Rohr Uwe D, Herold Jens
Department of Gynecology and Obstetrics, University Hospital, Essen, Germany.
Maturitas. 2002 Apr 15;41 Suppl 1:S85-104. doi: 10.1016/s0378-5122(02)00017-8.
The pineal hormone melatonin is the mediator of external light to physiologic adaptation to day and night rhythms, it regulates reproduction in animals but attempts to utilize melatonin in women for contraception have failed. Melatonin seems to be the natural hormone to facilitate sleep in insomniac patients and causes no hang over. When applied together with benzodiazepine it allows reduction of benzodiazepine without withdrawal effects. It should be applied 2 h before sleeping time in doses between 3 and 5 mg. Melatonin acts via the gamma-aminobutyric acid- and benzodiazepine receptor explaining its success in treatment of seizures in children and in adults. Constant application of benzodiazepine reduced the production of natural melatonin in rats, supporting the evidence that long-term application of benzodiazepine in humans does not restore sleeping habits but reduces natural sleeping habits even more. Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. Some oncostatic properties are supported by cell culture work and studies in animals. In Nordic countries indigenous people suffer less from breast and prostate cancer, winter darkness seems to protect. The supposedly increased melatonin levels created the 'melatonin hypothesis'. Epidemiological studies did show that blind people indeed have half the rate of breast cancers, supporting the hypothesis. Controversial results concerning melatonin and insulin resistance and glucose tolerance have been published. In postmenopausal women application of melatonin reduced glucose tolerance and insulin sensitivity. Pregnant women should avoid melatonin, since its teratogenic effect is not known. Patients suffering from non-hormone dependent tumors, like leukemia, should avoid melanin, since tumor growth was promoted in animal experiments. It can be expected that melatonin will receive wide consideration for treatment of sleeping disturbances, jet lag, and fibromyalgia once an oral formulation becomes available in Europe.
松果体激素褪黑素是外界光线与昼夜节律生理适应之间的介导物,它调节动物的繁殖,但试图将褪黑素用于女性避孕的尝试却失败了。褪黑素似乎是促进失眠患者睡眠的天然激素,且不会产生宿醉效应。与苯二氮䓬类药物合用时,它能减少苯二氮䓬类药物的用量且无戒断反应。应在睡眠时间前2小时服用,剂量为3至5毫克。褪黑素通过γ-氨基丁酸和苯二氮䓬受体发挥作用,这解释了其在治疗儿童和成人癫痫方面取得成功的原因。持续使用苯二氮䓬类药物会降低大鼠体内天然褪黑素的分泌,这支持了长期在人类中使用苯二氮䓬类药物不会恢复睡眠习惯反而会进一步降低天然睡眠习惯的证据。在贪食症、神经痛患者以及纤维肌痛女性患者中发现褪黑素水平较低;补充褪黑素可减轻纤维肌痛和贪食症患者的疼痛、睡眠障碍及抑郁症状。褪黑素水平可作为一种诊断工具,用于区分几种形式的抑郁症,如重度抑郁症、冬季抑郁症(季节性情感障碍)、单相抑郁症、睡眠时相延迟综合征(DSPS)。在重度抑郁症患者中,抗抑郁药治疗成功与褪黑素水平升高相关,但只有DSPS患者能用褪黑素成功治疗。在围绝经期女性中,服用褪黑素确实会使促黄体生成素、促卵泡生成素和甲状腺激素发生变化。细胞培养研究和动物研究支持了褪黑素的一些抑癌特性。在北欧国家,原住民患乳腺癌和前列腺癌的几率较低,冬季的黑暗似乎起到了保护作用。据此提出了“褪黑素假说”。流行病学研究确实表明盲人患乳腺癌的几率只有正常人的一半,这支持了该假说。关于褪黑素与胰岛素抵抗和葡萄糖耐量的研究结果存在争议。在绝经后女性中,服用褪黑素会降低葡萄糖耐量和胰岛素敏感性。孕妇应避免使用褪黑素,因为其致畸作用尚不清楚。患有非激素依赖性肿瘤(如白血病)的患者应避免使用褪黑素,因为在动物实验中肿瘤生长会被促进。一旦欧洲有口服制剂上市,预计褪黑素将在治疗睡眠障碍、时差反应和纤维肌痛方面得到广泛应用。