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Disorders of sex development

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Disorders of sex development

Disorders of sex development
Classification and external resources
MeSH D012734

Disorders of sex development (DSD), sometimes referred to as disorders of sex differentiation or differences of sex development,[1] are medical conditions involving the reproductive system. More specifically, these terms refer to "congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical."[2] Lee et al. in a 2006 Consensus statement on management of intersex disorders proposed a system of nomenclature based on "disorders of sex development" for clinical use, suggesting that "terms such as intersex, pseudohermaphroditism, hermaphroditism, sex reversal, and gender based diagnostic labels are particularly controversial," may be perceived as pejorative, and are confusing to practitioners and parents alike. In "We Used to Call Them Hermaphrodites," Eric Vilain states that "DSD" is not a synonym for intersex; he states that it replaces medical terms based on "hermaphrodite".[3]

Such views are contested - including at Parliamentary level. A committee of the [6][7]

The [10]

Contents

  • Overview 1
  • Conditions 2
  • Controversy 3
    • Academic and community responses to the controversy 3.1
    • Governmental and institutional responses to the controversy 3.2
  • See also 4
  • References 5
  • External links 6

Overview

DSDs are medical conditions involving the way the reproductive system develops from infancy (and before birth) through young adulthood. There are several types of DSDs and their effect on the external and internal reproductive organs varies greatly.

The medical adjective for people with DSDs can be "intersex". Intersex literally means that the body is between the two sexes, male and female. Nevertheless, most intersex people think of themselves as completely being either boys/men, or girls/women. For this reason, parents with DSD children and clinicians involved in DSD treatment usually try to make clear distinctions between biological sex, social gender, and sexual orientation. This helps clear up any lingering confusion about the differences between being intersex, being transgender, and being gay/lesbian.

The most common DSD is Congenital Adrenal Hyperplasia (CAH), which results in a person with female (XX) chromosomes having genitals that look somewhat masculine. In mild cases CAH results in a slightly enlarged clitoris, while in more severe cases it can be difficult to decide (just by looking) whether a baby is male or female (this is called having ambiguous genitals). Nevertheless, if they are old enough to know the difference, most children with CAH think of themselves as girls. CAH is caused by a problem with the adrenal glands and is usually treated by taking a daily medication to replace or supplement the missing adrenal hormones. (When this adrenal problem occurs in people with male (XY) chromosomes, the result is over-masculinization and premature puberty).

Another common DSD is Androgen Insensitivity Syndrome (AIS), which means that a person with male (XY) chromosomes does not respond to testosterone in the usual way. This results in a body that to some degree has a feminine appearance. In Complete Androgen Insensitivity Syndrome (CAIS) the result is a totally feminine appearance, including typical female breast development. Consequently, most young women with CAIS are unaware of their condition until the early teen years when they fail to menstruate. In the milder form, called Partial Androgen Insensitivity Syndrome (PAIS), the genitals can vary from mostly female to almost completely male. Some people with PAIS think of themselves as girls/women, while others regard themselves as boys/men. Some people with PAIS take hormones and/or undergo surgery to give the genitals a more ordinary appearance. In the past such surgeries were often performed in infancy, but in recent years the tendency has been to postpone surgery until the child has expressed a clear gender preference and is old enough to participate actively in decisions about his/her medical treatment.

One of the more unusual DSDs is 5-Alpha Reductase Deficiency (5ARD), popularly known as "Penis at 12." It is caused by a shortage early in life of an enzyme that activates testosterone. In this condition, a person with male (XY) chromosomes has a body that appears female before puberty. After puberty begins, other testosterone-activating enzymes become available and the body soon takes on a masculine appearance, with the scrotum and penis usually reaching typical or nearly-typical size. If 5ARD is diagnosed at a young age, the child is generally raised as a boy, since the vast majority of adults with this condition consider themselves men.

In addition to CAH, CAIS, PAIS, and 5ARD there are several rarer types of DSDs, and in some cases it is not possible to make a clear diagnosis of the underlying condition.

The penis and clitoris are essentially the same organ (differing only in size, and generically called the phallus). In typical males, the urethra is located at the tip of the penis, while in typical females the urethra is located below the base of the clitoris. When the phallus is of intermediate size, it is possible also to have a urethral opening located along the shaft; this condition is known as hypospadia.

In the past the term "hermaphrodite" was sometimes erroneously used to describe intersex people. This term is no longer used to describe humans (or any other mammals). The correct technical definition of a hermaphrodite is a single organism that has complete sets of both male and female sexual organs, as is the case with most trees and flowering plants.

Open-minded parenting, appropriate and conservative medical intervention, and age-appropriate child involvement in the treatment plan contribute greatly to successful outcomes for the entire range of DSDs.[11]

Conditions

  • 47,XXY females and Non-Klinefelter XXY - There are case reports of 47,XXY females; in some cases SRY or androgen receptor abnormalities are detected.[12]
  • 48, XXXX (also known as tetrasomy X, quadruple X, and XXXX syndrome) - A condition that describes a female with two extra female chromosomes. It is considered a variation of Triple X syndrome. Women with 48, XXXX may or may not have issues associated with the condition though most are developmentally delayed and only about 50% undergo puberty normally.
  • 48, XXYY (also known as XXYY syndrome) - A condition that describes a male with one extra female chromosome and one extra male chromosome. It occurs in 1 in 18,000 to 40,000 male births.[13] 48, XXYY may result in infertility, low testosterone, and neurodevelopmental disorders like ADHD or autism but some men have no issues.
  • 49, XXXXX (also known as pentasomy X and XXXXX syndrome) - A condition that describes a female with three extra female chromosomes. It is considered a variant of Triple X syndrome. Women with 49, XXXXX usually suffer from numerous health issues such as patent ductus arteriosus, scoliosis, kidney hypoplasia, and abnormal lobulation of the lungs. Physical deformities include microcephaly, micrognathia, and webbing of the neck.
  • 49, XXXXY - A condition that describes a male with three extra female chromosomes. It is rare, occurring in 1 in 85,000 to 100,000 males.[14][15] It is considered a variation of Klinefelter syndrome. Men with 49, XXXXY syndrome often suffer from mental retardation.
  • 5α-reductase deficiency (also known as 5-ARD) - An autosomal recessive condition caused by a mutation of the 5-alpha reductase type 2 gene. It only affects people with Y chromosomes, namely genetic males. People with this condition are fertile, with the ability to father children, but may be raised as females due to amibiguous or feminized genitalia.
  • 17β-Hydroxysteroid dehydrogenase deficiency - A condition characterized by impaired androgen and estrogen synthesis in males and females, respectively. Results in pseudohermaphroditism/undervirilization in males and in excessive virilization of adult females.
  • Androgen insensitivity syndrome (also known as AIS) - A condition which affects a genetic male's virilization. A man with androgen insensitivity syndrome produces androgens and testosterone but their body does not recognize it, either partially or completely. Mild androgen insensitivity syndrome generally causes no developmental issues and people with this form are raised as males. Partial androgen insensitivity syndrome results in ambiguous genitalia and there is no consensus regarding whether to raise a child with this form as male or female. Complete androgen insensitivity syndrome causes a genetic male to have a vagina (often incompletely developed, nearly always blind-ending), breasts, and a clitoris and people with this form are raised as females.
  • Aphallia - A rare occurrence where a male is born without a penis or where a female is born without a clitoris. As of 2005, only 75 cases of aphallia have been documented.[16] It should not be confused with intentional or accidental amputation of the genitalia.
  • Aposthia - A congenital defect where a male is born without a foreskin.
  • Aromatase deficiency - A disorder in which, in females, is characterized by androgen excess and estrogen deficiency, and can result in inappropriate virilization, though without pseudohermaphroditism (i.e., genitals are phenotypically appropriate) (with the exception of the possible incidence of clitoromegaly).
  • Aromatase excess syndrome (also known as familial hyperestrogenism) - A condition that causes excessive estrogen production, resulting in feminization without pseudohermaphroditism (i.e., male genitalia at birth and female secondary sexual characteristics at puberty) in males and hyperfeminization in females.
  • Clitoromegaly - A clitoris that is considered larger than average. While clitoromegaly may be a symptom of an intersex condition, it may also be considered a normal variation in clitoris size. Clitoromegaly causes no health issues. Surgical reduction of the clitoris or its complete removal may be performed to normalize the appearance of the genitalia. While female genital mutilation is outlawed in many countries, reduction or the removal of the clitoris in cases of clitoromegaly are generally exempt, despite the fact that it is a nontherapeutic and sexually damaging surgery. Clitoromegaly may also be caused by females using testosterone or anabolic steroids for purposes related to female to male gender transition or bodybuilding.
  • Combined 17α-hydroxylase/17,20-lyase deficiency - A condition in which presents as a combination of the symptoms of congenital adrenal hyperplasia and isolated 17,20-lyase deficiency. See those two conditions for more information.
  • Complete androgen insensitivity syndrome (also known as CAIS) - A condition which completely affects a genetic male's ability to recognize androgens. It is considered a form of androgen insensitivity syndrome and is the most severe form. People with complete androgen insensitivity are raised as females and usually do not discover they are genetic males until they experience amenorrhoea in their late teens or they need medical intervention due to a hernia caused by their undescended testes. Complete androgen insensitivity syndrome results in a genetic male having a vagina, clitoris, and breasts which are capable of breastfeeding. However, they will not have ovaries or a uterus. Because they do not have ovaries or sufficiently developed testicles, people with complete androgen insensitivity syndrome are infertile.
  • Congenital adrenal hyperplasia (also known as CAH) - A condition that causes excessive androgen production, which causes excessive virilization. It is most problematic in genetic females, where severe virilization can result in her having vaginal agenesis (absence of vagina) and a functional penis which is capable of penetrative intercourse. Females with this condition are usually fertile, with the ability to become pregnant and give birth. The salt-wasting variety of this condition is fatal in infants if left untreated.
  • Diphallia (also known as penile duplication, diphallic terata, and diphallasparatus) - A condition where a male is born with two penises. It's extremely rare, with only 100 cases being recorded since 1609 and an occurrence rate of 1 in 5,500,000 in the United States. The penises may be side by side or one on top of the other, being of equal size or with one penis being distinctively larger than the other, and both penises may be suitable for urination and intercourse. Men with diphallia may be sterile.
  • Estrogen insensitivity syndrome (EIS) - The estrogen counterpart to androgen insensitivity syndrome. Extremely rare, with only one verified case having been reported; a biological male presented with tall stature, a heightened risk of osteoporosis, and sterility.
  • Gonadal Dysgenesis - is any congenital developmental disorder of the reproductive system characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo.
  • Isolated 17,20-lyase deficiency - A condition that is characterized by an either partial or complete inability to produce androgens and estrogens. Results in partial or complete feminization and undervirilization in males and in a delayed, reduced, or absent puberty in both sexes, in turn causing sexual infantilism and infertility, among other symptoms.
  • Klinefelter syndrome (also known as 47, XXY and XXY syndrome) - A condition that describes a male born with at least one extra female chromosome. Though the most common variation is 47, XXY, a man may also be 48, XXXY or 49, XXXXY. It is a common occurrence, affecting 1 in 500 to 1,000 men.[17] While some men may have no issues related to the syndrome, some may experience gynecomastia, micropenis, cognitive difficulties, hypogonadism, reduced fertility/infertility, and/or little or no facial hair. Testosterone therapy may be pursued by men who desire a more masculine appearance and those with gynecomastia may opt to undergo a reduction mammoplasty. Men who wish to father children may be able to do so with the help of IVF.[18]
  • Leydig cell hypoplasia - A condition solely affecting biological males which is characterized by a partial or complete inactivation of the luteinizing hormone receptor, resulting in stymied androgen production. Patients may present at birth with a fully female phenotype, ambiguous genitalia, or only mild genital defects such as micropenis and hypospadias. Upon puberty, sexual development is either impaired or fully absent.
  • Micropenis (also known as microphallus) - A penis that measures 3 inches (7.62 centimeters) or less in length when erect. It is a common condition, occurring in 1 in 200 men.[19] Micropenis may be the result of undervirilization during fetal development or may be caused by an underlying intersex condition, such as mild androgen insensitivity syndrome, partial androgen insensitivity syndrome, or Klinefelter syndrome. It may also be considered a natural variation of penis size. While the majority of men have no issues with having a micropenis, some may opt to use a prosthetic penis or undergo penile enlargement to increase the size of their penis.
  • Mild androgen insensitivity syndrome (also known as MAIS) - A condition which mildly affects a genetic male's ability to recognize androgens. It is considered a form of androgen insensitivity syndrome and is considered the least severe form. While men generally do not need any specialized medical care related to this form, mild androgen insensitivity syndrome may result in gynecomastia and hypospadias. Neither gynecomastia nor hypospadias require surgerical intervention or adversely affect a man's health though some men may opt to undergo surgery to remove their breasts and/or repair their hypospadias. Men with mild androgen insensitivity syndrome may have reduced fertility.
  • Mixed gonadal dysgenesis - is a condition of unusual and asymmetrical gonadal development leading to an unassigned sex differentiation. A number of differences have been reported in the karyotype, most commonly a mosaicism 45,X/ 46, XY.
  • Partial androgen insensitivity syndrome (also known as PAIS) - A condition which partially affects a genetic male's ability to recognize androgens. It is considered a form of androgen insensitivity syndrome and while it is not as severe as complete androgen insensitivity syndrome, it is more severe than mild androgen insensitivity syndrome. Partial androgen insensitivity syndrome causes major problems with gender assignment because it causes ambiguous genitalia such as a micropenis or clitoromegaly in addition to breast development. People with partial androgen insensitivity syndrome who are assigned as males may undergo testosterone therapy to virilize their body while those who are assigned as females may undergo surgical reduction of the clitoris and/ or estrogen therapy.
  • Pseudovaginal perineoscrotal hypospadias (also known as PPSH) - A form of ambiguous genitalia which results in a phallic structure that is smaller than a penis but larger than a clitoris, a chordee, hypospadias, and a shallow vagina.
  • Swyer Syndrome (Also known as Pure Gonadal Dysgenesis or XY gonadal dysgenesis) is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and left untreated, will not experience puberty. Such gonads are typically surgically removed (as they have a significant risk of developing tumors) and a typical medical treatment would include hormone replacement therapy with female hormones.
  • Triple X syndrome - A condition that describes a female born with an extra female chromosome, making her karotype 47, XXX. It is a common occurrence, affecting 1 in 1,000 females.[20] It generally causes no health issues or abnormal development.
  • Turner syndrome (also known as Ullrich-Turner syndrome and gonadal dysgenesis) - A condition that describes a female born without a female chromosome or with an abnormal female chromosome, making her karotype 45, XO. It occurs in 1 in 2,000 to 5,000 females. Turner syndrome causes numerous health and development problems, including but not limited to short stature, lymphedema, infertility, webbed neck, coarctation of the aorta, ADHD, amenorrhoea, and obesity.
  • Uterus didelphys (also known as double uterus) - A condition where a female is born with two uteri. It is often accompanied by two vaginas. It is generally not considered a health issue and women with uterus didelphys usually have normal sex lives and pregnancies.[21]

Controversy

Use of the term disorder of sex development (DSD) is controversial among many activists and community organisations.[7][22][23] Many governments and international institutions use the term 'intersex' in preference to 'DSD'.

Academic and community responses to the controversy

Georgiann Davis described how:

In a series of articles on Preimplantation genetic diagnosis in The American Journal of Bioethics in 2013, bioethicists and related authors reference "intersex traits" or "intersex conditions". Professor Jeff Nisker describes how:

On 28 April 2014, the British Medical Journal published an article by Associate Professor Rebecca Jordan-Young, Emeritus Professor Peter Sönksen, and scholar Katrina Karkazis referencing "women with intersex conditions".[8]

Alternatives have been offered: Milton Diamond has suggested the use of "variation"[24][25] or of "difference",[26] and Elizabeth Reis has suggested "divergence";[27] the latter two suggestions would retain the initial D in DSD.

Governmental and institutional responses to the controversy

In an October 2013 report of a Parliamentary inquiry into the Involuntary or coerced sterilisation of intersex people in Australia, the Australian Senate's Community Affairs References Committee recommended a review of clinical use of the term.[4] Their recommendations include:

In a rationale, the Parliamentary report states that "2.4 Not everyone who is intersex has a health problem: whether they experience a 'disorder' is not defined by whether they are biologically 'intersex'" and the "history of the terminology is vexed":

A similar rejection of 'Disorders of Sex Development' was adopted elsewhere in Australia in decision-making guidelines, Decision-making principles for the care of infants, children and adolescents with intersex conditions, published in February 2013 by the Department of Health of the State of Victoria.[28]

Australia has also enacted anti-discrimination legislation that includes the attribute "intersex status"[29][30] and published identity recognition guidelines that use the same 'intersex' terminology.[31]

In May 2014, the OHCHR, UN Women, UNAIDS, UNDP, UNFPA and UNICEF. The report references the involuntary surgical "sex-normalising or other procedures" on "intersex persons". The report recommends a range of guiding principles for medical treatment, including ensuring patient autonomy in decision-making, ensuring non-discrimination, accountability and access to remedies.[32]

See also

References

  1. ^ Diamond, Milton; Hazel G. Beh (January 2008). "Changes in the management of children with intersex conditions". Nat Clin Pract Endocrinol Metab. 4 (1): 4–5.  
  2. ^ Lee P. A., Houk C. P., Ahmed S. F., Hughes I. A.; Houk; Ahmed; Hughes (2006). "Consensus statement on management of intersex disorders". Pediatrics 118 (2): e488–500.  
  3. ^ Vilain E, Achermann JC, Eugster EA, Harley VR, Morel Y, Wilson JD, Hiort O; Achermann; Eugster; Harley; Morel; Wilson; Hiort (2007). "We used to call them hermaphrodites". Genetics in Medicine 9 (2): 65–66.  
  4. ^ a b c Senate Community Affairs Committee, Involuntary or coerced sterilisation of intersex people in Australia, October 2013
  5. ^ a b Georgiann Davis (2011), "DSD is a Perfectly Fine Term": Reasserting Medical Authority through a Shift in Intersex Terminology, in PJ McGann, David J. Hutson (ed.) Sociology of Diagnosis (Advances in Medical Sociology, Volume 12), Emerald Group Publishing Limited, pp.155-182
  6. ^ a b Holmes, Morgan (2011). "The Intersex Enchiridion: Naming and Knowledge in the Clinic". Somatechnics 1 (2): 87–114.  
  7. ^ a b An Interview with Dr. Tiger Howard Devore PhD, We Who Feel Differently, February 7, 2011.
  8. ^ a b Rebecca Jordan-Young, Peter Sönksen, and Katrina Karkazis (28 April 2014) Sex, health, and athletes, British Medical Journal, BMJ 2014;348:g2926, doi: http://dx.doi.org/10.1136/bmj.g2926.
  9. ^ a b Nisker Jeff (2013). "Informed Choice and PGD to Prevent "Intersex Conditions". The American Journal of Bioethics 13 (10): 51–53.  
  10. ^  
  11. ^ Pediatric gender assignment : a critical reappraisal ; [proceedings from a conference ... in Dallas in the spring of 1999 which was entitled "pediatric gender assignment - a critical reappraisal"]. New York, NY [u.a.]: Kluwer Acad. / Plenum Publ. 2002.  
  12. ^ Röttger, S., K. Schiebel, G. Singer, S. Ebner, W. Schempp, and G. Scherer. Röttger, S., K. Schiebel, G. Singer, S. Ebner, W. Schempp, and G. Scherer. "An SRY-negative 47,XXY mother and daughter." Cytogenetics and Cell Genetics 91.1-4 (2000): 204-07. National Center for Biotechnology Information. U.S. National Library of Medicine, 2001. Web. 12 Aug. 2013.
  13. ^ Tartaglia N, Davis S, Hench A et al. (June 2008). "A New Look at XXYY Syndrome: Medical and Psychological Features". Am. J. Med. Genet. A 146A (12): 1509–22.  
  14. ^ What is XXXXY syndrome? Retrieved March 26, 2008.
  15. ^ Visootsak J, Graham JM; Graham Jr (2006). "Klinefelter syndrome and other sex chromosomal aneuploidies". Orphanet J Rare Dis 1: 42.  
  16. ^ Chibber PJ, Shah HN, Jain P, Yadav P; Shah; Jain; Yadav (2005). "Male gender assignment in aphallia: a case report and review of the literature". Int Urol Nephrol 37 (2): 317–9.  
  17. ^ The Focus Foundation. X & Y Variations. thefocusfoundation.org
  18. ^ Fullerton G, Hamilton M, Maheshwari A.; Hamilton; Maheshwari (2010). "Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009?". Hum Reprod. 25 (3): 588–97.  
  19. ^ Op can boost size of micro-penis, BBC News, Published December 6, 2004
  20. ^ National Library of Medicine (2007). "Genetics Home Reference: Triple X syndrome". Retrieved 2007-03-22. 
  21. ^ Double uterus Mayo Clinic, Published September 11, 2010
  22. ^ Submission to inquiry on involuntary or coerced sterilisation of people with disabilities, Organisation Intersex International Australia, 15 February 2013.
  23. ^ Hello World - I am not a DSD
  24. ^ Beh, Hazel; Diamond, Milton (2006). "Variations of Sex Development Instead of Disorders of Sex Development". Archives of Disease in Childhood (26 July 2006). 
  25. ^ Tamar-Mattis, Anne; Diamond, Milton (2007). "Managing variation in sex development.". Journal of Pediatric Endocrinology & Metabolism 20 (4): 552–553. 
  26. ^ Diamond, Milton; Beh, Hazel. (2008). "Changes In Management Of Children With Intersex Conditions.". Nature Clinical Practice Endocrinology & Metabolism 4 (1): 4–5.  
  27. ^ Reis, Elizabeth (2007). "Divergence or Disorder?". Perspectives in Biology and Medicine 50 (4): 535–543.  
  28. ^ Department of Health, Victoria, Australia, "Decision-making principles for the care of infants, children and adolescents with intersex conditions", 21 February 2013
  29. ^ Organisation Intersex International (OII) Australia, "On the historic passing of the Sex Discrimination Amendment (Sexual Orientation, Gender Identity and Intersex Status) Act 2013", 25 June 2013
  30. ^ ComLaw, "Sex Discrimination Amendment (Sexual Orientation, Gender Identity and Intersex Status) Act 2013, No. 98, 2013. C2013A00098", 2013
  31. ^ Australian Government Guidelines on the Recognition of Sex and Gender, 30 May 2013
  32. ^ Eliminating forced, coercive and otherwise involuntary sterilization, An interagency statement, World Health Organization, May 2014.

External links

  • Disorders of Sex Development Research Website provides information regarding the causes, frequency and implications of DSD, in plain language, from a genetics and biology research perspective. It also includes detailed scientific and medical information for clinicians and scientists who work with children, adolescents and adults affected by DSD or intersex, or analyse the genetic causes.
  • Accord Alliance Promoting comprehensive and integrated approaches to care that enhance the health and well-being of people and families affected by DSD by fostering collaboration among all stakeholders.
  • YourChild: Disorders of Sex Development (DSD) Resources University of Michigan Health System.
  • Sex Development: An Overview Animation of prenatal genital development from The Hospital for Sick Children, Toronto.
  • Handbook for Parents Consortium on the Management of Disorders of Sex Development.
  • Clinical Guidelines for the Management of Disorders of Sex Development in Childhood Consortium on the Management of Disorders of Sex Development.
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