Bone mineral density in response to increased energy intake in exercising women with oligomenorrhea/amenorrhea: the REFUEL randomized controlled trial

Abstract

Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad. The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances. Exercising women with oligomenorrhea/amenorrhea (Oligo/Amen) were randomly assigned to an intervention group (Oligo/Amen+Cal, n=40, mean±SEM age: 21.3±0.5 y; weight: 55.0±1.0kg; BMI: 20.4±0.3kg/m2) who increased energy intake 20%-40% above baseline energy needs for 12 mo or a control group (Oligo/Amen Control, n=36; mean±SEM age: 20.7±0.5 y; weight: 59.1±1.3kg; BMI: 21.3±0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed. Oligo/Amen+Cal improved energy status [increased body mass (2.6±0.4kg), BMI (0.9±0.2 kg/m2), fat mass (2.0±0.3kg), body fat percentage (2.7%±0.4%), and insulin-like growth factor 1 (37.4±14.6ng/mL)] compared with Oligo/Amen Control and experienced a greater likelihood of menses (P<0.05). Total body and spine aBMD remained unchanged (P>0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (-0.006g/cm2; 95% CI: -0.011, -0.0002g/cm2 ; time main effect P=0.043) and month 12 (-0.011g/cm2; 95% CI: -0.021, -0.001g/cm2; time main effect P=0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006g/cm2; 95% CI: -0.011, -0.002g/cm2; time main effect P=0.004). Although higher dietary energy intake increased weight, body fat, and menstrual frequency, bone mineral density was not improved, compared with the control group. The 12-mo intervention may have been too short and the increase in energy intake (∼352kcal/d), although sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological interventions for the recovery of bone health in athletes and exercising women with Oligo/Amen.This trial was registered at clinicaltrials.gov as NCT00392873.