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

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 B₁₂ 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 B₁₂ 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.