Effect of Cabergoline on Metabolism in Prolactinomas

Abstract

Introduction: Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. Patients and Methods: 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. Results: Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022). Conclusions: CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB.

Effect of Chronic Cabergoline Treatment and Testosterone Replacement on Metabolism in Male Patients with Prolactinomas

“…In this light, the current results seem to support the hypothesis that visceral obesity might be mainly influenced by testosterone deficiency and that weight loss might reflect a direct beneficial effect of both CAB treatment and adequate androgen replacement. Interestingly, VAI was found to be significantly increased after short-term CAB in both the HG and non-HG patients and decreased after 24-month treatment, with similar values as when compared to baseline, thus confirming the previous speculation that the significant improvement of adipose tissue dysfunction may occur only after long-term CAB therapy [54] and suggesting a potential direct beneficial effect of TR on adipose dysfunction. The significant reduction in body weight, BMI and WC recorded in the current series could explain per se the clinically relevant improvement seen also in the lipid and glucose profile as well as the significant decrease in MetS prevalence.…”

“…In hyperprolactinemic patients receiving treatment with CAB, the decrease in body weight and body fat following PRL normalization has been ascribed mainly to the direct activation of dopamine type 2 receptor (D 2 R) by CAB [50]. The reduction in body weight after PRL normalization during treatment with dopamine agonists has been consistently documented in several investigations [54,71,72]. In the present study, short- and long-term treatment with CAB induced a significant reduction in weight, BMI and WC, suggesting a clinically relevant improvement of visceral obesity, as confirmed by the significant decrease in the MetS prevalence both after short- and long-term treatment.…”

“…Clinical and hormonal evaluations were performed as previously described [54]. At diagnosis and thereafter at 3- to 6-month intervals, all patients were admitted to the hospital for a complete physical, biochemical and endocrine examination.…”

“…Long-term CAB treatment [53] has been demonstrated to significantly ameliorate the lipid, glucose and insulin profile in patients with prolactinomas, independently of the degree of reduction in PRL levels, particularly in case of the employment of high doses [53]. Consistently, in patients with prolactinomas long-term therapy with CAB has recently been demonstrated to significantly reduce MetS prevalence, to improve lipid profile and to reduce insulin resistance by decreasing FI, HOMA-IR and homeostatic model assessment of insulin secretion (HOMA-β) and increasing insulin sensitivity index (ISI₀) [54], with the CAB dose being the best predictor of a percent decrease in FI [54]. Noteworthy, in men with prolactinomas the recovery of the gonadal function and testosterone deficiency, even beginning soon after starting CAB treatment, is fully achieved in approximately half of the patients during long-term treatment [55,56,57].…”

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

“…A glucose-lowering effect of this agent as well as of cabergoline (being the most potent dopamine receptor agonist) [14] seems to be secondary to resetting of dopaminergic and sympathetic tone within the central nervous system [15]. 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].…”