Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic athletes and controls: a cross-sectional study.

OBJECTIVES: Neuroendocrine factors may predict which athletes develop amenorrhea and which athletes remain eugonadal. Specifically, ghrelin and leptin have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that adolescent athletes with amenorrhea (AA) would have higher ghrelin and lower leptin levels than eumenorrheic athletes (EA) and would predict levels of gonadal steroids.

DESIGN: Cross-sectional.

SUBJECTS AND MEASUREMENTS: We enrolled 58 girls, 21 AA, 19 EA and 18 nonathletic controls 12-18 years old. Fasting blood was drawn for active ghrelin, leptin, E(2) and testosterone. Athletes were > 85% of ideal body weight for age based on body mass index (BMI).

RESULTS: AA girls had lower BMI than EA and controls (P = 0.003). Log ghrelin was higher in AA than in EA and controls (P < 0.0001), and remained higher after controlling for BMI Z-scores. Leptin was lower in AA than in the other groups (P < 0.0001), however, the differences did not persist after controlling for BMI Z-scores. Testosterone was lower in AA than in EA and controls (P = 0.002) and log E(2) trended lower in AA (P = 0.07). We observed inverse associations of log active ghrelin with testosterone (P = 0.01), and positive associations of leptin with testosterone and log E(2) (P = 0.02 and 0.009).

CONCLUSION: Higher ghrelin levels, even after controlling for BMI, and lower leptin in AA compared with EA and controls, and their inverse and positive associations, respectively, with gonadal steroids suggest endocrine perturbations that may explain why hypogonadism occurs in some but not all athletes.