Display options
Cite
Tharakan T, Khoo CC, Giwercman A, et al. Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?. Nat Rev Urol. 2021;19(1):47-63doi: 10.1038/s41585-021-00535-4.
Tharakan, T., Khoo, C. C., Giwercman, A., Jayasena, C. N., Sofikitis, N., Salonia, A., & Minhas, S. (2022). Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?. Nature reviews. Urology, 19(1), 47-63. https://doi.org/10.1038/s41585-021-00535-4
Tharakan, Tharu, et al. "Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?." Nature reviews. Urology vol. 19,1 (2022): 47-63. doi: https://doi.org/10.1038/s41585-021-00535-4
Tharakan T, Khoo CC, Giwercman A, Jayasena CN, Sofikitis N, Salonia A, Minhas S. Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?. Nat Rev Urol. 2022 Jan;19(1):47-63. doi: 10.1038/s41585-021-00535-4. Epub 2021 Nov 18. PMID: 34795426; PMCID: PMC8600906.
Copy Download .nbib Format: NLM
Share it on

Nat Rev Urol. 2022 Jan;19(1):47-63. doi: 10.1038/s41585-021-00535-4. Epub 2021 Nov 18.

Are sex disparities in COVID-19 a predictable outcome of failing men's health provision?.

Nature reviews. Urology

Tharu Tharakan, Christopher C Khoo, Aleksander Giwercman, Channa N Jayasena, Nikolaos Sofikitis, Andrea Salonia, Suks Minhas

Affiliations

  1. Department of Urology, Imperial Healthcare NHS Trust, Charing Cross Hospital, London, UK. [email protected].
  2. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. [email protected].
  3. Department of Urology, Imperial Healthcare NHS Trust, Charing Cross Hospital, London, UK.
  4. Department of Translational Medicine, Lund University, Lund, Sweden.
  5. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  6. Department of Urology, Ioannina University School of Medicine, Ioannina, Greece.
  7. Division of Experimental Oncology/Unite of Urology, URI, IRCCS Ospedale, San Raffaele, Milan, Italy.
  8. University Vita-Salute San Raffaele, Milan, Italy.
  9. Department of Surgery and Cancer, Imperial College London, London, UK.

PMID: 34795426 PMCID: PMC8600906 DOI: 10.1038/s41585-021-00535-4

Abstract

The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has taken a catastrophic toll on society, health-care systems and the economy. Notably, COVID-19 has been shown to be associated with a higher mortality rate in men than in women. This disparity is likely to be a consequence of a failure to invest in men's health, as it has also been established that men have a lower life expectancy and poorer outcomes from non-communicable diseases than women. A variety of biological, social and economic factors have contributed to the sex disparities in mortality from COVID-19. A streamlined men's health programme - with the urologist as the gatekeeper of men's health - is needed to help prevent future tragedies of this nature.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

References

  1. Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565–574 (2020). - PubMed
  2. BBC. Coronavirus: risk of death is higher for ethnic minorities — BBC News. BBC https://www.bbc.co.uk/news/health-52889106 (2020). - PubMed
  3. Tharakan, T. et al. Male sexual and reproductive health — does the urologist have a role in addressing gender inequality in life expectancy? Eur Urol. Focus 6, 791–800 (2019). - PubMed
  4. Tharakan, T., Jayasena, C. & Minhas, S. Men’s health clinics: a real need or a marketing strategy. Int. J. Impot. Res. 32, 565–568 (2020). - PubMed
  5. Tharakan, T., Salonia, A. & Minhas, S. Male life expectancy is still inferior to that of women: urologists must refine and develop the concept of men’s health. Eur. Urol. 76, 712–713 (2019). - PubMed
  6. Perico, L., Benigni, A. & Remuzzi, G. Should COVID-19 concern nephrologists? Why and to what extent? The emerging impasse of angiotensin blockade. Nephron 144, 1–9 (2020). - PubMed
  7. Mason, R. J. Pathogenesis of COVID-19 from a cell biologic perspective. Eur. Respir. J. https://doi.org/10.1183/13993003.00607-2020 (2020). - PubMed
  8. Li, G. et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J. Autoimmun. 112, 1–7 (2020). - PubMed
  9. Oudkerk, M. et al. Diagnosis, prevention, and treatment of thromboembolic complications in COVID-19: report of the National Institute for Public Health of the Netherlands. Radiology 77, 1–15 (2020). - PubMed
  10. Ciceri, F. et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit. Care Resusc. 22, 95–97 (2020). - PubMed
  11. Bruce Aylward (WHO); Wannian Liang (PRC). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). WHO https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf (2020). - PubMed
  12. Coronavirus Resource Center. COVID-19 Map — Johns Hopkins Coronavirus Resource Center. JHU https://coronavirus.jhu.edu/map.html (2020). - PubMed
  13. GlobalHealth505. Covid-19 — Global Health 50/50. GlobalHealth505 https://globalhealth5050.org/covid19/ (2020). - PubMed
  14. Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020). - PubMed
  15. Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395, 1054–1062 (2020). - PubMed
  16. Du, R. H. et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study. Eur. Respir. J. 55, 1–8 (2020). - PubMed
  17. Zhang, J. et al. Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China. Clin. Microbiol. Infect. 26, 767–772 (2020). - PubMed
  18. WHO clinical management of COVID-19. WHO https://www.who.int/publications/i/item/clinical-management-of-covid-19 (2020). - PubMed
  19. Wan, S. et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J. Med. Virol. 92, 797–806 (2020). - PubMed
  20. Zhao, Q. et al. The impact of COPD and smoking history on the severity of COVID-19: a systemic review and meta-analysis. J. Med. Virol. 92, 1915–1921 (2020). - PubMed
  21. Guo, F. R. Smoking links to the severity of COVID-19: an update of a meta-analysis. J. Med. Virol. 92, 2304–2305 (2020). - PubMed
  22. Giacomelli, A. et al. 30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study. Pharmacol. Res. 158, 1–7 (2020). - PubMed
  23. Lippi, G., Mattiuzzi, C., Sanchis-Gomar, F. & Henry, B. M. Clinical and demographic characteristics of patients dying from COVID-19 in Italy versus China. J. Med. Virol. 92, 1759–1760 (2020). - PubMed
  24. Goumenou, M. et al. COVID‑19 in Northern Italy: an integrative overview of factors possibly influencing the sharp increase of the outbreak (Review). Mol. Med. Rep. 22, 20–32 (2020). - PubMed
  25. Onder, G., Rezza, G. & Brusaferro, S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 323, 1775–1776 (2020). - PubMed
  26. Chen, J. et al. COVID-19 infection: the China and Italy perspectives. Cell Death Dis. 11, 1–17 (2020). - PubMed
  27. Peng, F. et al. Management and treatment of COVID-19: the Chinese experience. Can. J. Cardiol. 36, 915–930 (2020). - PubMed
  28. Liu, W., Yue, X. G. & Tchounwou, P. B. Response to the COVID-19 epidemic: the Chinese experience and implications for other countries. Int. J. Environ. Res. Public Health 17, 1–6 (2020). - PubMed
  29. Mikami, T. et al. Risk factors for mortality in patients with COVID-19 in New York City. J. Gen. Intern. Med. 36, 1–10 (2020). - PubMed
  30. Cummings, M. J. et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet 395, 1763–1770 (2020). - PubMed
  31. Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584, 430–436 (2020). - PubMed
  32. Docherty, A. B. et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ 369, 1–12 (2020). - PubMed
  33. Barron, E. et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 8, 813–822 (2020). - PubMed
  34. WHO. Gender, women and the tobacco epidemic. WHO https://apps.who.int/iris/bitstream/handle/10665/44342/9789241599511_eng.pdf;jsessionid=937E58FF52F52314F08381C64FD6A095?sequence=1 (2020). - PubMed
  35. Pampel, F. C. Global patterns and determinants of sex differences in smoking. Int. J. Comp. Sociol. 47, 466–487 (2006). - PubMed
  36. Buist, A. S., Vollmer, W. M. & McBurnie, M. A. Worldwide burden of COPD in high- and low-income countries. Part I. The Burden of Obstructive Lung Disease (BOLD) Initiative. Int. J. Tuberc. Lung Dis. 12, 703–708 (2008). - PubMed
  37. Blanco-Cedres, L. et al. Relation of cigarette smoking to 25-year mortality in middle-aged men with low baseline serum cholesterol: the Chicago Heart Association detection project in industry. Am. J. Epidemiol. 155, 354–360 (2002). - PubMed
  38. Friedman, G. D., Dales, L. G. & Ury, H. K. Mortality in middle-aged smokers and nonsmokers. N. Engl. J. Med. 300, 213–217 (1979). - PubMed
  39. Jacob, L., Freyn, M., Kalder, M., Dinas, K. & Kostev, K. Impact of tobacco smoking on the risk of developing 25 different cancers in the UK: a retrospective study of 422,010 patients followed for up to 30 years. Oncotarget 9, 17420–17429 (2018). - PubMed
  40. Ntritsos, G. et al. Gender-specific estimates of COPD prevalence: a systematic review and meta-analysis. Int. J. COPD 13, 1507–1514 (2018). - PubMed
  41. NHS Digital. National Diabetes Audit. NHS https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-audit (2021). - PubMed
  42. Beeson, P. B. Age and sex associations of 40 autoimmune diseases. Am. J. Med. 96, 457–462 (1994). - PubMed
  43. Gale, E. A. M. & Gillespie, K. M. Diabetes and gender. Diabetologia 44, 3–15 (2001). - PubMed
  44. Blohmé, G. et al. Male predominance of type 1 (insulin-dependent) diabetes mellitus in young adults: results from a 5-year prospective nationwide study of the 15–34-year age group in Sweden. Diabetologia 35, 56–62 (1992). - PubMed
  45. Yang, W. et al. Prevalence of diabetes among men and women in China. N. Engl. J. Med. 362, 1090–1101 (2010). - PubMed
  46. Lipscombe, L. L. & Hux, J. E. Trends in diabetes prevalence, incidence, and mortality in Ontario, Canada 1995–2005: a population-based study. Lancet 369, 750–756 (2007). - PubMed
  47. NCD Risk Factor Collaboration. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet 387, 1513–1530 (2016). - PubMed
  48. Logue, J. et al. Do men develop type 2 diabetes at lower body mass indices than women? Diabetologia 54, 3003–3006 (2011). - PubMed
  49. Demerath, E. W. et al. Anatomical patterning of visceral adipose tissue: race, sex, and age variation. Obesity 15, 2984–2993 (2007). - PubMed
  50. Ross, R. et al. Sex differences in lean and adipose tissue distribution by magnetic resonance imaging: anthropometric relationships. Am. J. Clin. Nutr. 59, 1277–1285 (1994). - PubMed
  51. Lovejoy, J. C., Champagne, C. M., De Jonge, L., Xie, H. & Smith, S. R. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int. J. Obes. 32, 949–958 (2008). - PubMed
  52. Rytka, J. M., Wueest, S., Schoenle, E. J. & Konrad, D. The portal theory supported by venous drainage-selective fat transplantation. Diabetes 60, 56–63 (2011). - PubMed
  53. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387, 1377–1396 (2016). - PubMed
  54. Simonnet, A. et al. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity 28, 1195–1199 (2020). - PubMed
  55. WHO. By category | Mean systolic blood pressure trends, age-standardized (mmHg) — global estimates. WHO https://apps.who.int/gho/data/view.main.12467GLOBAL?lang=en (2020). - PubMed
  56. CDC. National Health and Nutrition Examination Survey 2020. CDC https://www.cdc.gov/nchs/data/factsheets/factsheet_nhanes.pdf (2020). - PubMed
  57. Waddell, T. K., Dart, A. M., Gatzka, C. D., Cameron, J. D. & Kingwell, B. A. Women exhibit a greater age-related increase in proximal aortic stiffness than men. J. Hypertens. 19, 2205–2212 (2001). - PubMed
  58. Bates B. et al. National Diet and Nutrition Survey — assessment of dietary sodium in adults (aged 19 to 64 years) in England, 2014. (Department of Health, 2016). - PubMed
  59. Benjamin, E. J. et al. Heart disease and stroke statistics — 2019 update: a report from the American Heart Association. Circulation 139, e56–e528 (2019). - PubMed
  60. Bots, S. H., Peters, S. A. E. & Woodward, M. Sex differences in coronary heart disease and stroke mortality: a global assessment of the effect of ageing between 1980 and 2010. BMJ Glob. Health 2, 1–8 (2017). - PubMed
  61. Millett, E. R. C., Peters, S. A. E. & Woodward, M. Sex differences in risk factors for myocardial infarction: cohort study of UK Biobank participants. BMJ 363, 1–11 (2018). - PubMed
  62. Leening, M. J. G. et al. Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study. BMJ 349, 1–13 (2014). - PubMed
  63. Anand, S. S. et al. Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. Eur. Heart J. 29, 932–940 (2008). - PubMed
  64. Rivera, C. M. et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 16, 15–23 (2009). - PubMed
  65. Rosenberg, L. et al. Early menopause and the risk of myocardial infarction. Am. J. Obstet. Gynecol. 139, 47–51 (1981). - PubMed
  66. Zhu, D. et al. Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data. Lancet Public. Health 4, 553–564 (2019). - PubMed
  67. Mendelsohn, M. E. & Karas, R. H. The protective effects of estrogen on the cardiovascular system. N. Engl. J. Med. 340, 1801–1811 (1999). - PubMed
  68. Office for National Statistics. English Life Tables — Office for National Statistics. ONS https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/lifeexpectancies/bulletins/englishlifetablesno17/2015-09-01 (1999). - PubMed
  69. Men’s Health Forum. Men’s Health Manifesto. Men’s Health Forum https://www.menshealthforum.org.uk/mens-health-manifesto (2014). - PubMed
  70. Payne S. How can gender equity be addressed through health systems? WHO https://www.euro.who.int/__data/assets/pdf_file/0006/64941/E92846.pdf (2009). - PubMed
  71. Baker, P. 25 years post-Calman: the state of men’s health in the UK. Trends Urol. Mens Health 8, 13–16 (2017). - PubMed
  72. GBD 2017 Population and Fertility Collaborators. Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1684–1735 (2018). - PubMed
  73. The WHO Regional Office For Europe. The health and well-being of men in the WHO European region: better health through a aender approach. WHO www.euro.who.int (2018). - PubMed
  74. Juel, K. & Christensen, K. Are men seeking medical advice too late? Contacts to general practitioners and hospital admissions in Denmark 2005. J. Public. Health 30, 111–113 (2008). - PubMed
  75. Wang, Y., Hunt, K., Nazareth, I., Freemantle, N. & Petersen, I. Do men consult less than women? An analysis of routinely collected UK general practice data. BMJ Open 3, 1–7 (2013). - PubMed
  76. NHS Digital. Hospital admitted patient care activity 2018–19. NHS https://digital.nhs.uk/data-and-information/publications/statistical/hospital-admitted-patient-care-activity/2018-19 (2019). - PubMed
  77. Deeks, A., Lombard, C., Michelmore, J. & Teede, H. The effects of gender and age on health related behaviors. BMC Public. Health 9, 1–8 (2009). - PubMed
  78. Green, C. A. & Pope, C. R. Gender, psychosocial factors and the use of medical services: a longitudinal analysis. Soc. Sci. Med. 48, 1363–1372 (1999). - PubMed
  79. Thompson, A. E. et al. The influence of gender and other patient characteristics on health care-seeking behaviour: a QUALICOPC study. BMC Fam. Pract. 17, 1–7 (2016). - PubMed
  80. Pinkhasov, R. M. et al. Are men shortchanged on health? Perspective on health care utilization and health risk behavior in men and women in the United States. Int. J. Clin. Pract. 64, 475–487 (2010). - PubMed
  81. Logan, R. F. A. et al. Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests. Gut 61, 1439–1446 (2012). - PubMed
  82. Seidler, Z. E., Dawes, A. J., Rice, S. M., Oliffe, J. L. & Dhillon, H. M. The role of masculinity in men’s help-seeking for depression: a systematic review. Clin. Psychol. Rev. 49, 106–118 (2016). - PubMed
  83. WHO. Suicide worldwide in 2019: global health estimates. WHO https://www.who.int/publications/i/item/9789240026643 (2021). - PubMed
  84. Baker, P. & Shand, T. Men’s health: time for a new approach to policy and practice? J. Glob. Health 7, 1–5 (2017). - PubMed
  85. Coles, R. et al. What men really want: a qualitative investigation of men’s health needs from the Halton and St Helens primary care trust men’s health promotion project. Br. J. Health Psychol. 15, 921–939 (2010). - PubMed
  86. Gascoigne, P. & Whitear, B. Making sense of testicular cancer symptoms: a qualitative study of the way in which men sought help from the health-care services. Eur. J. Oncol. Nurs. 3, 62–69 (1999). - PubMed
  87. Hall, J. A., Roter, D. L. & Katz, N. R. Meta-analysis of correlates of provider behavior in medical encounters. Med. Care 26, 657–675 (1988). - PubMed
  88. Verbrugge, L. M. & Steiner, R. P. Physician treatment of men and women patients: sex bias or appropriate care? Med. Care 19, 609–632 (1981). - PubMed
  89. Misener, T. R. & Fuller, S. G. Testicular versus breast and colorectal cancer screening. Early detection practices of primary care physicians. Cancer Pract. 3, 310–316 (1995). - PubMed
  90. Patasius, A., Krilaviciute, A. & Smailyte, G. Prostate cancer screening with PSA: ten years’ experience of population based early prostate cancer detection programme in Lithuania. J. Clin. Med. 9, 1–9 (2020). - PubMed
  91. Ahmed, H. U. et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 389, 815–822 (2017). - PubMed
  92. Kasivisvanathan, V. et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N. Engl. J. Med. 378, 1767–1777 (2018). - PubMed
  93. EAU. White paper on prostate cancer. EAU https://www.europa-uomo.org/wp-content/uploads/2020/05/EAU_PCa-WhitePaper-FINAL-VERSION.pdf (2020). - PubMed
  94. Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021). - PubMed
  95. Dennis, S. et al. Which providers can bridge the health literacy gap in lifestyle risk factor modification education: a systematic review and narrative synthesis. BMC Fam. Pract. 13, 1–29 (2012). - PubMed
  96. Nutbeam, D. & Kickbusch, I. Advancing health literacy: a global challenge for the 21st century. Health Promot. Int. 15, 183–184 (2000). - PubMed
  97. Von Wagner, C., Knight, K., Steptoe, A. & Wardle, J. Functional health literacy and health-promoting behaviour in a national sample of British adults. J. Epidemiol. Community Health 61, 1086–1090 (2007). - PubMed
  98. Robb, K. et al. Public awareness of cancer in Britain: a population-based survey of adults. Br. J. Cancer 101, 18–23 (2009). - PubMed
  99. Wong Y. J., Liu T., Klann E. M. The intersection of race, ethnicity, and masculinities: progress, problems, and prospects. In The psychology of men and masculinities (eds Levant, R. F. & Wong, Y. J.) 261–288 (American Psychological Association, 2017). - PubMed
  100. Ragonese, C. & Barker, G. Understanding masculinities to improve men’s health. Lancet 394, 198–199 (2019). - PubMed
  101. Griffith, D. M., Metzl, J. M. & Gunter, K. Considering intersections of race and gender in interventions that address US men’s health disparities. Public Health 125, 417–423 (2011). - PubMed
  102. Griffith, D. M. Biopsychosocial approaches to men’s health disparities research and policy. Behav. Med. 42, 211–215 (2016). - PubMed
  103. Griffith, D. M. An intersectional approach to men’s health. J. Mens Health 9, 106–112 (2012). - PubMed
  104. Ferlatte, O., Salway, T., Trussler, T., Oliffe, J. L. & Gilbert, M. Combining intersectionality and syndemic theory to advance understandings of health inequities among Canadian gay, bisexual and other men who have sex with men. Crit. Public Health 28, 509–521 (2018). - PubMed
  105. Stall, R. et al. Association of co-occurring psychosocial health problems and increased vulnerability to HIV/AIDS among urban men who have sex with men. Am. J. Public Health 93, 939–942 (2003). - PubMed
  106. Ruggieri, A., Anticoli, S., D’ambrosio, A., Giordani, L. & Viora, M. The influence of sex and gender on immunity, infection and vaccination. Ann. Ist. Super. Sanita 52, 198–204 (2016). - PubMed
  107. Berghöfer, B. et al. TLR7 ligands induce higher IFN-α production in females. J. Immunol. 177, 2088–2096 (2006). - PubMed
  108. Villacres, M. C., Longmate, J., Auge, C. & Diamond, D. J. Predominant type 1 CMV-specific memory T-helper response in humans: evidence for gender differences in cytokine secretion. Hum. Immunol. 65, 476–485 (2004). - PubMed
  109. Abdullah, M. et al. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell Immunol. 272, 214–219 (2012). - PubMed
  110. Engler, R. J. M. et al. Half- vs full-dose trivalent inactivated influenza vaccine (2004–2005): age, dose, and sex effects on immune responses. Arch. Intern. Med. 168, 2405–2414 (2008). - PubMed
  111. Cook, I. F., Barr, I., Hartel, G., Pond, D. & Hampson, A. W. Reactogenicity and immunogenicity of an inactivated influenza vaccine administered by intramuscular or subcutaneous injection in elderly adults. Vaccine 24, 2395–2402 (2006). - PubMed
  112. Tanaka, E., Sata, M., Nakano, H., Suzuki, H. & Tanikawa, K. Antibody response to inactivated hepatitis A vaccine. Hepatol. Res. 9, 103–112 (1997). - PubMed
  113. Kennedy, R. B. et al. Gender effects on humoral immune responses to smallpox vaccine. Vaccine 27, 3319–3323 (2009). - PubMed
  114. Van Lunzen, J. & Altfeld, M. Sex differences in infectious diseases-common but neglected. J. Infect. Dis. 209, S79–S80 (2014). - PubMed
  115. Gabriel, G. & Arck, P. C. Sex, immunity and influenza. J. Infect. Dis. 209, S93–S99 (2014). - PubMed
  116. Yu, L., Quinn, M. T., Cross, A. R. & Dinauer, M. C. Gp91phox is the heme binding subunit of the superoxide-generating NADPH oxidase. Proc. Natl Acad. Sci. USA 95, 7993–7998 (1998). - PubMed
  117. Banerjee, E. R. & Henderson, W. R. Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model. Clin. Mol. Allergy 10, 1–14 (2012). - PubMed
  118. Chandra, R. et al. Female X-chromosome mosaicism for NOX2 deficiency presents unique inflammatory phenotype and improves outcome in polymicrobial sepsis. J. Immunol. 186, 6465–6473 (2011). - PubMed
  119. Chandra, R. et al. IRAK1-dependent signaling mediates mortality in polymicrobial sepsis. Inflammation 36, 1503–1512 (2013). - PubMed
  120. Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). - PubMed
  121. Li, W. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450–454 (2003). - PubMed
  122. Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and Is blocked by a clinically proven protease inhibitor. Cell 181, 271–280 (2020). - PubMed
  123. Sama, I. E. et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. Eur. Heart J. 41, 1810–1817 (2020). - PubMed
  124. Cai, G. Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov. Preprint at medRxiv https://doi.org/10.1101/2020.02.05.20020107 (2020). - PubMed
  125. Xudong, X., Junzhu, C., Xingxiang, W., Furong, Z. & Yanrong, L. Age- and gender-related difference of ACE2 expression in rat lung. Life Sci. 78, 2166–2171 (2006). - PubMed
  126. Dong, Y. et al. Epidemiology of COVID-19 among children in China. Pediatrics 145, 1–12 (2020). - PubMed
  127. Guan, W. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020). - PubMed
  128. The World Bank. World Development Indicators: Health risk factors and future challenges. The World Bank http://wdi.worldbank.org/table/2.17 (2020). - PubMed
  129. Wambier, C. G. et al. Androgen sensitivity gateway to COVID-19 disease severity. Drug. Dev. Res. 81, 771–776 (2020). - PubMed
  130. Lucas, J. M. et al. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov. 4, 1310–1325 (2014). - PubMed
  131. Channappanavar, R. et al. Sex-based differences in susceptibility to SARS-CoV infection. J. Immunol. 198, 4046–4053 (2017). - PubMed
  132. Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16, 626–638 (2016). - PubMed
  133. Agostino, P. et al. Sex hormones modulate inflammatory mediators produced by macrophages. Ann. N. Y. Acad. Sci. 876, 426–429 (1999). - PubMed
  134. Iyer, S. S. & Cheng, G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit. Rev. Immunol. 32, 23–63 (2012). - PubMed
  135. Capobianco, M. P. et al. Human Interleukin 2 (IL-2) promotion of immune regulation and clinical outcomes: a review. J. Cytokine Biol. 1, 1–4 (2016). - PubMed
  136. Musabak, U. et al. Gonadotropin treatment restores in vitro interleukin-1β and tumour necrosis factor-α production by stimulated peripheral blood mononuclear cells from patients with idiopathic hypogonadotropic hypogonadism. Clin. Exp. Immunol. 132, 265–270 (2003). - PubMed
  137. Malkin, C. J. et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J. Clin. Endocrinol. Metab. 89, 3313–3318 (2004). - PubMed
  138. Han, X. et al. Gender influences herpes simplex virus type 1 infection in normal and gamma interferon-mutant mice. J. Virol. 75, 3048–3052 (2001). - PubMed
  139. Robinson, D. P. et al. Sex chromosome complement contributes to sex differences in coxsackievirus B3 but not influenza A virus pathogenesis. Biol. Sex. Differ. 2, 1–11 (2011). - PubMed
  140. Wang, Z. & Xu, X. scRNA-seq profiling of human testes reveals the presence of ACE2 receptor, a target for SARS-CoV-2 infection, in spermatogonia, Leydig and Sertoli cells. Cells 9, 1–9 (2020). - PubMed
  141. Ma, L. et al. Effect of SARS-CoV-2 infection upon male gonadal function: a single center-based study. Preprint at medRxiv https://doi.org/10.1101/2020.03.21.20037267 (2020). - PubMed
  142. Ruan, Y. et al. No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: a perspective and urogenital evaluation. Andrology 9, 99–106 (2021). - PubMed
  143. World Health Organization Department of Reproductive Health and Research. WHO laboratory manual for the examination and processing of human semen, fifth edition. WHO https://apps.who.int/iris/bitstream/handle/10665/44261/9789241547789_eng.pdf;jsessionid=F577E96867A29CC002AE25F470B4FFF3?sequence=1 (2010). - PubMed
  144. The Gates Foundation. What we do — Bill & Melinda Gates Foundation. The Gates Foundation https://www.gatesfoundation.org/What-We-Do (2010). - PubMed
  145. The Gates Foundation. Gender equality — Bill & Melinda Gates Foundation. The Gates Foundation https://www.gatesfoundation.org/What-We-Do/Global-Growth-and-Opportunity/Gender-Equality (2020). - PubMed
  146. Rovito, M. J. et al. A call for gender-inclusive global health strategies. Am. J. Mens Health 11, 1804–1808 (2017). - PubMed
  147. WHO. What is the global strategy? WHO https://www.who.int/life-course/partners/global-strategy/global-strategy-2016-2030/en/c (2016). - PubMed
  148. Christakis, N. A. & Allison, P. D. Mortality after the hospitalization of a spouse. N. Engl. J. Med. 354, 719–730 (2020). - PubMed
  149. Corden P. Financial implications of death of a partner (University of York, 2008). - PubMed
  150. Mohindra, K. S., Haddad, S. & Narayana, D. Debt, shame, and survival: becoming and living as widows in rural Kerala, India. BMC Int. Health Hum. Rights 12, 1–13 (2012). - PubMed
  151. Wyke, S. et al. Football Fans in Training (FFIT): a randomized controlled trial of a gender sensitised weight loss and healthy living programme delivered to men aged 35–65 by Scottish Premier League (SPL) football clubs. Public. Health Res. 3, 1–130 (2015). - PubMed
  152. Gray, C. M. et al. Long-term weight loss following a randomised controlled trial of a weight management programme for men delivered through professional football clubs: the Football Fans in Training follow-up study. Public. Health Res. 6, 1–114 (2018). - PubMed
  153. Russell, N., Harding, C., Chamberlain, C. & Johnston, L. Implementing a “Men’s Health Pitstop” in the Riverina, South-west New South Wales. Aust. J. Rural. Health 14, 129–131 (2006). - PubMed
  154. Wood, D. & Minhas, S. Science and society: the influence of charities in the field of men’s health. Nat. Rev. Urol. 12, 599–600 (2015). - PubMed
  155. Baker P. Review of the national men’s health policy and action plan 2008–2013 final report for the health service executive. MHFI https://www.mhfi.org/policyreview2015.pdf (2015). - PubMed
  156. Evans D. S., Walshe K., Gillen P. Farmers have heart project evaluation. Lenus https://www.lenus.ie/bitstream/handle/10147/84216/farmershaveheartsrepfJan21.pdf?sequence=1&isAllowed=y (2009). - PubMed
  157. Richardson, N. Building momentum, gaining traction: Ireland’s National Men’s Health Policy 5 years on. N. Male Stud. 2, 93–103 (2013). - PubMed
  158. Clarke N., Sharp L., O’Leary E. & Richardson N. A report on the excess burden of cancer among men in the Republic of Ireland (National Cancer Registry Ireland, 2013). - PubMed
  159. Richardson N., Clarke N., Fowler C. Men’s health in Ireland. An executive summary report on the All-Ireland Young Men and Suicide Project. MHFI www.mhfi.org (2013). - PubMed
  160. Murray, M., Campbell, C., Kendall, L., Whitt-Glover, M. C. & Watson, K. S. Perspectives from Project Brotherhood: facilitating engagement of African American men in research. Prog. Community Health Partnersh. 13, 137–142 (2019). - PubMed
  161. WHO. Preamble to the Constitution of the World Health Organization as adopted by the International Health Conference. WHO https://www.who.int/governance/eb/who_constitution_en.pdf (1946). - PubMed
  162. Schwartz, B. G. & Kloner, R. A. Cardiovascular implications of erectile dysfunction. Circulation 123, 609–611 (2011). - PubMed
  163. Vlachopoulos, C. V., Terentes-Printzios, D. G., Ioakeimidis, N. K., Aznaouridis, K. A. & Stefanadis, C. I. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction. Circ. Cardiovasc. Qual. Outcomes 6, 99–109 (2013). - PubMed
  164. Johannes, C. B. et al. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J. Urol. 163, 460–463 (2000). - PubMed
  165. Salonia, A. et al. Are infertile men less healthy than fertile men? Results of a prospective case-control survey. Eur. Urol. 56, 1025–1032 (2009). - PubMed
  166. Leisegang, K., Udodong, A., Bouic, P. J. D. & Henkel, R. R. Effect of the metabolic syndrome on male reproductive function: a case-controlled pilot study. Andrologia 46, 167–176 (2014). - PubMed
  167. Eisenberg, M. L. et al. Semen quality, infertility and mortality in the USA. Hum. Reprod. 29, 1567–1574 (2014). - PubMed
  168. Oh, J. Y., Barrett-Connor, E., Wedick, N. M. & Wingard, D. L. Endogenous sex hormones and the development of type 2 diabetes in older men and women: The Rancho Bernardo Study. Diabetes Care 25, 55–60 (2002). - PubMed
  169. Jones, T. H. et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care 34, 828–837 (2011). - PubMed
  170. Kupelian, V. et al. Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston area community health survey. J. Urol. 189, 107–114 (2009). - PubMed
  171. Pesonen, J. S. et al. The impact of nocturia on mortality: a systematic review and meta-analysis. J. Urol. 203, 486–495 (2020). - PubMed
  172. EAU Guidelines Committee. EAU Guidelines on Sexual and Reproductive Health. Uroweb https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-Sexual-and-Reproductive-Health-2020.pdf (2020). - PubMed
  173. Pastuszak, A. W. et al. Erectile dysfunction as a marker for cardiovascular disease diagnosis and intervention: s cost analysis. J. Sex. Med. 12, 975–984 (2015). - PubMed
  174. Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018). - PubMed
  175. Tsilidis, K. K. et al. Burden of cancer in a large consortium of prospective cohorts in Europe. J. Natl Cancer Inst. 108, 1–7 (2016). - PubMed
  176. Eisenberg, M. L., Betts, P., Herder, D., Lamb, D. J. & Lipshultz, L. I. Increased risk of cancer among azoospermic men. Fertil. Steril. 100, 681–685 (2013). - PubMed
  177. Jacobsen, R. et al. Risk of testicular cancer in men with abnormal semen characteristics: cohort study. Br. Med. J. 321, 789–792 (2000). - PubMed
  178. Skakkebæk, N. E., Rajpert-De Meyts, E. & Main, K. M. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod. 16, 972–978 (2001). - PubMed
  179. Office for National Statistics. Suicides in the UK: 2018 registrations. ONS https://www.ons.gov.uk/releases/suicidesintheuk2018registrations (2001). - PubMed
  180. Wasserman, D., Cheng, Q. & Jiang, G.-X. Global suicide rates among young people aged 15–19. World Psychiatry 4, 114–120 (2005). - PubMed
  181. Hawton, K. et al. Psychosocial interventions for self-harm in adults. Cochrane Database Syst. Rev. 5, 1–237 (2016). - PubMed
  182. Clayton, A. H., El Haddad, S., Iluonakhamhe, J. P., Ponce Martinez, C. & Schuck, A. E. Sexual dysfunction associated with major depressive disorder and antidepressant treatment. Expert. Opin. Drug. Saf. 13, 1361–1374 (2014). - PubMed
  183. King, K. E. Patient satisfaction in a one-stop haematuria clinic and urology outpatients: a comparison of clinics. Int. J. Urol. Nurs. 10, 127–136 (2016). - PubMed
  184. Gorman, M., Coelho, J., Gujral, S. & McKay, A. One-stop clinic utilization in plastic surgery: our local experience and the results of a UK-Wide National Survey. Plast. Surg. Int. 2015, 1–9 (2015). - PubMed
  185. Naspro, R., Da & Pozzo, L. F. Urology in the time of corona. Nat. Rev. Urol. 17, 251–253 (2020). - PubMed
  186. Ribal, M. J. et al. European Association of Urology Guidelines Office Rapid Reaction Group: an organisation-wide collaborative effort to adapt the European Association of Urology Guidelines Recommendations to the Coronavirus Disease 2019 era. Eur. Urol. 78, 21–28 (2020). - PubMed
  187. Teo, C. H., Ng, C. J., Ho, C. C. K. & Tan, H. M. A consensus on men’s health status and policy in Asia: a Delphi survey. Public Health 129, 60–67 (2015). - PubMed
  188. Rovito, M. & Leone, J. Faith and masculinity: a discussion on raising awareness and promoting cancer screening among Latino men. Calif. J. Health Promot. 10, 70–77 (2012). - PubMed
  189. Resnicow, K. et al. Body and soul: a dietary intervention conducted through African-American churches. Am. J. Prev. Med. 27, 97–105 (2004). - PubMed
  190. Resnicow, K. et al. A motivational interviewing intervention to increase fruit and vegetable intake through Black churches: results of the eat for life trial. Am. J. Public Health 91, 1686–1693 (2001). - PubMed
  191. Sugimoto, C. R., Ahn, Y. Y., Smith, E., Macaluso, B. & Larivière, V. Factors affecting sex-related reporting in medical research: a cross-disciplinary bibliometric analysis. Lancet 393, 550–559 (2019). - PubMed
  192. Milner A., Shields M., King T. The influence of masculine norms and mental health on health literacy among men: evidence from the Ten to Men Study. Am. J. Mens Health 13, 1557988319873532 (2019) - PubMed
  193. Short, S. E. & Mollborn, S. Social determinants and health behaviors: conceptual frames and empirical advances. Curr. Opin. Psychol. 5, 78–84 (2015). - PubMed
  194. Teo, C. H., Ng, C. J., Lo, S. K., Lim, C. D. & White, A. A mobile web app to improve health screening uptake in men (Screenmen): utility and usability evaluation study. JMIR mHealth uHealth 7, e10216 (2019). - PubMed
  195. Novara, G. et al. Telehealth in urology: a systematic review of the literature. how much can telemedicine be useful during and after the COVID-19 pandemic? Eur. Urol. 78, 786–811 (2020). - PubMed
  196. Chandra, R. et al. Cellular mosaicism for X-linked polymorphisms and IRAK1 expression presents a distinct phenotype and improves survival following sepsis. J. Leukoc. Biol. 95, 497–507 (2014). - PubMed

Publication Types