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Sexual anomalies, also known as sexual abnormalities, are a set of clinical conditions due to chromosomal, gonadal and/or genitalia variation. Individuals with congenital (inborn) discrepancy between sex chromosome, gonadal, and their internal and external genitalia are categorised as individuals with a disorder of sex development (DSD).^[1] Afterwards, if the family or individual wishes, they can partake in different management and treatment options for their conditions (e.g. hormone therapy).

Infants born with atypical genitalia often cause confusion and distress for the family. Psychosexual development is influenced by numerous factors that include, but are not limited to, gender differences in brain structure, genes associated with sexual development, prenatal androgen exposure, interactions with family, and cultural and societal factors.^[2] Because of the complex and multifaceted factors involved, communication and psychosexual support are all important.

A team of experts, or patient support groups, are usually recommended for cases related to sexual anomalies. This team of experts are usually derived from a variety of disciplines including pediatricians, neonatologists, pediatric urologists, pediatric general surgeons, endocrinologists, geneticists, radiologists, psychologists and social workers.^[3]^[4]^[5] These professionals are capable of providing first line (prenatal) and second line diagnostic (postnatal) tests to examine and diagnose sexual anomalies.

Overview

In the normal prenatal stages of fetal development, the fetus is exposed to testosterone - albeit more in male fetuses than female ones. Upon the presence of the 5α-reductase enzyme, testosterone is converted to dihydrotestosterone (i.e. DHT). If DHT is present, the male external genitalia will develop.

Development of male external genitalia:

Genital tubercle forms the penis^[6]
Urethral folds form the penile raphe^[7]^[8]
Genital swellings form the scrotum^[6]

On the other hand, if maternal placenta estrogen is present without DHT, then the development of female external genitalia occurs.^[9]

Development of female external genitalia (the vulva):

Genital tubercle forms the clitoris^[10]
Urethral folds form the labia minora^[10]
Genital swellings form the labia majora^[10]

**Chemical structure of dihydrotestosterone (DHT)**

However, in abnormal cases, sexual anomalies occur due to a variety of factors that lead to an excess of androgens in the fetus. The effects of excessive androgens differ in fetuses with XX chromosome (female) and XY chromosomes (male).

In XX chromosome fetuses, excess androgens result in ambiguous genitalia. This makes identification of external genitalia as male or female difficult.^[10] Additionally, the individual may have clitoromegaly, a shallow vagina, early and rapid growth of pubic hair in childhood, delayed puberty, hirsutism, virilisation, irregular menstrual cycle in adolescence and infertility due to anovulation.^[11]

In XY chromosome fetuses, excess androgens result in a functional and average-sized penis with extreme virilisation, but the inability for sperm production.^[12] Additionally, the individual will also experience early and rapid growth of pubic hair during childhood and precocious puberty stages.^[11]

Classification

Differences/disorders of sexual development (DSD) are classified into different categories: chromosomal variation, gonadal development disorders, abnormal genital development and others.

Chromosomal variation

DSDs caused by chromosomal variation generally do not present with genital ambiguity. This includes sex chromosome DSDs such as Klinefelter syndrome, Turner syndrome and 45,X or 46,XY gonadal dysgenesis.^[13]

Males with Klinefelter syndrome usually have a karyotype of 47,XXY as a result of having two or more X chromosomes.^[14] Affected patients generally have normal genital development, yet are infertile and have small, poor functioning testes, breast growth and delayed puberty.^[14] The incidence for 47,XXY is 1 in 500 males, but severe and rare cases of Klinefelter syndrome presents as three or more X chromosomes.^[14]

Turner syndrome is classified as aneuploidy or structural rearrangement of the X chromosome. Signs and symptoms of affected females vary among them, such as low birth weight, low-set ears, short stature, short neck and delayed puberty.^[15] The incidence is 1 in 2500 live-born females, while most patients do not survive for more than one year after birth.^[13]

Gonadal development disorders

Gonadal development disorders form a wide spectrum, classified by their cytogenetic and histopathological features. However, unsolved diagnosis and malignancy still represent difficulties in the sex determination of these patients.^[16] Such disorders include partial or complete gonadal dysgenesis, ovotesticular DSD, testicular DSD and sex reversal.^[3]

Abnormal genital development

Genital abnormality can occur in the penis, scrotum or testes in males; and vagina and labia in females.^[3] Sometimes, ambiguous genitalia could occur, where the clear distinction of external genitalia is absent in both male and female. Hence, examination (typically at birth) is carried out where the sex of the patient will be determined through imaging and blood tests.^[3] Abnormal genital development includes disorders of fetal origin, disorders in androgen synthesis or action, disorders in anti-Müllerian hormone synthesis or action.^[3]

Others

In addition to the aforementioned sexual anomalies, there are other unclassified sexual anomalies. In males, this includes severe early-onset intrauterine growth restriction, isolated hypospadias, congenital hypogonadotropic hypogonadism, hypogonadism and cryptorchidism. In females, this includes Malformation syndromes, Müllerian agenesis/hypoplasia, uterine anomalies, vaginal atresia and labial adhesions.^[3]

Causes

Sexual anomalies often generate from genetic abnormalities caused by many factors, leading to different sexual development. These genetic abnormalities occur during the prenatal stage of an individual's fetal development. During this stage, genetic mutations can result from endocrine disrupters in the mother's diet or environmental factors.^[17] The general causes of sexual anomalies can not be outlined due to the high variability of each individual's situations. Thus, the cause of each specific anomaly has to be studied independently.

Sexual differentiation occurs through various processes during the prenatal development period of the fetus. These processes are initiated and regulated by biological metabolites such as DNA, hormones and proteins. The initial steps of sexual differentiation begin with the development of the gonads and genitals. This process is consistent with both genders spanning over the course of the first 6 weeks following conception, during which the embryo remains pluripotent.^[18] Differentiation of the gonads begins after the 6th week, which is determined by the sex-determining region Y (SRY) gene in the Y chromosome.^[10]

The SRY gene plays an important role in developing the testes of a male individual. Following the development of the testes, hormones synthesized within the testes regulate the differentiation of both internal and external parts of the genitals. The absence of the testicles or the hormones synthesized may lead to irregular differentiation of the genitals. Genetic abnormalities or environmental factors that influence these procedures may lead to the incomplete development of the gonads and the genitals. These malformations can occur any time during the development or the birth of the embryo, manifesting as ambiguous genitals or dissonance within the genotypic and phenotypic sex of the individual, leading to a late onset of puberty, amenorrhea, a lack of or excess virilization, or later in life, infertility or early occurrence of menopause.^[19]

Diagnosis and symptoms

First line diagnostic tests (prenatal)

Family history

Symptoms such as infertility, early menopause, amenorrhea or sudden infant death syndrome (SIDS) could be a sign. Hence, an early check-up should be conducted.^[3]

Analysis of karyotype

Peripheral blood is collected for karyotyping. This helps classify the patient in one of the three main categories of DSD: chromosomal variation, gonadal development disorders and abnormal genital development.^[3]

Abdominal ultrasounds

The presence of gonads, uterus and vagina should be monitored. This can be done through abdominal ultrasounds. However, the absence of these sex organs will lead to difficulties in gender identification.^[3]

Second line diagnostic tests (postnatal)

Physical Examination

Inspection of the genitalia with care and palpation must be conducted with the following points in mind.^[3]
- Determining the degree of virilization or masculinisation:
  - In a female fetus, the Prader scale should be used to assess the extent of the virilisation if the karyotyping results are not out yet.^[3]
  - In males, the external masculinization score should be used.^[3]
Palpation of gonads from the labioscrotal fold to the abdomen (inguinal canal).^[3]
Hydration and blood pressure assessment should be conducted.^[3]
Additional dysmorphic features should be ruled out because genitalia malformations would occur if the patient has multiple malformation syndromes.^[3]

Evaluation of hormones 48 hours after birth

17-Hydroxyprogesterone can be used to screen for congenital adrenal hyperplasia (CAH). This is commonly found in patients with 46, XX DSD.^[3]^[20]
Dehydroepiandrosterone (DHEA) in addition to progesterone allows for the diagnosis of more uncommon forms of CAH and other inherited disorders.^[3]
Base testosterone, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels are precursors in individuals with 46,XX DSD. These tests are conducted within the timeframe of thirty hours post-birth to anywhere between fifteen and ninety days post-birth. This data collected within time frame can be used to gauge the growth of the fetus when it reaches six months of age.^[3]^[20]
Basal cortisol levels and adrenocorticotropic hormone (ACTH) is essential in diagnosing panhypopituitarism and enzymatic disorders affecting adrenal steroidogenesis.^[3]
The anti-Müllerian hormone is used for evaluating the function of Sertoli cells.^[3]
A urinary steroid profile shows the ratio of precursor metabolites within measured urine concentrations and the resultant products produced indicates the enzyme is the cause of a sexual defect. This is a more specific procedure in the detection of the defect in comparison to analysing blood.^[3]

Treatment and management

The treatment and/or management of DSDs with atypical genitalia will vary from person to person. This may include gender affirmation surgery, medical treatment and surgical treatment.

Gender affirmation surgery

Gender affirmation plays a critical role in the management of sexual anomaly cases. Ultimately, the parents and a multidisciplinary team are responsible for assigning the sex that is affirmative the gender of the concerned person. The current guidelines of gender affirmation include the psychosocial effects in adults with etiological diagnosis, the potential for fertility, surgical opportunities and hormone replacement therapy in the course of puberty.^[21]^[5]

There are other factors considered during this process. This may include cultural and religious factors as well as the implications it has on the individual in later life. It is regulated by reference centers with groups specialised in managing cases of sexual anomalies.^[5]

Medical treatment

Hormonal treatment is an accepted and standardised approach to treat different congenital sexual anomalies. Patients that are deficient in hormones produced by the adrenal glands require immediate medical attention. They are given a hormone called hydrocortisone, a form of hormone replacement therapy, with the objective to induce puberty.^[5]

Utilizing sex steroids as hormonal therapy is deemed controversial with concerns of its duration of initiation, dosage and regimen.^[5] However, it is agreed amongst most clinicians that low doses of hormonal treatment should begin around the age of 11 to 12 years old and should be increased progressively.^[5]

Surgical treatment

Surgical procedures are an alternative to hormonal treatment available for patients to address genital anomalies and improve the body's sexual functions. However, a common dilemma in these procedures is that they are often derived from the patient's expectation of 'normal' genitals from an aesthetic and functional standpoint. Oftentimes, this leads to extensive surgical interventions.^[22]

In most cases, surgical procedures result in permanent changes to the appearance and function of the patient's body. Therefore, the decision to proceed with this arrangement must be a joint agreement between the family and the multidisciplinary team. The most ideal situation would be to include the patient as part of the decision-making process. However, cases where surgical treatments were performed at an early age are recognised as mutilation of the body. Subsequently, it has become increasingly common to defer surgical treatments until the patient is of appropriate age to be involved in the decision-making process.^[5]

Controversy and implications

Even though the term disorder of sex development (DSD) is widely accepted by the medical community, its suitability and adequacy to represent these individuals are criticised by many support and advocacy groups. Firstly, the word 'disorder' carries negative connotations. Secondly, with current nomenclature, DSD is an overly generalised term for conditions that do not have differences in genital appearance or gender identity (e.g. Klinefelter syndrome and Turner syndrome). Thirdly, the term 'DSD' lacks specificity and clarity; and therefore unhelpful in the diagnosis process. Hence, many support groups and advocates believe that the medical community should discontinue the use of 'DSD' as a designation tool.^[23]

Furthermore, people who live with conditions regarding sexual abnormalities may encounter various mental and physical health problems. This may include traumatic experience with their own bodies, dissatisfaction with body image, low-self esteem, anxiety, depression, bipolar disorders, eating disorders, personality disorders, schizophrenia disorders, trauma and stress-related disorders, etc.^[24]

References

^ Sreenivasan, R.; Alankarage, D.; Harley, V. (2017-01-01). "Disorders of Sex Development Loci☆". Disorders of Sex Development Loci. Elsevier. doi:10.1016/B978-0-12-809633-8.06552-3. ISBN 9780128096338.
^ Achermann, John C.; Hughes, Ieuan A. (2016), "Pediatric Disorders of Sex Development", Williams Textbook of Endocrinology, Elsevier, pp. 893–963, doi:10.1016/b978-0-323-29738-7.00023-x, ISBN 978-0-323-29738-7, retrieved 2021-04-01
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u Guerrero-Fernández, Julio; Azcona San Julián, Cristina; Barreiro Conde, Jesús; Bermúdez de la Vega, José Antonio; Carcavilla Urquí, Atilano; Castaño González, Luis Antonio; Martos Tello, José María; Rodríguez Estévez, Amaya; Yeste Fernández, Diego; Martínez Martínez, Leopoldo; Martínez-Urrutia, María José (2018). "Management guidelines for disorders/different sex development (DSD)". Anales de Pediatría (English Edition). 89 (5): 315.e1–315.e19. doi:10.1016/j.anpede.2018.06.006. PMID 30033107.
^ "Ambiguous genitalia - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2021-04-01.
^ ^a ^b ^c ^d ^e ^f ^g Deligdisch-Schor, Liane; Mareş Miceli, Angelica, eds. (2020). Hormonal Pathology of the Uterus. Advances in Experimental Medicine and Biology. Vol. 1242. p. 133. doi:10.1007/978-3-030-38474-6. ISBN 978-3-030-38473-9. ISSN 0065-2598. S2CID 218624824.
^ ^a ^b Kinter, Kevin; Anekar, Aabha (2021-03-13). "Biochemistry, Dihydrotestosterone". StatPearls.
^ Hodges, Frederick Mansfield S.; Denniston, George C.; Milos, Marilyn Fayre (2007). Male and Female Circumcision: Medical, Legal, and Ethical Considerations in Pediatric Practice. Springer US. p. 10. ISBN 978-0-58539-937-9. Retrieved November 24, 2023.
^ Martin, Richard J.; Fanaroff, Avory A.; Walsh, Michele C. (2014). Fanaroff and Martin's Neonatal-Perinatal Medicine E-Book: Diseases of the Fetus and Infant. Elsevier Health Sciences. p. 1522. ISBN 978-0-32329-537-6. Retrieved November 24, 2023.
^ Flück, Christa E.; Güran, Tülay (November 13, 2023). "Ambiguous Genitalia in the Newborn". In Feingold, Kenneth R.; Anawalt, Bradley; Blackman, Marc R; et al. (eds.). Endotext. South Dartmouth, MA: MDText.com, Inc.
^ ^a ^b ^c ^d ^e A, Aatsha P.; Krishan, Kewal (2020-05-30). "Embryology, Sexual Development". StatPearls.
^ ^a ^b Momodu, Ifeanyi; Lee, Brian; Singh, Gurdeep (2021-02-05). "Congenital Adrenal Hyperplasia". StatPearls.
^ Witchel, Selma Feldman (April 2018). "Disorders of sex development". Best Practice & Research Clinical Obstetrics & Gynaecology. 48: 90–102. doi:10.1016/j.bpobgyn.2017.11.005. PMC 5866176. PMID 29503125.
^ ^a ^b Witchel, Selma Feldman (2018). "Disorders of sex development". Best Practice & Research Clinical Obstetrics & Gynaecology. 48: 90–102. doi:10.1016/j.bpobgyn.2017.11.005. PMC 5866176. PMID 29503125.
^ ^a ^b ^c "Klinefelter syndrome - Symptoms and causes". Mayo Clinic. Retrieved 2021-04-01.
^ Gravholt, Claus H; Andersen, Niels H; Conway, Gerard S; Dekkers, Olaf M; Geffner, Mitchell E; Klein, Karen O; Lin, Angela E; Mauras, Nelly; Quigley, Charmian A; Rubin, Karen; Sandberg, David E (2017). "Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting". European Journal of Endocrinology. 177 (3): G1 – G70. doi:10.1530/EJE-17-0430. ISSN 0804-4643. PMID 28705803.
^ Wolffenbuttel, K. P.; Hersmus, R.; Stoop, H.; Biermann, K.; Hoebeke, P.; Cools, M.; Looijenga, L. H. J. (2016-12-12). "Gonadal dysgenesis in disorders of sex development: Diagnosis and surgical management". Journal of Pediatric Urology. 12 (6): 411–416. doi:10.1016/j.jpurol.2016.08.015. ISSN 1873-4898. PMID 27769830.
^ Rogers, Kara (2016-12-05). "Endocrine disruptor | biochemistry". Encyclopedia Britannica. Retrieved 2021-04-13.
^ Peinkofer, Gabriel; Burkert, Karsten; Urban, Katja; Krausgrill, Benjamin; Hescheler, Jürgen; Saric, Tomo; Halbach, Marcel (2016). "From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of Native and Pluripotent Stem Cell-Derived Cardiomyocytes". Stem Cells and Development. 25 (19): 1397–1406. doi:10.1089/scd.2016.0073. ISSN 1547-3287. PMID 27484788.
^ Pal, AsokeK; Ambulkar, PrafullaS; Sontakke, BharatR; Talhar, ShwetaS; Bokariya, Pradeep; Gujar, VijayK (2019). "A study on chromosomal analysis of patients with primary amenorrhea". Journal of Human Reproductive Sciences. 12 (1): 29–34. doi:10.4103/jhrs.JHRS_125_17. ISSN 0974-1208. PMC 6472206. PMID 31007464.
^ ^a ^b Juniarto, A. Zulfa; van der Zwan, Yvonne G.; Santosa, Ardy; Ariani, Mahayu Dewi; Eggers, Stefanie; Hersmus, Remko; Themmen, Axel P.N.; Bruggenwirth, Hennie T.; Wolffenbuttel, Katja P.; Sinclair, Andrew; White, Stefan J. (2016). "Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia". Clinical Endocrinology. 85 (2): 247–257. doi:10.1111/cen.13051. hdl:11343/291143. PMID 26935236. S2CID 20604226.
^ Mareş Miceli, Angelica (2020), Deligdisch-Schor, Liane; Mareş Miceli, Angelica (eds.), "Replacement Hormone Therapy for Gender Dysphoria and Congenital Sexual Anomalies", Hormonal Pathology of the Uterus, Advances in Experimental Medicine and Biology, vol. 1242, Cham: Springer International Publishing, pp. 121–143, doi:10.1007/978-3-030-38474-6_7, ISBN 978-3-030-38474-6, PMID 32406031, retrieved 2023-10-11
^ "Klinefelter Syndrome". Physiopedia. 2020-10-22. Retrieved 2021-04-11.
^ Houk, Christopher P; Baskin, Laurence S; Levitsky, Lynne L (Jan 9, 2021). Geffner, Mitchell E; Hoppin, Alison G (eds.). "Management of the infant with atypical genitalia (disorder of sex development)". UpToDate. Retrieved April 9, 2021.
^ "Supporting yourself - Intersex people". headtohealth.gov.au. 2019-09-24. Retrieved 2021-04-01.

[1] Sreenivasan, R.; Alankarage, D.; Harley, V. (2017-01-01). "Disorders of Sex Development Loci☆". Disorders of Sex Development Loci. Elsevier. doi:10.1016/B978-0-12-809633-8.06552-3. ISBN 9780128096338.

[2] Achermann, John C.; Hughes, Ieuan A. (2016), "Pediatric Disorders of Sex Development", Williams Textbook of Endocrinology, Elsevier, pp. 893–963, doi:10.1016/b978-0-323-29738-7.00023-x, ISBN 978-0-323-29738-7, retrieved 2021-04-01

[:332-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u Guerrero-Fernández, Julio; Azcona San Julián, Cristina; Barreiro Conde, Jesús; Bermúdez de la Vega, José Antonio; Carcavilla Urquí, Atilano; Castaño González, Luis Antonio; Martos Tello, José María; Rodríguez Estévez, Amaya; Yeste Fernández, Diego; Martínez Martínez, Leopoldo; Martínez-Urrutia, María José (2018). "Management guidelines for disorders/different sex development (DSD)". Anales de Pediatría (English Edition). 89 (5): 315.e1–315.e19. doi:10.1016/j.anpede.2018.06.006. PMID 30033107.

[4] "Ambiguous genitalia - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2021-04-01.

[:432-5] ^ ^a ^b ^c ^d ^e ^f ^g Deligdisch-Schor, Liane; Mareş Miceli, Angelica, eds. (2020). Hormonal Pathology of the Uterus. Advances in Experimental Medicine and Biology. Vol. 1242. p. 133. doi:10.1007/978-3-030-38474-6. ISBN 978-3-030-38473-9. ISSN 0065-2598. S2CID 218624824.

[:1-6] Kinter, Kevin; Anekar, Aabha (2021-03-13). "Biochemistry, Dihydrotestosterone". StatPearls.

[7] Hodges, Frederick Mansfield S.; Denniston, George C.; Milos, Marilyn Fayre (2007). Male and Female Circumcision: Medical, Legal, and Ethical Considerations in Pediatric Practice. Springer US. p. 10. ISBN 978-0-58539-937-9. Retrieved November 24, 2023.

[8] Martin, Richard J.; Fanaroff, Avory A.; Walsh, Michele C. (2014). Fanaroff and Martin's Neonatal-Perinatal Medicine E-Book: Diseases of the Fetus and Infant. Elsevier Health Sciences. p. 1522. ISBN 978-0-32329-537-6. Retrieved November 24, 2023.

[9] Flück, Christa E.; Güran, Tülay (November 13, 2023). "Ambiguous Genitalia in the Newborn". In Feingold, Kenneth R.; Anawalt, Bradley; Blackman, Marc R; et al. (eds.). Endotext. South Dartmouth, MA: MDText.com, Inc.

[:0-10] A, Aatsha P.; Krishan, Kewal (2020-05-30). "Embryology, Sexual Development". StatPearls.

[Momodu-11] Momodu, Ifeanyi; Lee, Brian; Singh, Gurdeep (2021-02-05). "Congenital Adrenal Hyperplasia". StatPearls.

[12] Witchel, Selma Feldman (April 2018). "Disorders of sex development". Best Practice & Research Clinical Obstetrics & Gynaecology. 48: 90–102. doi:10.1016/j.bpobgyn.2017.11.005. PMC 5866176. PMID 29503125.

[Witchel_2018_90–102-13] Witchel, Selma Feldman (2018). "Disorders of sex development". Best Practice & Research Clinical Obstetrics & Gynaecology. 48: 90–102. doi:10.1016/j.bpobgyn.2017.11.005. PMC 5866176. PMID 29503125.

[:132-14] "Klinefelter syndrome - Symptoms and causes". Mayo Clinic. Retrieved 2021-04-01.

[15] Gravholt, Claus H; Andersen, Niels H; Conway, Gerard S; Dekkers, Olaf M; Geffner, Mitchell E; Klein, Karen O; Lin, Angela E; Mauras, Nelly; Quigley, Charmian A; Rubin, Karen; Sandberg, David E (2017). "Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting". European Journal of Endocrinology. 177 (3): G1 – G70. doi:10.1530/EJE-17-0430. ISSN 0804-4643. PMID 28705803.

[16] Wolffenbuttel, K. P.; Hersmus, R.; Stoop, H.; Biermann, K.; Hoebeke, P.; Cools, M.; Looijenga, L. H. J. (2016-12-12). "Gonadal dysgenesis in disorders of sex development: Diagnosis and surgical management". Journal of Pediatric Urology. 12 (6): 411–416. doi:10.1016/j.jpurol.2016.08.015. ISSN 1873-4898. PMID 27769830.

[17] Rogers, Kara (2016-12-05). "Endocrine disruptor | biochemistry". Encyclopedia Britannica. Retrieved 2021-04-13.

[18] Peinkofer, Gabriel; Burkert, Karsten; Urban, Katja; Krausgrill, Benjamin; Hescheler, Jürgen; Saric, Tomo; Halbach, Marcel (2016). "From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of Native and Pluripotent Stem Cell-Derived Cardiomyocytes". Stem Cells and Development. 25 (19): 1397–1406. doi:10.1089/scd.2016.0073. ISSN 1547-3287. PMID 27484788.

[19] Pal, AsokeK; Ambulkar, PrafullaS; Sontakke, BharatR; Talhar, ShwetaS; Bokariya, Pradeep; Gujar, VijayK (2019). "A study on chromosomal analysis of patients with primary amenorrhea". Journal of Human Reproductive Sciences. 12 (1): 29–34. doi:10.4103/jhrs.JHRS_125_17. ISSN 0974-1208. PMC 6472206. PMID 31007464.

[:532-20] Juniarto, A. Zulfa; van der Zwan, Yvonne G.; Santosa, Ardy; Ariani, Mahayu Dewi; Eggers, Stefanie; Hersmus, Remko; Themmen, Axel P.N.; Bruggenwirth, Hennie T.; Wolffenbuttel, Katja P.; Sinclair, Andrew; White, Stefan J. (2016). "Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia". Clinical Endocrinology. 85 (2): 247–257. doi:10.1111/cen.13051. hdl:11343/291143. PMID 26935236. S2CID 20604226.

[21] Mareş Miceli, Angelica (2020), Deligdisch-Schor, Liane; Mareş Miceli, Angelica (eds.), "Replacement Hormone Therapy for Gender Dysphoria and Congenital Sexual Anomalies", Hormonal Pathology of the Uterus, Advances in Experimental Medicine and Biology, vol. 1242, Cham: Springer International Publishing, pp. 121–143, doi:10.1007/978-3-030-38474-6_7, ISBN 978-3-030-38474-6, PMID 32406031, retrieved 2023-10-11

[:632-22] "Klinefelter Syndrome". Physiopedia. 2020-10-22. Retrieved 2021-04-11.

[23] Houk, Christopher P; Baskin, Laurence S; Levitsky, Lynne L (Jan 9, 2021). Geffner, Mitchell E; Hoppin, Alison G (eds.). "Management of the infant with atypical genitalia (disorder of sex development)". UpToDate. Retrieved April 9, 2021.

[24] "Supporting yourself - Intersex people". headtohealth.gov.au. 2019-09-24. Retrieved 2021-04-01.

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+{{merge|Disorders of sex development|discuss=Talk:Disorders of sex development #Merge Proposal|date=December 2024}}
-'''Sexual anomalies''', also known as '''sexual abnormalities''', are a set of clinical conditions due to chromosomal, gonadal and/or genitalia variation. Individuals with [[Birth defect|congenital (inborn) discrepancy]] between sex chromosome, gonadal, and the appearance of their external genitalia are categorised as having a [[Disorders of sex development|disorder of sexual development (DSD]])<ref>{{Cite journal|last=Lee|first=P. A.|last2=Houk|first2=C. P.|last3=Ahmed|first3=S. F.|last4=Hughes|first4=I. A.|last5=in collaboration with the participants in the International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology|date=2006-08-01|title=Consensus Statement on Management of Intersex Disorders|url=http://pediatrics.aappublications.org/cgi/doi/10.1542/peds.2006-0738|journal=PEDIATRICS|language=en|volume=118|issue=2|pages=e488–e500|doi=10.1542/peds.2006-0738|issn=0031-4005}}</ref>. Abnormalities that require immediate medical evaluation occur in approximately 1 in 1000 to 4500 live births<ref name=":2">{{Cite journal|last=Hughes|first=Ieuan A.|last2=Nihoul-Fékété|first2=C.|last3=Thomas|first3=B.|last4=Cohen-Kettenis|first4=P.T.|date=2007-2009|title=Consequences of the ESPE/LWPES guidelines for diagnosis and treatment of disorders of sex development|url=https://linkinghub.elsevier.com/retrieve/pii/S1521690X07000553|journal=Best Practice & Research Clinical Endocrinology & Metabolism|language=en|volume=21|issue=3|pages=351–365|doi=10.1016/j.beem.2007.06.003}}</ref><ref>{{Cite journal|last=Blackless|first=Melanie|last2=Charuvastra|first2=Anthony|last3=Derryck|first3=Amanda|last4=Fausto‐Sterling|first4=Anne|last5=Lauzanne|first5=Karl|last6=Lee|first6=Ellen|date=2000|title=How sexually dimorphic are we? Review and synthesis|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291520-6300%28200003/04%2912%3A2%3C151%3A%3AAID-AJHB1%3E3.0.CO%3B2-F|journal=American Journal of Human Biology|language=en|volume=12|issue=2|pages=151–166|doi=10.1002/(SICI)1520-6300(200003/04)12:23.0.CO;2-F|issn=1520-6300}}</ref><ref>{{Cite journal|last=Thyen|first=Ute|last2=Lanz|first2=Kathrin|last3=Holterhus|first3=Paul-Martin|last4=Hiort|first4=Olaf|date=2006|title=Epidemiology and Initial Management of Ambiguous Genitalia at Birth in Germany|url=https://www.karger.com/Article/FullText/94782|journal=Hormone Research in Paediatrics|language=en|volume=66|issue=4|pages=195–203|doi=10.1159/000094782|issn=1663-2818}}</ref><ref>{{Cite journal|last=Sax|first=Leonard|date=2002-08-01|title=How common is lntersex? A response to Anne Fausto‐Sterling|url=https://www.tandfonline.com/doi/full/10.1080/00224490209552139|journal=The Journal of Sex Research|language=en|volume=39|issue=3|pages=174–178|doi=10.1080/00224490209552139|issn=0022-4499}}</ref>. Afterwards, if the family or individual wishes, can partake in different management and treatment options for their conditions (e.g. [[hormone therapy]]).
+'''Sexual anomalies''', also known as '''sexual abnormalities''', are a set of clinical conditions due to [[Chromosome abnormality|chromosomal]], gonadal and/or genitalia variation. Individuals with [[Birth defect|congenital (inborn) discrepancy]] between sex chromosome, gonadal, and their internal and external genitalia are categorised as individuals with a [[Disorders of sex development|disorder of sex development (DSD)]].<ref>{{Cite book|date=2017-01-01|title=Disorders of Sex Development Loci|chapter=Disorders of Sex Development Loci☆ |publisher=Elsevier |chapter-url=https://www.sciencedirect.com/science/article/pii/B9780128096338065523|language=en|doi=10.1016/B978-0-12-809633-8.06552-3|isbn=9780128096338 |last1=Sreenivasan |first1=R. |last2=Alankarage |first2=D. |last3=Harley |first3=V. }}</ref> Afterwards, if the family or individual wishes, they can partake in different management and treatment options for their conditions (e.g. [[hormone therapy]]).
-Infants born with atypical genitalia often cause confusion and distress for the family. They possess a unique set of complicated management issues; so prompt communication and psychosexual support are all-important. The reason for this is because [[psychosexual development]] is influenced by numerous factors that include, but not limited to gender differences in brain structure, [[Gene|genes]] associated with sexual development, prenatal androgen exposure, interactions with family, and cultural and societal factors<ref>{{Citation|last=Achermann|first=John C.|title=Pediatric Disorders of Sex Development|date=2016|url=https://linkinghub.elsevier.com/retrieve/pii/B978032329738700023X|work=Williams Textbook of Endocrinology|pages=893–963|publisher=Elsevier|language=en|doi=10.1016/b978-0-323-29738-7.00023-x|isbn=978-0-323-29738-7|access-date=2021-04-01|last2=Hughes|first2=Ieuan A.}}</ref>. A team of experts, or patient support groups, are usually recommended for cases related to sexual anomalies. This team of experts are usually derived from a variety of disciplines like [[Pediatrics|paediatricians]], [[Neonatology|neonatologists]], paediatric [[urologists]], paediatric [[General surgery|general surgeons]], [[Endocrinologist|endocrinologists]], [[Geneticist|geneticists]], [[radiologists]], [[Psychologist|psychologists]] and [[Social work|social workers]]<ref name=":3">{{Cite journal|last=Guerrero-Fernández|first=Julio|last2=Azcona San Julián|first2=Cristina|last3=Barreiro Conde|first3=Jesús|last4=Bermúdez de la Vega|first4=José Antonio|last5=Carcavilla Urquí|first5=Atilano|last6=Castaño González|first6=Luis Antonio|last7=Martos Tello|first7=José María|last8=Rodríguez Estévez|first8=Amaya|last9=Yeste Fernández|first9=Diego|last10=Martínez Martínez|first10=Leopoldo|last11=Martínez-Urrutia|first11=María José|date=2018|title=Management guidelines for disorders/different sex development (DSD)|url=https://linkinghub.elsevier.com/retrieve/pii/S2341287918301637|journal=Anales de Pediatría (English Edition)|language=en|volume=89|issue=5|pages=315.e1–315.e19|doi=10.1016/j.anpede.2018.06.006}}</ref><ref>{{Cite web|title=Ambiguous genitalia - Diagnosis and treatment - Mayo Clinic|url=https://www.mayoclinic.org/diseases-conditions/ambiguous-genitalia/diagnosis-treatment/drc-20369278|access-date=2021-04-01|website=www.mayoclinic.org}}</ref><ref name=":4">{{Cite journal|date=2020|editor-last=Deligdisch-Schor|editor-first=Liane|editor2-last=Mareş Miceli|editor2-first=Angelica|title=Hormonal Pathology of the Uterus|url=https://doi.org/10.1007/978-3-030-38474-6|journal=Advances in Experimental Medicine and Biology|language=en-gb|doi=10.1007/978-3-030-38474-6|issn=0065-2598}}</ref>.
+Infants born with atypical genitalia often cause confusion and distress for the family. [[Psychosexual development]] is influenced by numerous factors that include, but are not limited to, gender differences in brain structure, [[gene]]s associated with sexual development, prenatal androgen exposure, interactions with family, and cultural and societal factors.<ref>{{Citation|last1=Achermann|first1=John C.|title=Pediatric Disorders of Sex Development|date=2016|url=https://linkinghub.elsevier.com/retrieve/pii/B978032329738700023X|work=Williams Textbook of Endocrinology|pages=893–963|publisher=Elsevier|language=en|doi=10.1016/b978-0-323-29738-7.00023-x|isbn=978-0-323-29738-7|access-date=2021-04-01|last2=Hughes|first2=Ieuan A.}}</ref> Because of the complex and multifaceted factors involved, communication and psychosexual support are all important.
+A team of experts, or patient support groups, are usually recommended for cases related to sexual anomalies. This team of experts are usually derived from a variety of disciplines including [[Pediatrics|pediatricians]], [[Neonatology|neonatologists]], pediatric [[urologists]], pediatric [[General surgery|general surgeons]], [[endocrinologist]]s, [[geneticist]]s, [[radiologists]], [[psychologist]]s and [[social work]]ers.<ref name=":332">{{Cite journal|last1=Guerrero-Fernández|first1=Julio|last2=Azcona San Julián|first2=Cristina|last3=Barreiro Conde|first3=Jesús|last4=Bermúdez de la Vega|first4=José Antonio|last5=Carcavilla Urquí|first5=Atilano|last6=Castaño González|first6=Luis Antonio|last7=Martos Tello|first7=José María|last8=Rodríguez Estévez|first8=Amaya|last9=Yeste Fernández|first9=Diego|last10=Martínez Martínez|first10=Leopoldo|last11=Martínez-Urrutia|first11=María José|date=2018|title=Management guidelines for disorders/different sex development (DSD)|journal=Anales de Pediatría (English Edition)|language=en|volume=89|issue=5|pages=315.e1–315.e19|doi=10.1016/j.anpede.2018.06.006|pmid=30033107 |doi-access=free}}</ref><ref>{{Cite web|title=Ambiguous genitalia - Diagnosis and treatment - Mayo Clinic|url=https://www.mayoclinic.org/diseases-conditions/ambiguous-genitalia/diagnosis-treatment/drc-20369278|access-date=2021-04-01|website=www.mayoclinic.org}}</ref><ref name=":432">{{Cite book|date=2020|editor-last=Deligdisch-Schor|editor-first=Liane|editor2-last=Mareş Miceli|editor2-first=Angelica|title=Hormonal Pathology of the Uterus|url=https://doi.org/10.1007/978-3-030-38474-6|series=Advances in Experimental Medicine and Biology|volume=1242 |language=en-gb|pages=133|doi=10.1007/978-3-030-38474-6|isbn=978-3-030-38473-9 |s2cid=218624824 |issn=0065-2598 }}</ref> These professionals are capable of providing first line (prenatal) and second line diagnostic (postnatal) tests to examine and diagnose sexual anomalies.
 == Overview ==
-[[File:Testosterone.PNG|thumb|Testosterone.]]
+[[File:Testosteron.svg|thumb|'''Chemical structure of testosterone''']]
-In the normal prenatal stages of [[fetal development]], the fetus is exposed to [[testosterone]] - albeit more in male fetus than female. Upon the presence of [[5α-Reductase|5α-reductase enzyme]], testosterone is converted to [[dihydrotestosterone]] (i.e. DHT).
+In the normal prenatal stages of [[fetal development]], the fetus is exposed to [[testosterone]] - albeit more in male fetuses than female ones. Upon the presence of the [[5α-Reductase|5α-reductase enzyme]], testosterone is converted to [[dihydrotestosterone]] (i.e. DHT). If DHT is present, the male external genitalia will develop.
-If DHT is present, male external genitalia will develop. The [[genital tubercle]] forms the [[penis]], urethral folds form the [[urethra]] and [[genital swelling]] forms the [[scrotum]]<ref name=":0">{{Cite journal|last=Blaschko|first=Sarah D.|last2=Cunha|first2=Gerald R.|last3=Baskin|first3=Laurence S.|date=2012|title=Molecular mechanisms of external genitalia development|url=https://linkinghub.elsevier.com/retrieve/pii/S0301468112000862|journal=Differentiation|language=en|volume=84|issue=3|pages=261–268|doi=10.1016/j.diff.2012.06.003|pmc=PMC3443292|pmid=22790208}}</ref>.
-On the other hand, if DHT is not present and maternal [[placenta]] [[estrogen]] is, then the development of female external genitalia occurs<ref name=":0" />. The genital tubercle forms the [[clitoris]], the urethral folds form the [[labia minora]] and the [[genital swelling]] forms the [[labia majora]]<ref name=":0" />.
-However, in abnormal cases, sexual anomalies occur due to a variety of factors that lead to an excess of [[Androgen|androgens]] in the fetus. The effects of excessive androgens differ in fetuses with XX chromosome and XY chromosomes.
-In XX chromosome fetuses, excess androgens result in a functional and average sized penis with extreme [[Virilization|virilisation]], but the inability for [[sperm production]]<ref name=":0" />. Additionally, the individual will also experience early and rapid growth of pubic hair during childhood and precocious puberty stages<ref name=":0" />.
-[[File:5β-Dihydrotestosterone.svg|thumb|Dihydrotestosterone.]]
-In XY chromosome fetuses, excess androgens result in [[ambiguous genitalia]]. This makes identification of external genitalia as male or female difficult<ref name=":0" />. Additionally, the individual may have [[clitoromegaly]], a shallow [[vagina]], early and rapid growth of pubic hair in childhood, [[delayed puberty]], [[hirsutism]], [[Virilization|virilisation]], [[irregular menstrual cycle]] in adolescence and infertility due to [[anovulation]]<ref name=":0" />.
+Development of male external genitalia:
+* [[Genital tubercle]] forms the [[Human penis|penis]]<ref name=":1">{{Cite journal|last1=Kinter|first1=Kevin|last2=Anekar|first2=Aabha|date=2021-03-13|title=Biochemistry, Dihydrotestosterone|url=https://www.statpearls.com/ArticleLibrary/viewarticle/20527|journal=StatPearls|language=en}}</ref>
+* [[Development of the reproductive system#External genitalia|Urethral folds]] form the [[penile raphe]]<ref>{{cite book|last1=Hodges|first1=Frederick Mansfield S.|last2=Denniston|first2=George C.|last3=Milos|first3=Marilyn Fayre|publisher=Springer US|year= 2007|title=Male and Female Circumcision: Medical, Legal, and Ethical Considerations in Pediatric Practice|page=10|access-date=November 24, 2023|isbn=978-0-58539-937-9|url=https://books.google.com/books?id=U0EyBwAAQBAJ&pg=PA10}}</ref><ref>{{cite book|last1=Martin|first1=Richard J.|last2=Fanaroff|first2=Avory A.|last3=Walsh| first3=Michele C.|publisher=Elsevier Health Sciences|year=2014|title=Fanaroff and Martin's Neonatal-Perinatal Medicine E-Book: Diseases of the Fetus and Infant|page=1522|access-date=November 24, 2023|isbn=978-0-32329-537-6|url=https://books.google.com/books?id=AnVYBAAAQBAJ&pg=PA1522}}</ref>
+* [[Genital swelling]]s form the [[scrotum]]<ref name=":1" />
+On the other hand, if maternal [[placenta]] [[estrogen]] is present without DHT, then the development of female external genitalia occurs.<ref>{{cite book |last1=Flück |first1=Christa E. |last2=Güran |first2=Tülay |editor-last1=Feingold |editor-first1=Kenneth R. |editor-last2=Anawalt |editor-first2=Bradley |editor-last3=Blackman |editor-first3=Marc R |editor-last4=Boyce |editor-first4=Allison |display-editors=3 |date=November 13, 2023 |title=Endotext |chapter=Ambiguous Genitalia in the Newborn |url=https://www.ncbi.nlm.nih.gov/books/NBK278943/ |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK279168/ |location=[[Dartmouth, Massachusetts|South Dartmouth]], MA |publisher=MDText.com, Inc. }}</ref>
+Development of female external genitalia (the [[vulva]]):
+* [[Genital tubercle]] forms the [[clitoris]]<ref name=":0">{{Cite journal|last1=A|first1=Aatsha P.|last2=Krishan|first2=Kewal|date=2020-05-30|title=Embryology, Sexual Development|url=https://www.statpearls.com/ArticleLibrary/viewarticle/28946|journal=StatPearls|language=en}}</ref>
+* [[Development of the reproductive system#External genitalia|Urethral folds]] form the [[labia minora]]<ref name=":0" />
+* [[Genital swelling]]s form the [[labia majora]]<ref name=":0" />
+ [[File:5β-Dihydrotestosterone.svg|thumb|'''Chemical structure of dihydrotestosterone (DHT)''']]
+However, in abnormal cases, sexual anomalies occur due to a variety of factors that lead to an excess of [[androgen]]s in the fetus. The effects of excessive androgens differ in fetuses with XX chromosome (female) and XY chromosomes (male).
+In XX chromosome fetuses, excess androgens result in [[ambiguous genitalia]]. This makes identification of external genitalia as male or female difficult.<ref name=":0" /> Additionally, the individual may have [[clitoromegaly]], a shallow [[vagina]], early and rapid growth of pubic hair in childhood, [[delayed puberty]], [[hirsutism]], [[Virilization|virilisation]], [[irregular menstrual cycle]] in adolescence and infertility due to [[anovulation]].<ref name="Momodu">{{Cite journal|last1=Momodu|first1=Ifeanyi|last2=Lee|first2=Brian|last3=Singh|first3=Gurdeep|date=2021-02-05|title=Congenital Adrenal Hyperplasia|url=https://www.statpearls.com/ArticleLibrary/viewarticle/17229|journal=StatPearls|language=en}}</ref>
+In XY chromosome fetuses, excess androgens result in a functional and average-sized penis with extreme [[Virilization|virilisation]], but the inability for [[sperm production]].<ref>{{Cite journal|last=Witchel|first=Selma Feldman|date=April 2018|title=Disorders of sex development|journal=Best Practice & Research Clinical Obstetrics & Gynaecology|language=en|volume=48|pages=90–102|doi=10.1016/j.bpobgyn.2017.11.005|pmc=5866176|pmid=29503125}}</ref> Additionally, the individual will also experience early and rapid growth of pubic hair during childhood and precocious puberty stages.<ref name="Momodu"/>
 == Classification ==
-Differences/[[Disorders of sex development|disorders of sexual development (DSD)]] are classified into different categories: [[Chromosome|chromosomal]] variation, [[Gonad|gonadal]] development disorders, abnormal [[genital]] development and others.
+Differences/[[Disorders of sex development|disorders of sexual development (DSD)]] are classified into different categories: chromosomal variation, gonadal development disorders, abnormal genital development and others.
 === Chromosomal variation ===
-[[File:Klinefelter's syndrome.jpg|thumb|Klinefelter's syndrome.]]
+[[File:Klinefelter's_syndrome.jpg|thumb|'''The symptoms of [[Klinefelter's syndrome]] in a human male.''']]
-DSDs caused by chromosomal variation generally do not present with genital ambiguity. This includes sex chromosome DSDs such as [[Klinefelter syndrome]], [[Turner syndrome]] and 45, X or 46, XY [[gonadal dysgenesis]]<ref>{{Cite journal|last=Witchel|first=Selma Feldman|date=2018|title=Disorders of sex development|url=https://linkinghub.elsevier.com/retrieve/pii/S1521693417301955|journal=Best Practice & Research Clinical Obstetrics & Gynaecology|language=en|volume=48|pages=90–102|doi=10.1016/j.bpobgyn.2017.11.005|pmc=PMC5866176|pmid=29503125}}</ref>.
+DSDs caused by chromosomal variation generally do not present with genital ambiguity. This includes sex chromosome DSDs such as [[Klinefelter syndrome]], [[Turner syndrome]] and 45,X or 46,XY [[gonadal dysgenesis]].<ref name="Witchel 2018 90–102">{{Cite journal|last=Witchel|first=Selma Feldman|date=2018|title=Disorders of sex development|journal=Best Practice & Research Clinical Obstetrics & Gynaecology|language=en|volume=48|pages=90–102|doi=10.1016/j.bpobgyn.2017.11.005|pmc=5866176|pmid=29503125}}</ref>
-Males with Klinefelter syndrome usually have a [[karyotype]] of 47, XXY as a result of having 2 or more X [[Chromosome|chromosomes]]<ref name=":1">{{Cite web|title=Klinefelter syndrome - Symptoms and causes|url=https://www.mayoclinic.org/diseases-conditions/klinefelter-syndrome/symptoms-causes/syc-20353949|access-date=2021-04-01|website=Mayo Clinic|language=en}}</ref>. Affected patients generally have normal genital development, yet are infertile and suffer from small, poor functioning [[Testicle|testes]], [[breast growth]] and delayed puberty<ref name=":1" />. The incidence for 47, XXY is 1 in 500 males, but more severe and rarer cases of Klinefelter syndrome are when 3 or more X chromosomes are present<ref name=":1" />.
+Males with Klinefelter syndrome usually have a [[karyotype]] of 47,XXY as a result of having two or more X [[chromosome]]s.<ref name=":132">{{Cite web|title=Klinefelter syndrome - Symptoms and causes|url=https://www.mayoclinic.org/diseases-conditions/klinefelter-syndrome/symptoms-causes/syc-20353949|access-date=2021-04-01|website=Mayo Clinic|language=en}}</ref> Affected patients generally have normal genital development, yet are infertile and have small, poor functioning [[Testicle|testes]], [[breast development|breast growth]] and delayed puberty.<ref name=":132" /> The incidence for 47,XXY is 1 in 500 males, but severe and rare cases of Klinefelter syndrome presents as three or more X chromosomes.<ref name=":132" />
-Turner syndrome is classified as [[aneuploidy]] or structural rearrangement of X chromosome. Signs and symptoms of affected females vary among them, such as low birth weight, low-set ears, short stature, short neck and delayed puberty<ref>{{Cite journal|last=Gravholt|first=Claus H|last2=Andersen|first2=Niels H|last3=Conway|first3=Gerard S|last4=Dekkers|first4=Olaf M|last5=Geffner|first5=Mitchell E|last6=Klein|first6=Karen O|last7=Lin|first7=Angela E|last8=Mauras|first8=Nelly|last9=Quigley|first9=Charmian A|last10=Rubin|first10=Karen|last11=Sandberg|first11=David E|date=2017|title=Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting|url=https://eje.bioscientifica.com/view/journals/eje/177/3/EJE-17-0430.xml|journal=European Journal of Endocrinology|volume=177|issue=3|pages=G1–G70|doi=10.1530/EJE-17-0430|issn=0804-4643}}</ref>. The incidence is 1 in 2500 live-born females, while most patients do not survive for more than 1 year after birth<ref>{{Cite journal|last=Witchel|first=Selma Feldman|date=2018|title=Disorders of sex development|url=https://linkinghub.elsevier.com/retrieve/pii/S1521693417301955|journal=Best Practice & Research Clinical Obstetrics & Gynaecology|language=en|volume=48|pages=90–102|doi=10.1016/j.bpobgyn.2017.11.005|pmc=PMC5866176|pmid=29503125}}</ref>.
+Turner syndrome is classified as [[aneuploidy]] or structural rearrangement of the X chromosome. Signs and symptoms of affected females vary among them, such as low birth weight, low-set ears, short stature, short neck and delayed puberty.<ref>{{Cite journal|last1=Gravholt|first1=Claus H|last2=Andersen|first2=Niels H|last3=Conway|first3=Gerard S|last4=Dekkers|first4=Olaf M|last5=Geffner|first5=Mitchell E|last6=Klein|first6=Karen O|last7=Lin|first7=Angela E|last8=Mauras|first8=Nelly|last9=Quigley|first9=Charmian A|last10=Rubin|first10=Karen|last11=Sandberg|first11=David E|date=2017|title=Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting|url=https://eje.bioscientifica.com/view/journals/eje/177/3/EJE-17-0430.xml|journal=European Journal of Endocrinology|volume=177|issue=3|pages=G1–G70|doi=10.1530/EJE-17-0430|pmid=28705803 |issn=0804-4643|doi-access=free}}</ref> The incidence is 1 in 2500 live-born females, while most patients do not survive for more than one year after birth.<ref name="Witchel 2018 90–102"/>
 === Gonadal development disorders ===
-Gonadal development disorders form a wide spectrum, classified by their [[Cytogenetics|cytogenetic]] and [[Histopathology|histopathological]] features. However, unsolved diagnosis and [[malignancy]] still cause difficulties in sex determination of these patients<ref>{{Cite journal|last=Siklar|first=Zeynep|last2=Berberoğlu|first2=Merih|last3=Adiyaman|first3=Pelin|last4=Salih|first4=Mustafa|last5=Tükün|first5=Ajlan|last6=Cetinkaya|first6=Ergun|last7=Aycan|first7=Zehra|last8=Evliyaoğlu|first8=Olcay|last9=Ergur|first9=Ayça T.|last10=Oçal|first10=Gönül|date=2007|title=Disorders of gonadal development: a broad clinical, cytogenetic and histopathologic spectrum|url=https://pubmed.ncbi.nlm.nih.gov/17551482|journal=Pediatric endocrinology reviews: PER|volume=4|issue=3|pages=210–217|issn=1565-4753|pmid=17551482}}</ref>. Such disorders include partial or complete gonadal dysgenesis, [[Ovotesticular disorder|ovotesticular]] DSD, testicular DSD and sex reversal<ref name=":3" />.
+Gonadal development disorders form a wide spectrum, classified by their [[Cytogenetics|cytogenetic]] and [[Histopathology|histopathological]] features. However, unsolved diagnosis and [[malignancy]] still represent difficulties in the sex determination of these patients.<ref>{{Cite journal|last1=Wolffenbuttel|first1=K. P.|last2=Hersmus|first2=R.|last3=Stoop|first3=H.|last4=Biermann|first4=K.|last5=Hoebeke|first5=P.|last6=Cools|first6=M.|last7=Looijenga|first7=L. H. J.|date=2016-12-12|title=Gonadal dysgenesis in disorders of sex development: Diagnosis and surgical management|url=https://pubmed.ncbi.nlm.nih.gov/27769830/|journal=Journal of Pediatric Urology|volume=12|issue=6|pages=411–416|doi=10.1016/j.jpurol.2016.08.015|issn=1873-4898|pmid=27769830}}</ref> Such disorders include partial or complete gonadal dysgenesis, [[Ovotesticular disorder|ovotesticular]] DSD, [[testicular]] DSD and [[sex reversal]].<ref name=":332" />
 === Abnormal genital development ===
-Genital abnormality can occur in the penis, scrotum or testes in males; vagina and labia in females<ref name=":3" />. Sometimes, ambiguous genitalia could occur, of which the external genitalia do not appear to be male or female clearly. Hence, examination, usually at birth, is done and the sex of the patient will be determined through [[Imaging biomarker|imaging]] and [[Blood test|blood tests]]<ref name=":3" />. Abnormal genital development includes disorders of foetal origin, disorders in androgen synthesis or action, disorders in [[anti-Müllerian hormone]] synthesis or action<ref>{{Cite journal|date=2018-11-01|title=Management guidelines for disorders/different sex development (DSD)|url=https://www.sciencedirect.com/science/article/pii/S2341287918301637|journal=Anales de Pediatría (English Edition)|language=en|volume=89|issue=5|pages=315.e1–315.e19|doi=10.1016/j.anpede.2018.06.006|issn=2341-2879}}</ref>.
+Genital abnormality can occur in the penis, scrotum or testes in males; and vagina and labia in females.<ref name=":332" /> Sometimes, ambiguous genitalia could occur, where the clear distinction of external genitalia is absent in both male and female. Hence, examination (typically at birth) is carried out where the sex of the patient will be determined through [[Imaging biomarker|imaging]] and [[blood test]]s.<ref name=":332" /> Abnormal genital development includes disorders of fetal origin, disorders in androgen synthesis or action, disorders in [[anti-Müllerian hormone]] synthesis or action.<ref name=":332" />
 === Others ===
+In addition to the aforementioned sexual anomalies, there are other unclassified sexual anomalies. In males, this includes severe early-onset [[intrauterine growth restriction]], isolated [[hypospadias]], [[congenital hypogonadotropic hypogonadism]], [[hypogonadism]] and [[cryptorchidism]]. In females, this includes [[Malformation syndrome]]s, [[Müllerian agenesis]]/[[hypoplasia]], [[Uterine malformation|uterine anomalies]], [[vaginal atresia]] and [[labial adhesions]].<ref name=":332" />
-These other anomalies are not classified in the above categories, which includes:
-Severe early-onset [[intrauterine]] growth restriction, isolated [[hypospadias]], [[Congenital hypogonadotropic hypogonadism|congenital hypogonadotropic]], [[hypogonadism]] and [[cryptorchidism]] in males; [[Malformation syndrome|Malformation syndromes]], [[Müllerian agenesis]]/[[Hypoplasia|hypoplasia,]] Uterine anomalies, [[vaginal atresia]] and [[labial adhesions]] in females<ref name=":3" />.
 == Causes ==
-Sexual anomalies are often caused by [[genetic]] reasons. There are many factors that may affect the genes of an individual leading to different sexual development. These genetic abnormalities stem from the prenatal stage of the individual as a result of their genetics but can also have secondary maternal factors resulting from hormones such as [[Endocrine disruptor|endocrine-disrupting chemicals]] (EDCs) or environmental factors<ref>{{Cite journal|last=Hood|first=Ernie|date=2005|title=Are EDCs Blurring Issues of Gender?|url=https://ehp.niehs.nih.gov/doi/10.1289/ehp.113-a670|journal=Environmental Health Perspectives|language=en|volume=113|issue=10|doi=10.1289/ehp.113-a670|issn=0091-6765|pmc=PMC1281309|pmid=16203228}}</ref>. The general causes of sexual anomalies can not be outlined due to the high variability of each individual's situations, thus the cause of each specific anomaly has to be studied independently.
+Sexual anomalies often generate from [[genetics|genetic]] abnormalities caused by many factors, leading to different sexual development. These genetic abnormalities occur during the prenatal stage of an individual's fetal development. During this stage, genetic mutations can result from endocrine disrupters in the mother's diet or environmental factors.<ref>{{Cite web|last=Rogers|first=Kara|date=2016-12-05|title=Endocrine disruptor {{!}} biochemistry|url=https://www.britannica.com/science/endocrine-disruptor|access-date=2021-04-13|website=Encyclopedia Britannica|language=en}}</ref> The general causes of sexual anomalies can not be outlined due to the high variability of each individual's situations. Thus, the cause of each specific anomaly has to be studied independently.
+Sexual differentiation occurs through various processes during the prenatal development period of the fetus. These processes are initiated and regulated by biological metabolites such as [[DNA]], [[hormone]]s and [[protein]]s. The initial steps of sexual differentiation begin with the development of the gonads and genitals. This process is consistent with both genders spanning over the course of the first 6 weeks following conception, during which the embryo remains [[Cell potency|pluripotent]].<ref>{{Cite journal|last1=Peinkofer|first1=Gabriel|last2=Burkert|first2=Karsten|last3=Urban|first3=Katja|last4=Krausgrill|first4=Benjamin|last5=Hescheler|first5=Jürgen|last6=Saric|first6=Tomo|last7=Halbach|first7=Marcel|date=2016|title=From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of Native and Pluripotent Stem Cell-Derived Cardiomyocytes|url=https://www.liebertpub.com/doi/10.1089/scd.2016.0073|journal=Stem Cells and Development|language=en|volume=25|issue=19|pages=1397–1406|doi=10.1089/scd.2016.0073|pmid=27484788 |issn=1547-3287}}</ref> Differentiation of the gonads begins after the 6th week, which is determined by the [[sex-determining region Y]] (SRY) gene in the Y chromosome.<ref name=":0"/>
-Sexual differentiation occurs during the prenatal development of a fetus. This consists of various processes which are initiated and regulated by biological metabolites such as [[DNA]], [[Hormone|hormones]] and [[Protein|proteins]]. The initial steps of sexual differentiation begin with the development of the gonads and genitals and this process is consistent with both genders spanning over the course of the first 6 weeks following conception. During this time the embryo remains pluripotent<ref>{{Cite journal|last=Peinkofer|first=Gabriel|last2=Burkert|first2=Karsten|last3=Urban|first3=Katja|last4=Krausgrill|first4=Benjamin|last5=Hescheler|first5=Jürgen|last6=Saric|first6=Tomo|last7=Halbach|first7=Marcel|date=2016|title=From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of Native and Pluripotent Stem Cell-Derived Cardiomyocytes|url=https://www.liebertpub.com/doi/10.1089/scd.2016.0073|journal=Stem Cells and Development|language=en|volume=25|issue=19|pages=1397–1406|doi=10.1089/scd.2016.0073|issn=1547-3287}}</ref>. Differentiation of the gonads begins after the 6th week and the major regulatory gene controlling this process is the [[sex-determining region Y]] (SRY) gene which remains in the Y chromosome<ref>{{Citation|last=Rey|first=Rodolfo|title=Sexual Differentiation|date=2000|url=http://www.ncbi.nlm.nih.gov/books/NBK279001/|work=Endotext|editor-last=Feingold|editor-first=Kenneth R.|place=South Dartmouth (MA)|publisher=MDText.com, Inc.|pmid=25905232|access-date=2021-04-01|last2=Josso|first2=Nathalie|last3=Racine|first3=Chrystèle|editor2-last=Anawalt|editor2-first=Bradley|editor3-last=Boyce|editor3-first=Alison|editor4-last=Chrousos|editor4-first=George}}</ref>. The SRY gene plays an important role in developing the testes of a male individual. Following its development, hormones synthesized within the testes regulate the differentiation of both internal and external parts of the genitals. The absence of the testicles or the hormones synthesized may lead to irregular differentiation of the genitals. Genetic abnormalities or environmental factors that influence these procedures may lead to the incomplete development of the gonads, the internal parts of the genitals and/or the external parts of the genitals. These malformations can occur any time from the development or the birth of the embryo, being interpreted as ambiguous genitals or dissonance within the genotypic and phenotypic sex of the individual leading to a late onset of  puberty, amenorrhea, a lack of or excess virilization, or later in life, resulting in infertility or an early occurrence of [[menopause]]<ref>{{Cite journal|last=Pal|first=AsokeK|last2=Ambulkar|first2=PrafullaS|last3=Sontakke|first3=BharatR|last4=Talhar|first4=ShwetaS|last5=Bokariya|first5=Pradeep|last6=Gujar|first6=VijayK|date=2019|title=A study on chromosomal analysis of patients with primary amenorrhea|url=http://www.jhrsonline.org/text.asp?2019/12/1/29/255777|journal=Journal of Human Reproductive Sciences|language=en|volume=12|issue=1|pages=29|doi=10.4103/jhrs.JHRS_125_17|issn=0974-1208|pmc=PMC6472206|pmid=31007464}}</ref>.
+The SRY gene plays an important role in developing the testes of a male individual. Following the development of the testes, hormones synthesized within the testes regulate the differentiation of both internal and external parts of the genitals. The absence of the testicles or the hormones synthesized may lead to irregular differentiation of the genitals. Genetic abnormalities or environmental factors that influence these procedures may lead to the incomplete development of the gonads and the genitals. These malformations can occur any time during the development or the birth of the embryo, manifesting as ambiguous genitals or dissonance within the genotypic and phenotypic sex of the individual, leading to a late onset of puberty, amenorrhea, a lack of or excess virilization, or later in life, infertility or early occurrence of [[menopause]].<ref>{{Cite journal|last1=Pal|first1=AsokeK|last2=Ambulkar|first2=PrafullaS|last3=Sontakke|first3=BharatR|last4=Talhar|first4=ShwetaS|last5=Bokariya|first5=Pradeep|last6=Gujar|first6=VijayK|date=2019|title=A study on chromosomal analysis of patients with primary amenorrhea|url=http://www.jhrsonline.org/text.asp?2019/12/1/29/255777|journal=Journal of Human Reproductive Sciences|language=en|volume=12|issue=1|pages=29–34|doi=10.4103/jhrs.JHRS_125_17|issn=0974-1208|pmc=6472206|pmid=31007464 |doi-access=free }}</ref>
 == Diagnosis and symptoms ==
-=== First line diagnostic tests (pre-natal) ===
+=== First line diagnostic tests (prenatal) ===
+[[File:Human male karyotype.gif|thumb|236x236px|'''Human male karyotype''']]
 ==== Family history ====
+* Symptoms such as infertility, early menopause, [[amenorrhea]] or [[Sudden infant death syndrome|sudden infant death syndrome (SIDS)]] could be a sign. Hence, an early check-up should be conducted.<ref name=":332" />
-* Symptoms such as infertility, early menopause, [[amenorrhea]] or [[Sudden infant death syndrome|sudden infant death syndrome (SIDS)]] could be a sign and early check-up should be done<ref name=":3" />.
-[[File:Human male karyotype.gif|thumb|236x236px|Human karyotype (male).]]
 ==== Analysis of karyotype ====
+* Peripheral blood is collected for karyotyping. This helps classify the patient in one of the three main categories of DSD: chromosomal variation, gonadal development disorders and abnormal genital development.<ref name=":332" />
-* Peripheral blood is collected for karyotyping, and it helps classify the patient in one of the 3 main categories of DSD: Chromosomal variation, gonadal development disorders and abnormal genital development. FISH analysis can be supplemented through the use of sex chromosome specific probes<ref name=":3" />.
 ==== Abdominal ultrasounds ====
+* The presence of gonads, uterus and vagina should be monitored. This can be done through abdominal ultrasounds. However, the absence of these sex organs will lead to difficulties in gender identification.<ref name=":332" />
+=== Second line diagnostic tests (postnatal) ===
-* The presence of gonads, uterus and vagina should be monitored, and can be done through abdominal ultrasounds. However, the lack of detection of such organs does not ensure their absence due to the difficulties in identification<ref name=":3" />.
+==== Physical Examination ====
-=== Second line diagnostic tests (post-natal) ===
+# Inspection of the genitalia with care and palpation must be conducted with the following points in mind.<ref name=":332" />
-==== Physical Examination<ref name=":3" /> ====
+#* Determining the degree of [[virilization]] or [[masculinisation]]:
+#** In a female fetus, the [[Prader scale]] should be used to assess the extent of the [[Virilization|virilisation]] if the karyotyping results are not out yet.<ref name=":332" />
+#** In males, the [[Quigley scale|external masculinization score]] should be used.<ref name=":332" />
+# Palpation of gonads from the [[Labioscrotal folds|labioscrotal fold]] to the [[abdomen]] ([[inguinal canal]]).<ref name=":332" />
+# Hydration and blood pressure assessment should be conducted.<ref name=":332" />
+# Additional dysmorphic features should be ruled out because genitalia malformations would occur if the patient has multiple malformation syndromes.<ref name=":332" />
+==== Evaluation of hormones 48 hours after birth ====
-* Inspection of the genitalia with care and palpation must be done, bearing the following points in mind.
+* [[17α-Hydroxyprogesterone|17-Hydroxyprogesterone]] can be used to screen for c[[Congenital adrenal hyperplasia|ongenital adrenal hyperplasia (CAH)]]. This is commonly found in patients with 46, XX DSD.<ref name=":332" /><ref name=":532">{{Cite journal|last1=Juniarto|first1=A. Zulfa|last2=van der Zwan|first2=Yvonne G.|last3=Santosa|first3=Ardy|last4=Ariani|first4=Mahayu Dewi|last5=Eggers|first5=Stefanie|last6=Hersmus|first6=Remko|last7=Themmen|first7=Axel P.N.|last8=Bruggenwirth|first8=Hennie T.|last9=Wolffenbuttel|first9=Katja P.|last10=Sinclair|first10=Andrew|last11=White|first11=Stefan J.|date=2016|title=Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia|url=http://doi.wiley.com/10.1111/cen.13051|journal=Clinical Endocrinology|language=en|volume=85|issue=2|pages=247–257|doi=10.1111/cen.13051|pmid=26935236 |hdl=11343/291143 |s2cid=20604226 |hdl-access=free}}</ref>
-** Determining the degree of [[virilization]] or [[masculinisation]]:
+* Dehydroepiandrosterone (DHEA) in addition to progesterone allows for the diagnosis of more uncommon forms of CAH and other inherited disorders.<ref name=":332" />
-***In females, the [[Prader scale|Prader staging system]] should be used if the karyotyping.
+* Base [[testosterone]], [[Follicle-stimulating hormone|follicle stimulating hormone]] (FSH) and [[Luteinizing hormone|luteinising hormone]] (LH) levels are precursors in individuals with 46,XX DSD. These tests are conducted within the timeframe of thirty hours post-birth to anywhere between fifteen and ninety days post-birth. This data collected within time frame can be used to gauge the growth of the fetus when it reaches six months of age.<ref name=":332" /><ref name=":532" />
-***In males, the [[Quigley scale|external masculinization score]] should be used.
+* Basal [[cortisol]] levels and [[adrenocorticotropic hormone]] (ACTH) is essential in diagnosing [[panhypopituitarism]] and [[enzymatic]] disorders affecting adrenal steroidogenesis.<ref name=":332" />
-*Palpation of gonads from the labioscrotal fold to the [[abdomen]] ([[inguinal canal]]).
+* The [[anti-Müllerian hormone]] is used for evaluating the function of Sertoli cells.<ref name=":332" />
-*Hydration and blood pressure assessment should be done.
+* A urinary steroid profile shows the ratio of precursor metabolites within measured urine concentrations and the resultant products produced indicates the enzyme is the cause of a sexual defect. This is a more specific procedure in the detection of the defect in comparison to analysing blood.<ref name=":332" />
-*Additional dysmorphic features should be ruled out, as genitalia malformations would occur if the patient suffers from multiple malformation syndromes.
-==== Evaluation of hormones 48 hours after birth<ref name=":3" /> ====
-* [[17α-Hydroxyprogesterone|17-Hydroxyprogesterone]] - Screens for c[[Congenital adrenal hyperplasia|ongenital adrenal hyperplasia (CAH)]], commonly found in patients with 46, XX DSD. The hormone levels of newborn children with bilateral [[cryptorchidism]] or genital ambiguity<ref name=":5">{{Cite journal|last=Juniarto|first=A. Zulfa|last2=van der Zwan|first2=Yvonne G.|last3=Santosa|first3=Ardy|last4=Ariani|first4=Mahayu Dewi|last5=Eggers|first5=Stefanie|last6=Hersmus|first6=Remko|last7=Themmen|first7=Axel P.N.|last8=Bruggenwirth|first8=Hennie T.|last9=Wolffenbuttel|first9=Katja P.|last10=Sinclair|first10=Andrew|last11=White|first11=Stefan J.|date=2016|title=Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia|url=http://doi.wiley.com/10.1111/cen.13051|journal=Clinical Endocrinology|language=en|volume=85|issue=2|pages=247–257|doi=10.1111/cen.13051}}</ref>.
-* Dehydroepiandrosterone (DHEA) in addition to progesterone allows for the diagnosis of a more uncommon form of CAH and other inherited disorders.
-* Base testosterone, [[Follicle-stimulating hormone|follicle stimulating hormone]] (FSH) and [[Luteinizing hormone|luteinising hormone]] (LH) levels are precursors in individuals with 46, XX DSD. Tests are conducted within 36 hours after birth and/or 15-90 days post birth<ref name=":5" />. The testing time frame is amplified to 6 months of age<ref name=":5" />.
-* Basal cortisol levels and [[adrenocorticotropic hormone]] (ACTH) is essential in diagnosing panhypopituitarism and enzymatic disorders affecting adrenal steroidogenesis.
-* Anti Mullerian Hormone - Used for evaluating the function of Sertoli cells<ref name=":3" />.
-* A urinary steroid profile shows the ratio of precursor metabolites within measured urine concentrations and the resultant products produced with the enzyme causing the sexual defect. This is a more specific procedure in the detection of the defect in comparison to analysing blood<ref name=":3" />.
-== Implications ==
-People who live with conditions regarding sexual abnormalities may encounter various mental and physical health problems. This may include traumatic experience with their own bodies, dissatisfaction with body image, low-self esteem, anxiety, depression, reproduction problems, impaired psychosexual development, declined sexual function, social isolation etc.<ref>{{Cite web|title=Supporting yourself - Intersex people|url=https://headtohealth.gov.au/supporting-yourself/support-for/intersex|access-date=2021-04-01|website=headtohealth.gov.au|language=en}}</ref><ref name=":6">{{Cite journal|last=Morel-Journel|first=N.|last2=Courtois|first2=F.|last3=Paparel|first3=P.|last4=Ruffion|first4=A.|last5=Carrier|first5=S.|last6=Leriche|first6=A.|date=2009-04-01|title=Reconstructive surgery for major sexual congenital anomalies in adults|url=https://www.sciencedirect.com/science/article/pii/S1158136009000401|journal=Sexologies|series=Disability and sexuality / Traumatismes sexuels et réhabilitation|language=en|volume=18|issue=2|pages=98–104|doi=10.1016/j.sexol.2009.01.013|issn=1158-1360}}</ref>.
 == Treatment and management ==
-The treatment and/or management of DSDs with atypical genitalia will vary from person-to-person.
+The treatment and/or management of DSDs with atypical genitalia will vary from person to person. This may include [[gender affirmation surgery]], medical treatment and surgical treatment.
-=== Gender assignment ===
+=== Gender affirmation surgery ===
+{{main|Gender affirmation surgery}}
-Gender assignment plays a critical role in the management of sexual anomaly cases. Ultimately, the parents and a multidisciplinary team are responsible for assigning the gender. The current guidelines of gender assignment include the psychosocial effects in adults with [[Etiology|etiological]] diagnosis, the potential for fertility, surgical opportunities and hormone replacement therapy in the course of puberty<ref name=":4" />.
+Gender affirmation plays a critical role in the management of sexual anomaly cases. Ultimately, the parents and a multidisciplinary team are responsible for assigning the sex that is affirmative the gender of the concerned person. The current guidelines of gender affirmation include the psychosocial effects in adults with etiological diagnosis, the potential for fertility, surgical opportunities and hormone replacement therapy in the course of puberty.<ref>{{Citation |last=Mareş Miceli |first=Angelica |title=Replacement Hormone Therapy for Gender Dysphoria and Congenital Sexual Anomalies |date=2020 |url=https://doi.org/10.1007/978-3-030-38474-6_7 |work=Hormonal Pathology of the Uterus |pages=121–143 |editor-last=Deligdisch-Schor |editor-first=Liane |access-date=2023-10-11 |series=Advances in Experimental Medicine and Biology |volume=1242 |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-030-38474-6_7 |pmid=32406031 |isbn=978-3-030-38474-6 |editor2-last=Mareş Miceli |editor2-first=Angelica}}</ref><ref name=":432" />
-There are other factors considered during this process. This may include cultural and religious factors as well as the implications it has on the individual in later life. It is regulated by reference centers with groups specialised in managing cases of sexual anomalies<ref name=":4" />.
+There are other factors considered during this process. This may include cultural and religious factors as well as the implications it has on the individual in later life. It is regulated by reference centers with groups specialised in managing cases of sexual anomalies.<ref name=":432" />
 === Medical treatment ===
-Hormonal treatment is generally an accepted standardised approach to treat different congenital sexual anomalies. Patients that are deficient in hormones produced by the adrenal glands require immediate medical attention. They are given a hormone called [[hydrocortisone]], a form of hormone replacement therapy, with the objective to induce puberty<ref name=":4" />.
+Hormonal treatment is an accepted and standardised approach to treat different congenital sexual anomalies. Patients that are deficient in hormones produced by the [[adrenal gland]]s require immediate medical attention. They are given a hormone called [[hydrocortisone]], a form of hormone replacement therapy, with the objective to induce puberty.<ref name=":432" />
-Utilizing [[sex steroids]] as hormonal therapy is deemed controversial with concerns of its duration of initiation, dosage and regimen. However, it is agreed amongst most clinicians that low doses of hormonal treatment should begin around the age of 11 to 12 years old and should be increased progressively<ref name=":4" /><ref name=":2" />.
+Utilizing [[sex steroids]] as hormonal therapy is deemed controversial with concerns of its duration of initiation, dosage and regimen.<ref name=":432" /> However, it is agreed amongst most clinicians that low doses of hormonal treatment should begin around the age of 11 to 12 years old and should be increased progressively.<ref name=":432" />
 === Surgical treatment ===
-Surgical procedures are an alternative to hormonal treatment available for patients to correct genital anomalies and improve the body’s sexual functions. However, a common dilemma in these procedures is that they are often derived from the patient’s expectation of ‘normal’ genitals from an aesthetic and functional standpoint. Oftentimes, this leads to extensive surgical interventions<ref name=":6" />.
+Surgical procedures are an alternative to hormonal treatment available for patients to address genital anomalies and improve the body's sexual functions. However, a common dilemma in these procedures is that they are often derived from the patient's expectation of 'normal' genitals from an aesthetic and functional standpoint. Oftentimes, this leads to extensive surgical interventions.<ref name=":632">{{Cite web|date=2020-10-22|title=Klinefelter Syndrome|url=https://www.physio-pedia.com/index.php?title=Klinefelter_Syndrome&oldid=256970|access-date=2021-04-11|website=Physiopedia|language=en}}</ref>
-In most cases, surgical procedures result in permanent changes to the patient’s [[phenotype]]<ref name=":2" />. The decision to proceed with this arrangement must be a joint agreement between the family and the multidisciplinary team. The most idealistic situation would be to include the patient as part of the decision-making process. However, cases where surgical treatments were performed at an early age are recognised as mutilation of the body. Subsequently, it has become increasingly common to defer surgical treatments until the patient is of appropriate age to be involved in the decision-making process.
+In most cases, surgical procedures result in permanent changes to the appearance and function of the patient's body. Therefore, the decision to proceed with this arrangement must be a joint agreement between the family and the multidisciplinary team. The most ideal situation would be to include the patient as part of the decision-making process. However, cases where surgical treatments were performed at an early age are recognised as [[mutilation]] of the body. Subsequently, it has become increasingly common to defer surgical treatments until the patient is of appropriate age to be involved in the decision-making process.<ref name=":432" />
-== Controversy ==
+== Controversy and implications ==
-Even though the term disorder of sex development (DSD) is widely accepted by the medical community, its appropriateness and usefulness to represent these individuals is criticised by many support and advocacy groups. Firstly, the word ‘disorder’ carries negative connotations. Secondly, with current nomenclature, DSD is an overly generalised term for conditions that do not have differences in genital appearance or gender identity (e.g. Klinefelter syndrome and Turner syndrome). Thirdly, the term ‘DSD’ lacks specificity and clarity; and therefore unhelpful in the diagnosis process. Hence, many support groups and advocates believe that the medical community should discontinue the use of ‘DSD’ as a designation tool.
+Even though the term disorder of sex development (DSD) is widely accepted by the medical community, its suitability and adequacy to represent these individuals are criticised by many support and [[advocacy group]]s. Firstly, the word 'disorder' carries negative connotations. Secondly, with current [[nomenclature]], DSD is an overly generalised term for conditions that do not have differences in genital appearance or gender identity (e.g. [[Klinefelter syndrome]] and [[Turner syndrome]]). Thirdly, the term 'DSD' lacks specificity and clarity; and therefore unhelpful in the diagnosis process. Hence, many support groups and advocates believe that the medical community should discontinue the use of 'DSD' as a designation tool.<ref>{{Cite web|last1=Houk|first1=Christopher P|last2=Baskin|first2=Laurence S|last3=Levitsky|first3=Lynne L|date=Jan 9, 2021|editor-last=Geffner|editor-first=Mitchell E|editor2-last=Hoppin|editor2-first=Alison G|title=Management of the infant with atypical genitalia (disorder of sex development)|url=https://www.uptodate.com/contents/management-of-the-infant-with-atypical-genitalia-disorder-of-sex-development|access-date=April 9, 2021|website=UpToDate}}</ref>
+Furthermore, people who live with conditions regarding sexual abnormalities may encounter various mental and physical health problems. This may include traumatic experience with their own bodies, dissatisfaction with [[body image]], low-self esteem, [[anxiety]], [[Depression (mood)|depression]], [[bipolar disorder]]s, [[eating disorder]]s, [[personality disorder]]s, [[schizophrenia]] disorders, trauma and stress-related disorders, etc.<ref>{{Cite web|date=2019-09-24|title=Supporting yourself - Intersex people|url=https://headtohealth.gov.au/supporting-yourself/support-for/intersex|access-date=2021-04-01|website=headtohealth.gov.au|language=en}}</ref>
-== See Also ==
+== See also ==
+{{Portal|Human sexuality}}
 * [[Intersex medical interventions]]
+* [[Intersex healthcare]]
 * [[Patient support groups|Patient support group]]
-== Reference ==
+== References ==
+<references />
+{{Human reproductive health}}
+{{Human sexuality|state=autocollapse}}
+[[Category:Sexuality]]
+[[Category:Sex organs]]
+[[Category:Diseases and disorders]]

v t e Sexual and reproductive health
Rights	Reproductive Justice Compulsory sterilization Contraceptive security Abortion-rights movements Genital integrity Circumcision controversy Intersex human rights
Education	Sex education Genetic counseling Pre-conception counseling
Planning	Childfreeness/childlessness Birth spacing Parenting adoption foster care Sperm theft
Contraception	Hormonal contraception Male contraception Safe sex Condom Intrauterine device Sterilization
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Health	Men's Women's vulvovaginal Research self-report sexual risk behaviors
Pregnancy	Maternal health Obstetrics Unintended pregnancy childbirth Abortion Options counseling Pregnancy from rape Pregnant patients' rights Prenatal care Teenage pregnancy Precocious puberty and pregnancy
Identity	Gender identity Sexual orientation Intersex Transgender Genital modification
Medicine	Andrology Genitourinary medicine Gynaecology Obstetrics and gynaecology Reproductive endocrinology and infertility Sexual medicine Transgender health care
Disorders	Disorders of sex development Infertility Reproductive system disease Sexual dysfunction Sexually transmitted infections clinic Gender dysphoria
By country	China India Iran Ireland Pakistan Philippines Singapore United Kingdom teen United States teen pregnancy birth control
History	Birth control movement in the United States History of condoms Social hygiene movement Timeline of reproductive rights legislation
Policy	One-child policy Two-child policy Three-child policy Financial baby bonus bachelor tax child benefit tax on childlessness Abortion law

v t e Human sexuality and sexology
Sexual relationship phenomena	Aromanticism Asexuality Gray asexuality Demisexuality Fictosexuality Bisexuality Pansexuality Casual relationship Casual sex Celibacy Love shyness Celibacy syndrome Herbivore men Committed relationship Conventional sex Flirting Free love Foreplay Friends with benefits relationships Group sex Heterosexuality Homosexuality Hypersexuality LGBT Marriage One-night stand Polyamory Promiscuity Female Romantic love Romantic orientation Queer heterosexuality Sex life Sexual abstinence Sexual orientation Sexual partner Sexual repression Single person Split attraction model Swinging
Sexual dynamics	Hypergamy Physical attractiveness Sexual attraction Sexual capital Sexual ethics Sexual frustration Sociosexuality
See also	Abortion-rights movement Adolescent sexuality Age of consent Decriminalization of sex work Dogging (sexual slang) Human female sexuality Human male sexuality LGBTQ rights by country or territory Porn for women Public sex Reproductive rights Right to privacy Right to sexuality Sex Addicts Anonymous Sex and drugs Sex worker movements Sex workers' rights Sexecology Sex-positive feminism Sex-positive movement Sexual addiction Sexual and reproductive health and rights Sexual jealousy Sexual norm Sexual revolution Sexual surrogate Sexuality and disability Stanley v. Georgia Women's erotica