Sex differences in medicine

Sex differences in medicine include sex-specific diseases or conditions which occur only in people of one sex due to underlying biological factors (for example, prostate cancer in males or uterine cancer in females); sex-related diseases, which are diseases that are more common to one sex (for example, breast cancer and systemic lupus erythematosus which occur predominantly in females);[1] and diseases which occur at similar rates in males and females but manifest differently according to sex (for example, peripheral artery disease).[2]

Sex differences should not be confused with gender differences. The US National Academy of Medicine recognizes sex differences as biological at the chromosomal and anatomical levels, whereas gender differences are based on self-representation and other factors including biology, environment and experience.[3][4] That said, both biological and behavioural differences influence human health, and may do so differentially. Such factors can be inter-related and difficult to separate. Evidence-based approaches to sex and gender medicine try to examine the effects of both sex and gender as factors when dealing with medical conditions that may affect populations differently.[5][6][3]

As of 2021, over 10,000 articles had been published addressing sex and gender differences in clinical medicine and related literature. Sex and gender affect cardiovascular,[7] pulmonary[8] and autoimmune systems,[9][10] gastroenterology,[11][12] hepatology,[5] nephrology,[13] endocrinology,[14][15] haematology,[16] neurology,[17][18][19][20] pharmacokinetics, and pharmacodynamics.[21][22][6][3]

Sexually transmitted diseases, which have a significant probability of transmission through sexual contact, can be contracted by either sex. Their occurrence may reflect economic and social as well as biological factors, leading to sex differences in the transmission, prevalence, and disease burden of STDs.[23]

Historically, medical research has primarily been conducted using the male body as the basis for clinical studies. The findings of these studies have often been applied across the sexes, and healthcare providers have traditionally assumed a uniform approach in treating both male and female patients. More recently, medical research has started to understand the importance of taking sex into account as evidence increases that the symptoms and responses to medical treatment may be very different between sexes.[24]

Background

Females and males exhibit many differences in terms of risk of developing disease, receiving an accurate diagnosis, and responding to treatments. A patient's sex has been increasingly recognized as one of the most important modulators of clinical decision making.[25] Sex differences have been found across a broad range of disease areas, including many diseases which are sex-specific. The sex chromosome complement and sex hormone environment are known to be the primary constitutive difference between females and males.[26] The imbalance of gene expression between the X and Y chromosomes is present within virtually all cells in the human body. Sex hormones are crucial in body development and function and also thought to contribute to sex differences in some diseases.[27] It is suspected that many differences between the sexes are also influenced by social, environmental, and psychological factors which are difficult to tease apart from biological ones.[4]

Causes

Sex-related illnesses have various causes:[5]

  • Genetic sex differences start at conception depending on whether an ovum fuses with a sperm cell carrying an X or a Y chromosome. This leads to sex-based differences at the molecular level for all male and female cells.[5]
  • In males, the X chromosome carries only maternal imprints, while in females X chromosomes are present with both maternal and paternal imprints. In female cells, random processes of X-inactivation "turn off" the extra X chromosome. As a result, females, but not males, are mosaics. Female cells may express higher levels of some genes.[28][29][30]
  • Sex differences at the chromosome and molecular level exist in all human cells, and persist life-long, independent of sex hormones in the body.[5]
  • Sex-linked genetic conditions that differ in males and females may reflect the effects of genetic damage on an X chromosome. In some cases, the presence of an "extra" X chromosome in female cells may lessen the impact of such damage. In severe cases, males may die during development and females may survive but display a sex-linked illness.[28]
  • The reproductive system develops differently for each sex. Sex-specific parts of the male and female reproductive systems affect the rest of the body and also can be affected differently by diseases.[31]
  • Socially constructed norms relate to gender roles, relationships, positional power, and a wide variety of behaviours. Norms affect people differentially depending on their sex and gender.[5]
  • Different levels of prevention, reporting, diagnosis, and treatment have been observed based on sex and gender.[5]

Females

Examples of sex-related illnesses and disorders in human females:[6]

Males

Examples of sex-related illnesses and disorders in male humans:[6]

See also

References

  1. ↑ Ngo ST, Steyn FJ, McCombe PA (August 2014). "Gender differences in autoimmune disease". Frontiers in Neuroendocrinology. 35 (3): 347–369. doi:10.1016/j.yfrne.2014.04.004. PMID 24793874.
  2. ↑ Barochiner J, Aparicio LS, Waisman GD (2014). "Challenges associated with peripheral arterial disease in women". Vascular Health and Risk Management. 10: 115–128. doi:10.2147/vhrm.s45181. PMC 3956880. PMID 24648743.
  3. 1 2 3 Oertelt-Prigione S, Regitz-Zagrosek V, eds. (2012). Sex and Gender Aspects in Clinical Medicine. London, UK: Springer Science & Business Media. ISBN 978-1-4471-6002-1.
  4. 1 2 Institute of Medicine (US) Committee on Understanding the Biology of Sex and Gender Differences. (2001). Wizemann TM, Pardue ML (eds.). Exploring the Biological Contributions to Human Health: Does Sex Matter?. Washington (DC): National Academies Press (. ISBN 978-0-309-07281-6. PMID 25057540.
  5. 1 2 3 4 5 6 7 Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, Brinton RD, Carrero JJ, DeMeo DL, et al. (August 2020). "Sex and gender: modifiers of health, disease, and medicine". Lancet. 396 (10250): 565–582. doi:10.1016/S0140-6736(20)31561-0. PMC 7440877. PMID 32828189.
  6. 1 2 3 4 Regitz-Zagrosek V (June 2012). "Sex and gender differences in health. Science & Society Series on Sex and Science". EMBO Reports. 13 (7): 596–603. doi:10.1038/embor.2012.87. PMC 3388783. PMID 22699937.
  7. ↑ Miller VM (May 2020). "Universality of sex differences in cardiovascular outcomes: where do we go from here?". European Heart Journal. 41 (17): 1697–1699. doi:10.1093/eurheartj/ehaa310. PMC 7194182. PMID 32357237.
  8. ↑ Weatherald J, Riha RL, Humbert M (December 2021). "Sex and gender in lung health and disease: more than just Xs and Ys". European Respiratory Review. 30 (162): 210217. doi:10.1183/16000617.0217-2021. PMID 34750117. S2CID 243861859.
  9. 1 2 Rose NR, Bona C (September 1993). "Defining criteria for autoimmune diseases (Witebsky's postulates revisited)". Immunology Today. 14 (9): 426–430. doi:10.1016/0167-5699(93)90244-F. PMID 8216719.
  10. 1 2 Hayter SM, Cook MC (August 2012). "Updated assessment of the prevalence, spectrum and case definition of autoimmune disease". Autoimmunity Reviews. 11 (10): 754–765. doi:10.1016/j.autrev.2012.02.001. PMID 22387972.
  11. ↑ Greuter T, Manser C, Pittet V, Vavricka SR, Biedermann L (2020). "Gender Differences in Inflammatory Bowel Disease". Digestion. 101 (1): 98–104. doi:10.1159/000504701. PMID 31995797. S2CID 210946741.
  12. ↑ van Kessel L, Teunissen D, Lagro-Janssen T (March 2021). "Sex-Gender Differences in the Effectiveness of Treatment of Irritable Bowel Syndrome: A Systematic Review". International Journal of General Medicine. 14: 867–884. doi:10.2147/IJGM.S291964. PMC 7979326. PMID 33758534.
  13. ↑ Bairey Merz CN, Dember LM, Ingelfinger JR, Vinson A, Neugarten J, Sandberg KL, et al. (December 2019). "Sex and the kidneys: current understanding and research opportunities". Nature Reviews. Nephrology. 15 (12): 776–783. doi:10.1038/s41581-019-0208-6. PMC 7745509. PMID 31586165.
  14. ↑ Bhargava A, Arnold AP, Bangasser DA, Denton KM, Gupta A, Hilliard Krause LM, et al. (May 2021). "Considering Sex as a Biological Variable in Basic and Clinical Studies: An Endocrine Society Scientific Statement". Endocrine Reviews. 42 (3): 219–258. doi:10.1210/endrev/bnaa034. PMC 8348944. PMID 33704446.
  15. ↑ Lauretta R, Sansone M, Sansone A, Romanelli F, Appetecchia M (21 October 2018). "Gender in Endocrine Diseases: Role of Sex Gonadal Hormones". International Journal of Endocrinology. 2018: 4847376. doi:10.1155/2018/4847376. PMC 6215564. PMID 30420884.
  16. ↑ Murphy WG (March 2014). "The sex difference in haemoglobin levels in adults - mechanisms, causes, and consequences". Blood Reviews. 28 (2): 41–47. doi:10.1016/j.blre.2013.12.003. PMID 24491804.
  17. ↑ Clayton JA (December 2016). "Sex influences in neurological disorders: case studies and perspectives". Dialogues in Clinical Neuroscience. 18 (4): 357–360. doi:10.31887/DCNS.2016.18.4/jclayton. PMC 5286721. PMID 28179807.
  18. ↑ Institute of Medicine (2011). Sex Differences and Implications for Translational Neuroscience Research : Workshop Summary. Washington, DC: National Academies Press. ISBN 978-0-309-16124-4.
  19. ↑ Rippon G, Eliot L, Genon S, Joel D (May 2021). "How hype and hyperbole distort the neuroscience of sex differences". PLOS Biology. 19 (5): e3001253. doi:10.1371/journal.pbio.3001253. PMC 8136838. PMID 33970901.
  20. ↑ Shansky RM, Murphy AZ (April 2021). "Considering sex as a biological variable will require a global shift in science culture". Nature Neuroscience. 24 (4): 457–464. doi:10.1038/s41593-021-00806-8. PMID 33649507. S2CID 232091204.
  21. ↑ Zucker I, Prendergast BJ (June 2020). "Sex differences in pharmacokinetics predict adverse drug reactions in women". Biology of Sex Differences. 11 (1): 32. doi:10.1186/s13293-020-00308-5. PMC 7275616. PMID 32503637.
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  23. ↑ Madkan VK, Giancola AA, Sra KK, Tyring SK (March 2006). "Sex differences in the transmission, prevention, and disease manifestations of sexually transmitted diseases". Archives of Dermatology. 142 (3): 365–370. doi:10.1001/archderm.142.3.365. PMID 16549716.
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