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

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 oligo/amenorrhea were randomized to an intervention group (Oligo/Amen+Cal, n=40, 21.3±0.5 yrs, 55.0±1.0kg, 20.4±0.3 kg/m2) who increased energy intake 20-40% above baseline energy needs for 12 months or a control group (Oligo/Amen Control, n=36, 20.7±0.5 yrs, 59.1±1.3kg, 21.3±0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed.The Oligo/Amen+Cal group improved energy status (increased body mass (2.6±0.4 kg), body mass index (0.9±0.2 kg/m2), fat mass (2.0±0.3 kg), body fat percentage (2.7±0.4%), and insulin-like growth factor 1 (37.4±14.6 ng/ml)) compared to the control group 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 (-0.006 g/cm2, 95%CI: -0.011, -0.0002 time main effect p=0.043) and month 12 (-0.011 g/cm2, 95%CI: -0.021, -0.001, time main effect p=0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006 g/cm2, 95%CI: -0.011, -0.002, 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 to the control group. The 12-month intervention may have been too short and the increase in energy intake (∼352 kcal/day), while sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological intervention(s) for the recovery of bone health in athletes and exercising women with oligo/amenorrhea. Clinical Trial Registry Number: NCT00392873 https://www.clinicaltrials.gov/ct2/show/NCT00392873.