Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2.
Thirty postmenopausal women were randomly treated with desogestrel (DG) or levonorgestrel (LN) 125 micrograms/day for 3 weeks. Desogestrel reduced the serum total and free (non-protein bound) testosterone concentrations. It caused a small decrease in the sex hormone binding globulin capacity (SHBG) but did not influence the free testosterone index (testosterone/SHBG ratio). Levonorgestrel, on the other hand, did not influence the free testosterone concentration, but caused a significant increase in the free testosterone index. Levonorgestrel reduced the HDL and particularly the HDL2 cholesterol concentrations (mean change from 1.75 to 1.45 mmol/l for HDL and from 0.73 to 0.50 mmol/l for HDL2, P less than 0.001). It also caused a reduction in the VLDL triglyceride (P less than 0.05) but not the total serum triglyceride concentration. Desogestrel did not cause any significant changes in HDL or HDL2 cholesterol concentrations, but it reduced the VLDL triglyceride (P less than 0.01) and total serum (P less than 0.05) triglyceride concentrations. Neither of the two progestins influenced the postheparin plasma lipoprotein lipase (LPL) activity or the serum cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT). It is therefore possible that both steroids decreased the hepatic output of triglycerides, which may be clinically important since both progestins are used in combination with ethinylestradiol (EE) which increases the hepatic TG synthesis. The failure of desogestrel to change HDL levels is consistent with earlier data on the lack of effects on HDL by non-androgenic progestins. Levonorgestrel increased the mean activity of postheparin plasma hepatic lipase (HL) from 23.3 to 28.0 mumol X h-1 X ml-1 (P less than 0.05). In contrast, this activity was not influenced by desogestrel. The magnitude of the changes in postheparin plasma HL activity and the free testosterone index (testosterone/SHBG ratio) showed significant positive correlation (+ 0.41, P less than 0.05). On the other hand, the changes in the HDL2 cholesterol and the postheparin plasma HL activity were inversely interrelated (r = 0.52, P less than 0.01). These relationships are consistent with the idea that the effects of different progestins on the HDL cholesterol are mediated by the sex steroid sensitive hepatic endothelial lipase.
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D000728:Androgens / Q000494:pharmacology*; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology; D017135:Desogestrel; D004727:Endothelium / Q000201:enzymology; D004951:Esterification; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D016912:Levonorgestrel; D008049:Lipase / Q000097:blood / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008099:Liver / Q000201:enzymology*; D008875:Middle Aged; D009644:Norgestrel / Q000494:pharmacology; D009652:Norpregnenes / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D000728:Androgens; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D003277:Contraceptives, Oral, Combined; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D009652:Norpregnenes; D012738:Sex Hormone-Binding Globulin; D009644:Norgestrel; D013739:Testosterone; D016912:Levonorgestrel; D017135:Desogestrel; D006493:Heparin; D002784:Cholesterol; D008049:Lipase