Webster J, Piscitelli G, Polli A, D'Alberton A, Falsetti L, Ferrari C, Fioretti P, Giordano G, L'Hermite M, Ciccarelli E
Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Clin Endocrinol (Oxf). 1992 Dec;37(6):534-41. doi: 10.1111/j.1365-2265.1992.tb01485.x.
Dopamine agonists have a well established place in the treatment of hyperprolactinaemic disorders but their use is associated with a high incidence of adverse effects. We have investigated the biochemical efficacy and side-effect profile of a range of doses of the novel, long-acting dopamine agonist, cabergoline, in suppressing prolactin (PRL) in hyperprolactinaemic women.
Multicentre, prospective, randomized, placebo controlled and double blind.
One hundred and eighty-eight women with hyperprolactinaemia secondary to microprolactinoma (n = 113), idiopathic disease (n = 67), empty sella syndrome (n = 7) or following failed surgery for a macroprolactinoma (n = 1).
Weekly assessment of adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function.
Patients received either placebo (n = 20) or cabergoline 0.125 (n = 43), 0.5 (n = 42), 0.75 (n = 42) or 1.0 mg (n = 41) twice weekly for 4 weeks. The five treatment groups were comparable in age (mean 31.8, range 16-46 years), diagnosis, previous therapy, and pretreatment serum PRL. PRL was suppressed to below half the pretreatment level in 5, 60, 90, 95 and 98% and normalized in 0, 30, 74, 74 and 95% of patients taking placebo or cabergoline 0.125, 0.5, 0.75 or 1.0 mg twice weekly respectively (Armitage's test, chi 2 = 39.3, P < 0.01). Cabergoline therapy (all doses) restored menses in 82% of the amenorrhoeic women not previously treated with dopamine agonists. Adverse events were recorded in 45% of patients in the placebo group and in 44, 50, 50 and 58% of those taking 0.125, 0.5, 0.75 and 1.0 mg cabergoline twice weekly (Armitage's test, P > 0.05). Over 95% of reported symptoms were relatively trivial, most frequently transient nausea, headache, dizziness, fatigue and constipation. More severe adverse events, interfering significantly with the patients' lifestyle, occurred in 13 (7.7%) patients taking cabergoline; treatment withdrawal was necessary in only one case. No adverse effects were detected on blood pressure or haematological or biochemical parameters.
We have shown a linear dose-response relationship for cabergoline in the treatment of hyperprolactinaemia in the range 0.125-1.0 mg twice weekly, with normalization of PRL in up to 95% of cases and acceptable tolerability throughout the dose range.
多巴胺激动剂在高泌乳素血症性疾病的治疗中具有公认的地位，但其使用与高不良反应发生率相关。我们研究了一系列剂量的新型长效多巴胺激动剂卡麦角林在抑制高泌乳素血症女性泌乳素（PRL）方面的生化疗效和副作用情况。
多中心、前瞻性、随机、安慰剂对照、双盲。
188名高泌乳素血症女性，继发于微泌乳素瘤（n = 113）、特发性疾病（n = 67）、空蝶鞍综合征（n = 7）或大泌乳素瘤手术失败后（n = 1）。
每周评估不良症状、血压和脉搏、血清PRL、血常规、肝肾功能。
患者接受安慰剂（n = 20）或卡麦角林0.125mg（n = 43）、0.5mg（n = 42）、0.75mg（n = 42）或1.0mg（n = 41），每周两次，共4周。五个治疗组在年龄（平均31.8岁，范围16 - 46岁）、诊断、既往治疗及治疗前血清PRL方面具有可比性。接受安慰剂或每周两次服用0.125mg、0.5mg、0.75mg或1.0mg卡麦角林的患者中，PRL被抑制至治疗前水平一半以下的比例分别为5%、60%、90%、95%和98%，PRL恢复正常的比例分别为0%、30%、74%、74%和95%（Armitage检验，χ2 = 39.3，P < 0.01）。卡麦角林治疗（所有剂量）使82%既往未用多巴胺激动剂治疗的闭经女性恢复月经。安慰剂组45%的患者记录到不良事件，每周两次服用0.125mg、0.5mg、0.75mg和1.0mg卡麦角林的患者中，不良事件发生率分别为44%、50%、50%和58%（Armitage检验，P > 0.05）。超过95%报告的症状相对轻微，最常见的是短暂性恶心、头痛、头晕、疲劳和便秘。服用卡麦角林的患者中有13例（7.7%）出现严重不良事件，显著影响患者生活方式；仅1例需要停药。未检测到对血压或血液学及生化参数的不良影响。
我们已表明卡麦角林在每周两次0.125 - 1.0mg剂量范围内治疗高泌乳素血症时存在线性剂量反应关系，高达95%的病例PRL恢复正常，且在整个剂量范围内耐受性可接受。
