Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women

Abstract

Background: Hyperprolactinemia has been reported to be associated with abnormalities of carbohydrate metabolism. The aim of this study was to evaluate the effects of hyperprolactinemia and bromocriptine (Brc) treatment on endothelial function, insulin sensitivity and inflammatory markers in pre-menopausal women. Methods: Sixteen hyperprolactinemic pre-menopausal women with pituitary adenomas were recruited and 20 healthy subjects were included as controls. Patients were given Brc in doses of 2.5-20 mg/dl until normal levels of prolactin were reached. Prior to treatment and 2 months after prolactin levels were normalized, the following tests were performed. Insulin sensitivity was determined by an oral glucose tolerance test based on a formula named the insulin sensitivity index (ISI composite). Endothelial function was measured as flow-mediated dilatation (FMD) on a brachial artery using high resolution ultrasound. Results: Serum glucose, insulin, estrogen, highly sensitive C-reactive protein (hsCRP), fibrinogen, homocysteine and uric acid levels were measured. Calculated ISI composite and FMD were significantly lower in the hyperprolactinemic group in comparison with the controls and improved after Brc treatment. Serum homocysteine, hsCRP and uric acid levels were significantly higher in hyperprolactinemic patients than in the controls and returned to normal levels with Brc treatment. Serum prolactin concentrations were inversely correlated with FMD measurements (r ¼ 20.68; P , 0.0001), ISI composite (r ¼ 2 0.48; P , 0.005) and serum estrogen (r ¼ 2 0.54; P , 0.005), and positively correlated with serum homocysteine concentrations (r ¼ 0.55; P , 0.0001) in the hyperprolactinemic group. Conclusions: The hyperprolactinemic state is associated with impaired endothelial function and decreased insulin sensitivity, which are early markers of atherosclerosis. These alterations may predispose to the development of atherosclerosis in non-treated cases. Correction of the hyperprolactinemic state is associated with improved endothelial function and insulin sensitivity.

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

“…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].…”

“…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].…”

Increased Lipid Levels Improves after Treatment with Cabergolin in Patients with Prolactinoma

“…Lipid abnormalities such as, hypercholesterolemia, hypertriglyceridemia and normal lipid profiles are reported in prolactinoma patients [14,18,19]. Some studies have suggested the influence of hyperprolactiemia on the lipid profile but the mechanism is not well established.…”

Hormones and Arterial Stiffness in Patients with Chronic Kidney Disease

“…Hyperprolactinemia is related to endothelial dysfunction and adverse cardiovascular outcomes in the general population, possibly as a result of the vasoconstrictive properties of prolactin 72) . Therefore, an elevation of the prolactin levels is observed in patients with essential hypertension, acute coronary syndrome, ischemic stroke, preeclampsia and heart failure that accompanies postpartum cardiomyopathy [73][74][75][76][77] .…”