A Comparative Review of the Tolerability Profiles of Dopamine Agonists in the Treatment of Hyperprolactinaemia and Inhibition of Lactation

Abstract

Dopamine agonists are the treatment of choice for the majority of patients with hyperprolactinaemic disorders. Although characterised by a relatively high incidence of adverse effects, most commonly gastrointestinal, cardiovascular and neurological, these are usually mild and transient, and can be minimised by starting with a low dose and gradually increasing it, or taking the drug with food or while recumbent. Bromocriptine, introduced in 1971, is the reference preparation against which newer dopamine agonists are compared. It is effective in suppressing prolactin secretion, reducing prolactinoma size and restoring gonadal function. However, up to 12% of patients cannot tolerate the drug at therapeutic dosages. Cabergoline, a long-acting dopamine agonist administered once or twice weekly, has been shown to be significantly more effective than bromocriptine in suppressing prolactin secretion in hyperprolactinaemic patients, and is better tolerated, particularly in terms of nausea and vomiting. In suppressing physiological lactation, cabergoline is at least as effective as bromocriptine, and is associated with significantly fewer rebound symptoms and adverse effects. Quinagolide is a non-ergot dopamine agonist that is administered once daily. It has similar efficacy to bromocriptine, but is probably less effective than cabergoline in hyperprolactinaemic patients; it is not licensed for suppression of lactation. It is better tolerated than twice-daily bromocriptine, but is probably inferior to cabergoline in this regard. Neither bromocriptine, cabergoline nor quinagolide has been associated with any detrimental effect on pregnancy or fetal development. However, experience with bromocriptine is far more extensive; thus, for women requiring treatment for subfertility, this drug remains the treatment of choice in most centres, with cabergoline and quinagolide as acceptable second-line drugs in bromocriptine-intolerant patients. In hyperprolactinaemic men, hyperprolactinaemic women not wishing to become pregnant, and for suppression of physiological lactation, cabergoline is recommended as first-line treatment.

ENDOCRINOLOGY IN PREGNANCY: Management of the pregnant patient with a prolactinoma

“…There were nine fetal malformations reported, including spina bifida, Trisomy 13, Down syndrome, talipes, cleft lip, arrhinencephaly, and Zellweger syndrome (39). Thus, quinagolide does not appear to be safe for the fetus if used when pregnancy is desired.…”

Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients

“…Bromocriptine, an ergot derivative that binds to and stimulates dopamine (D2) receptors on lactotroph cells, represents the initial and therefore reference compound. It has proved to be effective in suppressing PRL secretion, reducing prolactinoma size and restoring gonadal function in many studies (2)(3)(4)(5)(6)(7). In a collaborative European multicenter study on 459 women with prolactinomas, normoprolactinemia was achieved with bromocriptine in 59% (8).…”

“…However, up to 12% of these patients did not tolerate the drug in therapeutic doses because of side effects and 5-10% of patients showed only minimal or no response after bromocriptine therapy (8,9). Cabergoline, a long-acting dopamine agonist, has been shown to be more effective (83%) (8) than bromocriptine with a marked reduction in adverse effects (7,8,(10)(11)(12)(13)(14)(15). Thus, cabergoline and also quinagolide started to progressively replace bromocriptine in the medical therapy of prolactinomas during the last decade (16)(17)(18)(19)(20).…”

Aspectos clínicos e terapêuticos de prolactinomas em homens

“…Esta média foi semelhante às utilizadas em estudos sobre o uso de cabergolina em macroprolactinomas 22,23 . Os resultados relativos aos efeitos adversos com os agonistas dopaminérgicos confirmam os da literatura que descrevem menos efeitos colaterais com a cabergolina 24 . Apesar disto, há um grupo de pacientes que claramente se beneficiou da bromocriptina.…”