causes of any sex differences in telomere lengths. Collaborations between evolutionary biologists and gerontologists are especially needed to identify whether telomere lengths have a causal role in ageing, particularly in natural conditions, and whether this directly contributes to sex differences in lifespan.     

Renal cell cancer in Israel: Sex and ethnic differences in incidence and mortality, 1980–2004

Background: The causes of renal cell cancer (RCC) remain largely unexplained. While the incidence is generally higher in men than in women, little has been reported on ethnic differences. We examine trends in RCC incidence and mortality rates among Israeli Arab and Jewish populations and compared with the rates in other countries. Methods: Age-adjusted RCC incidence and mortality rates in Israel, during 1980–2004, were calculated by sex and population group, using the National Cancer Registry. They were compared with the United States based on the Surveillance Epidemiology and End Results [SEER] program and the IARC database for international comparisons. Results: While RCC incidence rates in Israel are similar to the United States and the European average, the rates are significantly higher among Israeli Jews than Arabs. Men are affected more than women. Incidence rates over the last 24 years have increased among all men and Jewish women, but not among Arab women. Among men, the incidence rate ratio for Jews to Arabs declined from 3.96 in 1980–1982 to 2.34 in 2001–2004, whereas for women there was no change. The mortality rates were higher among Jews than Arab and among men than women. There were no significant change in the mortality rates and rate ratios. Conclusions: Our findings demonstrate marked ethnic differences in RCC in Israel. The lower incidence among Arabs stands in contrast to the higher prevalence of potential risk factors for RCC in this population group. Genetic factors, diet and other lifestyle factors could play protective roles.     

Prospective associations between sedentary lifestyle and BMI in midlife

Objective: A strong positive cross‐sectional relationship between BMI and a sedentary lifestyle has been consistently observed in numerous studies. However, it has been questioned whether high BMI is a determinant or a consequence of a sedentary lifestyle. Research Methods and Procedures: Using data from four follow‐ups of the University of North Carolina Alumni Heart Study, we examined the prospective associations between BMI and sedentary lifestyle in a cohort of 4595 middle‐aged men and women who had responded to questionnaires at the ages of 41 (standard deviation 2.3), 44 (2.3), 46 (2.0), and 54 (2.0). Results: BMI was consistently related to increased risk of becoming sedentary in both men and women. The odds ratios of becoming sedentary as predicted by BMI were 1.04 (95% confidence limits, 1.00, 1.07) per 1 kg/m² from ages 41 to 44, 1.10 (1.07, 1.14) from ages 44 to 46, and 1.12 (1.08, 1.17) from ages 46 to 54. Controlling for concurrent changes in BMI marginally attenuated the effects. Sedentary lifestyle did not predict changes in BMI, except when concurrent changes in physical activity were taken into account (p < 0.001). The findings were not confounded by preceding changes in BMI or physical activity, age, smoking habits, or sex. Discussion: Our findings suggest that a high BMI is a determinant of a sedentary lifestyle but did not provide unambiguous evidence for an effect of sedentary lifestyle on weight gain.     

Sex,gender, and pharmaceutical politics: From drug development to marketing

Background: Biological sex differences and sociocultural gender norms affect the provision of health care products and services, but there has been little explicit analysis of the impact of sex differences and gender norms on the regulation of pharmaceutical development and marketing.Objectives: This article provides an overview of the regulation of pharmaceuticals and examines the ways that regulatory agencies account for sex and gender in their review of scientific data and marketing materials.Methods: The primary focus is on the US context, but information is also included about regulatory models in Europe, Canada, and Japan for comparative purposes. Specific examples show how sex differences and gender norms influence scientific and policy decisions about pharmaceuticals.Results: The United States and Canada were found to be the only countries that have explicit requirements to include women in clinical trials and to perform sex-based subgroup analysis on study results. The potential influence of politics on regulatory decisions may have led to an uneven application of standards, as seen through the examples of mifepristone (for abortion) and sildenafil citrate (for erectile dysfunction). Three detailed case studies illustrate the importance of considering sex and gender in pharmaceutical development and marketing: Phase I clinical trials; human papillomavirus quadrivalent vaccine; and tegaserod, a drug for irritable bowel syndrome.Conclusions: Sex and gender play important roles in pharmaceutical regulation, from the design of clinical trials and the approval of new drugs to advertising and postmarketing surveillance. However, regulatory agencies pay insufficient attention to both biological sex differences and sociocultural gender norms. This disregard perpetuates inequalities by ignoring drug safety problems that predominate in women and by allowing misleading drug marketing that reinforces gender stereotypes. Recommendations have been made to improve the regulation of pharmaceuticals in regard to sex and gender.     

Gender roles in persistent sex differences in health-related quality-of-life outcomes of patients with coronary artery disease

Background: The increased recognition of significant sex/gender differences in health status outcomes, and the implications for clinical practice and service delivery, has led to calls for more gender sensitivity and specificity in research endeavors as well as within clinical practice. Previous investigations by our research group have consistently identified important sex differences in both changes in health status from baseline to 1 year and in health status outcomes of patients treated for coronary artery disease (CAD), with women reporting poorer health-related quality of life (HRQoL) compared with men.Objective: The objective of this study was to examine whether persistent sex differences in the health status of patients with CAD may be attributed to social factors such as gender roles.Methods: Sex differences in baseline clinical and demographic characteristics of patients who completed the 1-year follow-up survey were examined using t tests and χ² analyses. Structural equation modeling, an inclusive statistical modeling approach for testing hypotheses about relationships among measured and latent variables (concepts not observed or measured directly), was used to test our theoretical model.Results: HRQoL data were collected on 2403 patients 1 year after index catheterization. The results indicated that the model fit was substantially improved by the addition of the conceptualized gender-role variable. Furthermore, there was a significant effect of gender role on QoL (?0.106; P < 0.05). Age, coronary anatomy, ejection fraction, physical limitation, anginal frequency, and gender role variables in this model were able to explain 51% of the variance in HRQoL. In particular, reported physical limitations, anginal frequency, and gender role had large statistically significant direct effects on HRQoL.Conclusions: Advances in the treatment of CAD have led to significant decreases in mortality rates. Our current challenge is to minimize the long-term impact of CAD on HRQoL outcomes. While a substantial body of literature has examined the correlations between gender-role attributes and a wide variety of both positive and negative outcomes, this area has not been explored in patients with cardiovascular disease. These findings suggest that further study of the influence of gender role (using a gender-role measurement) on HRQoL is needed.     

Same Sex Marriage and the Perceived Assault on Opposite Sex Marriage

Background

Marriage benefits both individuals and societies, and is a fundamental determinant of health. Until recently same sex couples have been excluded from legally recognized marriage in the United States. Recent debate around legalization of same sex marriage has highlighted for anti-same sex marriage advocates and policy makers a concern that allowing same sex couples to marry will lead to a decrease in opposite sex marriages. Our objective is to model state trends in opposite sex marriage rates by implementation of same sex marriages and other same sex unions.

Methods and Findings

Marriage data were obtained for all fifty states plus the District of Columbia from 1989 through 2009. As these marriage rates are non-stationary, a generalized error correction model was used to estimate long run and short run effects of same sex marriages and strong and weak same sex unions on rates of opposite sex marriage. We found that there were no significant long-run or short run effects of same sex marriages or of strong or weak same sex unions on rates of opposite sex marriage.

Conclusion

A deleterious effect on rates of opposite sex marriage has been argued to be a motivating factor for both the withholding and the elimination of existing rights of same sex couples to marry by policy makers–including presiding justices of current litigation over the rights of same sex couples to legally marry. Such claims do not appear credible in the face of the existing evidence, and we conclude that rates of opposite sex marriages are not affected by legalization of same sex civil unions or same sex marriages.     

Pregnancy Weight Retention in Morbid Obesity

HUNT, STEVEN C, MARIA M DAINES, TED D ADAMS, EDWARD M HEATH AND ROGER R WILLIAMS. Pregnancy weight retention in morbid obesity. Obes Res. 1995;3:121–130. Recent hypotheses suggest that for women who develop morbid obesity, increases in weight associated with pregnancy may represent a significant contribution to their obesity status. The effects of multiple pregnancies on weight gain were studied in 96 morbidly obese women (<13.6 kg over ideal weight at ages 20–24 or before an earlier first pregnancy and currently >44.5 kg over ideal weight) and 115 random control women from the Utah population. Self-reported weights for each pregnancy included: prepregnancy, greatest during pregnancy, and 6 weeks following delivery, which were validated against available hospital records. Mean number of pregnancies in each group were similar (4.2 and 4.3), ranging from 1 to 9. Mean current age was 46 and mean weight gain since ages 20–24 was 46.0 kg in the morbidly obese and 14.1 kg in controls. Regression of current weight on total number of pregnancies, adjusting for weight at ages 20–24, showed a 1.3 kg/pregnancy increase in current weight (p=0.03) with no difference between groups (p=0.6). Weight gain subsequent to the last pregnancy was not related to the number of pregnancies (p=0.2). Morbidly obese women gained more weight during pregnancy than controls only for the first pregnancy. Gains were similar for all other pregnancies. Morbidly obese women had smaller weight losses after delivery than the controls, but these differences were not significant. For the first pregnancy, morbidly obese women had a net weight retention that was 4.0 kg greater than the controls at 6 weeks post-partum and an average of 1.6 kg/pregnancy greater retention for the remaining pregnancies. Pregnancy weight gains for each pregnancy subsequent to the first pregnancy were constant. These findings suggest: 1) women who develop morbid obesity have slightly less weight loss after delivery and greater between-pregnancy weight gains than controls; 2) the number of pregnancies does not affect the amount of weight gained after the last pregnancy; and 3) while multiparity may augment weight gain in morbidly obese women, it is probably not a primary factor in the later development of morbid obesity.     

Predictors of Attrition in a Large Clinic‐Based Weight‐Loss Program

Objective: Identifying client factors that predict dropout is critical for the development of effective weight‐loss programs. Although demographic predictors are studied, there are few consistent findings. The purpose of this study was to identify predictors of dropout in a large clinic‐based weight‐loss program using readily attainable demographic variables. Research Methods and Procedures: All 866 weight‐loss patients in a clinic‐based weight‐loss program enrolled during 1998 to 1999 were followed. Attrition and retention rates were measured at 8 and 16 weeks. Six variables (sex, race, marital status, age, BMI, and treatment protocol) were evaluated using bivariate and multivariable statistics for relative association with dropout. Results: The overall attrition rate for the 16‐week program was 31%. The retention rate was 69%. Significant risk for dropout, measured as bivariate relative risk (95% confidence interval), was found among patients who were: females, 1.32 (1.01 to 1.73); divorced, 1.54 (1.13 to 2.09); African Americans, 1.68 (1.26 to 2.23); age < 40, 1.66 (1.27 to 2.18); and ages 40 to 50, 1.33 (1.01 to 1.76). There were no significant differences in retention rates by BMI group or program protocol. After logistic regression analysis to control for all variables, young age < 50 years had the only significant association with dropout [odds ratio = 1.39 (1.02 to 1.90)]. Discussion: Multivariable modeling was helpful for prioritizing risk factors for program dropout. These findings have important implications for improving weight‐loss program effectiveness and reducing attrition. By knowing the groups at risk for dropout, we can improve or target program treatments to these populations.     

Performance of a thermophilic sulfate and sulfite reducing high rate anaerobic reactor fed with methanol

Thermophilic sulfate and sulfite reduction was studied in lab-scale Expanded Granular Sludge Bed (EGSB) reactors operated at 65°C and pH 7.5 with methanol as the sole carbon and energy source for the sulfate- and sulfite-reducing bacteria. At a hydraulic retention time (HRT) of 10 h, maximum sulfite and sulfate elimination rates of 5.5 gSO₃ ^2- L^-1 day^-1 (100 % elimination) and 5.7 gSO₄ ^{2- -1} day^-1 (55% elimination) were achieved, resulting in an effluent sulfide concentration of approximately 1800 mgS L^-1. Sulfate elimination was limited by the sulfide concentration, as stripping of H₂S from the reactor with nitrogen gas was found to increase the sulfate elimination rate to 9.9 gSO₄ ^2- L^-1 day^-1 (100 % elimination). At a HRT of 3 h, maximum achievable sulfite and sulfate elimination rates were even 18 gSO₃ ^2- L^-1 day^-1 (100% elimination) and 11 gSO₄ ^2- L^-1 day^-1(50% elimination). At a HRT of 3 h, the elimination rate was limited by the biomass retention of the system. 5.5 ± 1.8% of the consumed methanol was converted to acetate, which was not further degraded by sulfate reducing bacteria present in the sludge. The acetotrophic activity of the sludge could not be stimulated by cultivating the sludge for 30 days under methanol-limiting conditions. Omitting cobalt as trace element from the influent resulted in a lower acetate production rate, but it also led to a lower sulfate reduction rate. Sulfate degradation in the reactor could be described by zeroth order kinetics down to a threshold concentration of 0.05 g L^-1, while methanol degradation followed Michaelis-Menten kinetics with a K_m of 0.037 gCOD L^-1.     

Evolutionary personality psychology and victimology: Sex differences in risk attitudes and short-term orientation and their relation to sex differences in victimizations

Men are more often victims of events like car accidents or (violent) crimes than women with the sole exception of sexual assault. Based on the theory of sexual selection, it has been argued that these sex differences in both perpetration and victimization rates can be attributed to sex differences in risk taking and short-term orientation. Men are expected to be more risk prone than women because throughout evolutionary history, men had to engage in a higher level of intrasexual competition. However, despite the theoretical plausibility and empirical evidence at the behavioral level, there is little direct evidence that risk attitudes and short-term orientation as a sexually dimorphic personality trait mediate rates of victimization. Measures of risk attitude and short-term orientation administered to a German student sample (N=275) showed that: (1) the likelihood of being victimized by different kinds of negative events did correlate with both the risk attitudes and short-term orientation of a (potential) victim, (2) men had a more positive attitude towards risks and were more short-term oriented than women, and (3) sex differences in victimization rates were mediated by sex differences in risk attitudes, implying a close link between risk attitude and short-term orientation. We also show that women's risk of being raped is related to their individual risk attitude scores.     

Volume and composition of hand sweat of white and black men and women in desert walks

Many investigators have sought, but failed to find, ethnic differences in the number and regional distribution of active sweat glands. In this study measurements have been made of sweat secreted on one hand and also on the whole body of Whites and Blacks walking in desert heat. Whites numbered 31 men and 27 women, ages 30 to 88 years; there were 21 Black men and 31 Black women, ages 16 to 61 years. Each walked on three occasions for 1 hour at a rate that required an oxygen consumption of about 40% of aerobic capacity. Ambient temperature ranged from 32 to 44°C in 1979 and 1980; means were 38.4°C in 1979 and 36.7°C in 1980. There was no sweat in the gloves of many Blacks; this was true of only a few Whites. Volume of body sweat increased in both races with rate of walking; volume of hand sweat increased more in Whites than in Blacks. The Mann-Whitney test revealed that volumes of hand sweat were significantly greater for Whites than for Blacks. It was concluded that in desert walks most Whites and few Blacks sweat freely on their hands. In samples of hand sweat, Na⁺, K⁺, and Cl^? were determined. Concentrations of each ion varied widely in both races, and were unrelated to race. Concentrations of Na⁺ and Cl^? generally are somewhat higher in hand sweat than in body sweat; concentrations of K⁺ are much higher. It follows that the values for concentration of Na⁺ and Cl^? reported in Table 3 probably are somewhat higher than would have been found in body sweat, and concentrations of K⁺ are probably much higher.     

Survival Analysis of Faculty Retention and Promotion in the Social Sciences by Gender

Background

Recruitment and retention of talent is central to the research performance of universities. Existing research shows that, while men are more likely than women to be promoted at the different stages of the academic career, no such difference is found when it comes to faculty retention rates. Current research on faculty retention, however, focuses on careers in science, technology, engineering, and mathematics (STEM). We extend this line of inquiry to the social sciences.

Methods

We follow 2,218 tenure-track assistant professors hired since 1990 in seven social science disciplines at nineteen U.S. universities from time of hire to time of departure. We also track their time to promotion to associate and full professor. Using survival analysis, we examine gender differences in time to departure and time to promotion. Our methods account for censoring and unobserved heterogeneity, as well as effect heterogeneity across disciplines and cohorts.

Results

We find no statistically significant differences between genders in faculty retention. However, we do find that men are more likely to be granted tenure than women. When it comes to promotion to full professor, the results are less conclusive, as the effect of gender is sensitive to model specification.

Conclusions

The results corroborate previous findings about gender patterns in faculty retention and promotion. They suggest that advances have been made when it comes to gender equality in retention and promotion, but important differences still persist.     

Sex differences in the pharmacokinetics and pharmacodynamics of antidepressants: An updated review

Background: An increasing number of studies have reported differences in the pharmacokinetics and/or pharmacodynamics of antidepressants between women and men.Objectives: This article updates previously published literature describing sex differences in the pharmacokinetics and pharmacodynamics of antidepressants, and examines specific issues that face women with psychiatric illness.Methods: An English-language literature search was performed with the PubMed database (March 2003–December 2008) using combinations of the search terms sex, gender, and antidepressants. In addition, each antidepressant was identified in the 63rd edition of the Physicians' Desk Reference.Results: The current data suggest that the pharmacokinetics of antidepressants can be substantially different between women and men. Likewise, the response to antidepressants can be quite variable, including sex differences in adverse effects and time to response.Conclusions: Despite the many sex differences reported, there is still little published work systematically evaluating potential sex differences in antidepressant pharmacokinetics and pharmacodynamics. More research is needed to guide the treatment of depression and other mental illnesses.     

Ambulatory Blood Pressure Monitoring for the Early Identification of Hypertension in Pregnancy

Gestational hypertension and preeclampsia are major contributors to perinatal morbidity and mortality. The diagnosis of gestational hypertension still relies on conventional clinic blood pressure (BP) measurements and thresholds of ≥140/90?mm Hg for systolic (SBP)/diastolic (DBP) BP. However, the correlation between BP level and target organ damage, cardiovascular disease risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than clinic BP measurement. Accordingly, ABPM has been suggested as the logical approach to overcoming the low sensitivity and specificity of clinic BP measurements in pregnancy. With the use of ABPM, differing predictable BP patterns throughout gestation have been identified for clinically healthy and hypertensive pregnant women. In normotensive pregnancies, BP steadily decreases up to the middle of gestation and then increases up to the day of delivery. In contrast, women who develop gestational hypertension or preeclampsia show stable BP during the first half of pregnancy and a continuous linear BP increase thereafter until delivery. Epidemiologic studies have also consistently reported sex differences in the 24-h patterns of ambulatory BP and heart rate. Typically, men exhibit a lower heart rate and higher BP than women, the differences being larger for SBP than DBP. Additionally, as early as in the first trimester of gestation, statistically significant increased 24-h SBP and DBP means characterize women complicated with gestational hypertension or preeclampsia compared with women with uncomplicated pregnancies. However, the normally lower BP in nongravid women as compared with men, additional decrease in BP during the second trimester of gestation in normotensive but not in hypertensive pregnant women, and significant differences in the 24-h BP pattern between healthy and complicated pregnancies at all gestational ages have not been taken into consideration when establishing reference BP thresholds for the diagnosis of hypertension in pregnancy. Several studies reported that use of the 24-h BP mean is not a proper test for an individualized early diagnosis of hypertension in pregnancy defined on the basis of cuff BP measurements, thus concluding that from such an awkward approach ABPM is not useful in pregnancy. The 24-h BP pattern that characterizes healthy pregnant women at all gestational ages suggests the use for diagnosis of a time-specified reference limit reflecting that mostly predictable BP variability. Once the time-varying threshold, given, for instance, by the upper limit of a tolerance interval, is available, the hyperbaric index (HBI), as a determinant of BP excess, can be calculated as the total area of any given subject's BP above the threshold. This tolerance-hyperbaric test, where diagnosis of gestational hypertension is based on the HBI calculated with reference to a time-specified tolerance limit, has been shown to provide high sensitivity and specificity for the early identification of subsequent hypertension in pregnancy, as well as a valuable approach for prediction of pregnancy outcome. ABPM during gestation, starting preferably at the time of the first obstetric check-up following positive confirmation of pregnancy, provides sensitive endpoints for use in early risk assessment and guide for establishing prophylactic or therapeutic intervention, and should thus be regarded as the required standard for the diagnosis of hypertension in pregnancy. (Author correspondence: rhermida@uvigo.es)     

Sex differences in mortality: results from a population-based study of 12 longitudinal cohorts

BACKGROUND:Women generally have longer life expectancy than men but have higher levels of disability and morbidity. Few studies have identified factors that explain higher mortality in men. The aim of this study was to identify potential factors contributing to sex differences in mortality at older age and to investigate variation across countries.METHODS:This study included participants age ≥ 50 yr from 28 countries in 12 cohort studies of the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. Using a 2-step individual participant data meta-analysis framework, we applied Cox proportional hazards modelling to investigate the association between sex and mortality across different countries. We included socioeconomic (education, wealth), lifestyle (smoking, alcohol consumption), social (marital status, living alone) and health factors (cardiovascular disease, diabetes, mental disorders) as covariates or interaction terms with sex to test whether these factors contributed to the mortality gap between men and women.RESULTS:The study included 179 044 individuals. Men had 60% higher mortality risk than women after adjustment for age (pooled hazard ratio [HR] 1.6; 95% confidence interval 1.5–1.7), yet the effect sizes varied across countries (I² = 71.5%, HR range 1.1–2.4). Only smoking and cardiovascular diseases substantially attenuated the effect size (by about 22%).INTERPRETATION:Lifestyle and health factors may partially account for excess mortality in men compared with women, but residual variation remains unaccounted for. Variation in the effect sizes across countries may indicate contextual factors contributing to gender inequality in specific settings.

Life expectancy has increased over the last 6 decades in many societies around the world.¹ Women generally have longer life expectancy than men, yet have higher levels of disability and morbidity.^2,3 Male:female mortality ratios increased from the beginning of the 19th century and slightly decreased over the last 3 decades.^4,5 It has been suggested that the biological differences between the sexes, including genetics and hormones, provide stronger resilience to disadvantageous situations for women than men.⁶ However, biological sex is related to gender, a construct that also incorporates cultural and social differences between men and women. Although some studies suggest that the recent reduction in the male:female mortality ratio is likely a result of improvements in men’s health, lifestyle or occupational environments, others attribute it to women’s changing societal roles and increasing mortality from diseases such as lung cancer, which have traditionally affected mostly men.^3,7–9 Many studies have examined the potential impact of social, behavioural and biological factors on sex differences in mortality,^10,11 but few have been able to investigate potential variation across countries. Different cultural traditions, historical contexts, and economic and societal development may influence gender experiences in different countries, and thus variably affect the health status of men and women.We aimed to identify factors that may explain the difference in mortality risk between men and women at older age and to investigate potential variation across countries, using the harmonized data set of 12 cohort studies from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium.¹²     

Narrowing sex differentials in life expectancy in the industrialized world: Early 1970's to early 1990's

Abstract

Between the early 1970's and 1990's, twelve industrialized nations experienced for the first time a narrowing of their sex differences in life expectancy at age zero. In another set of countries, the differential has not yet reached a stage of convergence, although in some of these nations the female advantage appears to be increasing at a slower pace than ever before. We discuss the demographic and epidemiologic conditions for this new and largely unanticipated trend, as well as its applied and theoretical implications in the context of the following questions: (1) Is the observed change a function of males’ faster pace of gains in life expectancy since the early 1970s? (2) What is the relationship between country differences in socioeconomic development (as measured by GNP) and the degree of convergence in the sex gap in average length of life? (3) What is the degree of association between temporal change in age‐sex specific death rates and change in the sex gap in life expectancy over the twenty‐year interval between the early 1970s and early 1990s? Our results indicate that where some convergence has taken place, in relation to women, men have experienced more rapid gains in survival; the higher a nation's level of social and economic development, the greater the amount of convergence in male and female life expectancies. The most pronounced age‐specific association with the changing sex gap in longevity is that of ages 25–59, where the greater reductions in male mortality, as compared to that for females, contributed to a significant portion of the observed convergence in life expectancy across industrialized nations.