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Macroprolactinaemia modulates cardiometabolic effects of fenofibrate in men with atherogenic dyslipidaemia: A pilot
Robert Krysiak1, Karolina Kowalcze2, Bogusław Okopień1
1Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
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 lipid-matched 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.
Insights
Macroprolactinaemia, characterized by elevated big-big prolactin, reduces the beneficial cardiometabolic effects of fenofibrate. This condition impairs insulin sensitivity and diminishes the drug's impact on lipids and inflammation markers.
Area of Science:
- Endocrinology
- Cardiology
- Pharmacology
Background:
- Cardiometabolic effects of lipid-lowering drugs are influenced by prolactin levels.
- Macroprolactinaemia is linked to increased cardiometabolic risk.
- The impact of macroprolactinaemia on drug efficacy is not well understood.
Purpose of the Study:
- To investigate if macroprolactinaemia modulates the pleiotropic effects of fenofibrate.
- To compare the cardiometabolic effects of fenofibrate in men with and without macroprolactinaemia.
Main Methods:
- Two groups of men, matched for age, weight, blood pressure, and lipids, were studied.
- 12 men had elevated big-big prolactin (macroprolactinaemia), and 16 had normal prolactin levels.
- All subjects received fenofibrate (200 mg daily) for 6 months, with various cardiometabolic markers assessed before and after treatment.
Main Results:
- Men with macroprolactinaemia exhibited higher hsCRP and fibrinogen, lower 25-hydroxyvitamin D, and reduced insulin sensitivity.
- Fenofibrate improved lipids, insulin sensitivity, and inflammatory markers in men without macroprolactinaemia.
- In men with macroprolactinaemia, fenofibrate's effects were less pronounced, primarily impacting HDL cholesterol, triglycerides, hsCRP, and homocysteine.
Conclusions:
- Macroprolactinaemia negatively impacts the cardiometabolic benefits of fenofibrate.
- The efficacy of fenofibrate in improving lipids, insulin sensitivity, and inflammation is diminished in the presence of macroprolactinaemia.
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