MP24-11 GNRH ANTAGONISTS ASSOCIATE WITH LESS WEIGHT GAIN AND MILDER CHARACTERISTICS OF THE METABOLIC SYNDROME AND ATHEROSCLEROSIS COMPARED TO SURGICAL CASTRATION AND GNRH ANALOGUES IN PRE-CLINICAL ANIMAL MODEL

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research I1 Apr 2014MP24-11 GNRH ANTAGONISTS ASSOCIATE WITH LESS WEIGHT GAIN AND MILDER CHARACTERISTICS OF THE METABOLIC SYNDROME AND ATHEROSCLEROSIS COMPARED TO SURGICAL CASTRATION AND GNRH ANALOGUES IN PRE-CLINICAL ANIMAL MODEL Wilhelmina CM. Duivenvoorden, Sarah Hopmans, Geoff Werstuck, and Pinthus Jehonathan Wilhelmina CM. DuivenvoordenWilhelmina CM. Duivenvoorden More articles by this author , Sarah HopmansSarah Hopmans More articles by this author , Geoff WerstuckGeoff Werstuck More articles by this author , and Pinthus JehonathanPinthus Jehonathan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.292AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy (ADT) is associated with weight gain, development of the metabolic syndrome (MS) and eventually cardiovascular (CVS) morbidity and mortality. While different modes of ADT can achieve castration, they affect serum FSH levels differently. Motivated by the observation that the incidence of adiposity, MS and CVD accompanies the incremental increase in serum FSH levels in menopause, we hypothesize that GnRH antagonists which maximally inhibit FSH levels will associate with reduced adiposity and development of MS and CVD compared to GnRH analogues and orchiectomy. METHODS In vivo, we used LDL receptor knockout mice on normal and high fat diet (n=12/group) as models for MS to investigate and compare the effects of orchiectomy, sham surgery, sham surgery plus GnRH antagonist (degarelix) and sham surgery plus GnRH agonist (enantone). Longitudinal weight gain (4 months), visceral fat accumulation (CT measurements), fasting blood glucose, glucose tolerance, serum triglycerides, FSH, LH and testosterone levels were studied along with characteristics of aortic atherosclerotic plaques. RESULTS Expectedly, the lowest and highest serum FSH levels were recorded in mice treated with degarelix vs. orchiectomy and significantly lower levels of FSH and LH in mice treated with degarelix vs. enantone were observed. Enantone-treated mice gained significantly more weight and visceral fat compared to mice treated with degarelix. Significantly lower levels of serum triglycerides and better response to glucose loading were recorded in mice treated with degarelix. Preliminary analysis of the atherosclerotic aortic plaques reveals that the plaque area in enantone-treated and orchiectomized mice was significantly larger than in control mice (p=0.019 and 0.018, respectively), but that this was not the case in degarelix-treated mice, where the plaque area was not significantly different from control. CONCLUSIONS In a preclinical mouse model, the use of GnRH antagonists as ADT attenuates weight gain and development of the MS and atherosclerosis. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e263 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Wilhelmina CM. Duivenvoorden More articles by this author Sarah Hopmans More articles by this author Geoff Werstuck More articles by this author Pinthus Jehonathan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...