Gender assignment and reassignment in 46,XY pseudohermaphroditism and related conditions.

T current intense debate of the management of patients with intersexuality and related conditions focuses on three major issues: 1) the assignment of gender; 2) the indication for genital surgery; and 3) the disclosure of medical information to the patient. For instance, in recently published guidelines for intersex management, Diamond and Sigmundson (1, 2) emphasized the growing evidence of prenatal androgen effects on the sexual differentiation of the brain and made strong recommendations for assigning to the male gender all 46,XY patients of the following categories: genital trauma (leading to loss of the penis), micropenis, androgen insensitivity (AIS) of Quigley et al. (3) stages 2 and 3, hypospadias, 5a-reductase deficiency (5a-RD), and 17b-hydroxysteroid dehydrogenase (HSD) deficiency. The Intersex Society of North America (4), a support group of mostly adult persons with intersexuality founded in 1994, has published recommendations that center on the avoidance of genital surgery—because of the potential consequences for sexual functioning—without the patient’s informed consent, “unless it is absolutely necessary for the physical health and comfort of the intersexual child,” and declare it “imperative that intersexuals learn of their status in a properly supportive emotional environment.” Similarly, a growing number of medical clinicians have begun to question prevailing practices of intersex management (e.g., Refs. 5–8). To evaluate such recommendations, we have to place them in historical context and review their empirical basis. The present comments are mostly confined to the gender question. The discussion pertains to both classical intersex patients born with ambiguous genitalia and to female-assigned 46,XY individuals with such nonhormonal genital abnormalities as penile agenesis, cloacal exstrophy of the bladder, and postnatal penile ablatio or traumatic loss of the penis, which may occur, for instance, after a circumcision accident. Historically, the decision on gender assignment in cases of patients with ambiguous genitalia assumed a two-gender heterosexual society in which reproduction was essential for the survival of most individuals, and sex assignment was based on the predominant sex—originally in terms of the appearance of the external genitalia, from the second half of the 19th century on in terms of the gonads and their histology, and from the 1950s on often also in terms of the sex chromosomes. Around the middle of the 20th century, reviews of the existing literature (9) and studies of intersex patients at Johns Hopkins Hospital (Baltimore, MD) by Money et al. (10) led to the conclusion that, in most cases, the gender assigned in infancy will be the one the patient stays with into adulthood, regardless of the status of the standard biological indicators of sex. As a consequence, the Hopkins group (11) replaced the then prevalent “true-sex policy” by an “optimal-gender policy” (12), which bases the assignment and reassignment of gender on the expected optimal outcome in terms of psychosexual, reproductive, and overall psychologic/psychiatric functioning. Early surgery for maximizing the gender-appropriate appearance of the external genitalia was recommended to facilitate gender-appropriate rearing. This policy was later extended to 46,XY cases with nonhormonal genital abnormalities (e.g., Ref. 13). In the original formulation of the optimal-gender policy, consideration of the sexual differentiation of the brain did not play a role because nothing was known about it at that time, and the intersex data then available were interpreted as showing that “psychologically, sexuality is undifferentiated at birth and that it becomes differentiated as masculine or feminine in the course of various experiences of growing up” (10), which is often referred to by others (e.g., Ref. 1) as the hypothesis of psychosexual neutrality at birth. In 1959, however, Phoenix et al. (14) demonstrated that perinatal sex hormones had a major organizing effect on the sexual differentiation of brain and behavior in guinea pigs, and these observations were soon replicated in other species. In the late1960s, Ehrhardt et al. (15–17) reported gender-role behavior shifts in the direction of masculinization in prenatally androgen-exposed 46,XX girls and women and demonstrated thereby that the pre-/perinatal sex hormone theory applied to the human species, at least to some extent. It is important to note, however, that also in the presence of markedly masculinized gender role behavior, gender identity usually remained female, even in the extreme situation of late-treated women with congenital adrenal hyperplasia who, in addition to prenatal masculinization, also showed massive postnatal virilization (16). Apparently, a given genReceived July 9, 1999. Revision received August 6, 1999. Accepted August 6, 1999. Address correspondence and requests for reprints to: Heino F. L. Meyer-Bahlburg, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, Unit 15, 1051 Riverside Drive, New York, New York 10032. 0021-972X/99/$03.00/0 Vol. 84, No. 10 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 1999 by The Endocrine Society