Patients with atypical genitalia present a challenge to professionals who engage in establishing their diagnosis and treatment. The lack of long term follow up data underwrites this dilemma. These patients present a large spectrum of phenotypes but most of these phenotypes were described long before the identification of molecular defects was available.

We present here an update on the long term follow up of patients born with atypical genital based on our three decades of experience with these patients in a tertiary centre in Sao Paulo, Brasil. The study was mainly retrospective, however all of the patients were interviewed and examined by the multidisciplinary team at the moment they answered a designed questionnaire containing 152 questions to analyze the impact of the disorder on the patients' social, professional and sexual behavior. The etiological diagnosis was established by the clinical, cytogenetic, hormonal and imaging evaluation and were complemented by the molecular study in most of the patients.

We studied 55 patients with the classical form of virilizing CAH (52 with 21- hydroxylase deficiency and 3 with 11-hydroxylase deficiency) and 96 patients with 46,XY DSD grouped in four categories:  DSD due to defects in T production comprising of gonadal dysgenesis, Leydig cell hypoplasia, 3β-HSD2 or 17α-hydroxylase or 17β-HSD3 deficiencies, a second group with 5α-RD2 deficiency, a third group with androgen insensitivity syndrome comprising its complete and partial forms and the last group with atypical genital with unknown etiology.

Attribution of female social sex was predominant in both 46,XX and 46,XY DSD groups. Social sex change to male occurred in 18% of 46,XY DSD and in 10% of 46,XX DSD patients. Childhood male or neutral games was the single variable significantly associated with the change of social sex to male in both 46,XY and 46,XX DSD patients registered as females (p<0.05). In 46,XX group, all CAH patients who changed to male sex were improperly treated and had severe virilization. In the 46,XY DSD group the only etiology significantly associated with female to male social sex change was 5a-RD2 deficiency. Exposure to high testosterone levels in prenatal life resulted in lessened interest in having children in female social sex patients.

Heterosexual orientation was reported by 94% of the 46,XY DSD patients and by 80% of the 46,XX DSD patients. There was a significant association of the sexual orientation with the etiological group (predominance of homo/bisexuals in the virilizing CAH group. Sexual satisfaction was more frequently reported by the 46,XY DSD patients (54%) than 46,XX DSD patients (33%). The penile length of the 4 groups of patients with DSD were compared; the patients with 5a-RD2 deficiency had the smallest penile length before and after therapy whereas the undetermined group presented the largest penis size. All but two patients with undetermined 46,XY DSD presented a final penile length corresponding to less than -2 SDS. However, there was no statistically significant difference in final penile length between sexual satisfied and unsatisfied groups, even though patients complained about penile length.

As far as the professional aspects, the majority of the patients reported being happy with their professional activities: (80% of the 46,XY DSD and 79% of the 46,XX DSD patients (p>0.05). Five patients with female social sex (4.7%) (3 from the 46,XX group and 2 from the 46,XY group) work in jobs that are typically male oriented in contrast with the male social group, in which, all of the patients work in male oriented or neutral jobs

Most patients reported high level of satisfaction after treatment, which showed the importance of a multidisciplinary team and psychological support in the treatment of sexual development disorders.