Metabolic Changes and Predictors of Menstrual Recovery Following a Diet Intervention in Exercising Females with Oligo/Amenorrhea: The REFUEL Study

Abstract Energy deficiency among exercising females is associated with metabolic adaptations to conserve energy, menstrual cycle disturbances, and poor bone health. The purpose of this paper is to describe how a randomized controlled trial (clinicaltrials.gov: NCT00392873) with a nutritional intervention influenced indicators of metabolic status and whether these indicators are associated with menstrual recovery among oligo/amenorrheic (Oligo/Amen) exercising women. Recreational and competitive female athletes with Oligo/Amen were randomized to a control group (Oligo/Amen Control, n = 36; 20.7 ± 0.5 yrs; 59.1 ± 1.3 kg; 21.3 ± 0.4 kg/m 2 ) or an intervention group (Oligo/Amen + Cal, n = 40; 21.3 ± 0.5 yrs; 55.0 ± 1.0 kg; 20.4 ± 0.3 kg/m 2 ), who increased energy intake 20–40% above baseline energy needs for 12 months. Daily energy intake and expenditure, resting metabolic rate (RMR), body composition, and metabolic hormones, including total triiodothyronine (TT3), leptin, ghrelin, insulin-like growth factor-1 (IGF-1), and peptide YY, were assessed every 3 months. Reproductive function was monitored continually. Oligo/Amen + Cal females significantly increased energy intake ( p = 0.002) and energy availability ( p = 0.003) with a balanced increase in macronutrients. Percent body fat, TT3, and IGF-1 also significantly increased from baseline in the Oligo/Amen + Cal group compared with the Control group ( p < 0.05) whereas leptin and RMR did not change. Longitudinal measures of body mass, body fat, and IGF-1 were significant predictors of menstrual recovery ( p < 0.02). A nutritional intervention of increased energy intake in Oligo/Amen exercising females improved metabolic hormones but didn’t completely reverse signs of metabolic compensation. Changes in body mass, body fat, and IGF-1 in response to a nutritional intervention may represent important factors for monitoring progress toward menstrual recovery.