Cohort profile: pathways to care among people with disorders of sex development (DSD).

PURPOSE: The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS). PARTICIPANTS: Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation. FINDINGS TO DATE: Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS. FUTURE PLANS: As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories.

Amative orientation: the hormonal hypothesis examined.

The hypothesis that human male and female amative orientation, arousal and courtship are sex-hormone dependent had as its precursor John Hunter's recorded but unpublished 18th century experiments of cross-sexed gonadal transplants in chicks. The hypothesis gained momentum in the 20th century after the discovery and eventual marketing of the sex hormones, and after the experimental demonstration by William C. Young that, in guinea-pigs, cross-sexed hormone administered prenatally influenced their subsequent male/female courtship and mating behavior. Comparatively and in review, human clinical syndromes of hypermasculinization and hypomasculinization do not disconfirm the hormonal hypothesis, but they do not adequately confirm it, either. They are compatible with the idea of a cofactor that governs whether amative orientation in practice, ideation and imagery is homosexual, heterosexual or bisexual.

Pediatric sexology and hermaphroditism.

Lacking an empirically based theory of erotosexual development and health in childhood, pediatrics too easily falls back on reductionistic hypotheses of the nature versus nurture type. A new, three-term paradigm, namely, nature/critical-period/nurture, is needed to explain, for example, the phenomenology of hermaphroditism, and the differentiation of gender-identity/role (G-I/R) in individual cases. In 30 young women with a history of the early-treated, 46,XX congenital virilizing adrenal hyperplasia (CVAH) syndrome, 37% (N = 11) had a history of bisexual imagery or practice, as compared with 7% in the control patients (chi 2 = 17.7; p less than .001); and 5 of these 11 rated themselves as exclusively or predominantly lesbian. In Kinsey's sample, 15% of females reported homoerotic imagery by age 20, and 2 out of 3 of them also had homoerotic partner contact. The CVAH finding may be a function of prenatal and/or neonatal brain androgenization, but other variables, such as the history of juvenile erotosexual rehearsal play, cannot be ruled out. Among adolescents with a history of hermaphroditism, sex-reassignment applications are honored predominantly if they are made by 46,XY hermaphrodites assigned neonatally as girls and with nonfeminizing hormonal puberty, as medical and folk traditions both favor approval of such applicants more than others. Parthenogenic whiptail lizards that alternately simulate the male and female mating behavior of related diecious species provide an animal model that demonstrates the existence of both male and female sexual schemas in the same brain. In human beings, the irreducible sex differences are that males impregnate, and females menstruate, gestate, and lactate. Otherwise, sexual dimorphism that is programmed into the brain under the influence of prenatal hormones appears to be not sex-irreducible, but sex-shared and threshold-dimorphic. A complete theory of the differentiation of all the constituents of masculinity or femininity of G-I/R needs to be both multivariate and sequential in type. It must be applicable to all of the syndromes of hermaphroditism, and to the genesis of all the G-I/R phenomena, including transvestism and transsexualism, as well as to the genesis of a heterosexual G-I/R.

Adult erotosexual status and fetal hormonal masculinization and demasculinization: 46,XX congenital virilizing adrenal hyperplasia and 46,XY androgen-insensitivity syndrome compared.

Among 30 young women with a history of the treated adrenogenital syndrome (CVAH), 11 (37%) rated themselves as bisexual or homosexual. Among a control group consisting of 15 women with the 46,XY androgen-insensitivity syndrome (AIS) plus 12 with the Rokitansky syndrome (MRKS), the corresponding figure was 2 (7%), both bisexual. Chi-square was significant beyond the 0.01 level. In Kinsey's 1953 sample 15% of women experienced homoerotic arousal imagery by age 20, and 10% had had homoerotic partner contact. The most likely hypothesis to explain the CVAH findings is that of a prenatal and/or neonatal masculinizing effect on sexual dimorphism of the brain in interaction with other developmental variables.