title: Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome.
abstract: BACKGROUND
  The lipodystrophies (LD) are characterized by metabolic abnormalities (insulin resistance, hypertriglyceridemia, and diabetes) and a polycystic ovarian syndrome (PCOS) phenotype. Therapeutic administration of leptin improves insulin sensitivity and the metabolic features.
  
  
  OBJECTIVE
  The objective of the study was to investigate whether the PCOS features are corrected by increasing insulin sensitivity as a function of leptin treatment.
  
  
  METHODS
  This was a prospective, open-label trial using leptin replacement in various forms of lipodystrophy.
  
  
  METHODS
  The study was performed at the Clinical Center at the National Institutes of Health.
  
  
  METHODS
  Twenty-three female patients with LD were enrolled in a leptin replacement trial from 2000 to the present. Different parameters were assessed at baseline and after 1 yr of therapy.
  
  
  METHODS
  Patients were treated with leptin for at least 1 yr.
  
  
  METHODS
  We evaluated free testosterone, SHBG, and IGF-I at baseline and after 1 yr of leptin.
  
  
  RESULTS
  Testosterone levels decreased from 3.05 ±0.6 ng/ml at baseline to 1.7 ±0.3 ng/ml (P = 0.02). SHBG increased from 14.5 ±2 to 25 ±3.5 nmol/liter after 1 yr of leptin therapy. There were no significant changes in the levels of gonadotropins and ovarian size as a result of leptin replacement therapy. IGF-I increased significantly after leptin therapy from 150 ±14 to 195 ±17. There was a significant decrease in triglycerides and glycosylated hemoglobin in the context of reduced insulin requirements.
  
  
  CONCLUSIONS
  In the present study, we show that LD may be a model for the common forms of PCOS and that the endocrine features are corrected by leptin therapy, which reduces insulin resistance.
authors.affiliation: Diabetes, Endocrine, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Andreea O
authors.initials: AO
authors.lastname: Lungu
authors.forename: Elika Safar
authors.initials: ES
authors.lastname: Zadeh
authors.forename: Anne
authors.initials: A
authors.lastname: Goodling
authors.forename: Elaine
authors.initials: E
authors.lastname: Cochran
authors.forename: Phillip
authors.initials: P
authors.lastname: Gorden
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000627:therapeutic use; D008060:Lipodystrophy / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D020738:Leptin
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