Insulin Sensitivity and Lipid Profiles in Girls with Central Precocious Puberty before and during Gonadal Suppression

Abstract

Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis. The objective of the study was to evaluate metabolic profiles in girls with early normal puberty (EP) and CPP. This was a combined cross-sectional and longitudinal study at a tertiary center of pediatric endocrinology. Twenty-three girls with EP or CPP and 115 controls with normal pubertal timing were evaluated by oral glucose tolerance test, dual-energy x-ray absorptiometry scan, and fasting blood samples. Fifteen girls (13 CPP) were treated with GnRH agonists (GnRHa) and reevaluated after 12 and 52 wk of treatment. Insulin and glucose levels during oral glucose tolerance test and fasting lipid levels were measured. At the time of diagnosis, girls with CPP had higher fasting insulin, triglyceride, and low-density lipoprotein-cholesterol levels as well as lower insulin sensitivity and high-density lipoprotein/total cholesterol ratios (all P<0.05) compared with controls after adjustment for pubertal stage and body fat percentage. Age at pubertal onset positively predicted insulin sensitivity for a given pubertal stage (P=0.04) in girls with EP and CPP. Insulin sensitivity decreased significantly during 1 yr of GnRHa treatment (P=0.04). Girls with CPP had adverse metabolic profiles at the time of diagnosis compared with puberty-matched controls. In addition, those with the earliest onset of puberty had the most adverse metabolic profiles. Surprisingly, metabolic profiles deteriorated even further after withdrawal of sex steroids by GnRHa treatment.