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

Abstract

We investigated in a pilot study the effect of testosterone suppression on lipoprotein metabolism, insulin, and leptin in 10 men who were treated either with cetrorelix, an antagonist of gonadotropin releasing hormone, or with placebo (P). Group C + C (n = 4) was treated with 10 mg cetrorelix as daily 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 daily intramuscular injections for five days and a subsequent injection of placebo 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 levels 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 of these parameters. Compared to baseline and group P + P, treatment with cetrorelix in groups C + C and C + P did not lead to considerable or consistent changes in the plasma activities of lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), lipoprotein lipase, and hepatic lipase (HL). Only the pooled data of groups C + C and C + P unraveled small but statistically significant decreases of HL and CETP activities in response to cetrorelix. In conclusion, the small or absent effects of cetrorelix on LCAT, CETP, PLTP, LPL, and HL indicate that testosterone regulates HDL levels by other metabolic pathways. The increases of insulin and leptin in response to cetrorelix suggest that testosterone influences HDL metabolism also via obesity and insulin resistance. These effects, however, are rather in contrast to the HDL raising effect of suppressed testosterone.

Evaluation of ovarian and metabolic effects of GnRH modulators in two rat models of polycystic ovary syndrome

“…Treatment with leuprolide and metformin combination reduces insulin levels in postmenopausal nondiabetic women (Elkind‐Hirsch et al, ). Contrary to this, cetrorelix treatment increases serum insulin level in young men (Buchter et al, ).…”

“…Cetrorelix suppressed estrogen, progesterone, and testosterone levels in female rats (Horvath et al, ). Cetrorelix suppresses testosterone in postmenopausal women (Chantler, Gordon, Millan, & Panarelli, ; Pechstein et al, ) and estrogen levels in women undergoing controlled ovarian hyperstimulation (Buchter et al, ; Chen et al, ).…”

Variations of plasma leptin in show horses during a work season

“…Peripheral leptin concentration is not affected by testosterone administration to mares (Cartmill et al., 2006) or by ovariectomy (Buff et al., 2005). In humans, testosterone suppresses leptin secretion and oestradiol stimulates leptin release independently of body fat (Buchter et al., 1999; Dicker et al., 2004; Puder et al., 2006).…”

The Confounding Factor of Apolipoprotein E on Response to Chemotherapy and Hormone Regulation Altering Long-Term Cognition Outcomes

“…In female ApoE -/-mice, the reduction in testosterone also leads to reduction in estradiol, insulin and HDL levels without effects on atherosclerosis [62]. In a pilot study conducted in men, treatment with cetrorelix resulted in increased ApoA-1, HDL, insulin and leptin consistently (Table 1) [63]. Therefore, when this drug is used within a chemotherapy treatment regiment it is important to carefully monitor lipid levels.…”