Effects of quetiapine on body mass index and reproductive hormonal levels in male schizophrenic patients

Objective: To asses the effects of quetiapine therapy on body mass index (BMI) and serum level of testosterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in newly diagnosed male schizophrenic patients in comparison to healthy controls. Patients and methods: Thirty male patients with schizophrenia were included in this study. The diagnosis of schizophrenia was made according to DSM-IV criteria of the American Psychiatric Association (APA). Another thirty apparently healthy male individuals were included in the study as a control group. Blood samples were taken initially from patients and controls and assay of serum testosterone, prolactin, FSH, LH, and E2 were done using enzyme –linked fluorescent immunoassay (ELFA) technique by vidas instrument. Later, after 6 months of quetiapine therapy, other blood samples were taken and assay of the same parameters were done. Calculation of BMI was done for the patients and controls using special equation. Results: There was an insignificant difference in the mean BMI, serum testosterone, prolactin, FSH, LH, and E2 levels between patients in the pre-therapy stage group and in both the post-therapy stage group and controls. Conclusion: Chronic quetiapine therapy might be regarded as a safe drug with regard to effects on BMI and serum levels of reproductive hormones in newly diagnosed male schizophrenic patients.

. It was approved in September 1997 by the Food and Drug Administration (FDA) and has since been introduced in most western European countries as well as in 70 other countries worldwide for the treatment of schizophrenia and related psychotic illnesses (2) .The use of atypical or second generation antipsychotic drugs is gaining popularity as a result of their tolerability and efficacy (3) .However, the use of these drugs has been associated with metabolic and endocrinal adverse effects beside their effects on body weight (4,5) .
According to our knowledge, no study was done previously evaluating the effect of quetiapine on BMI, testosterone, prolactin, FSH, LH and E2, so the present study was conducted to assess the effect of quetiapine therapy on such parameters in newly diagnosed male schizophrenic patients.

Patients and methods
Out of the 37 selected newly diagnosed patients with schizophrenia, only 30 patients completed the study.Patients were referred from private psychiatric clinics.The criteria of selection included: newly diagnosed male patients, above the age of 20 years (mean± SD 33.70±6.17years, ranged between 21 and 41 years), cooperative relatives, no other diseases (cardiovascular, hepatic, renal or endocrinal).Diagnosis of schizophrenia was made according to DSM-IV criteria of American Psychiatric Association (APA).Another thirty healthy male individuals above the age of 20 years (mean ± SD 32.62± 5.06 years, ranged between 21 and 42 years) participated in the study as a control group.
Initially, blood samples were taken from patients and controls and assay of serum levels of testosterone, prolactin, FSH, LH, and E2 were done using enzyme-linked fluorescent assay (ELFA by VIDAS instrument using commercial kits for each hormone from bioMerieux -Lyon-France).Patients then put on quetiapine (Seroquel) in a daily dose ranged between 200 mg and 400 mg for 6 months.By the end of the suggested period of the study, another blood samples were taken and assay of the same parameters was done.BMI was calculated for both patients and controls using the following equation: BMI = Weight (kg) / Height (m 2 ) (6)

Statistical methods
Standard statistical methods were used to determine the mean and standard deviation (SD).Unpaired t-test was used to compare the results of measured parameters of patients in the (pre and post-therapy stages) and controls.Paired t-test was used to compare the results of measured parameters in patients in the preand post-therapy stages.P-values equal or less than 0.05 were considered significant (7) .

Results
There were insignificant differences in the mean values of BMI, serum levels of testosterone, prolactin, FSH, LH, and E2 in patients in the pre-and post-therapy stages and the controls (Table 1).
There were insignificant differences in the mean values of BMI, serum levels of testosterone, prolactin, FSH, LH, and E2 in patients in the pre-and post-therapy stage groups (Table 2). Q

Discussion
The present study demonstrated that schizophrenic patients have normal BMI and that the administration of quetiapine for 6 months to schizophrenic male patients resulted in a non significant effects on BMI and serum levels of testosterone, prolactin, FSH, LH, and E2.Emsley et al (8) , in a randomized control trial, studied the effects of quetiapine and haloperidol on BMI and glycemic control.They reported that switching treatment from a conventional antipsychotic to quetiapine is not associated with weight gain or worsening of glycemic control even in the long term therapy which is also in agreement of this study.Furthermore, Gorobets (5) studied the weight gain in patients with schizophrenia and schizoaffective disorders induced by the long term treatment with atypical antipsychotic drugs.He concluded that long term therapy with olanzepine, clozapine and risperidone exert a more marked influence on the body mass as compared to quetiapine and amrisulpiride regardless of the patient sex, which is consistent with our findings.
Regarding serum levels of reproductive hormones and in agreement with our findings, Kaneda and Ghmor (9) , evaluated the effect of quetiapine administration for a mean duration of 104.7 days on hypothalamic-pituitarygonadal axis (HPG) hormones in patients with chronic schizophrenia and reported that quetiapine might not affect prolactin and HPG axis hormones at least in chronic schizophrenic patients with normal levels of HPG axis hormones.On the same line but with other atypical antipsychotic drugs, Konarzewska et al (10) studied the effects of risperidone and olanzapine on reproductive hormones, psychopathology, and sexual functioning in male patients with schizophrenia.They reported that the mean serum prolactin level was markedly higher in patients taking risperidone, whereas FSH levels were lower than in patients receiving olanzapine, and the mean levels of LH, testosterone, and estradiol were within normal reference ranges.

Conclusion
Chronic quetiapine therapy might be regarded safe, with regard to effects on BMI and serum levels of reproductive hormones in newly diagnosed male patients with schizophrenia.

Table ( 1
): Comparison of BMI and serum sex hormones levels between patients and control.
* Non significant difference at p< 0.05.