Baptista T, Molina M G, Martinez J L, de Quijada M, Calanche de Cuesta I, Acosta A, Páez X, Martinez J M, Hernández L
Laboratory of Behavioral Physiology, Medical School, Universidad de los Andes, Mérida, Venezuela.
Pharmacopsychiatry. 1997 Nov;30(6):256-62. doi: 10.1055/s-2007-979503.
Metabolic and endocrine abnormalities secondary to hyperprolactinemia, such as hypogonadism and hyperandrogenicity, may be involved in the excessive 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 administration, 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; blood lipids and the serum levels of the following hormones which are involved in body weight regulation were assessed at days 3, 10, 20 and 26 of the cycle: prolactin (PRL), 17-beta estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (T5), dehydroepiandrosterone sulfate (DHEAS), cortisol, tyrotropic hormone (TSH), tetraiodothyroxine (T4), and the areas under the insulin and glucose tolerance curve. During sulpiride administration, the following changes were observed when compared to placebo administration: PRL levels were significantly increased; E2 levels were significantly reduced at days 10 and 20; P4 levels were significantly reduced at day 20, and the area under the glucose tolerance curve was significantly increased. The other variables were not significantly affected. The body weight gain was higher during sulpiride than during placebo administration, but it did not reach statistical significance, perhaps because the period of treatment was too short. The decrease in the serum levels of E2 during sulpiride administration is probably secondary to hyperprolactinemia. It affects the E2/T5 ratio in the direction of increasing the androgenic activity, as observed in women with well-established obesity. This effect, along with a genetic predisposition, increased appetite, hypoactivity and ignorance of proper dietary habits, may explain the excessive weight gain and obesity observed in women during chronic treatment with sulpiride and other antipsychotic agents.
高催乳素血症继发的代谢和内分泌异常，如性腺功能减退和高雄激素血症，可能与女性抗精神病药物所致的体重过度增加有关。本研究针对健康的绝经前女性开展，旨在检测抗精神病药物给药继发的内分泌失衡，若这种失衡长期持续存在，可能与肥胖的发生有关。在一个对照月经周期后，舒必利（200mg/天）或安慰剂进行非盲法给药28天；在月经周期的第3、10、20和26天评估参与体重调节的以下激素的血脂和血清水平：催乳素（PRL）、17-β雌二醇（E2）、孕酮（P4）、促卵泡激素（FSH）、促黄体生成素（LH）、游离睾酮（T5）、硫酸脱氢表雄酮（DHEAS）、皮质醇、促甲状腺激素（TSH）、四碘甲状腺原氨酸（T4）以及胰岛素和葡萄糖耐量曲线下面积。与安慰剂给药相比，舒必利给药期间观察到以下变化：PRL水平显著升高；E2水平在第10天和第20天显著降低；P4水平在第20天显著降低，葡萄糖耐量曲线下面积显著增加。其他变量未受到显著影响。舒必利给药期间的体重增加高于安慰剂给药，但未达到统计学显著性，可能是因为治疗期太短。舒必利给药期间血清E2水平降低可能继发于高催乳素血症。它影响E2/T5比值，使雄激素活性增加，这在肥胖确诊的女性中也有观察到。这种效应，连同遗传易感性、食欲增加、活动减少以及对适当饮食习惯的忽视，可能解释了舒必利和其他抗精神病药物长期治疗期间女性出现的体重过度增加和肥胖。
