No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Ending the neglect of women’s health in research
... This is potentially problematic, considering that there are sex-specific side effects of antihypertensive therapies, sex differences in therapeutic compliance, and a lack of guidelines to treat hypertension in female-specific (i.e., pregnancy, postmenopause) or femalebiased (e.g., chronic autoimmune disorders) conditions. Moreover, women were underrepresented in clinical trials for the standard-of-care therapeutics (13). Studies that include real-world datasets suggest that BP is better controlled in men than women, while population research datasets, which often exclude older women, conclude that BP control is better in women (12). ...
... Moreover, understanding of the regulation of the female endocrine system during and after chronic stress and across the lifespan is incomplete. Adolescence, pregnancy, postpartum, and menopause are understudied sexually dimorphic periods, particularly in neurophysiology, that can have lasting effects on cardiovascular health (13). Future studies that examine neural ANS regulatory circuits across critical periods are needed to understand female hypertension risk. ...
Half of adults in the United States have hypertension as defined by clinical practice guidelines. Interestingly, women are generally more likely to be aware of their hypertension and have their blood pressure controlled with treatment compared with men, yet hypertension-related mortality is greater in women. This may reflect the fact that the female sex remains underrepresented in clinical and basic science studies investigating the effectiveness of therapies and the mechanisms controlling blood pressure. This Review provides an overview of the impact of the way hypertension research has explored sex as a biological variable (SABV). Emphasis is placed on epidemiological studies, hypertension clinical trials, the genetics of hypertension, sex differences in immunology and gut microbiota in hypertension, and the effect of sex on the central control of blood pressure. The goal is to offer historical perspective on SABV in hypertension, highlight recent studies that include SABV, and identify key gaps in SABV inclusion and questions that remain in the field. Through continued awareness campaigns and engagement/education at the level of funding agencies, individual investigators, and in the editorial peer review system, investigation of SABV in the field of hypertension research will ultimately lead to improved clinical outcomes.
... There is, and has historically been, an over-representation of male participants in biomedical research: only 20% of participants in phase 1 clinical trials are women, while up to 5.5 times more male than female cells and animals are included in preclinical research [1,2]. It is estimated that only 5%-14% of studies across disciplines analyse outcomes by sex [3]. Sex and gender bias in research reinforces inequities in medical knowledge and clinical care. ...
... Perinatal depression encompasses multiple subtypes. Research has identified distinct patterns, including depression onset restricted to pregnancy, early in the postpartum and/or in late postpartum [11]. Biomarker profiles undergo significant fluctuations across these stages; thus, recognising and delineating these subtypes is pivotal for advancing precision medicine approaches to perinatal depression. ...
... In some contexts, women were forced (at least for a time) out of their employment or had to choose between breastfeeding and their employment as government policy meant they could not be vaccinated in line with work requirements while pregnant or breastfeeding (Hare & Womersley, 2021). Women's health and medical conditions remain under-researched (Galea & Parekh, 2023;Smith, 2023) and women's contributions to economies and societies under or unmeasured and not counted (Gribble et al., 2023b). ...
Including women in research and collecting and disaggregating data on sex is an ethical imperative. However, increasingly gender identity is being prioritised over sex in data collection and language which has ethical implications. In this paper, the authors share their experiences as study participants; a health consumer advocate, patient research advisor, and lay researcher; and academic researchers of engaging with researchers, Human Research Ethics Committees (HRECs), university ethics offices, and editors and reviewers of journals regarding data collection and communication on sex and gender identity. We argue that HRECs, researchers, and publishers must carefully consider the implications of omitting data collection on sex, mandatory and universalising gender identity questions and use of desexed language. We also propose that reduced data collection and disaggregation by sex, universal imposition of gender identity, and use of desexed language in research is decreasing data quality, reducing the willingness of some to participate in research and is culturally imperialistic. Recommendations for HRECs are made and research needs in relation to sex and gender identity are outlined. Respect for women in the conduct of research requires their sex-related experiences and needs are considered and therefore that data on sex is appropriately collected and reported upon.
... Yet sex differences in the prion-like spreading of aSyn and the potential downstream consequences are not clearly understood. This is not altogether surprising as sex is often neglected as a biological variable in preclinical research [35][36][37] . This limitation extends to using the M83 mouse model, harboring an A53T mutation in the human aSyn transgene, that is commonly used to examine the prion-like spreading hypothesis 9,[15][16][17][18][19][20][21][22][23][24][25] . ...
Despite known sex differences in human synucleinopathies such as Parkinson’s disease, the impact of sex on alpha-synuclein pathology in mouse models has been largely overlooked. To address this need, we examine sex differences in whole brain signatures of neurodegeneration due to aSyn toxicity in the M83 mouse model using longitudinal magnetic resonance imaging (MRI; T1-weighted; 100 μm³ isotropic voxel; -7, 30, 90 and 120 days post-injection [dpi]; n ≥ 8 mice/group/sex/time point). To initiate aSyn spreading, M83 mice are inoculated with recombinant human aSyn preformed fibrils (Hu-PFF) or phosphate buffered saline in the right striatum. We observe more aggressive neurodegenerative profiles over time for male Hu-PFF-injected mice when examining voxel-wise trajectories. However, at 90 dpi, we observe widespread patterns of neurodegeneration in the female Hu-PFF-injected mice. These differences are not accompanied by any differences in motor symptom onset between the sexes. However, male Hu-PFF-injected mice reached their humane endpoint sooner. These findings suggest that post-motor symptom onset, despite accelerated disease trajectories for male Hu-PFF-injected mice, neurodegeneration may appear sooner in the female Hu-PFF-injected mice (prior to motor symptomatology). These findings suggest that sex-specific synucleinopathy phenotypes urgently need to be considered to improve our understanding of neuroprotective and neurodegenerative mechanisms.
... Hierzu ist es erforderlich, Forschung in diesen Bereichen zu fördern. Im Bereich der Gesundheit rund um die Geburt besteht hierzu großer Bedarf [19], insbesondere da derzeit hebammenwissenschaftliche Forschungsanträge in öffentlichen Ausschreibungen des BMBF, der DGF und des Innovationsfonds mit anderen hoch-relevanten Themen wie Herz-Kreislauf Erkrankungen, Onkologie, Molekulare Medizin konkurrieren. Es wird eine Forschungsagenda "Gesundheitsförderung und Prävention rund um die Geburt" benötigt, die dann im geplanten Bundesinstitut unter der Leitung von Expert*innen der Hebammenwissenschaft priorisiert und sukzessive umgesetzt wird. ...
... While knowledge of sex and gender differences in health issues has increased, 4 more research in this area is needed. [5][6][7] Furthermore, the transfer of new insights and knowledge into medical education and clinical practice is lagging. 8 9 This lack of transfer exists in medical schools and residency programmes, and among practising physicians. ...
Objectives
Over the past few decades, knowledge of women’s health regarding sex and gender differences in health has increased but transfer of these new insights into medical education and clinical practice is lagging, resulting in substandard care for women compared with men. This study aimed to reach consensus on what all physicians taking care of women should know about women’s health.
Methods
A Delphi study was executed involving statements prepared by experts in women’s health across 10 medical specialties and a patient advisory board. Participants were recruited from Europe and Northern America through the experts’ networks and snowball sampling. Participants voted IN/OUT on each statement based on its perceived relevance and feasibility for general physician knowledge, regardless of specialty. The statements were ranked according to a >80% consensus in the first Delphi round and a 4-point Likert scale in the second Delphi round.
Results
In the first round, 44 participants fully completed the survey. 18 statements progressed to the second round, in which four additional statements were included based on participant suggestions. In the final round, 35 responses on the 22 selected statements resulted in consensus on 18 statements of the highest importance, within the following domains: the societal position of women in health, patient perception of disease and treatment, differences in symptomatology, pharmacological considerations and the impact of the female life cycle on health and disease.
Conclusion
Consensus was reached on the top priority clinical conditions and public health issues in women’s health, resulting in a list of 18 statements on women’s health that every physician caring for women should know, regardless of specialty. There was also consensus on the importance of incorporating these insights into medical education. The next step involves implementing women’s health education in medical schools, postgraduate education and continuing education for medical specialists.
... Feminist scholars have long discussed the underrepresentation of women and women's health in biomedical research and policy, highlighting the sex and gender biases behind the research. Medical sciences have fragmented the body into distinct objects of inquiry, disproportionately targeting and pathologizing certain processes of the female body, such as reproduction (Martin, 1991), while neglecting others, such as menstrual health (Bobel et al., 2020;Galea & Parekh, 2023) and sexuality (tuana, 2004). the lack of literature on menstrual cycles and immunization, which is a consequence of systemic sex and gender bias in health research and in pharmacovigilance, shows the systemic neglect of health issues relevant to women and to people who menstruate. ...
... Yet, economic evaluations rely on a knowledge ecosystem biased against female-specific conditions, leading to underinvestment in women's health interventions and perpetuating inequities [74]. For example, a recent study found that the US National Institute of Health allocates a disproportionate share of its research funding to diseases that affect primarily men, to the detriment of those that affect primarily women [75]. ...
Economic evaluations play a crucial role in health resource allocation by assessing the costs and effects of various interventions. However, existing methodologies often overlook significant differences related to sex and gender, leading to a ‘blind spot’ in understanding patient heterogeneity. This paper highlights how biological and social factors influence costs and health outcomes differently for women, emphasising the need for a more explicit consideration of these differences in economic evaluations to ensure efficient and equitable resource allocation. The paper is structured to first outline how sex and gender factors impact costs and outcomes. It then identifies biases in current economic evaluation methods and practices, using real-world examples to illustrate the implications of these biases on policymaking and health equity. Notably, we argue that neglecting gender considerations can lead to inefficiencies and inequities in healthcare resource distribution. Key areas of gender bias include the estimation of productivity losses, quality of life variations and the secondary household effects of interventions. The analysis reveals that women often face higher healthcare costs and experience different health outcomes due to systemic biases in treatment and care. The paper concludes with practical recommendations for analysts, decision makers and research funders, advocating for the integration of sex and gender-responsive methodologies in health economic evaluations. Ultimately, this work calls for a paradigm shift in health economics to better reflect the complexities of sex and gender and improve health outcomes for all.
... We conclude by discussing important themes that emerge from these studies, emphasizing that the influence of HCs on the brain and behavior is often nuanced and suggest promising areas of focus for future work. Our goal is that with growing interest in studying factors influencing women's health (Deems and Leuner, 2020;Taylor et al., 2021;Galea and Parekh, 2023), greater attention will be given to the neuroscientific study of HCs. ...
Hormonal contraceptives (HCs) are one of the most highly prescribed classes of drugs in the world used for both contraceptive and noncontraceptive purposes. Despite their prevalent use, the impact of HCs on the brain remains inadequately explored. This review synthesizes recent findings on the neuroscience of HCs, with a focus on human structural neuroimaging as well as translational, nonhuman animal studies investigating the cellular, molecular, and behavioral effects of HCs. Additionally, we consider data linking HCs to mood disorders and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and stress response as a potential mediator. The review also addresses the unique sensitivity of the adolescent brain to HCs, noting significant changes in brain structure and function when HCs are used during this developmental period. Finally, we discuss potential effects of HCs in combination with smoking-derived nicotine on outcomes of ischemic brain damage. Methodological challenges, such as the variability in HC formulations and user-specific factors, are acknowledged, emphasizing the need for precise and individualized research approaches. Overall, this review underscores the necessity for continued interdisciplinary research to elucidate the neurobiological mechanisms of HCs, aiming to optimize their use and improve women's health.
... Yet sex differences in the prion-like spreading of aSyn and the potential downstream consequences are not clearly understood. This is not altogether surprising as sex is often neglected as a biological variable in preclinical research (Galea et al., 2020;Galea & Parekh 2023;. This limitation extends to using the M83 mouse model, harbouring an A53T mutation in the human aSyn transgene, that is commonly used to examine the prion-like spreading hypothesis (Bétemps et al., 2014;Froula et al., 2019;Lackie et al., 2022;Luk et al., 2012a;Luk et al., 2012b;Masuda-Suzukake et al., 2013;Masuda-Suzukake et al., 2014;Mougenot et al., 2012;Sacino et al., 2014;Sorrentino et al., 2022;Tullo et al., 2023;Watts et al., 2013). ...
Alpha-synuclein (aSyn) pathology has been extensively studied in mouse models harbouring human mutations. In spite of the known sex differences in age of onset, prevalence and disease presentation in human synucleinopathies, the impact of sex on aSyn propagation has received very little attention. To address this need, we examined sex differences in whole brain signatures of neurodegeneration due to aSyn toxicity in the M83 mouse model using longitudinal magnetic resonance imaging (MRI; T1-weighted; 100 μm3 isotropic voxel; acquired -7, 30, 90 and 120 days post-injection [dpi]; n≥8 mice/group/sex/time point). To initiate aSyn spreading, M83 mice were inoculated with recombinant human aSyn preformed fibrils (Hu-PFF) or phosphate buffered saline (PBS) injected in the right dorsal striatum. We observed more aggressive neurodegenerative profiles over time for male M83 Hu-PFF-injected mice when examining voxel-wise trajectories. However, at 90 dpi, we observed widespread patterns of neurodegeneration in the female Hu-PFF-injected mice. These differences were not accompanied with any differences in motor symptom onset between the male and female Hu-PFF-injected mice. However, male Hu-PFF-injected mice reached their humane endpoint sooner. These findings suggest that post-motor symptom onset, even though more accelerated disease trajectories were observed for male Hu-PFF-injected mice, neurodegeneration may appear sooner in female Hu-PFF-injected mice (prior to motor symptomatology). These findings suggest that sex-specific synucleinopathy phenotypes urgently need to be considered to improve our understanding of neuroprotective and neurodegenerative mechanisms.
... These findings are consistent with the broad underrepresentation of all women in clinical trials and in published research [25][26][27] and LBQ women in health research specifically 24 . Similar analyses in the US and in the European Union have indicated underfunding of female health 28 and have led to calls for a more concerted effort to fund women's health research 29 . The low inclusion of LBQ women has also been noted in research with women living with HIV 30 , in sexual health research and HIV research 31 . ...
Purpose: Gender identity and sexual orientation are essential factors that must be incorporated into health research to ensure we unearth comprehensive and inclusive insights about the healthcare needs and experiences of diverse people. Despite the calls for more focus on sex and gender in health research, scant attention has been paid to gender identity or sexual orientation. Past research found that 0.35% of Canadian Institutes of Health Research (CIHR) grant abstracts mentioned studying lesbian, gay, bisexual, transgender, queer and/or Two-Spirit (2S/LGBTQ+)-specific health outcomes. However, the nature of that research was not explored.
Methods: Here we examine the publicly available database of grant abstracts funded by CIHR from 2009-2020 to analyze what type of 2S/LGBTQ+-specific health outcomes would be studied.
Results: We found that 58% of awarded grant abstracts mentioned studying sexually transmitted diseases, the majority of which were on human immunodeficiency virus (HIV). Less than 7% of funded 2S/LGBTQ+ grant abstracts mentioned studying cisgender women. Almost 40% mentioned including trans women/girls, and 30% mentioned including trans men/ boys. None of the studies examined mentioned work with the Two- Spirit community.
Conclusion: These results reflect larger social and health inequities that require structural level changes in research to support lesbian, bisexual and queer women health.
Estrogen fluctuations during the menstrual cycle, puberty, postpartum, or in the menopausal transition are associated with cognitive, affective, and behavioral effects. Additionally, estrogens are essential in hormonal contraception, menopausal hormone therapy, or gender-affirming hormone therapy. This systematic review summarizes findings on the role of estrogens for structure, function, and connectivity of human brain networks.
We searched PubMed, Web of Science, and ScienceDirect for neuroimaging articles assessing estrogens published since 2008. We included 54 studies (N=2,494 participants) on endogenous estrogen, and 28 studies (N=1,740 participants) on exogenous estrogen conditions. Estrogen-related changes were reported for emotion, reward, memory, and resting-state networks, and in regional white and gray matter, with a particular neural plasticity in the hippocampus and amygdala. By examining study designs, imaging measures, and analysis methods, this review highlights the role of neuroimaging in advancing neuroendocrine and neurocognitive research, particularly promoting brain health for women and individuals with ovaries.
Importance
Female patients have higher mortality rates after high-risk surgery than male patients. It is unknown whether this mortality gap is due to different rates of postoperative complications or if complications are addressed differently by sex, causing complications to lead to death—so-called failure to rescue.
Objective
To evaluate sex differences in failure to rescue across high-risk surgical procedures.
Design, Setting, and Participants
This retrospective cohort study was conducted using data from Medicare beneficiaries from October 2015 to February 2020 who underwent high-risk vascular or cardiac surgical procedures, including abdominal aortic aneurysm repair, coronary artery bypass grafting, aortic valve replacement, and mitral valve replacement or repair. Data analysis was performed from August 2023 to March 2024.
Exposures
The primary exposure was patient sex.
Main Outcomes and Measures
The primary outcomes were risk-adjusted rates of complications, 30-day mortality, and failure to rescue, which was defined as a death occurring after a serious complication. Categorical variables are presented as frequencies and proportions and compared using χ ² analysis. Continuous variables were tested for normality and compared using a t test.
Results
A total of 863 305 Medicare beneficiaries were included in this study cohort, of whom 304 176 (35.2%) were female. Mean (SD) age was slightly higher in female patients (74.8 [9.3] years) than male patients (73.4 [8.5] years), and female patients had more comorbidities than male patients (≥2 Elixhauser comorbidities, female: 262 809 [86.4%] vs male: 465 231 [83.2%]). Female patients were more likely to receive care at large hospitals and hospitals with a higher surgical case volume. Overall, female and male patients had similar rates of complications (female: 14.98% vs male: 14.37%; adjusted relative risk [aRR], 1.04; 95% CI, 1.03-1.05; P < .001). However, female patients had higher rates of 30-day mortality (female: 4.22% vs male: 3.34%; aRR, 1.26; 95% CI, 1.23-1.29; P < .001) and higher rates of failure to rescue (female: 10.71% vs male: 8.58%; aRR, 1.25; 95% CI, 1.22-1.28; P < .001). A similar pattern was observed when stratified by each procedure.
Conclusions and Relevance
In this cohort study among Medicare beneficiaries undergoing high-risk surgery, male and female patients experienced similar rates of serious complications, but female patients with complications were more likely to die. In other words, clinicians fail to rescue female patients with complications after high-risk surgery more often than male patients. Improving the recognition and management of female patients’ complications postoperatively may narrow the sex disparity after high-risk surgery.
Context:
Heavy menstrual bleeding (HMB) is common and debilitating, but the precise endometrial mechanisms causing increased menstrual blood loss (MBL) remain undefined. We have previously identified a role for hypoxia in endometrial repair following progesterone withdrawal.
Objective:
As hypoxia inducible factor 2 alpha (HIF2A) is known to alter vascular function in other tissues, we hypothesised that endometrial HIF2A is involved in pre-menstrual optimisation of endometrial function during the secretory phase to limit MBL.
Results:
Women with objective HMB had higher endometrial HIF2A during the mid-secretory phase when compared to those with normal MBL (p=0.0269). In a mouse model of simulated menses, genetic or pharmacological manipulation of HIF2A did not significantly affect endometrial breakdown/repair, volume of MBL or endometrial hypoxia. However, 88% of Hif2a heterozygote mice reached early-full repair by 24h versus only 65% of wild-type mice. Mean MBL was 0.39 μl (±0.67) in Hif2a heterozygote mice versus 0.98 μl (±0.79) in wild-type mice. Conversely, when we increased HIF2A pre-menstrually, 11% reached early repair at by 8h versus 30% of vehicle-treated mice. Mean MBL was 2.61 μl (±1.10) in mice with HIF2A stabilisation and 2.24 μl (±1.14) in vehicle-treated mice. These non-significant but consistent trends indicate that increased endometrial HIF2A may contribute to delayed endometrial repair and HMB.
Conclusions:
Increased HIF2A in the secretory endometrium is unlikely to be sufficient to account for the phenotype of HMB, but limitation of HIF2 levels may optimise endometrial function at menstruation.
The female reproductive system is strongly influenced by nutrition and energy balance. It is well known that food restriction or energy depletion can induce suppression of reproductive processes, while overnutrition is associated with reproductive dysfunction. However, the intricate mechanisms through which nutritional inputs and metabolic health are integrated into the coordination of reproduction are still being defined. In this review, we describe evidence for essential contributions by hormones that are responsive to food intake or fuel stores. Key metabolic hormones—including insulin, the incretins (glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1), growth hormone, ghrelin, leptin, and adiponectin—signal throughout the hypothalamic-pituitary-gonadal axis to support or suppress reproduction. We synthesize current knowledge on how these multifaceted hormones interact with the brain, pituitary, and ovaries to regulate functioning of the female reproductive system, incorporating in vitro and in vivo data from animal models and humans. Metabolic hormones are involved in orchestrating reproductive processes in healthy states, but some also play a significant role in the pathophysiology or treatment strategies of female reproductive disorders. Further understanding of the complex interrelationships between metabolic health and female reproductive function has important implications for improving women's health overall.
The peripartum period, characterized by dynamic hormonal shifts and physiological adaptations, has been recognized as a potentially vulnerable period for the development of mood disorders such as postpartum depression (PPD). Stress is a well-established risk factor for developing PPD and is known to modulate mitochondrial function. While primarily known for their role in energy production, mitochondria also influence processes such as stress regulation, steroid hormone synthesis, glucocorticoid response, GABA metabolism, and immune modulation – all of which are crucial for healthy pregnancy and relevant to PPD pathology. While mitochondrial function has been implicated in other psychiatric illnesses, its role in peripartum stress and mental health remains largely unexplored, especially in relation to the brain. In this review, we first provide an overview of mitochondrial involvement in processes implicated in peripartum mood disorders, underscoring their potential role in mediating pathology. We then discuss clinical and preclinical studies of mitochondria in the context of peripartum stress and mental health, emphasizing the need for better understanding of this relationship. Finally, we propose mitochondria as biological mediators of resilience to peripartum mood disorders.
Nanna Maaløe and colleagues argue that resource challenges, unclear and outdated clinical practice guidelines, and lack of women’s perspectives lead to overdiagnosis and overtreatment of prolonged labour
Endometriosis is an incurable chronic condition associated with debilitating pain and subfertility, affecting 1 in 10 women. The current study aims to explore the perceptions and experiences of women with endometriosis regarding the diagnosis, support and treatment options available in Ireland. It will further determine whether additional supports or improvements are needed to care well and effectively for women with this disease in the Irish healthcare system. A qualitative study design was deemed most suitable. Twenty participants, women aged 18 and over with a diagnosis of endometriosis and experience of the Irish healthcare system, were recruited through purposeful sampling to complete semi-structured, one-to-one online interviews. Data was analysed using reflexive thematic analysis, and five themes were identified: ‘dismissive attitudes normalising severe pain’, ‘inadequate health system’, ‘the impact of delayed diagnoses’, ‘lack of education and awareness’ and ‘navigating ignorance, taboo and societal views’. Insights into the experiences and needs of women diagnosed with endometriosis in Ireland were gained, and we discuss the implications of our findings for Irish healthcare services with reference to feminist health equity and recent national action plans. We propose a series of recommendations for patient-centred care models including increased access to training and education, as well as support for longer-term chronic pain management.
Background
Evidence from clinical research indicates that men and women can differ in response to drug treatment. The knowledge database Janusmed Sex and Gender was developed to illuminate potential sex and gender differences in drug therapy and, therefore, achieve a better patient safety. The database contains non-commercial evidence-based information on drug substances regarding sex and gender aspects in patient treatment. Here, we describe our experiences and reflections from collecting, analyzing, and evaluating the evidence.
Janusmed Sex and Gender
Substances have been systematically reviewed and classified in a standardized manner. The classification considers clinically relevant sex and gender differences based on available evidence. Mainly biological sex differences are assessed except for gender differences regarding adverse effects and compliance. Of the 400 substances included in the database, clinically relevant sex differences were found for 20%. Sex-divided data were missing for 22% and no clinically relevant differences were found for more than half of the substances (52%). We noted that pivotal clinical studies often lack sex analyses of efficacy and adverse effects, and post-hoc analyzes are performed instead. Furthermore, most pharmacokinetic analyses use weight correction, but medicines are often prescribed in standard doses. In addition, few studies have sex differences as a primary outcome and some pharmacokinetic analyses are unpublished, which may complicate the classification of evidence.
Conclusions
Our work underlines the need of sex and gender analyses, and sex-divided data in drug treatment, to increase the knowledge about these aspects in drug treatment and contribute to a more individualized patient treatment.
There are marked sex differences in the prevalence, phenotypic presentation and treatment response for major depression. While genome-wide association studies (GWAS) adjust for sex differences, to date, no studies seek to identify sex-specific markers and pathways. In this study, we performed a sex-stratified genome-wide association analysis for broad depression with the UK Biobank total participants (N = 274,141), including only non-related participants, as well as with males (N = 127,867) and females (N = 146,274) separately. Bioinformatics analyses were performed to characterize common and sex-specific markers and associated processes/pathways. We identified 11 loci passing genome-level significance (P < 5 × 10⁻⁸) in females and one in males. In both males and females, genetic correlations were significant between the broad depression GWA and other psychopathologies; however, correlations with educational attainment and metabolic features including body fat, waist circumference, waist-to-hip ratio and triglycerides were significant only in females. Gene-based analysis showed 147 genes significantly associated with broad depression in the total sample, 64 in the females and 53 in the males. Gene-based analysis revealed “Regulation of Gene Expression” as a common biological process, but suggested sex-specific molecular mechanisms. Finally, sex-specific polygenic risk scores (PRSs) for broad depression outperformed total and the opposite sex PRSs in the prediction of broad major depressive disorder. These findings provide evidence for sex-dependent genetic pathways for clinical depression as well as for health conditions comorbid with depression.
Sex and gender impacts health outcomes and disease risk throughout life. Women and Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning, Intersex, and Asexual (2S/LGBTQIA+) health is often compromised as they experience delays in diagnosis. Distinct knowledge gaps in the health of these populations has prompted funding agencies to mandate incorporation of sex and gender into reearch. Sex- and gender-informed research perspectives and methodology increases rigor, promotes discovery, and expands the relevance of health research. The Canadian Institutes of Health Research (CIHR) implemented a Sex and Gender-based Analysis (SGBA) framework reccommending the inclusion of SGBA in project proposals in 2010 and in 2019, CIHR mandated the incorporation of SGBA into grant proposals. To examine whether these mandates resulted in increased SGBA uptake in research proposals, we searched the publicly available database of proposals funded by CIHR to analyze the amount of research that focused on sex and gender differences in health, as well as the 2S/LGBTQIA+ community. We categorized a total of 8,964 Project and Operating grant abstracts awarded from 2009-2020. Overall, under 10% of research funded by CIHR explicitly examined SGBA, with 1.94% of grants examining sex differences, 0.66% examining gender differences, 5.92% investigating female-specific outcomes, and 0.35% focusing on the 2S/LGBTQIA+ community. Although there was an increased number of grants funded for sex and 2S/LGBTQIA+ health across time, these increases were less than 2% between 2009 to 2020. The percentage of grants investigating female-specific health or gender differences did not change significantly. The percentage of funding dollars allocated to proposals analyzing SGBA also did not change substantially from 2009-2020, with grants examining sex differences or females increasing by 1.26% and 3.47% respectively, gender differences research funding decreasing by 0.49% and no change for 2S/LGBTQIA+-specific health. Our findings suggest more work needs to be done to increase researcher uptake in SGBA to advance health equity in research.
Highlights
Funded grants focusing on sex or gender differences in health research have largely remained unchanged from 2009 to 2020 with the largest increase of 1.57% for sex differences research.
Total funding amounts for sex or gender differences in health research have stagnated or declined across 2009 to 2020.
Grants focusing on female-specific health did not change across 2009-2020, but the percentage of funding dollars increased by 3.47%.
The percentage of grants focused on, and funding allocated to, 2S/LGBTQIA+-specific health more than tripled across 2009-2020 but remained less than 1% of all funded grants.
Numerous anecdotal accounts and qualitative research studies have reported on post-vaccination menstrual irregularities in women of reproductive age. However, none have quantified the impact. This is the first systematic review and meta-analysis to quantify and characterize the menstrual irregularities associated with vaccination for women of reproductive age. A search on July 20, 2022, retrieved articles published between December 1, 2019, and July 1, 2022, from MEDLINE, Embase, and Web of Science. The included articles were studies with full texts written in English that reported on menstrual irregularities for vaccinated vs. unvaccinated women of reproductive age. The quality of the studies was evaluated using the Study Quality Assessment Tool for Observation Cohort and Cross-Sectional Studies. Four observational studies were included. Review Manager was used to generating a forest plot with odds ratios (ORs) at the 95% confidence interval (CI), finding statistically significant associations between vaccination and menstrual irregularities for 25,054 women of reproductive age (OR = 1.91, CI: 1.76–2.07) with a significant overall effect of the mean (Z = 16.01, p < 0.0001). The studies were heterogeneous with significant dispersion of values (χ2 = 195.10 at df = 3, p < 0.00001, I2 = 98%). The findings of this systematic review and meta-analysis are limited by the availability of quantitative data. The results have implications for treating women of reproductive age with menstrual irregularities and informing them about the potential side effects of vaccinations.
Studies have shown that women on the Alzheimer’s disease (AD) continuum have more pathological tau in the brain and cerebrospinal fluid (CSF), than men. Some studies have found that higher levels of tau biomarkers are more strongly associated with clinical AD, cognitive decline and neurodegeneration in women than in men. Despite major developments in the use of plasma tau phosphorylated at threonine 181 (p-tau181) as an AD biomarker, it is unknown whether these sex differences apply to plasma p-tau181. In 1060 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants (47% women, 73.8 ± 7.6 years old), we examined sex differences in plasma p-tau181 levels and their association with other biomarkers, cognitive decline and incident AD. Linear regressions tested for an effect of sex on plasma p-tau181 levels and for plasma p-tau181 × sex interactions on CSF p-tau181, as well as entorhinal cortex tau, cortical amyloid-β (Aβ) deposition, and brain glucose metabolism, quantified using PET imaging. Linear mixed effects models tested for a sex × baseline plasma p-tau181 interaction on change in cognition over time. Finally, Cox models tested for a sex × plasma p-tau181 interaction on the risk of AD dementia in participants who were free of dementia at baseline. Despite similar plasma p-tau181 levels between sexes, women had lower brain glucose metabolism, greater brain Aβ and entorhinal cortex tau deposition, higher CSF p-tau181 and faster cognitive decline in relation to higher baseline plasma p-tau181 levels compared with men. Among Aβ positive, dementia-free participants, women had higher rates of incident AD dementia associated with increasing baseline plasma p-tau181 levels, relative to men. Our results suggest that sex may impact the clinical interpretation of plasma p-tau181 concentrations. If replicated, these findings could have important implications for the use of plasma p-tau181 as an accessible AD biomarker and screening tool for preventive and therapeutic clinical trials.
Endometriosis is an inflammatory chronic pain condition caused by uterine tissue growing outside of the uterus that afflicts at least 11% of women (and people assigned female at birth) worldwide. This condition results in a substantial burden to these women, and society at large. Although endometriosis was first identified over 160 years ago, substantial knowledge gaps remain, including confirmation of the disease's etiology. Research funding for endometriosis is limited, with funding from bodies like the National Institutes of Health (NIH) constituting only 0.038% of the 2022 health budget—for a condition that affects 6.5 million women in the US alone and over 190 million worldwide. A major issue is that diagnosis of endometriosis is frequently delayed because surgery is required to histologically confirm the diagnosis. This delay increases symptom intensity, the risk of central and peripheral sensitization and the costs of the disease for the patient and their nation. Current conservative treatments of presumed endometriosis are pain management and birth control. Both of these methods are flawed and can be entirely ineffective for the reduction of patient suffering or improving ability to work, and neither addresses the severe infertility issues or higher risk of certain cancers. Endometriosis research deserves the funding and attention that befits a disease with its substantial prevalence, effects, and economic costs. This funding could improve patient outcomes by introducing less invasive and more timely methods for diagnosis and treatment, including options such as novel biomarkers, nanomedicine, and microbiome alterations.
Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I ² = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73–0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I ² = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission ( p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.
Sex differences exist in many neurological and psychiatric diseases, but these have not always been addressed adequately in research. In order to address this, it is necessary to consider how sex is incorporated into the design (e.g. using a balanced design) and into the analyses (e.g. using sex as a covariate) in the published literature. We surveyed papers published in 2009 and 2019 across six journals in neuroscience and psychiatry. In this sample, we find a 30% increase in the percentage of papers reporting studies that included both sexes in 2019 compared with 2009. Despite this increase, in 2019 only 19% of papers in the sample reported using an optimal design for discovery of possible sex differences, and only 5% of the papers reported studies that analysed sex as a discovery variable. We conclude that progress to date has not been sufficient to address the importance of sex differences in research for discovery and therapeutic potential for neurological and psychiatric disease. Sex differences occur in many neurological and psychiatric diseases, and yet research is not always designed optimally to identify these. Here the authors perform a study of how sex was incorporated into the design and analyses of papers published six journals in neuroscience and psychiatry in 2009 compared with 2019.
Background
Despite a female advantage in verbal memory, normative data for verbal memory tests used to diagnose Alzheimer’s disease (AD) dementia and amnestic mild cognitive impairment (aMCI) often are not sex-adjusted.
Objective
To determine whether sex-adjusted norms improve aMCI diagnostic accuracy when accuracy was evaluated by progression to AD dementia over time.
Methods
Non-sex-specific and sex-specific verbal memory test norms were incorporated into Jak/Bondi aMCI criteria and applied to older (age 65–90) non-demented women (N = 1,036) and men (N = 355) from the Rush Memory and Aging Project. Using sex-specific aMCI diagnosis as the “true” condition versus non-sex-specific aMCI diagnosis as the “predicted” condition, we identified True Positives, False Positives, True Negatives, and False Negatives and compared AD dementia risk over 10 years among groups.
Results
Rates of aMCI were higher in men versus women (χ² = 15.39, p < 0.001) when determined based on typical diagnostic criteria, but this difference reversed when using sex-specific diagnostic criteria (χ² = 8.38, p = 0.004). We identified 8%of women as False Negatives and 12%of men as False Positives. Risk of incident AD dementia in False Positive men was significantly lower than in True Positive men (HR = 0.26, 95%CI = 0.12–0.58, p = 0.001). Risk of incident AD dementia in False Negative women was substantially higher than in True Negative women (HR = 3.11, 95%CI = 2.09–4.63, p < 0.001).
Conclusion
Results suggest that previous reports of higher aMCI rates in men versus women may be an artifact of non-sex-adjusted norms/cut-scores. Incorporation of sex-specific norms/cut-scores for verbal memory impairment into aMCI diagnostic criteria may improve diagnostic accuracy and avoid diagnostic errors in approximately 20%.
To improve the outcomes of research and medicine, government-based international research funding agencies have implemented various types of policies and mechanisms with respect to sex as a biological variable and gender as a sociocultural factor. After the 1990s, the US National Institutes of Health (NIH), the Canadian Institute for Health Research (CIHR), and the European Commission (EC) began 1) requesting that applicants address sex and gender considerations in grant proposals and 2) offering resources to help the scientific community integrate sex and gender into biomedical research. Although, it is too early to analyze data on the success of all of the policies and mechanisms implemented, here we review the use of both carrots (incentives) and sticks (requirements) developed to motivate researchers and the entire scientific research enterprise to consider sex and gender influences on health and in science. The NIH focused on sex as a biological variable (SABV) aligned with an initiative to enhance reproducibility through rigor and transparency; CIHR instituted a sex- and gender-based analysis (SGBA) policy; and the EC required the integration of the “gender dimension”, which incorporates sex, gender, and intersectional analysis into research and innovation. Other global efforts are briefly summarized. Although we are still learning what works, we share lessons learned to improve the integration of sex and gender considerations into research. In conjunction with refining and expanding the policies of funding agencies and mechanisms, private funders/philanthropic groups, editors of peer-reviewed journals, academic institutions, professional organizations, ethics boards, healthcare systems, and industry also need to make concerted efforts to integrate sex and gender into research, and we all must bridge across silos to promote system-wide solutions throughout the biomedical enterprise. For example, policies that encourage researchers to disaggregate data by sex and gender, the development of tools to better measure gender effects, or policies similar to SABV and/or SGBA adopted by private funders would accelerate progress. Uptake, accountability for, and a critical appraisal of sex and gender throughout the biomedical enterprise will be crucial to achieving the goal of relevant, reproducible, replicable, and responsible science that will lead to better evidence-based personalized care for all, but especially for women.
Background:
Gender bias has been an ongoing issue in health care, examples being underrepresentation of women in health studies, trivialization of women's physical complaints, and discrimination in the awarding of research grants. We examine here a different issue-gender disparity when it comes to the allocation of research funding among diseases.
Materials and Methods:
We perform an analysis of funding by the U.S. National Institutes of Health (NIH) to ascertain possible gender disparity in its allocation of funds across diseases. We normalize funding level to disease burden, as measured by the Disability Adjusted Life Year, and we specifically consider diseases for which both disease burden and funding level are provided. We apply a power-law regression analysis to model funding commensurate with disease burden.
Results:
We find that in nearly three-quarters of the cases where a disease afflicts primarily one gender, the funding pattern favors males, in that either the disease affects more women and is underfunded (with respect to burden), or the disease affects more men and is overfunded. Moreover, the disparity between actual funding and that which is commensurate with burden is nearly twice as large for diseases that favor males versus those that favor females. A chi-square test yields a p-value of 0.015, suggesting that our conclusions are representative of the full NIH disease portfolio.
Conclusions:
NIH applies a disproportionate share of its resources to diseases that affect primarily men, at the expense of those that affect primarily women.
Sex-stratified medicine is a fundamentally important, yet understudied, facet of modern medical care. A data-driven model for how to systematically analyze population-wide, longitudinal differences in hospital admissions between men and women is needed. Here, we demonstrate a systematic analysis of all diseases and disease co-occurrences in the complete Danish population using the ICD-10 and Global Burden of Disease terminologies. Incidence rates of single diagnoses are different for men and women in most cases. The age at first diagnosis is typically lower for men, compared to women. Men and women share many disease co-occurrences. However, many sex-associated incongruities not linked directly to anatomical or genomic differences are also found. Analysis of multi-step trajectories uncover differences in longitudinal patterns, for example concerning injuries and substance abuse, cancer, and osteoporosis. The results point towards the need for an increased focus on sex-stratified medicine to elucidate the origins of the socio-economic and ethological differences.
Background
Cancer research is essential in evaluating the safety and effectiveness of emerging cancer treatments, which in turn can lead to ground-breaking advancements in cancer care. Given limited research funding, allocating resources in alignment with societal burden is essential. However, evidence shows that such alignment does not typically occur. The objective of the present study was to provide an updated overview of site-specific cancer research investment in Canada and to explore potential discrepancies between the site-specific burden and the level of research investment.Methods
The 10 cancer sites with the highest mortality in 2015—which included brain, female breast, colorectal, leukemia, lung, non-Hodgkin lymphoma, ovary, pancreas, prostate, and uterus—were selected for the analysis. Information about site-specific research investment and cancer burden (raw incidence and mortality) was obtained from the Canadian Cancer Research Survey and Statistics Canada’s cansim (the Canadian Socio-Economic Information Management System) respectively. The ratio of site-specific research investment to site-specific burden was used as an indicator of overfunding (ratio > 1) or underfunding (ratio < 1).ResultsThe 3 cancer sites with the highest research investments were leukemia, prostate, and breast, which together represented 51.3% of 2015 cancer research funding. Conversely, the 3 cancer sites with the lowest investments were uterus, pancreas, and ovary, which together represented 7.8% of 2015 research funding. Relative to site-specific cancer burden, the lung, uterus, and colorectal sites were consistently the most underfunded.Conclusions
Observed discrepancies between cancer burden and research investment indicate that some cancer sites (such as lung, colorectal, and uterus) seem to be underfunded when site-specific incidence and mortality are taken into consideration.
Gender and sex analysis is increasingly recognized as a key factor in creating better medical research and health care ¹⁻⁷. Using a sample of more than 1.5 million medical research papers, our study examined the potential link between women's participation in medical science and attention to gender-related and sex-related factors in disease-specific research. Adjusting for variations across countries, disease topics and medical research areas, we compared the participation of women authors in studies that do and do not involve gender and sex analysis. Overall, our results show a robust positive correlation between women's authorship and the likelihood of a study including gender and sex analysis. These findings corroborate discussions of how women's participation in medical science links to research outcomes, and show the mutual benefits of promoting both the scientific advancement of women and the integration of gender and sex analysis into medical research.
Purpose:
The National Institutes of Health (NIH) Revitalization Act of 1993 requires NIH-funded clinical trials to include women and minorities as participants and assess outcomes by sex and race or ethnicity. The objective of this study was to investigate current levels of compliance with these guidelines for inclusion, analysis, and reporting in NIH-funded randomized controlled trials (RCTs) and compare the results with those from 2009 and 2004, which the authors reported previously.
Method:
The authors identified 782 RCTs published in 14 leading U.S. medical journals in 2015 with a PubMed search. Of those, 142 were the primary report of a NIH-funded RCT, conducted in the United States, and eligible for analysis. The authors reviewed abstract, text, and tables of each eligible study as well as any follow-up published commentary to determine compliance with NIH guidelines.
Results:
Thirty-five studies limited enrollment to one sex. The median enrollment of women in the remaining 107 studies was 46%, but 16 (15.0%) enrolled less than 30% women. Twenty-eight of the 107 (26%) reported at least one outcome by sex or explicitly included sex as a covariate in statistical analysis. Of the 142 studies, 19 (13.4%) analyzed or reported outcomes by race or ethnicity. There were no statistically significant changes in inclusion, analysis, or reporting by sex, race, or ethnicity compared with the previous studies.
Conclusions:
NIH policies have not resulted in significant increases in reporting results by sex, race, or ethnicity. The authors recommend strong journal policies to increase compliance with NIH policies.
Objective:
To evaluate the impact of menopause symptoms on work outcomes and to assess the estimated economic impact.
Patients and methods:
Women aged 45 to 60 years receiving primary care at 1 of the 4 Mayo Clinic sites were invited to participate in a survey study (Hormones and ExpeRiences of Aging) from March 1 through June 30, 2021. A total of 32,469 surveys were sent, with 5219 responses (16.1% response rate). Of the 5219 respondents, 4440 (85.1%) reported current employment information and were included in the study. The primary outcome was self-reported adverse work outcomes related to menopause symptoms assessed by the Menopause Rating Scale (MRS).
Results:
The mean age of the 4440 participants was 53.9±4.5 years, with the majority being White (4127 [93.0%]), married (3398 [76.5%]), and educated (2632 [59.3%] college graduate or higher); the mean total MRS score was 12.1, signifying moderate menopause symptom burden. Overall, 597 women (13.4%) reported at least one adverse work outcome due to menopause symptoms; 480 women (10.8%) reported missing work in the preceding 12 months (median, 3 days missed). The odds of reporting an adverse work outcome increased with increasing menopause symptom severity; women in the highest quartile of total MRS scores were 15.6 (95% CI, 10.7 to 22.7; P<.001) times more likely to have an adverse work outcome vs those in the first quartile. Based on workdays missed due to menopause symptoms, we estimate an annual loss of $1.8 billion in the United States.
Conclusion:
This large cross-sectional study identified a major negative impact of menopause symptoms on work outcomes and the need to improve medical treatment for these women and make the workplace environment more supportive. Additional studies are needed to confirm these findings in larger and more diverse groups of women.
Although COVID-19 vaccine access has increased nationwide, vaccination rates have been slow-moving, with many studies showing significant vaccine hesitancy in the U.S. We conducted an online survey using Amazon Mechanical Turk (MTurk) to identify reasons for vaccine hesitancy among unvaccinated adults between June 30 and July 1, 2021. We found that 58% of unvaccinated respondents were worried about unknown long-term adverse effects. Of these, 41% believed that the COVID-19 vaccines can negatively impact reproductive health and or fertility, and 38% were unsure of the effects on fertility. Our study demonstrates that fear regarding COVID-19 vaccine adverse effects and belief that they can negatively impact fertility is a major cause of vaccine hesitancy in the United States. We identified that urban residents, married individuals, those born outside the U.S., those with health insurance, and people with higher education and income greater than $100,000 felt that the vaccine would affect fertility more than their counterparts did. Finally, we found that 48% of unvaccinated respondents cited ‘more information and research conducted on the COVID-19 vaccines’ as the action that would most encourage vaccine uptake.
Although sex differences in psychiatric disorders abound, few neuropsychopharmacology (NPP) studies consider sex as a biological variable (SABV). We conducted a scoping review of this literature in humans by systematically searching PubMed to identify peer-reviewed journal articles published before March 2020 that (1) studied FDA-approved medications used to treat psychiatric disorders (or related symptoms) and (2) adequately evaluated sex differences using in vivo neuroimaging methodologies. Of the 251 NPP studies that included both sexes and considered SABV in analyses, 80% used methodologies that eliminated the effect of sex (e.g., by including sex as a covariate to control for its effect). Only 20% (50 studies) adequately evaluated sex differences either by testing for an interaction involving sex or by stratifying analyses by sex. Of these 50 studies, 72% found statistically significant sex differences in at least one outcome. Sex differences in neural and behavioral outcomes were studied more often in drugs indicated for conditions with known sex differences. Likewise, the majority of studies conducted in those drug classes noted sex differences: antidepressants (13 of 16), antipsychotics (10 of 12), sedative-hypnotics (6 of 10), and stimulants (6 of 10). In contrast, only two studies of mood stabilizers evaluated SABV, with one noting a sex difference. By mapping this literature, we bring into sharp relief how few studies adequately evaluate sex differences in NPP studies. Currently, all NIH-funded studies are required to consider SABV. We urge scientific journals, peer reviewers, and regulatory agencies to require researchers to consider SABV in their research. Continuing to ignore SABV in NPP research has ramifications both in terms of rigor and reproducibility of research, potentially leading to costly consequences and unrealized benefits.
Women constitute half of the world’s population, yet neuroscience research does not serve the sexes equally. Fifty years of preclinical animal evidence documents the tightly-coupled relationship between our endocrine and nervous systems, yet human neuroimaging studies rarely consider how endocrine factors shape the structural and functional architecture of the human brain. Here, we quantify several blind spots in neuroimaging research, which overlooks aspects of the human condition that impact women’s health (e.g. the menstrual cycle, hormonal contraceptives, pregnancy, menopause). Next, we illuminate potential consequences of this oversight: today over 100 million women use oral hormonal contraceptives, yet relatively few investigations have systematically examined whether disrupting endogenous hormone production impacts the brain. We close by presenting a roadmap for progress, highlighting the University of California Women’s Brain Initiative which is addressing unmet needs in women’s health research.
Clinicians can encounter sex and gender disparities in diagnostic and therapeutic responses. These disparities are noted in epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment. This Review discusses the fundamental influences of sex and gender as modifiers of the major causes of death and morbidity. We articulate how the genetic, epigenetic, and hormonal influences of biological sex influence physiology and disease, and how the social constructs of gender affect the behaviour of the community, clinicians, and patients in the health-care system and interact with pathobiology. We aim to guide clinicians and researchers to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
Individuals do not react to radiation in a homogeneous manner. Recent radiogenomic research has proven that individual polymorphisms can correlate with treatment response most likely due to variation in the ability to recognise and repair DNA breaks. The difference in radiosensitivity between genders has been well documented, yet most radiotherapeutic guidelines are based solely on population averages rather than demographic subgroups such as age, race and gender. This paper is a review of the burgeoning literature available on the differences in efficacy and outcome of radiotherapy between genders. The work examines the effect of radiation on gender both from a tumour control as well as normal tissue toxicity perspective. While the literature reporting such findings is limited, the results show a small but significant difference in response to radiotherapy between sexes. Prospective and retrospective studies for evaluating these gender-specific differences are encouraged as a next step in personalised medicine.
Asthma comprised of highly heterogeneous subphenotypes resulting from complex interplay between genetic and environmental stimuli. While much focus has been placed on extrinsic environmental stimuli, intrinsic environment such as sex can interact with genes to influence asthma risk. However, few studies have examined sex-specific genetic effects. The overall objective of this study was to evaluate if sex-based differences exist in genomic associations with asthma. We tested 411 asthmatics and 297 controls for presence of interactions and sex-stratified effects in 51 genes using both SNP and gene expression data. Logistic regression was used to test for association. Over half (55%) of the genetic variants identified in sex-specific analyses were not identified in the sex-combined analysis. Further, sex-stratified genetic analyses identified associations with significantly higher median effect sizes than sex-combined analysis for girls (p-value =6.5E-15) and for boys (p-value =1.0E-7). When gene expression data was analyzed to identify genes that were differentially expressed in asthma versus non-asthma, nearly one third (31%) of the probes identified in the sex-specific analyses were not identified in the sex-combined analysis. Both genetic and gene expression data suggest that the biologic underpinnings for asthma may differ by sex. Failure to recognize sex interactions in asthma greatly decreases the ability to detect significant genomic variation and may result in significant misrepresentation of genes and pathways important in asthma in different environments.
Copyright © 2015 Elsevier Inc. All rights reserved.
Are we moving the dial? Canadian health research funding trends for women's health, 2S/LGBTQ+ health, sex, or gender considerations
- T N Stranges
- A B Namchuk
- Tfl Splinter
- K N Moore
- L A Galea
Stranges TN, Namchuk AB, Splinter TFL, Moore KN, Galea LA. Are we moving the dial? Canadian
health research funding trends for women's health, 2S/LGBTQ+ health, sex, or gender
considerations.BioRxiv 2023. [Preprint.] doi: 10.1101/2022.11.30.518613
etalAlzheimer's Disease Neuroimaging Initiative. Sex differences in plasma p-tau181 associations with Alzheimer's disease biomarkers, cognitive decline, and clinical progression
- A A Tsiknia
- S D Edland
- E E Sundermann
Tsiknia AA, Edland SD, Sundermann EE, etalAlzheimer's Disease Neuroimaging Initiative. Sex
differences in plasma p-tau181 associations with Alzheimer's disease biomarkers, cognitive
decline, and clinical progression. Mol Psychiatry 2022;27:-22.
doi: 10.1038/s41380-022-01675-8 pmid: 35768637
Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy
- S Prasad
- E Kalafat
- H Blakeway
Prasad S, Kalafat E, Blakeway H, etal. Systematic review and meta-analysis of the effectiveness
and perinatal outcomes of COVID-19 vaccination in pregnancy. Nat Commun 2022;13:.
doi: 10.1038/s41467-022-30052-w pmid: 35538060