1915 Ghrelin is a peripheral metabolic signal of energy status involved with the regulation of hunger, food intake, body weight, and energy balance. While recent evidence supports a potential physiological role of ghrelin in reproductive function, the relationship of ghrelin to exercise-associated menstrual disturbances and other endocrine adaptations to low energy availability has not been evaluated. PURPOSE: To test whether differences in fasting ghrelin levels exist in exercising women exhibiting alterations in metabolic status and menstrual cycle abnormalities. METHODS: Menstrual cycle status, defined as ovulatory, luteal phase deficient (LPD), anovulatory, or amenorrheic, was determined through daily urine collections examining estrone conjugates (E1C), pregnanediol-3-glucuronide (PdG), and luteinizing hormone (LH) for two to three consecutive cycles or equivalent time periods in 10 sedentary and 30 moderately active women. Both groups were matched for age (27.7 1.2 yrs), body mass (60.2 3.3 kg), menstrual cycle length (28.4 0.9 days), and reproductive age (14.4 1.2 yrs). A blood sample was collected once during the follicular phase of each menstrual cycle or on an arbitrary day in amenorrheic subjects and analyzed for total ghrelin, insulin, total T3, and leptin concentrations. Each subject was classified according to individual exercise status and the predominant menstrual cycle status displayed in at least two of the three, or two of the two, menstrual cycles evaluated. This classification resulted in 10 sedentary ovulatory subjects (SedOvul), 11 exercise ovulatory subjects (ExOvul), 11 exercise LPD or anovulatory subjects (ExLPD/ANOV), and 8 exercise amenorrheic (ExAmen) subjects. RESULTS: Ghrelin was significantly elevated in the ExAmen category (723.7 ± 40.8 pmol/L) when compared to all other categories (p<0.001), SedOvul (392.8 ± 32.0 pmol/L), ExOvul (418.0 ± 34.6 pmol/L), and ExLPD/Anov (380.4 ± 31.4 pmol/L). Leptin levels were lower in all groups versus SedOvul (P <0.001), while insulin was lower in both ExLPD/Anov and ExAmen categories versus SedOvul and ExOvul (p<0.018). Total T3 was lower in ExAmen compared to all other groups (P<0.001) with concentrations in ExLPD/Anov and ExOvul exceeding those in SedOvul (p<0.05). CONCLUSION: These data indicate a metabolic hormonal profile consistent with low energy availability in exercising women across a range of menstrual abnormalities. This study also introduces ghrelin as a potential additional indicator of energy status that uniquely discriminates amenorrheic athletes from athletes with other more subtle menstrual disturbances.