Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity ABSTRACTAndrogens act through a receptor protein (AR) to mediate sex differentiation and development of the male phenotype. We have isolated the eight exons in the amino acid coding region of the AR gene from a human X chromosome library. Nucleotide sequences of the AR gene intron/exon boundaries were determined for use in designing synthetic

ABSTRACT. Objectives. To identify and study adults (21 years or older) who have a 46,XY karyotype and presented as infants or children with genital ambiguity, including a small phallus and perineoscrotal hypospadias, reared male or female.Methods. Participants were classified according to the cause underlying their intersex condition based on review of medical and surgical records. Long-term medical and surgical outcome was assessed with a written questionnaire and physical examination. Long-term psychosexual development was assessed with a written questionnaire and semistructured interview.Results. Thirty-nine (72%) of 54 eligible patients participated. The cause underlying genital ambiguity of participants included partial androgen insensitivity syndrome (n ‫؍‬ 14; 5 men and 9 women), partial gonadal dysgenesis (n ‫؍‬ 11; 7 men and 4 women), and other intersex conditions. Men had significantly more genital surgeries (mean: 5.8) than women (mean: 2.1), and physician-rated cosmetic appearance of the genitalia was significantly worse for men than for women. The majority of participants were satisfied with their body image, and men and women did not differ on this measure. Most men (90%) and women (83%) had sexual experience with a partner. Men and women did not differ in their satisfaction with their sexual function. The majority of participants were exclusively heterosexual, and men considered themselves to be masculine and women considered themselves to be feminine. Finally, 23% of participants (5 men and 4 women) were dissatisfied with their sex of rearing determined by their parents and physicians.Conclusions. Either male or female sex of rearing can lead to successful long-term outcome for the majority of cases of severe genital ambiguity in 46,XY individuals.We discuss factors that should be considered by parents and physicians when deciding on a sex of rearing for such infants. Pediatrics 2002;110(3). URL: http://www. pediatrics.org/cgi/content/full/110/3/e31; intersex, sex assignment, gender, androgen insensitivity, gonadal dysgenesis, psychosexual, genital reconstruction, hormone replacement.ABBREVIATIONS. PAIS, partial androgen insensitivity syndrome; PGD, partial gonadal dysgenesis. D uring fetal sex differentiation, genetic males who are unable to masculinize their sex ducts and external genitalia can be classified into 2 major etiologic groups: 1) the inability of the fetus to produce sufficient amounts of testosterone and dihydrotestosterone or 2) the inability of the fetus to respond to androgens that are present in normal amounts. 1 We previously described a population of 46,XY subjects who presented to the Pediatric Endocrinology Clinic of Johns Hopkins Hospital with varying degrees of undermasculinized genitalia. 2 In this population, the most difficult group to treat in terms of gender assignment is that of individuals who were born with ambiguous genitalia that includes a small phallus and perineoscrotal hypospadias. 3 For this group of patients, there is a lack of agreement about optimal sex ...

Among 80 women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (40 with the simple virilizing form and 40 with the salt-losing form), 40 reported having an adequate introitus and being heterosexually active. In 15 of 25 patients with the simple virilizing form, 25 pregnancies resulted in 20 normal children, whereas only 1 of 15 women with the salt-losing form became pregnant; this pregnancy was electively terminated. Several factors seem to be responsible for the low fertility rates: noncompliance with therapy was probably high, as suggested by hirsutism and poor endocrine follow-up in 25 percent of patients; whereas 49 patients had regular menstrual periods, 14 had irregular periods, 10 had amenorrhea, 5 had undergone hysterectomy, and 2 had entered menopause; 87 percent of patients with salt loss and 50 percent of those with simple virilization (P less than 0.001) had remained single; the vaginal introitus was reported to be inadequate for intercourse by 35 percent of patients (53 percent of those with salt loss and 18 percent of those with simple virilization; P less than 0.002); and heterosexual activity was reported less frequently among patients with an inadequate introitus. The status of the introitus seemed to have a more important role in the sexual activity reported than did the degree of prenatal exposure to androgen (which was higher among patients with salt loss than among those with simple virilization). However, our data did not rule out an effect of androgen exposure on female fetuses. Our experience indicates that improved surgical correction of the external genitalia and better compliance with therapy will be necessary to improve fertility rates among women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Controversy concerning the most appropriate treatment guidelines for intersex children currently exists. This is due to a lack of long-term information regarding medical, surgical, and psychosexual outcome in affected adults. We have assessed by questionnaire and medical examination the physical and psychosexual status of 14 women with documented complete androgen insensitivity syndrome (CAIS). We have also determined participant knowledge of CAIS as well as opinion of medical and surgical treatment. As a whole, secondary sexual development of these women was satisfactory, as judged by both participants and physicians. In general, most women were satisfied with their psychosexual development and sexual function. Factors reported to contribute to dissatisfaction were sexual abuse in one case and marked obesity in another. All of the women who participated were satisfied with having been raised as females, and none desired a gender reassignment. Although not perfect, the medical, surgical, and psychosexual outcomes for women with CAIS were satisfactory; however, specific ways for improving long-term treatment of this population were identified. (J Clin Endocrinol