Why are sex and gender important to basic physiology and translational and individualized medicine?

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 306, Issue 6, 2014, Pages

  Miller, Virginia M ^a  

^a MAYO GRADUATE SCHOOL   (United States)

Author keywords

Behavior; Chromosomes; Health disparities; Hormones; Personality

Indexed keywords

ANDROGEN; NORADRENALIN; XENOBIOTIC AGENT; HORMONE;

APOPTOSIS; BLOOD PRESSURE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; ENERGY METABOLISM; FEMININITY; FUNDING; GENETIC VARIABILITY; HEALTH DISPARITY; HUMAN; INNATE IMMUNITY; KARYOTYPE; MASCULINITY; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PERSONALIZED MEDICINE; PHYSIOLOGY; POSTGRADUATE EDUCATION; PRIORITY JOURNAL; REVIEW; SEX CHROMOSOME; SEX DIFFERENCE; SEXISM; TRANSLATIONAL RESEARCH; TREATMENT OUTCOME; AGE; BEHAVIOR; CHROMOSOME; COMPARATIVE STUDY; DISEASES; FEMALE; GENDER IDENTITY; MALE; MEDICAL EDUCATION; NOMENCLATURE; PERSONALITY; PUBLICATION; SEXUAL DEVELOPMENT;

BEHAVIOR; CHROMOSOMES; HEALTH DISPARITIES; HORMONES; PERSONALITY;

AGE FACTORS; DISEASE; EDUCATION, MEDICAL; FEMALE; GENDER IDENTITY; HUMANS; INDIVIDUALIZED MEDICINE; MALE; PHYSIOLOGY; PUBLICATIONS; SEX CHARACTERISTICS; SEX FACTORS; TERMINOLOGY AS TOPIC; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84900547046     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00994.2013     Document Type: Review

References (81)

1. Antoniucci D, Miller VM, Sieck GC, Fitzpatrick LA. Gender-related differences in proliferative responses of vascular smooth muscle cells to endothelin-1. Endothelium 8: 137-145, 2001.
2. Arnold AP. Sex chromosomes and brain gender. Nat Rev Neurosci 5: 701-708, 2004.
3. Arnold AP, Burgoyne PS. Are XX and XY brain cells intrinsically different? Trends Endocrinol Metab 15: 6-11, 2004.
4. Arnold AP, Chen X. What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues? Front Neuroendocrinol 30: 1-9, 2009.
5. Barber DA, Burnett JC Jr, Fitzpatrick LA, Sieck GC, Miller VM. Gender and relaxation to C-Type natriuretic peptide in porcine coronary arteries. J Cardiovasc Pharmacol 32: 5-11, 1998.
6. Barber DA, Burnett JC Jr, Miller VM. Gender differences in relaxations evoked by C-Type natriuretic peptide in porcine coronary arteries. Endothelium 2: s2, 1995.
7. Barber DA, Miller VM. Gender differences in endothelium-dependent relaxations do not involve NO in porcine coronary arteries. Am J Physiol Heart Circ Physiol 273: H2325-H2332, 1997.
8. Blaustein JD. Animals have a sex, and so should titles and methods sections of articles in Endocrinology. Endocrinology 153: 2539-2540, 2012.
9. Bloomer LD, Nelson CP, Eales J, Denniff M, Christofidou P, Debiec R, Moore J, Consortium C, Zukowska-Szczechowska E, Goodall AH, Thompson J, Samani NJ, Charchar FJ, Tomaszewski M. Male-specific region of the Y chromosome and cardiovascular risk: phylogenetic analysis and gene expression studies. Arterioscler Thromb Vasc Biol 33: 1722-1727, 2013.
10. Bulckaen H, Prevost G, Boulanger E, Robitaille G, Roquet V, Gaxatte C, Garcon G, Corman B, Gosset P, Shirali P, Creusy C, Puisieux F. Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging. Am J Physiol Heart Circ Physiol 294: H1562-H1570, 2008.
11. Charchar FJ, Bloomer LD, Barnes TA, Cowley MJ, Nelson CP, Wang Y, Denniff M, Debiec R, Christofidou P, Nankervis S, Dominiczak AF, Bani-Mustafa A, Balmforth AJ, Hall AS, Erdmann J, Cambien F, Deloukas P, Hengstenberg C, Packard C, Schunkert H, Ouwehand WH, Ford I, Goodall AH, Jobling MA, Samani NJ, Tomaszewski M. Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome. Lancet 379: 915-922, 2012.
12. Clifton PM, Nestel PJ. Influence of gender, body mass index, and age on response of plasma lipids to dietary fat plus cholesterol. Arterioscler Thromb 12: 955-962, 1992.
13. Dhruva SS, Bero LA, Redberg RF. Gender bias in studies for Food and Drug Administration premarket approval of cardiovascular devices. Circ Cardiovasc Qual Outcomes 4: 165-171, 2011.
14. Dhruva SS, Redberg RF. Evaluating sex differences in medical device clinical trials: time for action. JAMA 307: 1145-1146, 2012.
15. Donawa M. Successful recruitment for medical device clinical studies. Med Device Technol 15: 25-27, 2004.
16. Ely D, Milsted A, Dunphy G, Boehme S, Dunmire J, Hart M, Toot J, Martins A, Turner M. Delivery of sry1, but not sry2, to the kidney increases blood pressure and sns indices in normotensive wky rats. BMC Physiol 9: 10, 2009.
17. Feletou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 291: H985-H1002, 2006.
18. Geller SE, Koch A, Pellettieri B, Carnes M. Inclusion, analysis and reporting of sex and race/ethnicity in clinical trials: have we made progress? J Womens Health 20: 315-320, 2011.
19. Gibson FC 3rd, Hong C, Chou HH, Yumoto H, Chen J, Lien E, Wong J, Genco CA. Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation 109: 2801-2806, 2004.
20. Goodarzi MO, Li X, Krauss RM, Otter JI, Chien YI. Relationship of sex to diabetes risk in statin trials. Diabetes Care 36: e100-e101, 2013.
21. Hamm TE Jr, Kaplan JR, Clarkson TB, Bullock BC. Effects of gender and social behavior on the development of coronary artery atherosclerosis in cynomolgus macaques. Atherosclerosis 48: 221-233, 1983.
22. Harvey W. Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus, Springfield, IL: Thomas, 1928.
23. Heinrich J. General Accounting Office, GAO-01-286R Drugs Withdrawn From Market, 2001. http://www.gao.gov/new.items/d01286r.pdf.
24. Hunt K, Lewars H, Emslie C, Batty GD. Decreased risk of death from coronary heart disease amongst men with higher 'femininity' scores: a general population cohort study. Int J Epidemiol 36: 612-620, 2007.
25. Inacio MC, Ake CF, Paxton EW, Khatod M, Wang C, Gross TP, Kaczmarek RG, Marinac-Dabic D, Sedrakyan A. Sex and risk of hip implant failure: assessing total hip arthroplasty outcomes in the United States. JAMA Intern Med 173: 435-441, 2013.
26. Ingalhalikar M, Smith A, Parker D, Satterthwaite TD, Elliott MA, Ruparel K, Hakonarson H, Gur RE, Gur RC, Verma R. Sex differences in the structural connectome of the human brain. Proc Natl Acad Sci USA 111: 823-828, 2014.
27. Institute of Medicine (US) Board on Population Health and Public Health Practice. Sex-Specific Reporting of Scientific Research: A Workshop Summary. Washington, DC: National Academic Press, 2012.
28. Isensee J, Ruiz Noppinger P. Sexually dimorphic gene expression in mammalian somatic tissue. Gend Med 4, Suppl B: S75-S95, 2007.
29. Ji H, Zheng W, Wu X, Liu J, Ecelbarger CM, Watkins R, Arnold AP, Sandberg K. Sex chromosome effects unmasked in angiotensin II-induced hypertension. Hypertension 55: 1275-1282, 2010.
30. Kuroki Y, Tsuchida K, Go I, Aoyama M, Naganuma T, Takemoto Y, Nakatani T. A study of innate immunity in patients with end-stage renal disease: special reference to toll-like receptor-2 and-4 expression in peripheral blood monocytes of hemodialysis patients. Int J Mol Med 19: 783-790, 2007.
31. Kwekel JC, Desai VG, Moland CL, Vijay V, Fuscoe JC. Sex differences in kidney gene expression during the life cycle of F344 rats. Biol Sex Differ 4: 14, 2013.
32. Lagace M, Xuan JY, Young SS, McRoberts C, Maier J, Rajcan-Separovic E, Korneluk RG. Genomic organization of the X-linked inhibitor of apoptosis and identification of a novel testis-specific transcript. Genomics 77: 181-188, 2001.
33. Lenaz G, Bovina C, D'Aurelio M, Fato R, Formiggini G, Genova ML, Giuliano G, Merlo Pich M, Paolucci U, Parenti Castelli G, Ventura B. Role of mitochondria in oxidative stress and aging. Ann NY Acad Sci 959: 199-213, 2002.
34. Li Z, Yang F, Dunn S, Gross AK, Smyth SS. Platelets as immune mediators: Their role in Host defense responses and sepsis. Thromb Res 127: 184-186, 2011.
35. Libby P. Fat fuels the flame: triglyceride-rich lipoproteins and arterial inflammation. Circ Res 100: 299-301, 2007.
36. Lin TH, Yeh S, Chang C. Tissue-specific knockout of androgen receptor in mice. Methods Mol Biol 776: 275-293, 2011.
37. Mahalik JR, Locke BD, Ludlow LH, Diemer MA, Scott RP, Gottfried M, Freitas G. Development of the conformity to masculine norms inventory. Psychol Men Masc: 3-25, 2003.
38. Martin SS, Ou FS, Newby LK, Sutton V, Adams P, Felker GM, Wang TY. Patient-and trial-specific barriers to participation in cardiovascular randomized clinical trials. J Am Coll Cardiol 61: 762-769, 2013.
39. McIntyre TM, Prescott SM, Weyrich AS, Zimmerman GA. Cell-cell interactions: leukocyte-endothelial interactions. Curr Opin Hematol 10: 150-158, 2003.
40. Melloni C, Berger JS, Wang TY, Gunes F, Stebbins A, Pieper KS, Dolor RJ, Douglas PS, Mark DB, Newby LK. Representation of women in randomized clinical trials of cardiovascular disease prevention. Circ Cardiovasc Qual Outcomes 3: 135-142, 2010.
41. Miller VM. In pursuit of scientific excellence: sex matters. Am J Physiol Heart Circ Physiol 302: H1771-H1772, 2012.
42. Miller VM, Flynn PM, Lindor KD. Evaluating sex and gender competencies in the medical curriculum: a case study. Gend Med 9: 180-186, e183, 2012.
43. Miller VM, Lewis DA, Barber DA. Gender differences and endotheliumand platelet-derived factors in the coronary circulation. Clin Exp Pharmacol Physiol 26: 132-136, 1999.
44. Miller VM, Rice M, Schiebinger L, Jenkins MR, Werbinski J, Nunez A, Wood S, Viggiano TR, Shuster LT. Embedding concepts of sex and gender health differences into medical curricula. J Womens Health 22: 194-202, 2013.
45. Misra MK, Sarwat M, Bhakuni P, Tuteja R, Tuteja N. Oxidative stress and ischemic myocardial syndromes. Med Sci Monit 15: RA209-RA219, 2009.
46. Money J. Gender: history, theory and usage of the term in sexology and its relationship to nature/nurture. J Sex Marital Ther 11: 71-79, 1985.
47. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pina IL, Roger VL, Shaw LJ, Zhao D, Beckie TM, Bushnell C, D'Armiento J, Kris-Etherton PM, Fang J, Ganiats TG, Gomes AS, Gracia CR, Haan CK, Jackson EA, Judelson DR, Kelepouris E, Lavie CJ, Moore A, Nussmeier NA, Ofili E, Oparil S, Ouyang P, Pinn VW, Sherif K, Smith SC Jr, Sopko G, Chandra-Strobos N, Urbina EM, Vaccarino V, and Wenger NK. Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women-2011 Update: A Guideline from the American Heart Association. Circulation 123: 1243-1262, 2011.
48. Negrin CD, McBride MW, Carswell HV, Graham D, Carr FJ, Clark JS, Jeffs B, Anderson NH, Macrae M, Dominiczak AF. Reciprocal consomic strains to evaluate Y chromosome effects. Hypertension 37: 391-397, 2001.
49. Njolstad I, Arnesen E, Lund-Larsen PG. Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark study. Circulation 93: 450-456, 1995.
50. Ober C, Loisel DA, Gilad Y. Sex-specific genetic architecture of human disease. Nat Rev Genet 9: 911-922, 2008.
51. Ogawa S, Lozach J, Benner C, Pascual G, Tangirala RK, Westin S, Hoffmann A, Subramaniam S, David M, Rosenfeld MG, Glass CK. Molecular determinants of crosstalk between nuclear receptors and tolllike receptors. Cell 122: 707-721, 2005.
52. Ohno S. Sex chromosomes and sex-linked genes: Springer-Verlag, Berlin, Heidelberg, New York, 1967.
53. Pierce GL, Eskurza I, Walker AE, Fay TN, Seals DR. Sex-specific effects of habitual aerobic exercise on brachial artery flow-mediated dilation in middle-aged and older adults. Clin Sci (Lond) 120: 13-23, 2011.
54. Pierce JP, Kievits J, Graustein B, Speth RC, Iadecola C, Milner TA. Sex differences in the subcellular distribution of angiotensin type 1 receptors and NADPH oxidase subunits in the dendrites of C1 neurons in the rat rostral ventrolateral medulla. Neuroscience 163: 329-338, 2009.
55. Radecki Breitkopf C, Parker M, Balls-Berry J, Halyard M, Pinn V, Hayes S. African-American women's perceptions and attitudes regarding participation in health research. J Womens Health 22: 38-39, 2013.
56. Raffetto JD, Khalil RA. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 75: 346-359, 2008.
57. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriuretic peptide concentration: Impact of age and gender. J Am Coll Cardiol 40: 976-982, 2002.
58. Reilly SL, Kottke BA, Sing CF. The effects of generation and gender on the joint distributions of lipid and apolipoprotein phenotypes in the population at large. J Clin Epidemiol 43: 921-940, 1990.
59. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.[see comment]. N Engl J Med 352: 1293-1304, 2005.
60. Ristvedt SL. The Evolution of Gender. JAMA Psychiatry 71: 13-14, 2014.
61. Sandberg K, Verbalis JG. Sex and the basic scientist: is it time to embrace Title IX? Biol Sex Differ 4: 13, 2013.
62. Schmidt EP, Lee WL, Zemans RL, Yamashita C, Downey GP. On, around, and through: neutrophil-endothelial interactions in innate immunity. Physiology (Bethesda) 26: 334-347, 2011.
63. Seremetis SV. Sex-related differences in hemostasis and thrombosis. J Gend Specif Med 4: 59-64, 2001.
64. Shah K, McCormack CE, ABN. Do you know the sex of your cells? Am J Physiol Cell Physiol 306: C3-C18, 2014.
65. Shaul PW, Wells LB, Horning KM. Acute and prolonged hypoxia attenuated endothelial nitric oxide production in rat pulmonary arteries by different mechanisms. J Cardiovasc Pharmacol 22: 819-827, 1993.
66. Smulyan H. Nitrates, arterial function, wave reflections and coronary heart disease. Adv Cardiol 44: 302-314, 2007.
67. Strehlow K, Rotter S, Wassmann S, Adam O, Grohe C, Laufs K, Bohm M, Nickenig G. Modulation of antioxidant enzyme expression and function by estrogen. Circ Res 93: 170-177, 2003.
68. Taylor KE, Vallejo-Giraldo C, Schaible NS, Zakeri R, Miller VM. Reporting of sex as a variable in cardiovascular studies using cultured cells. Biol Sex Differ 2: 11, 2011.
69. Turner ME, Jenkins C, Milsted A, Ely DL. Sex chromosomes. Adv Mol Cell Biol 34: 1-13, 2004.
70. van Heerebeek L, Franssen CP, Hamdani N, Verheugt FW, Somsen GA, Paulus WJ. Molecular and cellular basis for diastolic dysfunction. Curr Heart Fail Rep 9: 293-302, 2012.
71. Van PL, Bakalov VK, Zinn AR, Bondy CA. Maternal X chromosome, visceral adiposity, and lipid profile. JAMA 295: 1373-1374, 2006.
72. Voghel G, Thorin-Trescases N, Farhat N, Nguyen A, Villeneuve L, Mamarbachi AM, Fortier A, Perrault LP, Carrier M, Thorin E. Cellular senescence in endothelial cells from atherosclerotic patients is accelerated by oxidative stress associated with cardiovascular risk factors. Mech Ageing Dev 128: 662-671, 2007.
73. Wadman M. NIH mulls rules for validating key results. Nature 500: 14-16, 2013.
74. Wang X, Barber DA, Lewis DA, McGregor CGA, Sieck GA, Fitzpatrick LA, Miller VM. Gender and transcriptional regulation of NO synthase and ET-1 in porcine aortic endothelial cells. Am J Physiol Heart Circ Physiol 273: H1962-H1967, 1997.
75. Waxman DJ, Holloway MG. Sex differences in the expression of hepatic drug metabolizing enzymes. Mol Pharmacol 76: 215-228, 2009.
76. Wizemann TM, Pardue ML. Exploring the Biological Contributions to Human Health: Does Sex Matter? Board on Health Sciences Policy. Washington, DC: Institute of Medicine, 2001.
77. World Health Organization. WHO Expert Committee on Biological Standardization. Thirty-seventh Report. WHO Health Organization Technical Report Series, 1987.
78. Xu J, Disteche CM. Sex differences in brain expression of X-and Y-linked genes. Brain Res 1126: 50-55, 2006.
79. Yang X, Schadt EE, Wang S, Wang H, Arnold AP, Ingram-Drake L, Drake TA, Lusis AJ. Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res 16: 995-1004, 2006.
80. Yasunari K, Maeda K, Minami M, Yoshikawa J. HMG-CoA reductase inhibitors prevent migration of human coronary smooth muscle cells through suppression of increase in oxidative stress. Arterioscler Thromb Vasc Biol 21: 937-942, 2001.
81. Zucker I, Beery AK. Males still dominate animal studies. Nature 465: 690, 2010.