Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
Department of Paediatrics in Bytom, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland.
J Clin Pharm Ther. 2020 Feb;45(1):115-121. doi: 10.1111/jcpt.13036. Epub 2019 Aug 24.
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.
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.
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.
The results of the study indicate that macroprolactinaemia exerts a negative impact on cardiometabolic effects of fenofibrate.
降脂药物的心脏代谢作用取决于单体催乳素的血浆水平。虽然大催乳素血症似乎与增加的心脏代谢风险相关，但以前没有研究调查过大催乳素血症是否调节降脂药物的多效性作用。
研究人群包括两组年龄、体重、血压和血脂匹配的男性：12 名催乳素水平升高的大-大催乳素血症患者和 16 名催乳素水平在参考范围内的男性。由于动脉粥样硬化性血脂异常，所有患者均接受非诺贝特（每日 200 毫克）治疗 6 个月。在研究开始和结束时，测定患者的葡萄糖稳态标志物和血浆脂质，以及尿酸、高敏 C 反应蛋白（hsCRP）、纤维蛋白原、同型半胱氨酸和 25-羟维生素 D 的血浆水平。
催乳素水平升高的男性的 hsCRP 和纤维蛋白原水平较高，25-羟维生素 D 水平较低，胰岛素敏感性降低，而催乳素水平在参考范围内的男性则较低。在没有大催乳素血症的男性中，非诺贝特降低了总胆固醇、LDL 胆固醇、甘油三酯、尿酸、hsCRP 和纤维蛋白原的循环水平，增加了 HDL 胆固醇、同型半胱氨酸和 25-羟维生素 D 的浓度，并改善了胰岛素敏感性。在催乳素水平升高的男性中，非诺贝特的作用仅限于 HDL 胆固醇、甘油三酯、hsCRP 和同型半胱氨酸的变化。除了同型半胱氨酸外，非诺贝特对无大催乳素血症患者的心脏代谢作用强于有大催乳素血症患者。
研究结果表明，大催乳素血症对非诺贝特的心脏代谢作用产生负面影响。
