Opinion: Focus on preclinical sex differences will not address women’s and men’s health disparities

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C-reactive protein, Epstein-Barr virus, and cortisol trajectories in refugee and non-refugee youth: Links with stress, mental health, and cognitive function during a randomized controlled trial.

Experiencing childhood adversity has been associated with significant changes in inflammation, cell-mediated immunocompetence, and cortisol secretion. Relatively few studies have examined, longitudinally, alterations to inflammatory processes during adolescence, especially outside Western contexts; none have evaluated biomarker trajectories for at-risk youth in response to a structured behavioral intervention. We conducted a randomized controlled trial evaluating the efficacy of a humanitarian intervention targeting stress-alleviation, with 12-18 year-old Syrian refugees (n = 446) and Jordanian non-refugees (n = 371) living side-by-side in war-affected communities in Jordan. We measured C-reactive protein (CRP), Epstein-Barr virus antibodies (EBV), and hair cortisol concentration (HCC) at three timepoints (pre/post intervention and 11 month follow-up), and assessed three main outcomes (psychosocial stress, mental health, and cognitive function). Using growth mixture models, regressions, and growth curve models, we identified three distinct trajectories for CRP, two for EBV, and three for HCC, and examined their associations with age, gender, BMI, poverty, and trauma. We found associations with BMI for CRP, refugee status for EBV, and BMI and gender with HCC trajectory. In terms of health outcomes, we found associations between rising CRP levels and perceived stress (B =  -2.92, p = .007), and between HCC hypersecretion and insecurity (B = 7.21, p = .017). In terms of responses to the intervention, we observed no differential impacts by CRP or EBV trajectories, unlike HCC. These results suggest that commonly-assayed biomarkers do not associate with health outcomes and respond to targeted interventions in straightforward ways. Our study is the first to examine multiple biomarker trajectories in war-affected adolescents, in order to better evaluate the extent, timing, and malleability of the biological signatures of poverty, conflict, and forced displacement

Sex/Gender and the Biosocial Turn

Feminist scientists have offered clear frameworks and research methods for empirically investigating sex/gender within the biological sciences (Schiebinger 2008; Springer, Stellman, and Jordan-Young 2012; Ritz 2014; Singh and Klinge 2015; Kreiger 2003). Yet many scientists continue to struggle to operationalize gender in research design (Ruiz-Cantero et al. 2007; Jahn et al. 2017). In a review of epidemiological research conducted between 2006 and 2014, Jahn et al. found that researchers frequently discuss sex/gender in the introduction and discussion sections of a publication, but rarely actually incorporate sex/gender theory into study design or statistical analysis. Recent policies by elite bioscience funders and journals that require documentation of sex differences in preclinical research exemplify and amplify this disconnect. For example, a 2016 National Institutes of Health (NIH) guidance and infographic (figure 1) released in tandem with its new mandate for analyzing sex in basic research included but one example of how gender may influence a biological trait: the simplistic and highly stereotyped scenario of the effects of wearing high heels on knee joints. The NIH’s guidance is a high-profile example of how the influence of gender on biological traits and health outcomes is frequently poorly understood or downplayed among biomedical researchers. Despite the routine inclusion of the concept of gender alongside that of sex in NIH literature, in practice the NIH assumes that biological differences between men and women stem primarily from intrinsic sex differences, and the NIH’s policy mandates only the consideration of sex, not gender, in research

Energetics and the immune system: Trade-offs associated with non-acute levels of CRP in adolescent Gambian girls

Abstract Background and objectives: The human immune system is an ever-changing composition of innumerable cells and proteins, continually ready to respond to pathogens or insults. The cost of maintaining this state of immunological readiness is rarely considered. In this paper we aim to discern a cost to non-acute immune function by investigating how low levels of C-reactive protein (CRP) relate to other energetic demands and resources in adolescent Gambian girls. Methodology: Data from a longitudinal study of 66 adolescent girls was used to test hypotheses around investment in immune function. Non-acute (under 2 mg/L) CRP was used as an index of immune function. Predictor variables include linear height velocity, adiposity, leptin, and measures of energy balance. Results: Non-acute log CRP was positively associated with adiposity (β = 0.16, P < 0.001, R2 = 0.17) and levels of the adipokine leptin (β = 1.17, P = 0.006, R2 = 0.09). CRP was also negatively associated with increased investment in growth, as measured by height velocity (β = −0.58, P < 0.001, R2 = 0.13) and lean mass deposition β = −0.42, P = 0.005, R2 = 0.08). Relationships between adiposity and growth explained some, but not all, of this association. We do not find that CRP was related to energy balance. Conclusions and implications: These data support a hypothesis that investment in non-acute immune function is facultative, and sensitive to energetic resources and demands. We also find support for an adaptive association between the immune system and adipose tissue

Sex Disparities in COVID-19 Mortality Vary Across US Racial Groups

Background: Inequities in COVID-19 outcomes in the USA have been clearly documented for sex and race: men are dying at higher rates than women, and Black individuals are dying at higher rates than white individuals. Unexplored, however, is how sex and race interact in COVID-19 outcomes. Objective: Use available data to characterize COVID-19 mortality rates within and between race and sex strata in two US states, with the aim of understanding how apparent sex disparities in COVID-19 deaths vary across race. Design and Participants: This observational study uses COVID-19 mortality data through September 21, 2020, from Georgia (GA) and Michigan (MI). Main Measures: We calculate age-specific rates for each sex-race-age stratum, and age-standardized rates for each race-sex stratum. We investigate the sex disparity within race groups and the race disparity within sex groups using age-standardized rate ratios, and rate differences. Key Results: Within race groups, men have a higher COVID-19 mortality rate than women. Black men have the highest rate of all race-sex groups (in MI: 254.6, deaths per 100,000, 95% CI: 241.1–268.2, in GA:128.5, 95% CI: 121.0-135.9). In MI, the COVID-19 mortality rate for Black women (147.1, 95% CI: 138.7–155.4) is higher than the rate for white men (39.1, 95% CI: 37.3–40.9), white women (29.7, 95% CI: 28.3–31.0), and Asian/Pacific Islander men and women. COVID-19 mortality rates in GA followed the same pattern. In MI, the male:female mortality rate ratio among Black individuals is 1.7 (1.5–2.0) while the rate ratio among White individuals is only 1.3 (1.2–1.5). Conclusion: While overall, men have higher COVID-19 mortality rates than women, our findings show that this sex disparity does not hold across racial groups. This demonstrates the limitations of unidimensional reporting and analyses and highlights the ways that race and gender intersect to shape COVID-19 outcomes

Sex Disparities in COVID-19 Mortality Vary Across US Racial Groups

Objective Use available data to characterize COVID-19 mortality rates within and between race and sex strata in two US states, with the aim of understanding how apparent sex disparities in COVID-19 deaths vary across race. Design and Participants This observational study uses COVID-19 mortality data through September 21, 2020, from Georgia (GA) and Michigan (MI). Main Measures We calculate age-specific rates for each sex-race-age stratum, and age-standardized rates for each race-sex stratum. We investigate the sex disparity within race groups and the race disparity within sex groups using age-standardized rate ratios, and rate differences. Key Results Within race groups, men have a higher COVID-19 mortality rate than women. Black men have the highest rate of all race-sex groups (in MI: 254.6, deaths per 100,000, 95% CI: 241.1–268.2, in GA:128.5, 95% CI: 121.0-135.9). In MI, the COVID-19 mortality rate for Black women (147.1, 95% CI: 138.7–155.4) is higher than the rate for white men (39.1, 95% CI: 37.3–40.9), white women (29.7, 95% CI: 28.3–31.0), and Asian/Pacific Islander men and women. COVID-19 mortality rates in GA followed the same pattern. In MI, the male:female mortality rate ratio among Black individuals is 1.7 (1.5–2.0) while the rate ratio among White individuals is only 1.3 (1.2–1.5). Conclusion While overall, men have higher COVID-19 mortality rates than women, our findings show that this sex disparity does not hold across racial groups. This demonstrates the limitations of unidimensional reporting and analyses and highlights the ways that race and gender intersect to shape COVID-19 outcomes