Objective: To study the effect of drugs on the hypothalamo-pituitary-gonadal (HPG) axis we compared the endocrine actions of two neuroleptics with different receptor affinity profiles-risperidone and olanzapine in male schizophrenic patients.
Methods: We investigated the levels of prolactin, estradiol, testosterone, LH, FSH and testicular peptide hormone-inhibin B, and we assessed psychopathology (PANSS), sexual function (ASEX) and treatment adherence (DAI-10) in 89 male schizophrenic inpatients treated with olanzapine or risperidone administered orally. The initial and final evaluations were carried out at weeks 3 and 8 after the onset of treatment, respectively.
Results: At initial evaluation the mean serum prolactin and inhibin B levels were markedly higher, whereas testosterone level was lower in patients treated with risperidone, than in those treated with olanzapine. In 5 out of 50 subjects from risperidone group (10%) and in 1 from olanzapine group (2.6%) testosterone levels were below the lower limit (<241ng/ml), which reflected Leydig's cell impairment. In one patient receiving risperidone and in three receiving olanzapine, inhibin B level was below 80pg/ml, indicating Sertoli's cell dysfunction. At the final evaluation the mean serum prolactin level was markedly higher in patients taking risperidone, whereas their FSH levels were lower than in patients receiving olanzapine. In all investigated groups, except for the risperidone-hyperprolactinemic group inhibin B levels were negatively correlated with serum FSH. The mean LH, FSH, testosterone and estradiol levels were within the normal reference range at initial and final evaluation. The non-adherence to medications and ASEX scores were significantly higher in risperidone groups. Sexual dysfunction and medication non-adherence was not related to prolactin or gonadal hormone levels.
Conclusions: Risperidone elicited higher PRL elevation than olanzapine. Treatment with this medication can be associated with disturbances in reproductive hormones (testosterone) and gonadotropins (FSH). The cause of olanzapine-elicited reduction of inhibin B level and the lack of negative correlation between FSH and inhibin B in patients with risperidone-induced hyperprolactinemia require further investigation. Patients receiving risperidone showed higher level of sexual dysfunction and treatment non-adherence than those treated with olanzapine.