This research begins to characterize the distinct biomarker profiles associated with mood disorders sensitive to gonadal steroid hormone changes. This work intrinsically addresses key issues in women’s health by focusing on the impact of these hormonal shifts and distinguishing clinically similar presentations by underlying gender-based biological contributors.
Gender disparities in treatment of cardiovascular risk are well established. However, the reasons for them are not fully understood. In the present study we leveraged artificial intelligence technology to shed light on a previously unexplored phenomenon – rejection of statin therapy by patients – and found that it involved significant gender differences. These newly identified disparities could be an important contributor to the lower rates of statin therapy and LDL control in women. The present study therefore has established a novel area of women’s health research that could potentially bring about significant improvements in quality and outcomes of cardiovascular care of women.
There is a misconception that ischemic heart disease (IHD) mostly affects males in high-income countries. However, about 80% of CVD mortalities predominantly occur in LMICs, and IHD remains a major cause of death globally. Even less is known about the sex burden of IHD in females. Our work explores the trends in IHD in the most populous LMICs and describes trends in mortality rates from IHD among females. We highlight that the burden of IHD is increasing in LMICs. While the age standardized mortality rate is improving in most countries, the improvement is not consistent across time, and is starting to reverse among females, with a slower decline in many countries than in males. The proportion of deaths amongst females from IHD doubled from 6% in 1990 to 13% in 2019. Sex-specific interventions are needed in LMICs to address the rising prevalence of IHD in females.
In this study we analyzed differences in the prevalence and outcomes of airway mucus plugs (MP) between women and men living with COPD. We found an increased prevalence of MP in women in our sample, and no clinically significant differences in COPD outcomes for women and men with MP. We welcome opinions and ideas from the Brigham research community on biological and behavioral differences among women and men living with COPD that could explain the differences we found in the prevalence of MP in our sample. We have special interest in input from endocrinologists.
Increasingly, EHR data are being used for clinical research study and patient-oriented interventions to address women’s health, sex and gender differences. At MGB, EHR data are also linked to MGB Biobank samples, which may be used for translational and mechanistic study. Data quality regarding gender and sex should therefore be of paramount concern to researchers. While there is a strong literature on gender field implementation best practices, a post-implementation, longitudinal assessment of gender demographic field use is lacking, highlighting a knowledge gap for research and care of gender diverse populations. Our study addresses this gap. In doing so, we identified potential data quality concerns and system-level vulnerabilities in gender demographic data that may impact research efforts to incorporate sex and gender as research variables as well as patient safety. More broadly, the user-level trends may inform system interoperability initiatives and provider- and patient-level education and training regarding sex and gender.
In addition to chronological aging, women undergo reproductive aging in midlife, during which they experience a depletion of ovarian hormones including estradiol. Estradiol is a master regulator of many neurological and physiological functions, including memory circuitry and metabolic function. With menopause, there is a 15-25% decrease in cerebral glucose metabolism resulting in a period of vulnerability in women that may increase susceptibility to neurodegeneration and cognitive impairment. Here, we assessed the longitudinal impact of metabolic health, in relation to sex and reproductive aging, on memory performance and cellular aging in early midlife. Women live a third of their life after menopause and thus, understanding the impact of ovarian decline on the brain is particularly important for women’s health. This work will inform in women, critical windows of vulnerability, mechanistic targets for intervention, identify early in life high-risk populations, and will highlight key differences with aged-matched men.
The present work holds value in both neuroscientific, as well as clinical terms. Our findings suggest a greater vulnerability of the female brain to stroke lesions affecting left-hemispheric posterior circulation regions. In particular, the implications of the observed female brain vulnerability may not be limited to stroke, but could also explain some of sex differences in other neuropsychiatric diseases, including Alzheimer’s disease. Our findings indicate that a sex-aware approach to the management of stroke may be justified to improve outcomes for both men and women. Further, our study paves the way for a novel line of research utilizing clinical sex differences (e.g., menopausal status) in diagnosis, treatment, rehabilitation and, ultimately, prevention of stroke. Lastly, our findings of novel sex-specific brain lesion patterns linked to post-stroke outcomes offer a unique and timely insight into mechanisms of brain resilience, and the opportunity to develop personalized approaches to the overall population brain health.
This work demonstrates for the first-time comprehensive sex specific differences in gene expression relating to various biological pathways. We have used this data to understand the biology of sex specific gene expression changes between men and women as it relates to insulin resistance and type 2 diabetes.
Anorexia nervosa is a serious psychiatric disorder (showing the highest standardized mortality rate among psychiatric disorders) and predominantly affects females, in particular during adolescence and with a high risk of long-term negative health consequences (e.g., neuroendocrine alterations, amenorrhea, low bone density, psychiatric burdens). Thus, anorexia nervosa and its associated sequelae play an important role in women’s health research. Studying the neurobiology underlying this devastating disorder is important for developing potential novel treatment approaches and for improving outcomes of the females suffering from anorexia nervosa currently or in the past.
The global prevalence of obesity is greater in women compared to men. The gut microbiome is implicated in the sexual dimorphic nature of metabolic disease development. Understanding how the composition and function of the gut microbiome differs between sexes and determining the factors that regulate these differences is critical to develop improved gut-based therapeutic strategies to improve metabolic health for all. Here, we identify Bacteroides thetaiotaomicron (Bt) as a probiotic that associates with insulin sensitivity and report its beneficial effects on fortifying the gut epithelium and improving host metabolism when it is supplemented in HFD-fed female mice. This work highlights the therapeutic potential of leveraging the gut microbiome to improve metabolic health outcomes for women.
