EFFECTS OF THE ANTIPSYCHOTIC DRUG SULPIRIDE ON REPRODUCTIVE HORMONES IN HEALTHY PREMENOPAUSAL WOMEN - RELATIONSHIP WITH BODY-WEIGHT REGULATION

Metabolic and endocrine abnormalities secondary to hyperprolactinemia, such as hypogonadism and hyperandrogenicity, may be involved in the e xcessive body weight gain induced by antipsychotic drugs in women. The present study was conducted in healthy premenopausal women, in order to detect an endocrine imbalance secondary to antipsychotic drug admin istration, which, if sustained in the long term, might be involved in the development of obesity. After a control menstrual cycle, sulpiride (200 mg/day) or placebo was nonblindly administered for 28 days; bloo d lipids and the serum levels of the following hormones which are invo lved in body weight regulation were assessed at days 3, 10, 20 and 26 of the cycle: prolactin (PRL), 17-beta estradiol (E-2), progesterone ( P-4), follicle stimulating hormone (FSH), luteinizing hormone (LH), fr ee testosterone (T-5), dehydroepiandrosterone sulfate (DHEAS), cortiso l, tyrotropic hormone (TSH), tetraiodothyroxine (T-4), and the areas u nder the insulin and glucose tolerance curve. During sulpiride adminis tration, the following changes were observed when compared to placebo administration: PRL levels were significantly increased; E-2 levels we re significantly reduced at days 10 and 20; P-4 levels were significan tly reduced at day 20, and the area under the glucose tolerance curve was significantly increased. The other variables were not significantl y affected. The body weight gain was higher during sulpiride than duri ng placebo administration, but it did not reach statistical significan ce, perhaps because the period of treatment was too short. The decreas e in the serum levels of E-2 during sulpiride administration is probab ly secondary to hyperprolactinemia. It affects the E-2/T-5 ratio in th e direction of increasing the androgenic activity, as observed in wome n with well-established obesity. This effect, along with a genetic pre disposition, increased appetite, hypoactivity and ignorance of proper dietary habits, may explain the excessive weight gain and obesity obse rved in women during chronic treatment with sulpiride and other antips ychotic agents.