General Medical Information

Gender Assignment

Claude J. Migeon and Gary D. Berkovitz

Gender assignment is a complex issue, yet decisions need to be made as quickly as possible after the birth of an intersex child concerning male or female sex of rearing. Gender assignment is best guided by an experienced medical team including a pediatric endocrinologist/urologist/gynecologist and medical psychologist so that parents can make a well-informed decision. The team should be organized as a standing committee with its own self-imposed rules. One rule is to use only the neutral terms in early discussions with the parents (e.g., phallus rather than penis or clitoris, gonad rather than testis or ovary). This rule should be imposed on all hospital personnel in contact with the family. One other important rule is that, after appropriate discussion, the members of the team should come up with a unanimous decision as to advice for gender to be presented to the parents. Although the team members would be expected to inform the parents of the value of their advice, the parents should make the final decision. The team should make it clear that whatever the parental decision, support will be given to the family in the future. In general, decisions about gender assignment depend on the results of studies performed as part of the etiologic evaluation of the child. In particular, informed decisions will require detailed information from the physical examination, karyotype, genitourethrogram and/or sonogram, studies of androgen production, including 5a-reductase activity, and, if possible, studies of androgen receptor function.

Decisions regarding gender assignment in infants with an XX karyotype tend to be less complicated. A 46,XX individual who has been virilized by the hyperandrogenism associated with adrenal hyperplasia, or by maternal androgens, has a normal uterus, fallopian tubes, and ovaries. Hence, the potential for normal reproductive function in these patients makes a female gender assignment the reasonable choice. However, in some cultures, parents put greater value in being a man than a woman. In these cases, the medical team must explain fully the consequences of such decisions to the parents but, again, the team must respect parental decisions.

Infants with an abnormal karyotype, such as 45,X/46,XY, present a somewhat special situation. Infertility, the potential for gonadal malignancy, and the likelihood of short stature suggest that female gender assignment is the better choice in the majority of these patients. The exception is in cases with well-masculinized external genitalia and with testes that are located or can be brought into the scrotum so the development of a gonadal tumor can be monitored.

Gender assignment in individuals with a 46,XY karyotype can be particularly complex. A variety of criteria regarding anatomy of the genitalia and the potential for future function need to be examined:

1.Phallic length should be determined by measuring the “stretched length” from the tip of the glans to the base of the phallus at the pubic symphysis. This can be easily accomplished in the newborn by applying slight pressure with the second and third fingers at the base of the phallus to cause erection of phallic tissue. In considering the potential for normal function if the child is raised male, one needs to question whether the penile length will be adequate for sexual function later in life. A phallic length of 1.9 cm is 2.5 SD below the mean for a normal newborn male and may be considered a lower limit in assessing future function. However, the multiple surgeries necessary for gender reassignment may also be problematic.

2.The position of the urethral meatus is important, as it determines, in part, the number and complexity of the surgical procedures necessary to reconstruct the child as a male. In general, recent advances in surgical technique have greatly improved the outlook for repair of severe perineal hypospadias.

3.The presence of a vaginal pouch may strongly influence the decision regarding gender assignment. Removal of a large utriculovaginal pouch often is necessary if the child is raised as a male, as it can otherwise become the site of urinary stasis and recurrent infection. However, removal of a utriculovaginal pouch in a male invariably damages the vas deferens and results in infertility. By contrast, the absence of a vaginal pouch may argue against a female gender assignment as construction of a vaginal pouch de novo may be a difficult procedure.

4.The presence of normal müllerian structures is important, as their presence raises the possibility of menses or even a future pregnancy with a donor egg.

5.The adequacy of testosterone production can be assessed by determining blood levels in the first 3 months of life or later, after hCG stimulation. This information is useful in judging the potential for normal testosterone production at puberty and in adult life.

6.Evidence of androgen insensitivity in an infant with ambiguous genitalia creates a special case. As mentioned earlier, male subjects with partial androgen insensitivity virilize poorly at puberty despite high levels of androgens, usually develop gynecomastia, and invariably are infertile. On the other hand, female subjects of partial androgen insensitivity also can experience difficulties related to their feminizing surgery. For these reasons, we recommend gender assignment for infants with partial androgen insensitivity on a case-by-case basis.

Advances in medical diagnosis and surgical technique have had a significant impact on our approach to gender assignment over the past 20 years. Long-term follow-up of patients born with ambiguous genitalia will ultimately provide information on the soundness of these decisions.