When a child is born with ambiguous genitalia, the medical team must mobilize for a neonatal emergency: in addition to the urgent need to rule out such life-threatening conditions as salt wasting, determination of the most appropriate sex for rearing must be made as rapidly as possible. It cannot be emphasized enough that the parents desperately need to know whether their baby is a girl or a boy! The unambiguous designation of a baby’s sex is a key step in the birth process and for the parents of an intersex neonate, the period of waiting to learn their baby’s sex is often agonizing. Birth is the meeting of parents’ dreams and a real infant, alive and present in the world. When a child is born, one of the first announcements is whether the mother has delivered a boy or a girl – we can easily imagine the profound distress, the helplessness, of parents who are confronted with the intersex status of their newborn.
The clinical examination provides an assessment of the degree of undervirilization and the presence of gonads. Biological assessments are mandatory for plasma 17-OHP and the SRY gene.
Once the investigations have been concluded, the medical team should be ready to undertake their greatest responsibility: the assignment of sex for rearing.
This decision must be guided by three parameters: the anatomic condition and functional abilities of the genitalia; the etiology of the genital malformation, and family considerations, which must include recognition of cultural factors, religious convictions, and so on. The choice of declared sex must be – and this bears repeating – the result of full discussion between all protagonists: (a) In cases of female pseudohermaphroditism, the newborn with ambiguous genitalia should always be declared to be of female sex. With normal ovaries and uterus, the female pseudohermaphrodite is potentially capable of bearing children. (b) In cases of male pseudohermaphroditism, great care should be taken in the declaration of male sex. Major considerations will be the potential for reconstructive surgery, the probability of pubertal virilization, and the ‘programmed’ response of the external genitalia to exogenous and endogenous testosterone. The presence of testicular tissue, on the other hand, is not an essential factor in this decision.
In cases of gonadal dysgenesis, sex assignment will be based on several criteria. A defect in 5α-reductase is an indication for male sex for rearing because pubertal virilization will lead to penile development, though it will be subnormal; normal pubic hair development, and the acquisition of male sexual identity. In contrast, for inborn errors of testosterone biosynthesis, female orientation is advisable if effective male reconstructive surgery appears highly unlikely. When a vagina and uterus are present, female orientation is also preferable if it appears that vaginoplasty can be easily accomplished.
In cases of androgen resistance, a female orientation is unquestionably correct for complete resistance, and it is preferable in cases of partial resistance confirmed by therapeutic testing. In true hermaphroditisms, which are very rare, female sex assignment is to be preferred since ovarian function may be preserved.
Castration is indicated for male pseudohermaphrodites reared as girls.
When they are reared as boys, careful gonadal follow-up throughout life is crucial. Since the cumulative risk of gonadal tumor in the intersex child is present even before puberty, we advocate castration in the XY intersex infant with testicular dysgenesis.
A methodical clinical examination and hormonal, radiographic, molecular and genetic investigations are the bases for determining the diagnosis, etiology and optimal management of ambiguous genitalia in the newborn. In conversations with family members, terms such as ‘ambiguous genitalia’ and ‘pseudohermaphrodite’ should be avoided and more neutral terms such as ‘genital malformation’ can be substituted. The family should be informed of the various difficulties and therapeutic options, but excessive detail is unnecessary. Once a decision for the assignment of sex is made, it should be definitive for the parents.
The baby will hereafter be referred to by name and as either ‘he’ or ‘she’ by all staff in order to help the parents to fix their child’s gender firmly in their minds.
Because of the far-ranging consequences, the assignment of sex for rearing should never be the decision of a single physician. The entire multidisciplinary team should remain involved in every step of the diagnostic procedure, the choice of sex for rearing and the treatment strategy. The team also has an important role in guiding the family and ensuring family agreement with and support for the decision, which is the sole means of guaranteeing that the child will be raised with an unambiguous sexual identity.
- Migeon CJ, Berkovitz GD, Brown TR: Sexual differentiation and ambiguity; in Kappy MS, Blizzard RM, Migeon CJ (eds): The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence. Springfield, Thomas, 1994, pp 573–681.
- Sultan C, Savage MO: Intersex states; in Grossman AB (eds): Clinical Endocrinology. London, Blackwell Science, 1998, pp 795–809.
- New M, Mercado A, Cheng K, Jackowski M, Wilson R: Steroid 21-hydroxylase deficiency: Genotype may not predict phenotype; in De Bellis A, Schipani E (eds): Frontiers in Endocrinology. Rome, Ares Serono Symp Publications, 1995, vol 14, pp 17–27.
- Simard J, Rheaume E, Sanchez R, Merbaki F, Morel Y, Zerah M, New M, Labrie F: Relation between molecular defect and phenotypic manifestation of human 3-hydroxysteroid dehydrogenase deficiency; in De Bellis A, Schipani E (eds): Frontiers in Endocrinology. Rome, Ares Serono Symp Publications, 1995, vol 14, pp 39–68.
- New MI: Steroid 21-hydroxylase deficiency (congenital adrenal hyperplasia). Am J Med 1995;98: 2S–8S.
- White PC, Curnow KM, Pascoe L: Disorders of steroid 11β-hydroxylase isozymes. Endocr Rev 1994;15:421–438.
- Sultan C, Lumbroso S, Poujol N, Lobaccaro J: Intrauterine virilization of female fetuses; in Azziz R, Nestler JE, Dewailly D (eds): Androgen Excess Disorders in Women. Philadelphia, Lippincott- Raven, 1997, pp 593–599.
- Quigley CA, Debellis A, Marschke KB, Elawady MK, Wilson EM, French FS: Androgen receptor defects: Historical, clinical and molecular perspectives. Endocr Rev 1995;16:271–321.
- Wilson JD, Griffin JE, Russell DW: Steroid 5-reductase-2 deficiency. Endocr Rev 1993;14: 577–593.
- Sultan C, Lumbroso S: LH receptor defects; in Kempers RD, Cohen J, Haney AF, Younger JB (eds): Fertility and Reproductive Medicine. Proc XVI World Congress on Fertility and Sterility, San Francisco, Oct 4–9 1998. New York, Elsevier, 1998.
- Dewing P, Bernard P, Vilain E: Disorders of gonadal development. Semin Reprod Med 2002;20: 189–197.
- Themmen A, Verhoef-Post M: LH receptor defects. Semin Reprod Med 2002;20:199–204.
- Miller W: Disorders of androgen biosynthesis. Semin Reprod Med 2002;20:205–215.
- Sultan C, Lumbroso S, Paris F, Jeandel C, Terouanne B, Belon C, Andran F, Poujol N, Georget V, Gobinet J, Jalaguier S, Auzou G, Nicolas JC: Disorders of androgen action. Semin Reprod Med 2002;20:217–227.
- Hughes IA: Congenital adrenal hyperplasia: 21-Hydroxylase deficiency in the newborn and during infancy. Semin Reprod Med 2002;20:229–241.
- Peter M: Congenital adrenal hyperplasia: 11β-Hydroxylase deficiency. Semin Reprod Med 2002;20:249–254.
- Simar J, Moisan AM, Morel Y: Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase/Δ5–Δ4 isomerase deficiency. Semin Reprod Med 2002;20:255–276.
- Toppari J: Environmental endocrine disrupters and disorders of sexual differentiation. Semin Reprod Med 2002;20:305–311.
Revision date: July 7, 2011
Last revised: by Dave R. Roger, M.D.