Effects of testosterone suppression in young men by the gonadotropin releasing hormone antagonist cetrorelix on plasma lipids, lipolytic enzymes, lipid transfer proteins, insulin, and leptin

We investigated in a pilot study the effect of testosterone suppression on lipoprotein metabolism, insulin, and leptin in 10 men who were treated eith er with cetrorelix, an antagonist of gonadotropin releasing hormone, or wit h placebo (P). Group C + C (n = 4) was treated with 10 mg cetrorelix as dai ly subcutaneous injections for five days and with a subsequent injection of 60 mg cetrorelix depot. Group C + P (n = 3) received 10 mg cetrorelix as d aily intramuscular injections for five days and a subsequent injection of p lacebo depot. Group P + P (n = 3) received placebo both as daily and depot injections. Treatment with cetrorelix reversibly suppressed testosterone to castrate levels for three weeks in group C + C and for one week in group C + P. Compared to baseline, treatment with cetrorelix increased serum level s of apolipoprotein (apo) A-I, HDL subclass LpA-I, insulin, and leptin. In the group P + P,treatment with placebo was not associated with any change o f these parameters. Compared to baseline and group P + P, treatment with ce trorelix ill groups C + C and C + P did not lead to considerable or consist ent changes in the plasma activities of lecithin:cholesterol acyltransferas e (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), lipoprotein lipase, and hepatic lipase (HL). Only the poole d data of groups C + C and C + P unraveled small but statistically signific ant decreases of HL and CETP activities in response to cetrorelix. In concl usion, the small or absent effects of cetrorelix on LCAT, CETP, PLTP, LPL, and HL indicate that testosterone regulates HDL levels by other metabolic p athways. The increases of insulin and leptin in response to cetrorelix sugg est that testosterone influences HDL metabolism also via obesity and insuli n resistance. These effects, however, are rather in contrast to the HDL rai sing effect of suppressed testosterone.