Different Effects of Cabergoline and Bromocriptine on Metabolic and Cardiovascular Risk Factors in Patients with Elevated Prolactin Levels

Abstract

Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine-resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin-like growth factor-1 (IGF-1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and circulating levels of IGF-1, free fatty acids (FFA), uric acid, highsensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA-IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post-challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine.Apart from oligomenorrhea, infertility, galactorrhoea, loss of libido and sexual dysfunction, long-term prolactin excess is often complicated by impaired glucose tolerance, hyperinsulinaemia, insulin resistance, atherogenic dyslipidaemia, subclinical atherosclerosis, endothelial dysfunction and weight gain [1][2][3][4][5][6][7][8]. These abnormalities may be alleviated or reversed by dopamine agonists, being the drugs of choice in the treatment of prolactin-secreting tumours and elevated prolactin levels secondary to other disorders [9]. Dopamine agonist-induced normalization of elevated prolactin levels reduced body-weight [7,10] and improved insulin receptor action [4]. The effect of cabergoline on waist circumference, plasma lipids, glycated haemoglobin, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), despite dose dependency, was observed regardless of the degree of reduction in prolactin levels [11]. Cabergoline administered to patients with newly diagnosed prolactinoma exerted systemic anti-inflammatory effects, as well as reduced carotid intima-media thickness, and these effects were independent from a decrease in prolactin levels, b...

Different Effects of Atorvastatin on Cardiometabolic Risk Factors in Young Women With and Without Hyperprolactinemia

“…Although lipid levels slightly correlated with plasma levels of extralipid markers assessed in our study, differences in baseline concentrations of uric acid, hsCRP, homocysteine, and fibrinogen do not seem to result from dyslipidemia because all groups of patients were characterized by similar levels of plasma lipids. Interestingly, previously we found that both bromocriptine and cabergoline reduced circulating levels of cardiovascular risk factors, but the effect of cabergoline, which is a more potent prolactin‐lowering agent than bromocriptine, was stronger . These findings and the results of our current study may suggest that oligosymptomatic or asymptomatic women with hyperprolactinemia should be treated with dopamine agonists to reduce cardiometabolic risk.…”

“…Interestingly, previously we found that both bromocriptine and cabergoline reduced circulating levels of cardiovascular risk factors, but the effect of cabergoline, which is a more potent prolactin-lowering agent than bromocriptine, was stronger. 29 These findings and the results of our current study may suggest that oligosymptomatic or asymptomatic women with hyperprolactinemia should be treated with dopamine agonists to reduce cardiometabolic risk. From a cardiometabolic point of view, dopaminergic agents are better drugs than those used by some symptomatic women with hyperprolactinemia oral contraceptive pills, which were found to increase circulating levels of cardiometabolic risk factors.…”

The Effect of Atorvastatin on Cardiometabolic Risk Factors in Bromocriptine‐Treated Premenopausal Women with Isolated Hypercholesterolemia

“…In turn, our patients were included only if total and LDL cholesterol levels were elevated and many of them had glucose metabolism abnormalities. For this reason and because pleiotropic effects of dopamine receptors agonists partially correlated with the effects on plasma prolactin [19], it may be assumed that concentrations of the assessed biomarkers would be lower than in our study if participants received higher doses of bromocriptine, stronger reducing plasma prolactin. Importantly, plasma levels of the investigated variables were similar to those found in prolactin-matched women receiving chronic metformin therapy.…”

“…Beyond lowering fasting [16][17][18] and postchallenge [10] plasma glucose, which was accompanied by an improvement in insulin sensitivity [16,[18][19][20][21] and a decrease in glycated hemoglobin [18], dopamine agonists reduced plasma lipids [16,18,19], body mass index [22,23], waist circumference [24], visceral adiposity [18,21], circulating levels of cardiometabolic risk factors [18][19][20]25], and the prevalence of metabolic syndrome [21]. These cardiometabolic effects of dopamine agonists depended on dose [18] but were only partially associated with the effect of treatment on circulating prolactin levels [19]. They may partially explain why in a long-term, randomized, double-blind trial, quick-release bromocriptine, in addition to their usual diabetes therapy, led to a reduction in the composite cardiovascular endpoint by 42% [26].…”

A polycystás ovarium szindróma szövődményeinek prevenciója, kezelése és a kórkép bizonyítékokon alapuló, interdiszciplináris ellátásának fontossága

“…A hyperprolactinaemia nemcsak a menstruációt és a peteérést befolyásolja, hanem a szénhidrát-és a lipidanyagcserére is kedvezőtlen hatása van. Mind a bromocriptin, mind a Magyarországon nem forgalmazott cabergolin kedvező-en csökkenti a prolaktinszintet és a HOMA-IR-t, de a cabergolin kedvezőbb a többi cardiovascularis rizikófak-tor -IGF-1, FFA, húgysav, hsCRP, homocisztein, fi brinogén, HDL-C, 25(OH)D -szempontjából [24]. A cabergolin nem cukorbeteg elhízottaknál csökkenti az inzulin-és a vércukorszintet [25].…”