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 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.
Palomba
Stefano
S
Department of Obstetrics & Gynaecology, University of Catanzaro Magna Graecia, Catanzaro, Italy. stephanopalumbo@tin.it
Russo
Tiziana
T
Orio
Francesco
F
Sammartino
Annalidia
A
Sbano
Francesco Maria
FM
Nappi
Carmine
C
Colao
Annamaria
A
Mastrantonio
Pasquale
P
Lombardi
Gaetano
G
Zullo
Fulvio
F
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D001824:Body Constitution; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D005260:Female; D005492:Folic Acid / Q000097:blood; D006706:Homeostasis; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007889:Leiomyoma / Q000188:drug therapy; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects*; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D010919:Placebos; D017697:Premenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood; D014594:Uterine Neoplasms / Q000188:drug therapy; D014805:Vitamin B 12 / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D007328:Insulin; D008055:Lipids; D010919:Placebos; D014280:Triglycerides; D006710:Homocysteine; D020849:Raloxifene Hydrochloride; D005492:Folic Acid; D002784:Cholesterol; D016729:Leuprolide; D014805:Vitamin B 12