Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome.

ABSTRACT

CONTEXT 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. DESIGN: This was a prospective, open-label trial using leptin replacement in various forms of lipodystrophy. SETTING: The study was performed at the Clinical Center at the National Institutes of Health. PATIENTS OR OTHER PARTICIPANTS: 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. INTERVENTION(S) Patients were treated with leptin for at least 1 yr. MAIN OUTCOME MEASURE(S) 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.