FAMILIAL MALE PSEUDOHERMAPHRODITISM DUE TO DEFICIENCY OF 5α‐REDUCTASE

Abstract

Two brothers of Greek Cypriot origin, karyotype 46 XY, aged 17 and 19 years were brought up as females because of predominantly female external genitalia with clitoromegaly and urogenital sinus. At puberty there was genital masculinization with testicular enlargment and descent and development of male musculature and body habitus without gynaecomastia. Both subjects acquired male gender identity and changed from a female to a male gender role. The internal genitalia were normally formed with an ejaculate containing mature spermatozoa. In both subjects plasma testosterone levels were slightly elevated, dihydrotestosterone was in the low normal range and the plasma testosterone to dihydrotestosterone ratio was markedly elevated. Plasma oestrogens were normal whereas SHBG binding capacity was elevated. The urinary 5 beta-aetiocholanolone to 5 alpha-androsterone ratios were elevated compared with normal subjects. Basal plasma LH was normal but, the LH response to LHRH was exaggerated and basal and peak plasma levels of FSH were elevated. 5 alpha-reductase activity in genital skin homogenates was higher when androstenedione was used as a substrate, compared with testosterone, suggesting a decreased affinity of the enzyme for testosterone. The clinical and hormonal features in the two siblings are consistent with an impaired peripheral conversion of testosterone to dihydrotestosterone due to deficiency of the enzyme 5 alpha-reductase.

Molecular genetics of steroid 5 alpha-reductase 2 deficiency.

“…Clinical misdiagnosis is unlikely as these patients met all the criteria of 5a-reductase deficiency and have been thoroughly characterized at the biochemical and endocrine levels. In fact, the 5R2-London-3 family has been studied by two different groups ( 18,24). The existence of the type 1 isozyme of 5a-reductase renders genetic heterogeneity a formal possibility; however, in the case of 5R2-Los Angeles-3 the type 1 gene was excluded as the disease locus ( 13).…”

Neurohormonal functioning and sexual orientation: A theory of homosexuality–heterosexuality.

“…Although 5a-reductase is normally present in both sexes, its only known function is in males, where it converts testosterone to DHT (see Figure 5). Because DHT is required to masculinize the external genitals (Savage et al, 1980), when 5a-reductase is absent, the genitals develop an F/dM appearance no matter how much testosterone the testes produce.…”

Steroidal Control of Behavioural, Neuroendocrine and Brain Sexual Differentiation: Studies in a Carnivore, the Ferret

“…A final clinical example relevant to the question of whether perinatal steroid hormones influence the differentiation of sexual orientation in humans is the case of male Sa-reductasedeficient men, in which the external genital organs are feminine until the age of puberty, when phallic growth occurs under the influence of testosterone secreted by the testes. Many of these people have been reared as girls until genital virilization occurred at the age of puberty, whereupon they, reportedly, switched gender role and sexual orientation to that of heterosexual men (74)(75)(76). The reported ability of these males to assume the masculine heterosexual role so readily may reflect the perinatal actions of testosterone or its oestrogenic metabolites in the developing nervous system.…”