Lipid, glucose and homocysteine metabolism in women treated with a GnRH agonist with or without raloxifene

Hum Reprod. 2004 Feb;19(2):415-21. doi: 10.1093/humrep/deh053.


Background: Although GnRH analogues are widely used to treat a variety of sex hormone-related diseases, little is known about their effect on metabolism. Therefore, we have evaluated the effect of a GnRH analogue, administered with or without raloxifene, on serum levels of lipoproteins, glucose, insulin and homocysteine (Hcy).

Methods: One hundred premenopausal women with symptomatic uterine leiomyomas were initially enrolled and randomized to receive 3.75 mg/28 days leuprolide acetate depot associated with 60 mg/day raloxifene hydrochloride (group A) or 1 placebo tablet/day (group B) for six cycles of 28 days. At entry and at cycle 6, subjects underwent anthropometric measurements, including body mass index and waist-to-hip ratio measurements, and blood chemistry assays for serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, Hcy, vitamin B(12) and folate concentrations. Insulin resistance was evaluated with the homeostasis model assessment (HOMA) score.

Results: Baseline parameters were similar in the two groups. At cycle 6, TC, HDL-C, LDL-C and TG levels were significantly increased (P < 0.05) in group B. In group A, LDL-C levels were unchanged, and TC, HDL-C and TG levels were increased (P < 0.05). Serum TC and LDL-C levels differed (P < 0.05) between the groups. Glucose levels were unchanged between and within groups, whereas insulin levels and HOMA scores increased (P < 0.05) versus baseline in group B. Post-treatment Hcy levels were higher (P < 0.05) versus baseline in group B; they were unchanged in group A. Serum vitamin B(12) and folate concentrations were unchanged in both groups.

Conclusions: GnRH analogues alter serum lipoprotein and Hcy levels and increase insulin resistance. These acute metabolic changes may be prevented or reduced by raloxifene.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose / analysis*
  • Body Constitution
  • Body Mass Index
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Delayed-Action Preparations / administration & dosage
  • Female
  • Folic Acid / blood
  • Homeostasis
  • Homocysteine / blood*
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Leiomyoma / drug therapy
  • Leuprolide / administration & dosage
  • Leuprolide / adverse effects*
  • Lipids / blood*
  • Middle Aged
  • Placebos
  • Premenopause
  • Raloxifene Hydrochloride / administration & dosage*
  • Triglycerides / blood
  • Uterine Neoplasms / drug therapy
  • Vitamin B 12 / blood


  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Delayed-Action Preparations
  • Insulin
  • Lipids
  • Placebos
  • Triglycerides
  • Homocysteine
  • Raloxifene Hydrochloride
  • Folic Acid
  • Cholesterol
  • Leuprolide
  • Vitamin B 12