title: Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: a placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Multicentre, prospective, randomized, placebo controlled and double blind.
  
  
  METHODS
  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).
  
  
  METHODS
  Weekly assessment of adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: J
authors.initials: J
authors.lastname: Webster
authors.forename: G
authors.initials: G
authors.lastname: Piscitelli
authors.forename: A
authors.initials: A
authors.lastname: Polli
authors.forename: A
authors.initials: A
authors.lastname: D'Alberton
authors.forename: L
authors.initials: L
authors.lastname: Falsetti
authors.forename: C
authors.initials: C
authors.lastname: Ferrari
authors.forename: P
authors.initials: P
authors.lastname: Fioretti
authors.forename: G
authors.initials: G
authors.lastname: Giordano
authors.forename: M
authors.initials: M
authors.lastname: L'Hermite
authors.forename: E
authors.initials: E
authors.lastname: Ciccarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000077465:Cabergoline; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004873:Ergolines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D004873:Ergolines; D000077465:Cabergoline