Semin Reprod Med 2002 Aug;20(3):217-28


Disorders of androgen action.

Sultan C, Lumbroso S, Paris F, Jeandel C, Terouanne B, Belon C,
Audran F, Poujol N, Georget V, Gobinet J, Jalaguier S, Auzou G,
Nicolas JC.

Pediatric Endocrine Unit, Department of Pediatrics, Hopital A. de
Villeneuve, Montpellier, France.

Disorders of androgen action are the main cause of male
pseudohermaphroditism and include 5alphaR deficiency and androgen
receptor defects. 5alphaR deficiency is characterized by female
genitalia with some degree of masculinization, clitoromegaly, and
severely bifid scrotum corresponding to the so-called pseudovaginal
perineoscrotal hypospadias. At the onset of puberty, increased muscle
mass, development of pubic hair, and phallic growth are associated
with the acquisition of male gender identity. Normal or increased
levels of testosterone and an elevated testosterone-to-
dihydrotestosterone ratio after human chorionic gonadotropin
stimulation testing suggest 5alphareductase deficiency, and the
diagnosis can be ascertained by identifying the mutation in the
5alphaR-2 gene. Whatever the patient's age at diagnosis,
psychological evaluation with 5alphaRD is vital. Androgen receptor
defects encompass two clinical expressions: the complete and partial
androgen insensitivity syndromes. Complete androgen insensitivity
syndrome should be suspected at birth in the presence of inguinal
hernia in a girl without genital ambiguity. At puberty, the sign of
alert is primary amenorrhea with normal female phenotype and
harmonious mammary development but no pubic hair growth. Partial
androgen insensitivity syndrome covers a wide spectrum of
undervirilized phenotypes ranging from clitoromegaly at birth to
infertile men. In all cases, complementary investigations should
include plasma testosterone and luteinizing hormone as well as
androgen-binding capacity in cultured genital skin fibroblasts.
Diagnosis is confirmed by identification of the androgen receptor
gene mutation. Although patients with complete androgen insensitivity
syndrome are raised as females, patients with partial androgen
insensitivity syndrome should be managed according to age at
diagnosis, response to treatment with exogenous androgens, and the
presence of an androgen gene mutation. Gonadectomy in complete
androgen insensitivity syndrome should be performed before puberty,
and androgen substitution may improve the development of external
genitalia in some patients with partial androgen insensitivity
syndrome. Psychological follow-up is necesssary.

PMID: 12428202 [PubMed - in process]


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