MALE PSEUDOHERMAPHRODITISM DUE TO PRIMARY 5-ALPHA-REDUCTASE DEFICIENCY - VARIATION IN GENDER IDENTITY REVERSAL IN 7 MEXICAN PATIENTS FROM 5 DIFFERENT PEDIGREES

In the present study, we describe the clinical, endocrinological, psychosexual and biochemical features of 7 Mexican male pseudohermaphrodites with primary 5 alpha-reductase deficiency in whom heterogeneity in the pattern of gender identity change at puberty was observed. The patients belonged to 5 different pedigrees from diverse locations in Mexico. Six of them were admitted to the Hospital during or after puberty. The one prepubertal subject was the sibling of a previously studied patient. Basal serum gonadotropins were determined by double antibody radioimmunoassay. Basal and choriogonadotropin (CG)-stimulated concentrations of androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) were determined by radioimmunoassay after extraction and separation by celite chromatography. Urinary aetiocholanolone, androsterone and C19 and C21 5 beta/5 alpha metabolite ratios were analyzed by capillary gas chromatography. Enzyme activity and androgen receptors were studied in fibroblasts cultured from genital skin. Psychological assessment was performed using the Bender-Gestalt Wechsler Adult Intelligence Scale, the Rorschach Ink Blot and the Thematic Apperception Tests. All 7 patients were unambiguously reared as females; three spontaneously changed their gender identity and role from female to male after puberty, another one changed during psychotherapy at the end of puberty. Two patients (one prepubertal and the other pubertal) have been under therapy during 1.5 years, but due to familial and social factors a female gender has prevailed. The remaining patient consulted at age 15 because of virilization; her female gender identity did not change after more than one year of treatment and due to the fact she was depressed and had suicidal tendencies, the penis and testes were removed. Immediately after starting to feminize with exogenous estrogens, she changed her gender identity and role. Baseline serum T concentrations were normal in 4 of the postpubertal cases, while 2 had low levels; DHT values were low to low normal. In all 7 cases the T/DHT (pre and/or post CG) ratio was increased while high urinary aetiocholanolone/androsterone ratios and C19 and C21 5 beta/5 alpha metabolite ratios were always documented. Five subjects had decreased 5 alpha-reductase activity in fibroblasts cultured from genital skin, whilst the remaining 2 had a normal activity. A normal amount and stability of the androgen receptor at 42C was detected in all cases. This report confirms and extends previous studies that patients with primary 5 alpha-reductase deficiency, despite being reared as females, generally change their gender role during or after puberty due to virilization of their external genitalia and theoretically to the masculinization of the brain. The development and course of this change also depends on the subject's personality traits, personal insight and the sociocultural factors sorrounding him.