The safety of dopamine agonists: clinical perspectives
Dopamine agonists (DA) are very effective and the first-line treatment for hyperprolactinemia. In prolactinoma, DA therapy is the treatment of choice. DA decrease prolactin levels, restore gonadal function, improve visual field defects and reduce tumor size. In some patients drug therapy can lead to a complete remission, including eradication of the tumor, and thereby allow discontinuation of treatment. The majority of the patients, however, have to be treated for many years. Cabergoline is the most potent DA and, due to its favorable pharmacokinetic profile and good tolerance, is the most commonly used DA in the treatment of prolactinoma. Recently, however, questions regarding safety of medical treatment of prolactinoma patients with cabergoline emerged when reports indicated an increased risk of fibrotic valvulopathy in patients with Parkinsons disease treated with the ergot-derived DA pergolide or cabergoline. These ergot-derived DA have binding affinity for D2-receptors as well as serotonin receptors, especially 5HT2B which are highly expressed on cardiac valves. Stimulation of 5-HT2B receptors activates fibroblast mitogenesis, leading to valvular fibrosis and subsequent valvular dysfunction. Prospective trials evaluating the effect of DA on cardiac valves in patients with prolactinoma have not been performed, but to date, observational studies have not reported clinical relevant cardiac valve disease after treatment with cabergoline for prolactinomas. The findings obtained with much higher cumulative doses of cabergoline in Parkinson patients, however, underscore that unnecessary prolongation of treatment is undesirable. Another safety issue in the treatment of prolactinomas with DA is pregnancy: Restoration of ovulation and fertility might expose early fetal development to potential effects of DA before a pregnancy is diagnosed. Bromocriptine and cabergoline appear to be safe, although data on pregnancy outcome for the latter are limited. Finally, the safety and efficacy of DA after reintroduction for symptomatic growth of a macroprolactinoma, will be discussed.