Sex differences in medicine

(Redirected from Gender-based 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.[citation needed] Sex and gender affect cardiovascular,[7] pulmonary[8] and autoimmune systems,[9][10] gastroenterology,[11][12][13] hepatology,[5] nephrology,[14] endocrinology,[15][16] haematology,[17] neurology,[18][19][20][21] pharmacokinetics, and pharmacodynamics.[22][23][6][3]

Sexually transmitted infections, 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 STIs.[24]

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.[25]

Background

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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.[26] 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.[27] 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.[28] 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

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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.[29][30][31]
  • 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.[29]
  • 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.[32]
  • 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]
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Females

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

Males

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

Reasons for sex differences in incidence and prevalence

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Hypertension

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Hypertension is a worldwide disease affecting the sexes.[82] Women are less frequently affected by high blood pressure . Since blood pressure rises in women after menopause,[83] this suggests that the cause of the sex-specific differences lies not only in possible external factors, such as lifestyle, but also in the sex hormones . It is likely due to sex hormones not external factors. One possible mechanism is the influence of the renin-angiotensin system (RAAS).[84]

Angiotensinogen (liver) is converted into angiotensin I (Ang I) by renin (kidney). Ang I is converted to angiotensin II (Ang II) by the angiotensin-converting enzyme (ACE). This binds to the Ang II type I receptor (A2T1), which causes vasoconstriction and water and sodium reabsorption in the kidneys, and in turn increases blood pressure.

Less well known is that Ang II can also bind to Ang II type II receptor (A2T2) or be converted by angiotensin-converting enzyme II (ACE II) into angiotensin III (Ang III), which binds to MAS receptors.[85] Both A2T2 and MAS receptors trigger vasodilation.[86]

Animal experiments have shown that female ovariectomised mice treated chronically with testosterone have increased blood pressure (mean arterial pressure ~180mmHg) compared to female mice from the control group (~155mmHg).[87] This difference was reduced by ACE inhibition (enalapril (250 mg/L)) in both groups to a similar level ( ~115mmHg).[88] It can therefore be assumed that male androgens have an high increasing influence (up to 25mmHg in middle blood pressure) on angiotensinogen.[89]

Autoimmune diseases (Sjögren's syndrome)

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In autoimmune diseases, like Sjögren's syndrome (SS), the body produces hyperreactive autoantibodies against the salivary and lacrimal gland tissue. This results in symptoms like dry mouth and dry eyes.

The gender distribution in Sjögren's syndrome is heavily skewed towards women, with a ratio of 16:1 in the UK.[90] Various reasons have been suggested, but the evidence is not strong. One common reason is the hormonal differences between women and men. In women, estrogen dominates, as does the hormone progesterone during pregnancy. Androgens (e.g. testosterone) are only present in small quantities. In men, testosterone, an androgen, dominates, and estrogen is only present to a small extent. Estrogen stimulates the immune system more than androgens. Accordingly, it stands to reason that an autoimmune reaction, which is based on a hyperreactive immune sensitivity to autoantigens, can manifest itself much more easily in women.

In Sjögren's syndrome, B cells and interferons are of particular importance. Generally, hormone receptors are expressed on immune cells (e.g., B cells), such as the estrogen receptor (ER-alpha/ß) or the androgen receptor. These receptors are steroid hormone receptors, i.e., they influence gene expression in the nucleus of the immune cells.

Pregnancy, including hormonal changes, appears to increase the risk of developing SS and also exacerbate the course of the disease if it is already present. During pregnancy, more hormones than just estrogen are secreted that also have an immune system-stimulating effect, such as prolactin. So, an overstimulated immune system seems to be the result.

On the other hand, estrogen protects glandular cells and prevents them from cell death. Menopause causes a decreased level of hormones like estrogen and thus reduces the protective effect on glandular cell health. Increased apoptosis (cell death) and inflammatory effects on damaged and aged cells are the result. As a result, there is an increased level of autoantibodies against the glandular cells. Estrogen is important, but only in the right amount. The study showed that the prevalence of women developing SS after menopause is quite higher than before menopause. This leads to the assumption that the protective effect of estrogen on glandular tissue is more important than the stimulation effect on B cells for the development of SS.[90]

Another study investigated the hormonal influence on the pathogenesis of autoimmune diseases, including SS. Female mice had their ovaries removed to investigate the effect of missing estrogen on the pathogenesis of SS.[91] In this study, low estrogen levels promoted apoptosis and the formation of apoptotic bodies and microparticles containing membrane antigens. These are recognized as pathogens via TLR (toll-like receptors) of the dendritic and B cells, which then secrete increased levels of INF alpha/ß and cytokines. These cytokines stimulate other immune cells (e.g., DC, T-cells), which can lead to autoreactivity and thus to an autoimmune reaction.

In men, the preliminary stage of testosterone, DHT (dihydrotestosterone), is synthesized from testosterone in one simple step. DHT has an anti-apoptotic effect on the glandular tissue. In women, DHEA (dehydroepiandrosterone) takes over this task. Synthesizing this product in women is much more complex and involves several steps that are difficult to ensure when estrogen levels are low (menopause, etc.). This might be another reason for increased apoptosis and the pathogenesis of SS in women compared to men.

Another key player in the pathogenesis of SS is INF1. It is stimulated by estrogen receptor interaction. INF1 ensures a higher level of autoantibodies and inflammatory cytokines. A study has shown that interferon type I and type II are more pronounced in women than in men. [90]That might be a reason for the increased level of autoantibodies and prevalence of SS in women.

Androgens generally have stimulating effects on the production of the lipid layer in the tear film and oral mucosa.[91] Androgens increase the level of integrins alpha1 and 2, which promote the differentiation of mesenchymal stem cells into acinar cells. In the absence of androgens, this differentiation and regulation are defective. In SS, the conversion of testosterone to DHT (in men) or DHEA (in women) in the lacrimal glands is defective. The enzymes are not functional. This means that the lipid layer, which is important for maintaining moisture in the mouth and on the eyes and providing protection against pathogens, is missing. This could be a leading reason for symptoms like dry mouth and dry eyes.

Another study investigated the effects of gene expression of the sex chromosomes.[92] Normally, one X chromosome is inhibited in women (Barr body). However, not completely. Some of the genes of the inhibited X chromosome are still (single or double) expressed, including genes relevant to the immune system. This is supposed to ensure better immunity, among other things, but also results in a higher risk of autoimmunity.

The study has shown that the prevalence of SS in triple-X individuals is 2.9 times higher than in healthy women and 41 times higher than in healthy men, despite physiological hormone levels. This suggests an involvement of the double gene expression of the 2nd X chromosome in the pathogenesis of SS,[91] which could also affect XX genotype women. An explanation how the double gene expression, which can also be normal, can be manifesting investigated another study.

Another study investigated the influence of a long non coding RNA protein, called XIST, which is a leading factor of the double X chromosome expression.[93] XIST is only present in women where it is inactivating genes of the second “restoring” X chromosome. Dysfuncitonal XIST proteins seem to be a leading cause of higher prevalence of autoimmune diseases of women, so as in SS.

Furthermore, intestinal microbiome differences, elevated levels of certain miRNAs, and microchimerism during pregnancy are discussed and investigated as possible risk factors in the pathogenesis of SS.[91]

See also

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Notes

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  1. ^ Endometriosis very rarely affects men.[34]

References

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  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. ^ a b c Oertelt-Prigione S, Regitz-Zagrosek V, eds. (2012). Sex and Gender Aspects in Clinical Medicine. Springer. ISBN 978-1-4471-6002-1.
  4. ^ a b 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. ^ a b c d e f g 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. ^ a b c d 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): 1697–9. 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. PMC 9488524. PMID 34750117. S2CID 243861859.
  9. ^ a b 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. ^ a b 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. ^ a b Fracas E, Costantino A, Vecchi M, Buoli M (June 2023). "Depressive and Anxiety Disorders in Patients with Inflammatory Bowel Diseases: Are There Any Gender Differences?". Int J Environ Res Public Health. 20 (13): 6255. doi:10.3390/ijerph20136255. PMC 10340762. PMID 37444101.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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. NBK53393.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ Soldin OP, Mattison DR (2009). "Sex differences in pharmacokinetics and pharmacodynamics". Clinical Pharmacokinetics. 48 (3): 143–157. doi:10.2165/00003088-200948030-00001. PMC 3644551. PMID 19385708.
  24. ^ 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.
  25. ^ Mauvais-Jarvis F, Merz BN, Barnes PJ, Brinton RD, Carrero JJ, DeMeo DL, et al. (22 August 2020). "Sex and gender: modifiers of health, disease, and medicine". The Lancet. 396 (10250): 565–582. doi:10.1016/S0140-6736(20)31561-0. PMC 7440877. PMID 32828189.
  26. ^ Legato, Marianne J.; Johnson, Paula A.; Manson, JoAnn E. (8 November 2016). "Consideration of Sex Differences in Medicine to Improve Health Care and Patient Outcomes". JAMA. 316 (18): 1865–6. doi:10.1001/jama.2016.13995. PMID 27802499.
  27. ^ Miller, Leah R.; Marks, Cheryl; Becker, Jill B.; Hurn, Patricia D.; Chen, Wei-Jung; Woodruff, Teresa; McCarthy, Margaret M.; Sohrabji, Farida; Schiebinger, Londa; Wetherington, Cora Lee; Makris, Susan; Arnold, Arthur P.; Einstein, Gillian; Miller, Virginia M.; Sandberg, Kathryn; Maier, Susan; Cornelison, Terri L.; Clayton, Janine A. (January 2017). "Considering sex as a biological variable in preclinical research". The FASEB Journal. 31 (1): 29–34. doi:10.1096/fj.201600781r. PMC 6191005. PMID 27682203.
  28. ^ Maeng, Lisa Y.; Milad, Mohammed R. (1 November 2015). "Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones". Hormones and Behavior. 76: 106–117. doi:10.1016/j.yhbeh.2015.04.002. ISSN 0018-506X. PMC 4823998. PMID 25888456.
  29. ^ a b c Migeon BR (2014). Females are mosaics : X inactivation and sex differences in disease (2nd ed.). Oxford: Oxford University Press. ISBN 978-0-19-992753-1.
  30. ^ a b Migeon BR (June 2007). "Why females are mosaics, X-chromosome inactivation, and sex differences in disease". Gender Medicine. 4 (2): 97–105. doi:10.1016/S1550-8579(07)80024-6. PMID 17707844.
  31. ^ a b Brown C (September 2007). "Patchwork women". Nature Genetics. 39 (9): 1043. doi:10.1038/ng0907-1043. S2CID 32145544.
  32. ^ Zimmermann KA (22 March 2018). "Reproductive System: Facts, Functions & Diseases". Live Science. Retrieved 11 November 2021.
  33. ^ "Male Breast Cancer Treatment". National Cancer Institute. 2014. Archived from the original on 4 July 2014. Retrieved 29 June 2014.
  34. ^ Rei, Christina; Williams, Thomas; Feloney, Michael (2018). "Endometriosis in a Man as a Rare Source of Abdominal Pain: A Case Report and Review of the Literature". Case Reports in Obstetrics and Gynecology. 2018: 1–6. doi:10.1155/2018/2083121.
  35. ^ Reid BM, Permuth JB, Sellers TA (February 2017). "Epidemiology of ovarian cancer: a review". Cancer Biology & Medicine. 14 (1): 9–32. doi:10.20892/j.issn.2095-3941.2016.0084. PMC 5365187. PMID 28443200.
  36. ^ a b Ursin RL, Klein SL (September 2021). "Sex Differences in Respiratory Viral Pathogenesis and Treatments". Annual Review of Virology. 8 (1): 393–414. doi:10.1146/annurev-virology-091919-092720. PMID 34081540. S2CID 235333732.
  37. ^ Klein SL, Flanagan KL (October 2016). "Sex differences in immune responses". Nature Reviews. Immunology. 16 (10): 626–638. doi:10.1038/nri.2016.90. PMID 27546235. S2CID 2258164.
  38. ^ Alswat KA (May 2017). "Gender Disparities in Osteoporosis". Journal of Clinical Medicine Research. 9 (5): 382–7. doi:10.14740/jocmr2970w. PMC 5380170. PMID 28392857.
  39. ^ Franceschini, Anna; Fattore, Liana (5 April 2021). "Gender-specific approach in psychiatric diseases: Because sex matters". European Journal of Pharmacology. 896: 173895. doi:10.1016/j.ejphar.2021.173895. ISSN 0014-2999. PMID 33508283. S2CID 231753879. Retrieved 23 December 2021.
  40. ^ Sweeting H, Walker L, MacLean A, Patterson C, Räisänen U, Hunt K (2015). "Prevalence of eating disorders in males: a review of rates reported in academic research and UK mass media". International Journal of Men's Health. 14 (2). PMC 4538851. PMID 26290657.
  41. ^ Stice E, Marti CN, Rohde P (May 2013). "Prevalence, incidence, impairment, and course of the proposed DSM-5 eating disorder diagnoses in an 8-year prospective community study of young women". Journal of Abnormal Psychology. 122 (2): 445–457. doi:10.1037/a0030679. PMC 3980846. PMID 23148784.
  42. ^ Gagne DA, Von Holle A, Brownley KA, Runfola CD, Hofmeier S, Branch KE, Bulik CM (November 2012). "Eating disorder symptoms and weight and shape concerns in a large web-based convenience sample of women ages 50 and above: results of the Gender and Body Image (GABI) study". The International Journal of Eating Disorders. 45 (7): 832–844. doi:10.1002/eat.22030. PMC 3459309. PMID 22729743.
  43. ^ Schaumberg K, Welch E, Breithaupt L, Hübel C, Baker JH, Munn-Chernoff MA, et al. (November 2017). "The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders". European Eating Disorders Review. 25 (6): 432–450. doi:10.1002/erv.2553. PMC 5711426. PMID 28967161.
  44. ^ American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. pp. 338–349. ISBN 978-0-89042-555-8.
  45. ^ Hanamsagar, Richa; Bilbo, Staci D. (June 2016). "Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on microglial function and neuroinflammation during development". The Journal of Steroid Biochemistry and Molecular Biology. 160: 127–133. doi:10.1016/j.jsbmb.2015.09.039. PMC 4829467. PMID 26435451.
  46. ^ a b c d Ullah, Mohammad Fahad; Ahmad, Aamir; Bhat, Showket Hussain; Abu-Duhier, Faisel M.; Barreto, George E.; Ashraf, Ghulam Md (1 July 2019). "Impact of sex differences and gender specificity on behavioral characteristics and pathophysiology of neurodegenerative disorders". Neuroscience & Biobehavioral Reviews. 102: 95–105. doi:10.1016/j.neubiorev.2019.04.003. ISSN 0149-7634. PMID 30959072. S2CID 102487049. Retrieved 28 December 2021.
  47. ^ Zielonka D, Stawinska-Witoszynska B (2020). "Gender Differences in Non-sex Linked Disorders: Insights From Huntington's Disease". Frontiers in Neurology. 11: 571. doi:10.3389/fneur.2020.00571. PMC 7358529. PMID 32733356.
  48. ^ American Psychiatric Association (2013), Diagnostic and Statistical Manual of Mental Disorders (5th ed.), Arlington: American Psychiatric Publishing, pp. 160–68, ISBN 978-0-89042-555-8, retrieved 22 July 2016
  49. ^ Schmitt A, Malchow B, Hasan A, Falkai P (February 2014). "The impact of environmental factors in severe psychiatric disorders". Frontiers in Neuroscience. 8 (19): 19. doi:10.3389/fnins.2014.00019. PMC 3920481. PMID 24574956.
  50. ^ Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). American Psychiatric Publishing. 2013. pp. 645, 663–6. ISBN 978-0-89042-555-8.
  51. ^ "Definition & Facts for Irritable Bowel Syndrome | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 2019-07-04.
  52. ^ Clauw DJ (April 2014). "Fibromyalgia: a clinical review". JAMA. 311 (15): 1547–55. doi:10.1001/jama.2014.3266. PMID 24737367.
  53. ^ Mallampalli MP, Carter CL (July 2014). "Exploring sex and gender differences in sleep health: a Society for Women's Health Research Report". Journal of Women's Health. 23 (7): 553–562. doi:10.1089/jwh.2014.4816. PMC 4089020. PMID 24956068.
  54. ^ "Chronic fatigue syndrome". womenshealth.gov. 21 February 2017. Retrieved 13 May 2019.
  55. ^ Benarroch EE (December 2012). "Postural tachycardia syndrome: a heterogeneous and multifactorial disorder". Mayo Clinic Proceedings. 87 (12): 1214–25. doi:10.1016/j.mayocp.2012.08.013. PMC 3547546. PMID 23122672.
  56. ^ Dworetzky, Barbara A.; Baslet, Gaston (December 2017). "Psychogenic Nonepileptic Seizures in Women". Seminars in Neurology. 37 (6): 624–631. doi:10.1055/s-0037-1607971. ISSN 1098-9021. PMID 29270935. S2CID 11959147.
  57. ^ Türe, H. Sabiha; Tatlidil, Işıl; Kiliçarslan, Esin; Akhan, Galip (September 2019). "Gender-Related Differences in Semiology of Psychogenic Non-Epileptic Seizures". Archives of Neuropsychiatry. 56 (3): 178–181. doi:10.29399/npa.23420. PMC 6732800. PMID 31523142.
  58. ^ Asadi-Pooya, Ali A.; Homayoun, Maryam (1 February 2020). "Psychogenic nonepileptic seizures: The sex ratio trajectory across the lifespan". Seizure. 75: 63–65. doi:10.1016/j.seizure.2019.12.017. ISSN 1059-1311. PMID 31874361. S2CID 209413248.
  59. ^ a b Romeo DM, Sini F, Brogna C, Albamonte E, Ricci D, Mercuri E (August 2016). "Sex differences in cerebral palsy on neuromotor outcome: a critical review". Developmental Medicine and Child Neurology. 58 (8): 809–813. doi:10.1111/dmcn.13137. PMID 27098195.
  60. ^ Kruszka, Paul; Silberbach, Michael (March 2019). "The state of Turner syndrome science: Are we on the threshold of discovery?". American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 181 (1): 4–6. doi:10.1002/ajmg.c.31688. PMID 30790455. S2CID 73499005. [Turner Syndrome] is one of the most common genetic syndromes that occurs only in females...
  61. ^ "Prostate vs. testicular cancer: Similarities and differences". Medical News Today. 25 October 2021. Retrieved 10 November 2021.
  62. ^ "U.S. National Library of Medicine". Archived from the original on 12 October 2007. Retrieved 2 December 2007.
  63. ^ Oksuzyan A, Gumà J, Doblhammer D (February 12, 2018). "Sex Differences in Health and Survival §Effects of Sex Hormones on the Immune System". In Doblhammer D, Gumà J (eds.). A Demographic Perspective on Gender, Family and Health in Europe. Springer. p. 78. ISBN 978-1-01-326907-3. Retrieved 11 November 2021.
  64. ^ Latimer, Caitlin S.; Keene, C. Dirk; Flanagan, Margaret E.; Hemmy, Laura S.; Lim, Kelvin O.; White, Lon R.; Montine, Kathleen S.; Montine, Thomas J. (1 June 2017). "Resistance to Alzheimer Disease Neuropathologic Changes and Apparent Cognitive Resilience in the Nun and Honolulu-Asia Aging Studies". Journal of Neuropathology and Experimental Neurology. 76 (6): 458–466. doi:10.1093/jnen/nlx030. ISSN 1554-6578. PMC 6334750. PMID 28499012.
  65. ^ "Men to get aneurysm screening". BBC. 5 January 2008. Retrieved 6 June 2016.
  66. ^ Newschaffer CJ, Croen LA, Daniels J, Giarelli E, Grether JK, Levy SE, et al. (2007). "The epidemiology of autism spectrum disorders". Annual Review of Public Health. 28: 235–258. doi:10.1146/annurev.publhealth.28.021406.144007. PMID 17367287.
  67. ^ Werling, Donna M.; Geschwind, Daniel H. (April 2013). "Sex differences in autism spectrum disorders". Current Opinion in Neurology. 26 (2): 146–153. doi:10.1097/WCO.0b013e32835ee548. PMC 4164392. PMID 23406909.
  68. ^ Picchioni MM, Murray RM (July 2007). "Schizophrenia". BMJ. 335 (7610): 91–95. doi:10.1136/bmj.39227.616447.BE. PMC 1914490. PMID 17626963.
  69. ^ Alegria AA, Blanco C, Petry NM, Skodol AE, Liu SM, Grant B, Hasin D (July 2013). "Sex differences in antisocial personality disorder: results from the National Epidemiological Survey on Alcohol and Related Conditions". Personality Disorders. 4 (3): 214–222. doi:10.1037/a0031681. PMC 3767421. PMID 23544428.
  70. ^ Galanter M, Kleber HD, Brady KT (17 December 2014). Galanter M, Kleber HD, Brady KT (eds.). The American Psychiatric Publishing Textbook of Substance Abuse Treatment. doi:10.1176/appi.books.9781615370030. ISBN 978-1-58562-472-0.
  71. ^ "5.4 Stomach Cancer". World Cancer Report 2014. World Health Organization. 2014. pp. 383–391. ISBN 978-92-832-0429-9.
  72. ^ Montgomery EA (2014). 5.3 Oesophageal Cancer. pp. 528–543. In World Cancer Report 2014
  73. ^ Hefaiedh R, Ennaifer R, Romdhane H, Ben Nejma H, Arfa N, Belhadj N, et al. (Aug–Sep 2013). "Gender difference in patients with hepatocellular carcinoma". La Tunisie Médicale. 91 (8–9): 505–8. PMID 24227507.
  74. ^ Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, et al. (December 2013). "Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers". Journal of Clinical Oncology. 31 (36): 4550–9. doi:10.1200/jco.2013.50.3870. PMC 3865341. PMID 24248688.
  75. ^ Hertz D, Schneider B (March 2019). "Sex differences in tuberculosis". Seminars in Immunopathology. 41 (2): 225–237. doi:10.1007/s00281-018-0725-6. PMID 30361803. S2CID 53030554.
  76. ^ O'Driscoll DN, McGovern M, Greene CM, Molloy EJ (May 2018). "Gender disparities in preterm neonatal outcomes". Acta Paediatrica. 107 (9): 1494–9. doi:10.1111/apa.14390. PMID 29750838. S2CID 21676905.
  77. ^ Gorrell, Sasha; Murray, Stuart B. (October 2019). "Eating Disorders in Males". Child and Adolescent Psychiatric Clinics of North America. 28 (4): 641–651. doi:10.1016/j.chc.2019.05.012. ISSN 1558-0490. PMC 6785984. PMID 31443881.
  78. ^ Strother, Eric; Lemberg, Raymond; Stanford, Stevie Chariese; Turberville, Dayton (October 2012). "Eating Disorders in Men: Underdiagnosed, Undertreated, and Misunderstood". Eating Disorders. 20 (5): 346–355. doi:10.1080/10640266.2012.715512. ISSN 1064-0266. PMC 3479631. PMID 22985232.
  79. ^ Nagata, Jason M.; Ganson, Kyle T.; Murray, Stuart B. (August 2020). "Eating disorders in adolescent boys and young men: an update". Current Opinion in Pediatrics. 32 (4): 476–481. doi:10.1097/MOP.0000000000000911. PMC 7867380. PMID 32520822.
  80. ^ Stormont, Gavin D.; Deibert, Christopher M. (March 2021). "Genetic causes and management of male infertility". Translational Andrology and Urology. 10 (3): 1365–72. doi:10.21037/tau.2020.03.34. PMC 8039619. PMID 33850772.
  81. ^ Shah, K; Sivapalan, G; Gibbons, N; Tempest, H; Griffin, Dk (1 July 2003). "The genetic basis of infertility". Reproduction. 126 (1): 13–25. doi:10.1530/rep.0.1260013. PMID 12814343. Klinefelter syndrome and the subsequent infertility phenotype caused by it are specific to males.
  82. ^ NCD Risk Factor Collaboration (January 2017). "Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants". Lancet. 389 (10064): 37–55. doi:10.1016/S0140-6736(16)31919-5. PMC 5220163. PMID 27863813.NCD Risk Factor Collaboration. "Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants". Lancet. Retrieved 15 June 2024.
  83. ^ Izumi, Yoichi; Matsumoto, Koichi; Ozawa, Yukio; Kasamaki, Yuji; Shinndo, Atsusi; Ohta, Masakatsu; Jumabay, Madet; Nakayama, Tomohiro; Yokoyama, Eise; Shimabukuro, Hiroaki; Kawamura, Hiroshi; Cheng, Zuheng; Ma, Yitong; Mahmut, Masum (1 October 2007). "Effect of Age at Menopause on Blood Pressure in Postmenopausal Women". American Journal of Hypertension. 20 (10): 1045–50. doi:10.1016/j.amjhyper.2007.04.019. PMID 17903686. Retrieved 15 June 2024.
  84. ^ Reckelhoff, Jane F. (August 2023). "Mechanisms of sex and gender differences in hypertension". Journal of Human Hypertension. 37 (8): 596–601. doi:10.1038/s41371-023-00810-4. PMID 36797338. Retrieved 15 June 2024.
  85. ^ Miller, Amanda J.; Arnold, Amy C. (1 April 2022). "The renin-angiotensin system and cardiovascular autonomic control in aging". Peptides. 150: 170733. doi:10.1016/j.peptides.2021.170733. PMC 8923940. PMID 34973286.
  86. ^ Reckelhoff, Jane F. (August 2023). "Mechanisms of sex and gender differences in hypertension". Journal of Human Hypertension. 37 (8): 596–601. doi:10.1038/s41371-023-00810-4. PMID 36797338.
  87. ^ Reckelhoff, Jane F.; Zhang, Huimin; Srivastava, Kumud (January 2000). "Gender Differences in Development of Hypertension in Spontaneously Hypertensive Rats: Role of the Renin-Angiotensin System". Hypertension. 35 (1): 480–3. doi:10.1161/01.HYP.35.1.480. PMID 10642345.
  88. ^ Miller, Amanda J.; Arnold, Amy C. (1 April 2022). "The renin-angiotensin system and cardiovascular autonomic control in aging". Peptides. 150: 170733. doi:10.1016/j.peptides.2021.170733. PMC 8923940. PMID 34973286.
  89. ^ Miller, Amanda J.; Arnold, Amy C. (1 April 2022). "The renin-angiotensin system and cardiovascular autonomic control in aging". Peptides. 150: 170733. doi:10.1016/j.peptides.2021.170733. PMC 8923940. PMID 34973286.
  90. ^ a b c Brandt, Jessica E.; Priori, Roberta; Valesini, Guido; Fairweather, DeLisa (2015-11-03). "Sex differences in Sjögren's syndrome: a comprehensive review of immune mechanisms". Biology of Sex Differences. 6 (1): 19. doi:10.1186/s13293-015-0037-7. ISSN 2042-6410. PMC 4630965. PMID 26535108.
  91. ^ a b c d Xuan, Yuhao (2024). "Impact of sex differences on the clinical presentation, pathogenesis, treatment and prognosis of Sjögren's syndrome". Immunology. 171 (4): 513–524. doi:10.1111/imm.13740. PMID 38156505.
  92. ^ Liu, Ke; Kurien, Biji T.; Zimmerman, Sarah L.; Kaufman, Kenneth M.; Taft, Diana H.; Kottyan, Leah C.; Lazaro, Sara; Weaver, Carrie A.; Ice, John A.; Adler, Adam J.; Chodosh, James; Radfar, Lida; Rasmussen, Astrid; Stone, Donald U.; Lewis, David M. (May 2016). "X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome". Arthritis & Rheumatology. 68 (5): 1290–1300. doi:10.1002/art.39560. ISSN 2326-5191. PMC 5019501. PMID 26713507.
  93. ^ Dou, Diana R. (2024-02-01). "Xist ribonucleoproteins promote female sex-biased autoimmunity". Cell. 187 (3): 733–749. doi:10.1016/j.cell.2023.12.037. PMC 10949934. PMID 38306984.