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

Year: 2026

Type: article

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.

Source: Clinical & Translational Metabolism

DOI: 10.1007/s12018-026-09331-3