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To the Editor:

Cabergoline is a new long-acting dopamine receptor agonist that is usedfor the treatment of hyperprolactinemic disorders. Binding studies showthat cabergoline has high affinity for dopamine D2 receptors and lowaffinity for dopamine D1, α1- and α2-adrenergic, and 5-HT1- and5-HT2-serotonin receptors. After noting weight loss in a number ofpatients treated with cabergoline for hyperprolactinemia in ourNeuroendocrine Unit, we conducted a retrospective chart review todetermine the effect of cabergoline on body weight in this population. Patients with panhypopituitarism or previously treated with anotherdopamine agonist were excluded. Of the 27 patients who met thesecriteria, initial and follow-up body weights were available for 16patients (10 men; 6 women), and height measurements used to calculatebody mass index were available for 13 patients. Mean initial bodyweight ± SEM was 86.1 ± 5.0 kg, and initial body mass indexwas 30.0 ± 1.6 kg/m2. The mean dose ofcabergoline was a total of 0.92 ± 0.14 mg per week, and the meanduration of therapy was 13.5 ± 1.7 months. The mean change inweight was −6.1 ± 1.4 kg (p < 0.001 by pairedStudent's t test of initial and final weights). Of the 16patients, 13 patients lost weight, 1 remained stable, and 2 gainedweight (Figure 1). The mean percentage of change in body weight was −7.0 ± 1.5%:five patients lost 5% to 10% and four patients lost >10% of initialbody weight. Of the 16 patients, 10 reported side effects that could beattributable to cabergoline: dizziness, n = 3;fatigue/sleepiness, n = 3; nausea, n =3; paresthesias/tremor, n = 2; depression,n = 2; headache, n = 1; and vomiting,n = 1. Symptoms resolved within the first few weeks oftherapy without a change in dosage, except in one case when the dosewas reduced from 1 mg to 0.5 mg twice per week with resolution ofdizziness and nausea.

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Figure 1. : Change in body weight for 16 patients on cabergoline for hyperprolactinemia. Symbols indicate weekly dose: ♦, ≤0.5 mg; ▵, ≥1.0 and <2.0 mg; •, ≥2.0 mg. Solid line: men. Dashed line: women.

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The contribution of the dopaminergic system to the regulation of bodyweight has been difficult to elucidate because of the presence ofmultiple receptor subtypes throughout the nervous system and theeffects of dopamine on motor activity. Weight loss has been reported inobese leptin deficient ob/ob mice after dopamineadministration (1), and weight gain with administration ofdopamine antagonists in rodents and humans (2)(3). On theother hand, dopamine-deficient mice are hypophagic (4), and dopamine is required for hyperphagia in ob/ob mice(5). These apparently discrepant results are indicative ofthe complex role of dopamine in food intake.

There is some evidence that hyperprolactinemia is associated withobesity and that patients with prolactinomas treated withbromocriptine, another D2 receptor agonist, lose weight(6). Others have studied the effects on body weight of aquick release form of bromocriptine in patients without prolactinomas, but the results of these studies have been variable, and interpretationis complicated because of differences in study design and adverseeffects of nausea and vomiting (7)(8)(9). This is the firstreport to date that notes a weight loss effect from cabergolinetreatment. Cabergoline is longer acting and better tolerated thanbromocriptine (10). The results of this study suggest thatcabergoline may be an effective weight reduction therapy, and the useof this medication for the treatment of obesity warrants furtherinvestigation.

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