(Some of our readers may recall that many years ago Dr. John Money, the senior author of the present article, published a series of articles dealing with patients with a variety of intersex problems, including congenital adrenal hyperplasia (CAH) and testicular feminization (complete androgen insensitivity) syndrome (CAIS) (e. g., JM Money et al., Arch Neurol Psychol 1957:77:333; JM Money, Annu Rev Med 1965:16:67). In essence, he suggested that women with CAH had more aggressive behavior and other “masculine” behaviors than their normal counterparts. At the time, it was recommended that patients with CAH who had phallic enlargement and urogenital sinus derivative abnormalities have these surgically corrected at a young age. More recently, both of these proposals have been called into question, and some suggest that the patient herself should decide whether to have surgery when she is old enough to understand the ramifications.
There is also some controversy about when surgery should be performed in patients with CAIS. In these patients, there is a high (>30%) incidence of gonadal malignancies, particularly dysgerminoma and gonadoblastoma. Although there is no “ideal” time at which to perform gonadectomy (the testes may be in either the pelvis, scrotal folds, or inguinal hernias), my preference is to allow patients to undergo feminization before gonadectomy, even though gonadal malignancies have been reported in these patients before puberty. Gonadectomy is often perceived as castration by the patient whenever it is performed, unless the patient is too young to understand. In my experience, it has seldom been necessary to perform vaginoplasty on these patients for satisfactory intercourse. Either use of vaginal dilators or intercourse itself often is sufficient. In the present study, 8 of the 14 individuals did not require vaginoplasty. In addition, the majority who responded (8 of 10) indicated that adolescence or adulthood was the most appropriate time for surgery, whereas 2 thought it should have been done in infancy.
In any event, as the authors in the present article point out, if androgens are the sole determinants of male psychosexual behavior, patients with CAIS would not exhibit a male bias because they have end-organ resistance to the effects of androgen. Furthermore, these patients permit assessment of the effects of estrogen on gender development in 46,XY patients because they are not responsive to androgens but are responsive to estrogens.
Patients with CAIS have a defect in the mechanism of androgen action, often owing to a mutation in the gene encoding the androgen receptor, and all 14 individuals in the present study had a mutation in the receptor gene in addition to the pathognomonic scant or absent pubic and axillary hair (this usually is the easiest way to make the differential diagnosis between these patients and those with congenital absence of the vagina).
The authors found that 11 of the subjects with CAIS reported satisfaction with their genitalia in regard to sexual function. Interestingly, the majority of the subjects reported a self-estimated libido of average strength or stronger, and 10 of the 13 patients who responded reported an ability to experience orgasms. This is of particular interest because there is a common belief that androgens are necessary for orgasms, and, as our readers know, androgens often are prescribed for women who report decreased libido. Apparently, although androgens may contribute to libido and orgasmic potential in women without this disorder, both can be experienced by individuals with CAIS. Also, no individual reported difficulty with vaginal lubrication.
Additionally, the subjects with CAIS reported a high degree of femininity and a low degree of masculinity during development, and most reported female heterosexual orientation. Seven of the subjects were married to men, and one was engaged; five of the married individuals and one unmarried individual had adopted children. All reported being satisfied that they were reared as women. The majority of the subjects had received some form of counseling on aspects of their syndrome, but eight had no understanding of CAIS. Thus, although there were some difficulties with some of the subjects, for most the medical, surgical, and psychosocial outcomes were satisfactory. This is reassuring, although improvements in several aspects could have been made.—RBJ)