BACKGROUND: Antipsychotic drugs for the treatment of schizophrenia provide effective treatment of psychotic symptoms but might lead to neuroendocrine abnormalities. OBJECTIVE: The aim of this study was to assess hypothalamic-pituitary-gonadal (HPG) axis function by comparing serum hormone profiles of newly admitted patients with psychotic disorders who were receiving antipsychotic drugs with those who were antipsychotic-drug-free during the preceding 6 months. METHODS: Adult male patients admitted during a 1-year period (December 1999 to December 2000) to 1 of 2 Brazilian public psychiatric inpatient units that provide care for severely ill patients were eligible for this cross-sectional study if they had a diagnosis of schizophrenia based on the criteria given in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and a score >24 on the Brief Psychiatric Rating Scale. On the morning after admission, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), prolactin, free testosterone (FT), and total testosterone (TT) were determined. A commercial laboratory provided the normal serum hormone concentrations of healthy Brazilian men in the same age range as that of the study patients. RESULTS: Sixty-three adult male patients, aged 18 to 55, were included in the study. Forty-eight (76.2%) patients (mean [SD] age, 30.6 [8.9] years) were receiving antipsychotic drugs (treated). Fifteen (23.8%) patients (mean [SD] age, 36.5 [9.8] years) were antipsychotic-drug-free for 6 months before admission (untreated). The only significant between-group difference was for disease duration (treated, 7.6 [8.1] years vs untreated, 12.3 [9.7] years; P = 0.044). Treated patients were more likely to have higher dispersed serum hormone concentrations than the untreated patients. Serum concentration of FSH was numerically higher in the treated patients than in the untreated patients, although the difference was not statistically significant. Compared with the control group (1436 men and women for prolactin; 226 men for LH; 207 for FSH; 128 for TT; 128 for FT; and 128 for SHBG), patients in the treated group had significantly different mean [SD] serum concentrations of all hormones (treated vs control: prolactin, 24.3 [23.7] µg/L vs 6.8 [0.12] µg/L, P < 0.001; LH, 4.9 [3.4] U/L vs 3.3 [0.13] U/L, P = 0.001; FSH, 4.4 [3.9] U/L vs 3.0 [0.06] U/L, P = 0.025; TT, 17.5 [7.8] nmol/L vs 20.1 [1.64] nmol/L, P = 0.004; FT, 0.056 [0.08] nmol/L vs 0.06 [0.003] nmol/L, P < 0.001; and SHBG, 33.3 [18.9] nmol/L vs 48.4 [1.45] nmol/L, P= 0.002). Compared with the control group, patients in the untreated group had significantly different mean (SD) serum concentrations of all hormones except FSH and TT (untreated vs control: prolactin, 19.9 [12.8] µg/L vs 6.8 [0.12] µg/L, P = 0.001; LH, 6.0 [1.9] U/L vs 3.3 [0.13] U/L, P = 0.002; FT, 0.08 [0.04] nmol/L vs 0.06 [0.003] nmol/L, P= 0.001; and SHBG, 26.6 [11.6] nmol/L vs 48.4 [1.45] nmol/L, P < 0.001). No differences were found between the TT distribution curve of the control group and that of the untreated patients. CONCLUSION: This study supports further investigation of a potential difference in the HPG axis among treated and untreated patients with schizophrenia and those who do not have that condition.