title: Discontinuous low-dose flutamide-metformin plus an oral or a transdermal contraceptive in patients with hyperinsulinaemic hyperandrogenism: normalizing effects on CRP, TNF-alpha and the neutrophil/lymphocyte ratio.
abstract: BACKGROUND
  Low-dose flutamide-metformin (Flu-Met) with an oral contraceptive is a therapeutic option for women with hyperinsulinaemic hyperandrogenism. We questioned (i) whether Flu-Met maintains efficacy if given discontinuously; (ii) how the efficacy of discontinuous Flu-Met plus a transdermal contraceptive compares with Flu-Met plus oral contraceptive; and (iii) whether these treatments also lower circulating C-reactive protein (CRP) and tumour necrosis factor alpha (TNF-alpha) and the high neutrophil/lymphocyte ratio.
  
  
  METHODS
  Non-obese, young patients (n = 31) with hyperinsulinaemic hyperandrogenism were started on Flu-Met (21/28 days) and randomized to receive in addition either a drospirenone oral contraceptive or a transdermal contraceptive for 6 months.
  
  
  RESULTS
  The effects of Flu-Met were similar whether combined with oral or transdermal contraceptive. In both groups, CRP and TNF-alpha levels fell and the high neutrophil/lymphocyte ratio normalized (P < 0.001). Lean body mass increased (P < 0.001) in both groups but, in contrast to earlier experience with continuous Flu-Met, fat mass failed to decrease in either group.
  
  
  CONCLUSIONS
  Flu-Met seems less lipolytic, if given for only 21 days in every 28-day period. The efficacy of Flu-Met is comparable when combined with an oral contraceptive or a transdermal contraceptive. The range of Flu-Met effects may henceforth include lower levels of CRP and TNF-alpha, and a normalization of the neutrophil/lymphocyte ratio.
authors.affiliation: Endocrinology Unit and Hormonal Laboratory, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain. libanez@hsjdbcn.org
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
authors.forename: Carme
authors.initials: C
authors.lastname: Valls
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000627:therapeutic use; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005485:Flutamide / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000188:drug therapy*; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects; D008687:Metformin / Q000008:administration & dosage* / Q000627:therapeutic use; D009504:Neutrophils / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D003271:Contraceptive Agents, Female; D003276:Contraceptives, Oral; D014409:Tumor Necrosis Factor-alpha; D005485:Flutamide; D002097:C-Reactive Protein; D008687:Metformin