Cabergoline for hyperprolactinemia: getting to the heart of it

Excerpt

The hypothesis that dopamine agonists cause valvular heart disease stems from prior case reports and clinical studies in men with Parkinson’s disease [1, 2]. The finding that subtype 2 5-hydroxy tryptamine (5HT2B) receptor activation is responsible for cardiac valvular disease associated with certain serotonergic drugs, particularly the appetite suppressor, fenfluramine, supports the concept that dopamine agonists might cause cardiac valvular damage via stimulation of the this receptor [3]. The 5HT2B receptor is widely expressed in cardiac valves and its activity results in fibroblast proliferation and structural abnormalities, as demonstrated in heart disease promoted by carcinoid tumors which produce excessive serotonin [4]. Cabergoline, a highly effective drug for the therapy of hyperprolatinemia, while known to activate the 5HT2B receptor [5], was not proven to cause cardiac risk until 2007, when two studies in the New England Journal of Medicine (NEJM) reported that dopamine agonists were associated with valvular regurgitation in men treated for Parkinson’s [1, 2]. This revelation caused a stir among endocrinologists and pituitary specialists throughout the world, since the use of dopamine agonists as first-line therapy for the treatment of prolactinomas was the standard of care. …