title: Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women.
abstract: Evidence suggests that hyperinsulinemic insulin resistance may increase serum levels of ovarian androgens and reduce sex hormone-binding globulin (SHBG) levels in humans. The present study was conducted to assess the effect of administration of the biguanide metformin, a drug commonly used in the treatment of diabetes mellitus, on androgen and insulin levels in 24 hirsute patients. The patients selected for the study were obese, with a body mass index higher than 25 kg/m2 and high fasting insulin (> 90 pmol/L) and low SHBG levels (< 30 nmol/L). All patients were given a low calorie diet (1500 Cal/day) and randomized for either metformin administration at a dose of 850 mg or a placebo, twice daily for 4 months, in a double blind study. In the placebo group, diet resulted in a significant decrease in body mass index (30.8 +/- 1.0 vs. 32.7 +/- 1.5 kg/m2; P < 0.0001), fasting insulin (127 +/- 11 vs. 156 +/- 14 pmol/L; P < 0.01), non-SHBG-bound testosterone (0.19 +/- 0.02 vs. 0.28 +/- 0.03 nmol/L; P < 0.02), androstenedione (5.8 +/- 0.5 vs. 9.0 +/- 1.1 nmol/L; P < 0.03), and 3 alpha-diolglucuronide (8.6 +/- 1.1 vs. 11.7 +/- 1.9; P < 0.005) plasma concentrations and a significant increase in the glucose/insulin ratio (0.047 +/- 0.005 vs. 0.035 +/- 0.003; P < 0.001) and plasma concentrations of SHBG (26.0 +/- 3.3 vs. 19.1 +/- 1.9 nmol/L; P < 0.001) and dehydroepiandrosterone sulfate (8.7 +/- 1.5 vs. 8.4 +/- 1.3; P < 0.05). Beneficial effects of diet were not significantly different in the patients who were given metformin instead of placebo. These results confirm that weight loss induced by a low calorie diet is effective in improving hyperinsulinemia and hyperandrogenism in obese and hirsute women. With our study design, metformin administration had no additional benefit over the effect of diet.
authors.affiliation: Hospices Civils de Lyon, Laboratoire de la Clinique Endocrinologique, Hôpital de l'Antiquaille, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Crave
authors.forename: S
authors.initials: S
authors.lastname: Fimbel
authors.forename: H
authors.initials: H
authors.lastname: Lejeune
authors.forename: N
authors.initials: N
authors.lastname: Cugnardey
authors.forename: H
authors.initials: H
authors.lastname: Déchaud
authors.forename: M
authors.initials: M
authors.lastname: Pugeat
mesh_terms: D000728:Androgens / Q000097:blood / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D018752:Diet, Fat-Restricted; D004038:Diet, Reducing; D005260:Female; D006628:Hirsutism / Q000178:diet therapy / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy / Q000503:physiopathology*; D010919:Placebos; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D014280:Triglycerides / Q000097:blood
chemical_list: D000728:Androgens; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D010919:Placebos; D012738:Sex Hormone-Binding Globulin; D014280:Triglycerides; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D008687:Metformin; D002784:Cholesterol