GnRH antagonist associates with less adiposity and reduced characteristics of metabolic syndrome and atherosclerosis compared with orchiectomy and GnRH agonist in a preclinical mouse

  • Hopmans S
  • Duivenvoorden W
  • Werstuck G
 et al. 
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Abstract

Objectives: Observational studies relate androgen deprivation therapy (ADT) to metabolic syndrome (MS) and cardiovascular disease, an association potentially subject to uncontrollable confounding factors, especially diet and genetic/metabolic risk factors. In the absence of prospective randomized clinical trials, causality remains unproven. We comparatively investigated the effects of different ADT modalities on the development of MS and atherosclerosis in a mouse model. Materials and methods: Low-density lipoprotein receptor knockout mice underwent orchiectomy plus vehicle (2.5% mannitol), sham surgery plus vehicle (control), sham surgery plus gonadotropin-releasing hormone (GnRH) antagonist (degarelix), or sham surgery plus GnRH agonist (leuprolide) (n = 9-13/group) and were followed for 4 months. Visceral fat accumulation, lean body mass, adipocyte size, fasting blood glucose, glucose tolerance, serum levels of leptin, follicle-stimulating hormone, luteinizing hormone, and testosterone, along with atherosclerotic plaque size and characteristics were measured. Results: All 3 modes of ADT decreased circulating testosterone levels in mice, although leuprolide treatment reached nadir levels of testosterone later. Orchiectomized and leuprolide-treated mice gained significantly more visceral fat compared with degarelix-treated mice. Improved glucose tolerance tests were recorded in degarelix-treated mice. The aortic atherosclerotic plaque area in leuprolide-treated and orchiectomized mice was larger than in control mice (P

Author-supplied keywords

  • Androgen deprivation therapy
  • Cardiovascular disease
  • Degarelix
  • Leuprolide
  • Metabolic syndrome
  • Orchiectomy

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Authors

  • Sarah N. Hopmans

  • Wilhelmina C.M. Duivenvoorden

  • Geoff H. Werstuck

  • Laurence Klotz

  • Jehonathan H. Pinthus

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