Acylated Ghrelin and Leptin in Adolescent Athletes With Amenorrhea, Eumenorrheic Athletes and Controls: A Cross-Sectional Study

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Previous reports suggest that adolescent endurance athletes such as gymnasts and swimmers may be at higher risk of amenorrhea (AA) than other adolescent athletes. Neuroendocrine factors that differentiate athletes with AA from eumenorrheic athletes (EA) have been investigated but are not completely understood. Two neuroendocrine peptides, leptin and ghrelin, appear to be involved in regulation of the hypothalamo-pituitary-gonadal axis. Low leptin levels and high ghrelin levels have been implicated in the occurrence of amenorrhea in adult athletes. The investigators hypothesized that blood levels of leptin and/or ghrelin could predict levels of gonadal steroids in adolescent athletes and identify which will develop ammenorhea. This cross-sectional study compared the levels of leptin, ghrelin, and gonadal steroids among adolescent athletes with AA, EA, and nonathletic controls at a large urban hospital. The study enrolled 58 adolescent girls, 12-18 years old, including 21 AA, 19 EA and 18 nonathletic controls. There was no history of amenorrhea or menarchal delay in the nonathletic controls. Active ghrelin, leptin, estrogen (E 2 ), and testosterone were measured in fasting blood. The body mass index (BMI) in AA was significantly lower than among EA and controls at baseline (P = 0.003). Log active ghrelin levels were significantly higher in AA compared to the other two groups (P < 0.0001); the difference was maintained after controlling for BMI Z-scores (P = 0.0007). Leptin levels were lower in AA compared to the other two groups (P < 0.0001), but did not remain significant after controlling for BMI Z-scores. Total testosterone levels were lower among AA compared to the EA and controls (P = 0.002), and the differences remained significant after controlling for BMI Z-scores (P = 0.03. There was a significant trend for lower E 2 scores among AA than the EA (P = 0.07), but the effect was not significant after controlling for BMI Z-scores. Inverse associations of log active ghrelin with testosterone were noted (P = 0.05), whereas there were positive associations of leptin with testosterone (P = 0.05) and log E 2 (P = 0.01). These data show that ghrelin and leptin are independent predictors of levels of gonadal steroids. The investigators conclude from these findings that lower leptin levels and especially higher ghrelin levels may predict which athletes will develop amenorrhea.