Baptista T, Lacruz A, Angeles F, Silvera R, de Mendoza S, Mendoza M T, Hernández L
Department of Physiology, Los Andes University Medical School, Merida, Venezuela.
Pharmacopsychiatry. 2001 Nov;34(6):223-31. doi: 10.1055/s-2001-18034.
In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.
在本研究中，作者评估了长期接受典型抗精神病药物（AP）治疗的肥胖和非肥胖女性的内分泌系统及糖耐量。具体而言，我们检验了以下假设：与体重匹配的健康对照组相比，这些受试者存在性腺功能减退和胰岛素抵抗增加的情况，因为这些异常会导致体重过度增加的倾向。26名接受AP治疗的女性与26名健康女性在年龄、体重指数和月经周期日方面进行了匹配。对每位受试者评估了以下血清变量：口服葡萄糖负荷后的糖耐量、胰岛素、瘦素、β-内啡肽、生殖激素、肾上腺类固醇和脂质。与对照组相比，接受AP治疗的女性基础血糖、葡萄糖负荷60分钟后的胰岛素、催乳素、促甲状腺激素和β-内啡肽水平显著更高，而C肽、孕酮、17-羟孕酮、雄烯二酮和高密度脂蛋白胆固醇水平更低。两组之间雌二醇、雌酮和瘦素水平无差异。因此，接受典型AP治疗的女性似乎比健康对照组表现出更多的胰岛素抵抗，使她们易于体重过度增加。当受试者改用非典型AP给药时，胰岛素敏感性可能会进一步受损。二甲双胍及相关药物可能会减轻这些受试者的体重。阿片类β-内啡肽水平升高表明，纳洛酮和纳曲酮等阿片类拮抗剂可能也有用。尽管月经周期的黄体期似乎受到严重干扰，但雌二醇和雌酮的正常血清水平并不支持来自动物实验研究中关于使用雌激素或他莫昔芬来对抗AP诱导的肥胖的提议。
