a male gender role. History An autosomal recessive disorder of sex development, described as pseudovaginal perineoscrotal hypospadias (PPSH), was discovered in males in 1961. The main feature of this syndrome was female appearing external genitalia with the presence of bilateral testes and male urogenital tracts in which the ejaculatory ducts terminate in a blind-ending vagina. This disorder was consistent with 5αR2D as the underlying cause as observed in animal models. 5αR2D was confirmed as the cause in humans in 1974, when studies of 24 participants in the Dominican Republic and 2 in Dallas Texas, USA. One of the cases in Dallas began to virilize at puberty and underwent surgery to remove testes and "repair" the apparent clitoromegaly. During surgery, a normal male urogenital tract was observed as well as other features consistent with PPSH. DHT was almost undetectable in cultured fibroblasts from foreskin, epididymis and the presumed "labia majora" whereas in normal males DHT is detected, suggesting impaired DHT formation. Similar conclusions were obtained for participants in a family in the Dominican Republic study in whom high serum concentration ratios of T to DHT and low concentrations of urinary 5a-reduced androgens were observed. This disorder is now known to be due to homozygous or compound heterozygous loss-of-function mutations of the SRD5A2 gene. Society and culture Sport In April 2014, the BMJ reported that four elite women athletes with 5-ARD were subjected to sterilization and "partial clitoridectomies" in order to compete in sport. The authors noted that "partial clitoridectomy" was "not medically indicated, does not relate to real or perceived athletic 'advantage, relating to elevated androgen levels. The athletes were all from developing countries where lifetime access to hormone replacement may prove elusive. Intersex advocates regard this intervention as "a clearly coercive process". Popular culture In the Nip/Tuck season three episode "Quentin Costa", it is revealed that Quentin Costa had 5-ARD. Jeffrey Eugenides' Pulitzer Prize-winning 2002 novel Middlesex is about a young man with 5-ARD. The character was originally born Calliope and raised as a girl, but upon realizing his genetic sex, he transitions into Cal. Notable people Caster Semenya See also Intersex Disorders of sexual development, pseudohermaphroditism, and ambiguous genitalia Inborn errors of steroid metabolism 5α-Reductase (I, II) Androgen (testosterone and dihydrotestosterone) Ambiguous genitalia Intersex surgery Androgen insensitivity syndrome Congenital adrenal hyperplasia References External links OMIM article Cholesterol and steroid metabolism disorders Endocrine gonad disorders Intersex variations