Macroprolactinaemia modulates cardiometabolic effects of fenofibrate in men with atherogenic dyslipidaemia: A pilot study

Abstract

What is known and objective: Cardiometabolic effects of hypolipidaemic agents depend on plasma levels of monomeric prolactin. Although macroprolactinaemia seems to be associated with increased cardiometabolic risk, no previous study has investigated whether macroprolactinaemia modulates pleiotropic effects of hypolipidaemic agents. Methods: The study population included two age-, weight-, blood pressure-and lipidmatched groups of men: 12 men with elevated levels of big-big prolactin and 16 men with prolactin levels within the reference range. Because of atherogenic dyslipidaemia, all subjects were treated for 6 months with fenofibrate (200 mg daily). Glucose homeostasis markers and plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D, were determined in patients at the beginning and at the end of the study. Results and discussion: Men with elevated levels of big-big prolactin were characterized by higher levels of hsCRP and fibrinogen and lower levels of 25-hydroxyvitamin D as well as decreased insulin sensitivity than subjects with prolactin levels within the reference range. In men without macroprolactinaemia, fenofibrate decreased circulating levels of total and LDL cholesterol, triglycerides, uric acid, hsCRP and fibrinogen, and increased concentrations of HDL cholesterol, homocysteine and 25-hydroxyvitamin D, as well as improved insulin sensitivity. In subjects with macroprolactinaemia, fenofibrate action was limited to the changes in HDL cholesterol, triglycerides, hsCRP and homocysteine. With the exception of homocysteine, cardiometabolic effects of fenofibrate were stronger in subjects without than in subjects with elevated levels of big-big prolactin. What is new and conclusion: The results of the study indicate that macroprolactinaemia exerts a negative impact on cardiometabolic effects of fenofibrate.

Macroprolactinemia Attenuates the Impact of Levothyroxine on Hypothalamic‐Pituitary‐Thyroid Axis Activity and Thyroid Autoimmunity in Women With Autoimmune Hypothyroidism

“…Negative predictors of the changes in hormone levels and antibody titers in our study were total prolactin levels and macroprolactin content, inversely correlating with levothyroxine action. Interestingly, both prolactin before polyethylene glycol precipitation and big‐big prolactin were found to be sensitive markers for hypolipidemic and pleiotropic effects of hypolipidemic drugs in our previous studies 12,13 . The presence of a correlation between macroprolactin and total prolactin in women with macroprolactinemia indicates that both variables were reciprocally related.…”

“…Subjects with diabetes and elevated levels of big‐big prolactin were characterized by higher values of glycated hemoglobin than their counterparts with diabetes and prolactin levels within the reference range 9 . Irrespective of sex, the presence of macroprolactinemia increased circulating levels of cardiometabolic risk factors, 10,11 as well as impaired lipid‐lowering and pleiotropic effects of statins and fibrates 12,13 …”

The impact of vitamin D status on cardiometabolic effects of fenofibrate in women with atherogenic dyslipidemia

“…These pleiotropic effects partially explain why fibrate treatment may bring cardiovascular benefits, which are observed mainly in subjects with atherogenic dyslipidaemia 4,5 . Unfortunately, some endocrine disorders may negatively affect extra‐lipid properties of hypolipidaemic agents 6‐11 . Previous studies showed that pleiotropic effects of fenofibrate were attenuated by thyroid hypofunction, 9 elevated levels of monomeric prolactin 10 and macroprolactinemia, 11 despite the fact that these studies included only patients with mild or moderate forms of these disorders (for ethical reasons subjects with overt hypothyroidism and severe prolactin excess were excluded).…”

“…Unfortunately, some endocrine disorders may negatively affect extra‐lipid properties of hypolipidaemic agents 6‐11 . Previous studies showed that pleiotropic effects of fenofibrate were attenuated by thyroid hypofunction, 9 elevated levels of monomeric prolactin 10 and macroprolactinemia, 11 despite the fact that these studies included only patients with mild or moderate forms of these disorders (for ethical reasons subjects with overt hypothyroidism and severe prolactin excess were excluded). However, if hypothalamic–pituitary–thyroid axis activity or prolactin concentrations were normalized by levothyroxine or dopamine agonist treatment, 9,10 the strength of pleiotropic effects of fenofibrate did not differ in comparison to subjects with intact hypothalamic–pituitary–thyroid axis activity or intact lactotroph function.…”