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Canadian Journal of Cardiology

Sex and Gender and Allostatic Mechanisms of Cardiovascular Risk and Disease

  • Christophe Longpré-Poirier
    Correspondence
    Corresponding author: Dr Christophe Longpré-Poirier, Research Center, University Institute of Mental Health at Montréal, 7331, rue Hochelaga, Montréal, Québec H1N 3V2, Canada. Tel.: +1-514-251-4015.
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychiatry and Addiction, University of Montréal, Montréal, Québec, Canada
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  • Jade Dougoud
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychology, University of Montréal, Montréal, Québec, Canada
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  • Silke Jacmin-Park
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychology, University of Montréal, Montréal, Québec, Canada
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  • Fadila Moussaoui
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada
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  • Joanna Vilme
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychology, University of Montréal, Montréal, Québec, Canada
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  • Gabriel Desjardins
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychology, University of Montréal, Montréal, Québec, Canada
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  • Louis Cartier
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychiatry and Addiction, University of Montréal, Montréal, Québec, Canada
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  • Enzo Cipriani
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychiatry and Addiction, University of Montréal, Montréal, Québec, Canada
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  • Philippe Kerr
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychiatry and Addiction, University of Montréal, Montréal, Québec, Canada
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  • Cécile Le Page
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada
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  • Robert-Paul Juster
    Affiliations
    Research Centre, University Institute of Mental Health at Montréal, University of Montréal, Montréal, Québec, Canada

    Department of Psychiatry and Addiction, University of Montréal, Montréal, Québec, Canada
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Published:September 20, 2022DOI:https://doi.org/10.1016/j.cjca.2022.09.011

      Abstract

      Cardiovascular diseases are leading causes of mortality and morbidity in adults worldwide. Multiple studies suggest that there are clinically relevant sex differences in cardiovascular disease. Women and men differ substantially in terms of prevalence, presentation, management, and outcomes of cardiovascular disease. To date, however, little is known about why cardiovascular disease affects women and men differently. Because many studies do not differentiate the concept of sex and gender, it is sometimes difficult to discriminate sociocultural vs biological contributors that drive observed clinical differences. Female sex has some biological advantages in relation to cardiovascular disease, but many of these advantages seem to disappear as soon as women develop cardiovascular risk factors (eg, type 2 diabetes, hypertension, dyslipidemia). Furthermore, stress and allostatic load could play an important role in the relationship between sex/gender and cardiovascular diseases. In this narrative review, we argue that chronic stress and psychosocial factors might better encompass the patterns of allostatic load increases seen in women, while biological risk factors and unhealthy behaviours might be more important mechanisms that drive increased allostatic load in men. Indeed, men show allostatic load patterns that are more associated with impaired anthropometric, metabolic, and cardiovascular functioning and women have greater dysregulation in neuroendocrine and immune functioning. Thus gender-related factors might contribute to the pathogenesis of cardiovascular disease especially through stress mechanisms. It is important to continue to study the mechanisms by which gender influences chronic stress, because chronic stress could influence modifiable gendered factors to promote cardiovascular disease prevention.

      Résumé

      Les maladies cardiovasculaires figurent parmi les principales causes de morbidité et de mortalité chez les adultes du monde entier. De nombreuses études révèlent des différences entre les sexes pertinentes sur le plan clinique en ce qui concerne la maladie cardiovasculaire. La prévalence, le tableau clinique, la prise en charge et les résultats diffèrent considérablement chez les hommes et les femmes. À ce jour, on en sait toutefois peu sur les raisons pour lesquelles la maladie cardiovasculaire touche différemment les hommes et les femmes. Comme de nombreuses études ne font pas de distinction entre les concepts de sexe et de genre, il est parfois difficile de distinguer les facteurs biologiques des facteurs socioculturels qui sont à l’origine des différences cliniques observées. Le sexe féminin présente certains avantages biologiques en ce qui a trait à la maladie cardiovasculaire, mais un grand nombre de ces avantages semblent disparaître en présence de facteurs de risque cardiovasculaire (p. ex., diabète de type 2, hypertension, dyslipidémie). En outre, le stress et la charge allostatique pourraient jouer un rôle important dans le lien entre le sexe/genre et les maladies cardiovasculaires. Dans cette revue narrative, nous soutenons que le stress chronique et les facteurs psychosociaux pourraient expliquer les augmentations de la charge allostatique chez la femme, tandis que des facteurs de risque biologiques et des facteurs comportementaux pourraient contribuer davantage à l’accroissement de la charge allostatique chez l’homme. En effet, on remarque que chez les hommes, la charge allostatique est davantage associée à un dérèglement de la fonction cardiovasculaire, métabolique et anthropométrique, tandis que chez les femmes, on observe plus souvent un dérèglement de la fonction immunitaire et neuroendocrinienne. Des facteurs liés au sexe pourraient donc contribuer à la pathogenèse de la maladie cardiovasculaire, particulièrement par des mécanismes liés au stress. Il est important de continuer à étudier les liens entre le sexe et le stress chronique, car ce dernier pourrait influencer des facteurs modifiables propres au sexe afin de promouvoir la prévention de la maladie cardiovasculaire.
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      References

        • Laslett L.J.
        • Alagona P.
        • Clark B.A.
        • et al.
        The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology.
        J Am Coll Cardiol. 2012; 60: S1-S49
        • GBD 2013 Mortality and Causes of Death Collaborators
        Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
        Lancet. 2015; 385: 117-171
        • Roth G.A.
        • Huffman M.D.
        • Moran A.E.
        • et al.
        Global and regional patterns in cardiovascular mortality from 1990 to 2013.
        Circulation. 2015; 132: 1667-1678
        • Lloyd-Jones D.M.
        • Leip E.P.
        • Larson M.G.
        • et al.
        Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age.
        Circulation. 2006; 113: 791-798
        • Andersson C.
        • Vasan R.S.
        Epidemiology of cardiovascular disease in young individuals.
        Nat Rev Cardiol. 2018; 15: 230-240
        • Berenson G.S.
        • Srinivasan S.R.
        • Bao W.
        • et al.
        Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults.
        N Engl J Med. 1998; 338: 1650-1656
        • Nerenberg K.A.
        • Roeters van Lennep J.E.
        Advancing sex and gender considerations in perioperative cardiovascular-risk assessment.
        Can J Cardiol. 2021; 37: 1912-1914
        • Azizi Z.
        • Gisinger T.
        • Bender U.
        • et al.
        Sex, gender, and cardiovascular health in Canadian and Austrian populations.
        Can J Cardiol. 2021; 37: 1240-1247
        • Connelly P.J.
        • Azizi Z.
        • Alipour P.
        • et al.
        The importance of gender to understand sex differences in cardiovascular disease.
        Can J Cardiol. 2021; 37: 699-710
        • Fleury M.-A.
        • Clavel M.-A.
        Sex and race differences in the pathophysiology, diagnosis, treatment, and outcomes of valvular heart diseases.
        Can J Cardiol. 2021; 37: 980-991
        • Mosca L.
        • Barrett-Connor E.
        • Kass Wenger N.
        Sex/gender differences in cardiovascular disease prevention: what a difference a decade makes.
        Circulation. 2011; 124: 2145-2154
        • Tunstall-Pedoe H.
        • Kuulasmaa K.
        • Mähönen M.
        • et al.
        Contribution of trends in survival and coronar y-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA Project populations.
        Lancet. 1999; 353: 1547-1557
        • Pérez-López F.R.
        • Larrad-Mur L.
        • Kallen A.
        • Chedraui P.
        • Taylor H.S.
        Gender differences in cardiovascular disease: hormonal and biochemical influences.
        Reprod Sci. 2010; 17: 511-531
        • McEwen B.S.
        • Seeman T.
        Protective and damaging effects of mediators of stress: elaborating and testing the concepts of allostasis and allostatic load.
        Ann N Y Acad Sci. 1999; 896: 30-47
        • Chu B.
        • Marwaha K.
        • Sanvictores T.
        • Ayers D.
        Physiology, Stress Reaction.
        StatPearls, 2021
        • Parker H.W.
        • Abreu A.M.
        • Sullivan M.C.
        • Vadiveloo M.K.
        Allostatic load and mortality: a systematic review and meta-analysis.
        Am J Prev Med. 2022; 63: 131-140
        • Rincón-Cortés M.
        • Herman J.P.
        • Lupien S.
        • Maguire J.
        • Shansky R.M.
        Stress: influence of sex, reproductive status and gender.
        Neurobiol Stress. 2019; 10100155
        • McEwen B.S.
        • Stellar E.
        Stress and the individual: mechanisms leading to disease.
        Arch Intern Med. 1993; 153: 2093-2101
        • Suvarna B.
        • Suvarna A.
        • Phillips R.
        • et al.
        Health risk behaviours and allostatic load: a systematic review.
        Neurosci Biobehav Rev. 2020; 108: 694-711
        • Breiman L.
        • Friedman J.H.
        • Olshen R.A.
        • Stone C.J.
        Classification and Regression Trees.
        Chapman and Hall/CRC, 1984
        • Zhang M.
        • Rost K.M.
        • Fortney J.C.
        • Smith G.R.
        A community study of depression treatment and employment earnings.
        Psychiatr Serv. 1999; 50: 1209-1213
        • Manton K.G.
        • Woodbury M.A.
        • Tolley H.D.
        Statistical Applications Using Fuzzy Sets.
        Wiley-Interscience, 1994
        • Aldenderfer M.
        • Blashfield R.
        Cluster Analysis.
        Sage, 1984
        • Goertzel B.N.
        • Pennachin C.
        • de Souza Coelho L.
        • et al.
        Allostatic load is associated with symptoms in chronic fatigue syndrome patients.
        Pharmacogenomics. 2006; 7: 485-494
        • Koza J.R.
        Genetic Programming II: Automatic Discovery of Reusable Programs.
        MIT Press, 1994
        • Mooney C.Z.
        • Mooney C.F.
        • Mooney C.L.
        • Duval R.D.
        • Duvall R.
        Bootstrapping: A Nonparametric Approach to Statistical Inference.
        Sage, 1993
        • Thompson B.
        Canonical Correlation Analysis: Uses and Interpretation.
        Sage, 1984
        • Liu S.H.
        • Juster R.P.
        • Dams-O‘Connor K.
        • Spicer J.
        Allostatic load scoring using item response theory.
        Compr Psychoneuroendocrinol. 2021; 5100025
        • Seeman E.
        • Singer B.H.
        • Rowe J.
        • Horwitz R.I.
        • McEwen B.
        Price of adaptation—allostatic load and its health consequences.
        Arch Intern Med. 1997; 157: 2259-2268
        • Juster R.P.
        • McEwen B.S.
        • Lupien S.J.
        Allostatic load biomarkers of chronic stress and impact on health and cognition.
        Neurosci Biobehav Rev. 2010; 35: 2-16
        • Seeman T.E.
        • McEwen B.S.
        • Rowe J.W.
        • Singer B.H.
        Allostatic load as a marker of cumulative biological risk: MacArthur Studies of Successful Aging.
        Proc Natl Acad Sci U S A. 2001; 98: 4770-4775
        • Karlamangla A.S.
        • Singer B.H.
        • McEwen B.S.
        • Rowe J.W.
        • Seeman T.E.
        Allostatic load as a predictor of functional decline. MacArthur Studies of Successful Aging.
        J Clin Epidemiol. 2002; 55: 696-710
        • Hyde J.S.
        • Bigler R.S.
        • Joel D.
        • Tate C.C.
        • van Anders S.M.
        The future of sex and gender in psychology: five challenges to the gender binary.
        Am Psychol. 2019; 74: 171-193
        • Spence J.D.
        • Pilote L.
        Importance of sex and gender in atherosclerosis and cardiovascular disease.
        Atherosclerosis. 2015; 241: 208-210
        • Currie G.
        • Delles C.
        Precision medicine and personalized medicine in cardiovascular disease.
        Adv Exp Med Biol. 2018; 1065: 589-605
        • Jousilahti P.
        • Vartiainen E.
        • Tuomilehto J.
        • Puska P.
        Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland.
        Circulation. 1999; 99: 1165-1172
        • Kappert K.
        • Böhm M.
        • Schmieder R.
        • et al.
        Impact of sex on cardiovascular outcome in patients at high cardiovascular risk: analysis of the telmisartan randomised assessment study in ACE-intolerant subjects with cardiovascular disease (TRANSCEND) and the ongoing telmisartan alone and in combination with ramipril global end point trial (ONTARGET).
        Circulation. 2012; 126: 934-941
        • Charchar F.J.
        • Bloomer L.D.
        • Barnes T.A.
        • et al.
        Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome.
        Lancet. 2012; 379: 915-922
        • El Khoudary S.R.
        • Aggarwal B.
        • Beckie T.M.
        • et al.
        Menopause transition and cardiovascular disease risk: implications for timing of early prevention: a scientific statement from the American Heart Association.
        Circulation. 2020; 142: e506-e532
        • Stevenson J.C.
        • Tsiligiannis S.
        • Panay N.
        Cardiovascular risk in perimenopausal women.
        Curr Vasc Pharmacol. 2019; 17: 591-594
        • Zhao D.
        • Guallar E.
        • Ouyang P.
        • et al.
        Endogenous sex hormones and incident cardiovascular disease in post-menopausal women.
        J Am Coll Cardiol. 2018; 71: 2555-2566
        • Pilote L.
        • Dasgupta K.
        • Guru V.
        • et al.
        A comprehensive view of sex-specific issues related to cardiovascular disease.
        CMAJ. 2007; 176: S1-S44
        • Woodward M.
        Cardiovascular disease and the female disadvantage.
        Int J Environ Res Public Health. 2019; 16: 1165
        • Yusuf S.
        • Hawken S.
        • Ôunpuu S.
        • et al.
        Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
        Lancet. 2004; 364: 937-952
        • Appelman Y.
        • van Rijn B.B.
        • Monique E.
        • Boersma E.
        • Peters S.A.
        Sex differences in cardiovascular risk factors and disease prevention.
        Atherosclerosis. 2015; 241: 211-218
        • Khan S.I.
        • Andrews K.L.
        • Jennings G.L.
        • Sampson A.K.
        Chin-Dusting JP. Y chromosome, hypertension and cardiovascular disease: is inflammation the answer?.
        Int J Mol Sci. 2019; 20: 2892
        • Lopes-Ramos C.M.
        • Chen C.-Y.
        • Kuijjer M.L.
        • et al.
        Sex differences in gene expression and regulatory networks across 29 human tissues.
        Cell Rep. 2020; 31107795
        • Blaak E.
        Gender differences in fat metabolism.
        Curr Opin Clin Nutr Metab Care. 2001; 4: 499-502
        • Karastergiou K.
        • Smith S.R.
        • Greenberg A.S.
        • Fried S.K.
        Sex differences in human adipose tissues—the biology of pear shape.
        Biol Sex Diff. 2012; 3: 1-12
        • Fried S.K.
        • Lee M.J.
        • Karastergiou K.
        Shaping fat distribution: new insights into the molecular determinants of depot- and sex-dependent adipose biology.
        Obesity. 2015; 23: 1345-1352
        • Matsuzawa Y.
        • Funahashi T.
        • Nakamura T.
        The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism.
        J Atheroscler Thromb. 2011; 18: 629-639
        • Gao J.Y.
        • Zhang M.N.
        • Zhu C.L.
        • et al.
        The change in the percent of android and gynoid fat mass correlated with increased testosterone after laparoscopic sleeve gastrectomy in Chinese obese men: a 6-month follow-up.
        Obes Surg. 2018; 28: 1960-1965
        • Sumino H.
        • Ichikawa S.
        • Yoshida A.
        • et al.
        Effects of hormone replacement therapy on weight, abdominal fat distribution, and lipid levels in Japanese postmenopausal women.
        Int J Obes Relat Metab Disord. 2003; 27: 1044-1051
        • Mauvais-Jarvis F.
        Epidemiology of gender differences in diabetes and obesity.
        Adv Exp Med Biol. 2017; 1043: 3-8
        • Mauvais-Jarvis F.
        Gender differences in glucose homeostasis and diabetes.
        Physiol Behav. 2018; 187: 20-23
        • Contreras-Zentella M.L.
        • Hernandez-Munoz R.
        Possible gender influence in the mechanisms underlying the oxidative stress, inflammatory response, and the metabolic alterations in patients with obesity and/or type 2 diabetes.
        Antioxidants (Basel). 2021; 10: 1729
        • Rivellese A.A.
        • Riccardi G.
        • Vaccaro O.
        Cardiovascular risk in women with diabetes.
        Nutr Metab Cardiovasc Dis. 2010; 20: 474-480
        • Song J.J.
        • Ma Z.
        • Wang J.
        • Chen L.X.
        • Zhong J.C.
        Gender differences in hypertension.
        J Cardiovasc Transl Res. 2020; 13: 47-54
        • Colafella K.M.M.
        • Denton K.M.
        Sex-specific differences in hypertension and associated cardiovascular disease.
        Nat Rev Nephrol. 2018; 14: 185-201
        • Reckelhoff J.F.
        Gender differences in the regulation of blood pressure.
        Hypertension. 2001; 37: 1199-1208
        • Gillis E.E.
        • Sullivan J.C.
        Sex Differences in hypertension: recent advances.
        Hypertension. 2016; 68: 1322-1327
        • Zore T.
        • Palafox M.
        • Reue K.
        Sex differences in obesity, lipid metabolism, and inflammation—a role for the sex chromosomes?.
        Mol Metab. 2018; 15: 35-44
        • Schnatz P.F.
        • Schnatz J.D.
        Dyslipidemia in menopause: mechanisms and management.
        Obstet Gynecol Surv. 2006; 61: 608-613
        • Stachowiak G.
        • Pertynski T.
        • Pertynska-Marczewska M.
        Metabolic disorders in menopause.
        Prz Menopauzalny. 2015; 14: 59-64
        • Welty F.K.
        Cardiovascular disease and dyslipidemia in women.
        Arch Intern Med. 2001; 161: 514-522
        • Shah T.
        • Virani S.S.
        Lipid-lowering therapies: risks in women and evidence-based options.
        Tex Heart Inst J. 2018; 45: 238-239
        • Fairweather D.
        Sex differences in inflammation during atherosclerosis.
        Clin Med Insights Cardiol. 2015; 8: 49-59
        • Santosa A.
        • Rosengren A.
        • Ramasundarahettige C.
        • et al.
        Psychosocial risk factors and cardiovascular disease and death in a population-based cohort from 21 low-, middle-, and high-income countries.
        JAMA Netw Open. 2021; 4e2138920
        • Moller-Leimkuhler A.M.
        Higher comorbidity of depression and cardiovascular disease in women: a biopsychosocial perspective.
        World J Biol Psychiatry. 2010; 11: 922-933
        • Dar T.
        • Radfar A.
        • Abohashem S.
        • et al.
        Psychosocial stress and cardiovascular disease.
        Curr Treat Options Cardiovasc Med. 2019; 21: 1-17
        • Osborne M.T.
        • Shin L.M.
        • Mehta N.N.
        • et al.
        Disentangling the links between psychosocial stress and cardiovascular disease.
        Circ Cardiovasc Imaging. 2020; 13e010931
        • Sher L.D.
        • Geddie H.
        • Olivier L.
        • et al.
        Chronic stress and endothelial dysfunction: mechanisms, experimental challenges, and the way ahead.
        Am J Physiol Heart Circ Physiol. 2020; 319: H488-H506
        • Mocayar Maron F.J.
        • Ferder L.
        • Saraví F.D.
        • Manucha W.
        Hypertension linked to allostatic load: from psychosocial stress to inflammation and mitochondrial dysfunction.
        Stress. 2019; 22: 169-181
        • Mulvihill N.
        • Foley B.
        • Crean P.
        • Walsh M.
        Prediction of cardiovascular risk using soluble cell adhesion molecules.
        Eur Heart J. 2002; 23: 1569-1574
        • Moore K.J.
        • Sheedy F.J.
        • Fisher E.A.
        Macrophages in atherosclerosis: a dynamic balance.
        Nat Rev Immunol. 2013; 13: 709-721
        • Davies M.J.
        • Gordon J.
        • Gearing A.
        • et al.
        The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis.
        J Pathol. 1993; 171: 223-229
        • Logan J.G.
        • Barksdale D.J.
        Allostasis and allostatic load: expanding the discourse on stress and cardiovascular disease.
        J Clin Nurs. 2008; 17: 201-208
        • Seeman T.E.
        • Singer B.H.
        • Rowe J.W.
        • Horwitz R.I.
        • McEwen B.S.
        Price of adaptation—allostatic load and its health consequences. MacArthur Studies of Successful Aging.
        Arch Intern Med. 1997; 157: 2259-2268
        • Guidi J.
        • Lucente M.
        • Sonino N.
        • Fava G.A.
        Allostatic load and its impact on health: a systematic review.
        Psychother Psychosom. 2021; 90: 11-27
        • Brooks K.P.
        • Gruenewald T.
        • Karlamangla A.
        • et al.
        Social relationships and allostatic load in the MIDUS study.
        Health Psychol. 2014; 33: 1373-1381
        • Zilioli S.
        • Slatcher R.B.
        • Ong A.D.
        • Gruenewald T.L.
        Purpose in life predicts allostatic load ten years later.
        J Psychosom Res. 2015; 79: 451-457
        • Hämmerle P.
        • Eick C.
        • Blum S.
        • et al.
        Heart rate variability triangular index as a predictor of cardiovascular mortality in patients with atrial fibrillation.
        J Am Heart Assoc. 2020; 9e016075
        • Koenig J.
        • Thayer J.F.
        Sex differences in healthy human heart rate variability: a meta-analysis.
        Neurosci Biobehav Rev. 2016; 64: 288-310
        • Vaillancourt D.E.
        • Newell K.M.
        Changing complexity in human behaviour and physiology through aging and disease.
        Neurobiol Aging. 2002; 23: 1-11
        • Anavekar N.S.
        • Oh J.K.
        Doppler echocardiography: a contemporary review.
        J Cardiol. 2009; 54: 347-358
        • Juster R.P.
        • Bizik G.
        • Picard M.
        • et al.
        A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development.
        Dev Psychopathol. 2011; 23: 725-776
        • Juster R.P.
        • de Torre M.B.
        • Kerr P.
        • et al.
        Sex differences and gender diversity in stress responses and allostatic load among workers and LGBT people.
        Curr Psychiatry Rep. 2019; 21: 110
        • Verma R.
        • Balhara Y.P.
        • Gupta C.S.
        Gender differences in stress response: role of developmental and biological determinants.
        Ind Psychiatry J. 2011; 20: 4-10
        • Bangasser D.A.
        • Valentino R.J.
        Sex differences in stress-related psychiatric disorders: neurobiological perspectives.
        Front Neuroendocrinol. 2014; 35: 303-319
        • Mayor E.
        Gender roles and traits in stress and health.
        Front Psychol. 2015; 6: 779
        • Rothbart M.K.
        • Ahadi S.A.
        • Evans D.E.
        Temperament and personality: origins and outcomes.
        J Pers Soc Psychol. 2000; 78: 122-135
        • Kachel S.
        • Steffens M.C.
        • Niedlich C.
        Traditional masculinity and femininity: validation of a new scale assessing gender roles.
        Front Psychol. 2016; 7: 956
        • Martin C.L.
        • Ruble D.N.
        • Szkrybalo J.
        Cognitive theories of early gender development.
        Psychol Bull. 2002; 128: 903-933
        • Wegener I.
        • Alfter S.
        • Geiser F.
        • Liedtke R.
        • Conrad R.
        Schema change without schema therapy: the role of early maladaptive schemata for a successful treatment of major depression.
        Psychiatry. 2013; 76: 1-17
        • Dedovic K.
        • Wadiwalla M.
        • Engert V.
        • Pruessner J.C.
        The role of sex and gender socialisation in stress reactivity.
        Develop Psychol. 2009; 45: 45
        • Schmitt D.P.
        • Long A.E.
        • McPhearson A.
        • et al.
        Personality and gender differences in global perspective.
        Int J Psychol. 2017; 52: 45-56
        • Bem S.L.
        Androgyny and gender schema theory: a conceptual and empirical integration.
        Nebr Symp Motiv. 1984; 32: 179-226
        • Lecic-Tosevski D.
        • Vukovic O.
        • Stepanovic J.
        Stress and personality.
        Psychiatriki. 2011; 22: 290-297
        • Bach B.
        • Lockwood G.
        • Young J.E.
        A new look at the schema therapy model: organisation and role of early maladaptive schemas.
        Cogn Behav Ther. 2018; 47: 328-349
        • Stroud L.R.
        • Salovey P.
        • Epel E.S.
        Sex differences in stress responses: social rejection vs achievement stress.
        Biol Psychiatry. 2002; 52: 318-327
        • Ferguson T.J.
        • Eyre H.L.
        • Ashbaker M.
        Unwanted identities: A key variable in shame-anger links and gender differences in shame.
        Sex Roles. 2000; 42: 133-157
        • Zwicker A.
        • DeLongis A.
        Gender, stress, and coping.
        in: Chrisler J.C. McCreary D.R. Handbook of Gender Research in Psychology. Springer, 2010: 495-515
        • Taylor S.E.
        • Klein L.C.
        • Lewis B.P.
        • et al.
        Biobehavioural responses to stress in females: tend-and-befriend, not fight-or-flight.
        Psychol Rev. 2000; 107: 411-429
        • Kinnunen M.-L.
        • Kaprio J.
        • Pulkkinen L.
        Allostatic load of men and women in early middle age.
        J Individ Differ. 2005; 26: 20-28
        • Kerr P.
        • Kheloui S.
        • Rossi M.
        • Désilets M.
        • Juster R.-P.
        Allostatic load and women’s brain health: a systematic review.
        Front Neuroendocrinol. 2020; 59100858
        • Shivpuri S.
        • Gallo L.C.
        • Crouse J.R.
        • Allison M.A.
        The association between chronic stress type and C-reactive protein in the multi-ethnic study of atherosclerosis: does gender make a difference?.
        J Behav Med. 2012; 35: 74-85
        • Fleming P.J.
        • Agnew-Brune C.
        Current trends in the study of gender norms and health behaviours.
        Curr Opin Psychol. 2015; 5: 72-77
        • Courtenay W.H.
        Constructions of masculinity and their influence on men’s well-being: a theory of gender and health.
        Soc Sci Med. 2000; 50: 1385-1401
        • Sánchez–López MdP.
        • Cuellar–Flores I.
        • Dresch V.
        The impact of gender roles on health.
        Women Health. 2012; 52: 182-196
        • Peralta R.L.
        College alcohol use and the embodiment of hegemonic masculinity among European American men.
        Sex Roles. 2007; 56: 741-756
        • Sobal J.
        Men, meat, and marriage: models of masculinity.
        Food Foodways. 2005; 13: 135-158
        • Etienne C.F.
        Addressing masculinity and men’s health to advance universal health and gender equality.
        Rev Panam Salud Publica. 2019; 42: e196
        • Nakagawa S.
        • Hart C.
        Where’s the beef? How masculinity exacerbates gender disparities in health behaviours.
        Socius. 2019; 52378023119831801
        • Cla T.
        Time to tackle the physical activity gender gap.
        Health (Irvine Calif). 2018; 6: e1077-e1086
        • Hands B.P.
        • Parker H.
        • Larkin D.
        • Cantell M.
        • Rose E.
        Male and female differences in health benefits derived from physical activity: implications for exercise prescription.
        J Womens Health Issues Care. 2016; 5 (doi:)
        • Casey M.
        • Eime R.
        • Harvey J.
        • et al.
        The influence of a healthy welcoming environment on participation in club sport by adolescent girls: a longitudinal study.
        BMC Sports Sci Med Rehabil. 2017; 9: 1-9
        • World Health Organisation
        WHO global report on trends in prevalence of tobacco smoking 2000-2025.
        third edition. 2019 (2019. Available at:)
        • Amos A.
        • Greaves L.
        • Nichter M.
        • Bloch M.
        Women and tobacco: a call for including gender in tobacco control research, policy and practice.
        Tob Control. 2012; 21: 236-243
        • Schiller C.E.
        • Saladin M.E.
        • Grey K.M.
        • Hartwell K.J.
        • Carpenter M.J.
        Association between ovarian hormones and smoking behaviour in women.
        Exp Clin Psychopharmacol. 2012; 20: 251
        • Ozbay N.
        • Shevorykin A.
        • Smith P.H.
        • Sheffer C.E.
        The association between gender roles and smoking initiation among women and adolescent girls.
        J Gend Stud. 2020; 29: 664-684
        • Rahmanian S.D.
        • Diaz P.T.
        • Wewers M.E.
        Tobacco use and cessation among women: research and treatment-related issues.
        J Womens Health. 2011; 20: 349-357
        • Bizik G.
        • Picard M.
        • Nijjar R.
        • et al.
        Allostatic load as a tool for monitoring physiological dysregulations and comorbidities in patients with severe mental illnesses.
        Harv Rev Psychiatry. 2013; 21: 296-313
        • Finlay S.
        • Rudd D.
        • McDermott B.
        • Sarnyai Z.
        Allostatic load and systemic comorbidities in psychiatric disorders.
        Psychoneuroendocrinology. 2022; 140105726
        • McEwen B.S.
        Allostasis and allostatic load: implications for neuropsychopharmacology.
        Neuropsychopharmacology. 2000; 22: 108-124
        • Berger M.
        • Juster R.P.
        • Westphal S.
        • et al.
        Allostatic load is associated with psychotic symptoms and decreases with antipsychotic treatment in patients with schizophrenia and first-episode psychosis.
        Psychoneuroendocrinology. 2018; 90: 35-42
        • Hough C.M.
        • Bersani F.S.
        • Mellon S.H.
        • et al.
        Pre-treatment allostatic load and metabolic dysregulation predict SSRI response in major depressive disorder: a preliminary report.
        Psychol Med. 2020; : 1-9
        • Kerr P.
        • Lupien S.
        • Juster R.P.
        Rx risk or resistance? Psychotropic medication use in relation to physiological and psychosocial functioning of psychiatric hospital workers.
        Psychoneuroendocrinology. 2020; 115104634
        • Norris C.M.
        • Yip C.Y.Y.
        • Nerenberg K.A.
        • et al.
        State of the science in women’s cardiovascular disease: a Canadian perspective on the influence of sex and gender.
        J Am Heart Assoc. 2020; 9e015634
        • McDermott B.J.
        • Grey G.A.
        Biological sex themed section: incorporating the female dimension into cardiovascular pharmacology.
        Br J Pharmacol. 2014; 171: 537-540
        • Rouxel P.
        • Chandola T.
        • Kumari M.
        • Seeman T.
        • Benzeval M.
        Biological costs and benefits of social relationships for men and women in adulthood: the role of partner, family and friends.
        Sociol Health Illn. 2022; 44: 5-24
        • Wiley J.F.
        • Bei B.
        • Bower J.E.
        • Stanton A.L.
        Relationship of psychosocial resources with allostatic load.
        a systematic review. 2017; 79: 283-292
        • Slopen N.
        • Chen Y.
        • Priest N.
        • Albert M.A.
        • Williams D.R.
        Emotional and instrumental support during childhood and biological dysregulation in midlife.
        Prev Med. 2016; 84: 90-96
        • Carroll J.E.
        • Gruenewald T.L.
        • Taylor S.E.
        • et al.
        Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study.
        Proc Natl Acad Sci U S A. 2013; 110: 17149-17153
        • Ungar N.
        • Michalowski V.I.
        • Baehring S.
        • et al.
        Joint goals in older couples: associations with goal progress, allostatic load, and relationship satisfaction.
        Front Psychol. 2021; 12623037
        • Seeman T.
        • Glei D.
        • Goldman N.
        • et al.
        Social relationships and allostatic load in Taiwanese elderly and near elderly.
        Soc Sci Med. 2004; 59: 2245-2257
        • Grundy E.
        • Tomassini C.
        Marital history, health and mortality among older men and women in England and Wales.
        BMC Public Health. 2010; 10: 554
        • Chiu C.-J.
        • Lin Y.-C.
        Spousal health and older adults’ biomarker change over six years: Investigation of gender differences.
        Arch Gerontol Geriatr. 2019; 83: 44-49
        • Seeman T.E.
        • Gruenewald T.L.
        • Cohen S.
        • Williams D.R.
        • Matthews K.A.
        Social relationships and their biological correlates: Coronary Artery Risk Development in Young Adults (CARDIA) study.
        Psychoneuroendocrinology. 2014; 43: 126-138
        • Bem S.L.
        The measurement of psychological androgyny.
        J Consult Clin Psychol. 1974; 42: 155-162
        • Spence J.T.
        • Helmreich R.
        • Stapp J.
        The Personal Attributes Questionnaire: A Measure of Sex Role Stereotypes and Masculinity-Feminity.
        University of Texas, 1974
        • Storms M.D.
        Sex-role identity and its relationships to sex-role attributes and sex-role stereotypes.
        J Pers Soc Psychol. 1979; 37: 1779-1789
        • Ferrer-Pérez V.
        • Bosch-Fiol E.
        The measure of the masculinity–femininity construct today: some reflections on the case of the Bem Sex Role Inventory.
        Int J Soc Psychol. 2014; 29: 180-207
        • National Academies of Sciences, Engineering, and Medicine
        Measuring Sex, Gender Identity, and Sexual Orientation.
        National Academies Press, Washington, DC2022
        • Pelletier R.
        • Humphries K.H.
        • Shimony A.
        • et al.
        Sex-related differences in access to care among patients with premature acute coronary syndrome.
        CMAJ. 2014; 186: 497-504
        • Pelletier R.
        • Ditto B.
        • Pilote L.
        A composite measure of gender and its association with risk factors in patients with premature acute coronary syndrome.
        Psychosom Med. 2015; 77: 517-526
        • Pelletier R.
        • Khan N.A.
        • Cox J.
        • et al.
        Sex vs gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
        J Am Coll Cardiol. 2016; 67: 127-135
        • Juster R.P.
        • Pruessner J.C.
        • Desrochers A.B.
        • et al.
        Sex and gender roles in relation to mental health and allostatic load.
        Psychosom Med. 2016; 78: 788-804
        • Juster R.-P.
        Sex × gender and sexual orientation in relation to stress hormones and allostatic load.
        Gend Genome. 2019; 32470289719862555
        • DuBois L.Z.
        • Gibb J.K.
        • Juster R.P.
        • Powers S.I.
        Biocultural approaches to transgender and gender diverse experience and health: Integrating biomarkers and advancing gender/sex research.
        Am J Hum Biol. 2021; 33e23555
        • Meyer I.H.
        Prejudice, social stress, and mental health in lesbian, gay, and bisexual populations: conceptual issues and research evidence.
        Psychol Bull. 2003; 129: 674
        • Hatzenbuehler M.L.
        How does sexual minority stigma “get under the skin”? A psychological mediation framework.
        Psychol Bull. 2009; 135: 707
        • Mays V.M.
        • Juster R.-P.
        • Williamson T.J.
        • Seeman T.E.
        • Cochran S.D.
        Chronic physiologic effects of stress among lesbian, gay, and bisexual adults: results from the National Health and Nutrition Examination Survey.
        Psychosom Med. 2018; 80: 551-563
        • Louden E.
        The association of sexual orientation with allostatic load and cardiovascular health: an analysis of the National Health and Nutrition Examination Survey (NHANES) [thesis].
        College of Public Health, Ohio State University, 2020
        • Jabson J.M.
        • Farmer G.W.
        • Bowen D.
        Does stress mediate the relationship between sexual orientation and behavioural risk disparities? [abstract].
        Ann Behav Med. 2014; 47: A-A191
        • Dubois L.Z.
        • Juster R.P.
        Lived experience and allostatic load among transmasculine people living in the United States.
        Psychoneuroendocrinology. 2022; 143105849
        • Chyu L.
        • Upchurch D.M.
        Racial and ethnic patterns of allostatic load among adult women in the United States: findings from the National Health and Nutrition Examination Survey 1999-2004.
        J Womens Health (Larchmt). 2011; 20: 575-583
        • Geronimus A.T.
        • Hicken M.
        • Keene D.
        • Bound J.
        “Weathering” and age patterns of allostatic load scores among blacks and whites in the United States.
        Am J Public Health. 2006; 96: 826-833
        • Peek M.K.
        • Cutchin M.P.
        • Salinas J.J.
        • et al.
        Allostatic load among non-hispanic whites, non-hispanic blacks, and people of Mexican origin: effects of ethnicity, nativity, and acculturation.
        Am J Public Health. 2010; 100: 940-946
        • Mandelbaum J.
        Advancing health equity by integrating intersectionality into epidemiological research: applications and challenges.
        J Epidemiol Community Health. 2020; 74: 761-762
        • Rai S.S.
        • Peters R.M.H.
        • Syurina E.V.
        • et al.
        Intersectionality and health-related stigma: insights from experiences of people living with stigmatized health conditions in Indonesia.
        Int J Equity Health. 2020; 19: 206
        • Geronimus A.T.
        The weathering hypothesis and the health of African-American women and infants: evidence and speculations.
        Ethn Dis. 1992; 2: 207-221
        • Lin J.
        • Kelley-Moore J.
        Intraindividual variability in late-life functional limitations among white, black, and hispanic older adults.
        Res Aging. 2017; 39: 549-572
        • Link B.G.
        • Phelan J.
        Social conditions as fundamental causes of disease.
        J Health Soc Behav. 1995; (spec no): 80-94
        • Juster R.-P.
        • Seeman T.
        • McEwen B.S.
        • et al.
        Social inequalities and the road to allostatic load: from vulnerability to resilience.
        in: Cicchetti D D. Developmental Psychopathology: Risk, Resilience, and Intervention. Wiley, New York2016