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

Background: Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad. Objectives: The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances. Methods: 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 ± 1.0 kg; BMI: 20.4 ± 0.3 kg/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 ± 1.3 kg; 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. Results: Oligo/Amen + Cal improved energy status [increased body mass (2.6 ± 0.4 kg), BMI (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 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 (-0.006 g/cm2; 95% CI: -0.011, -0.0002 g/cm2; time main effect P = 0.043) and month 12 (-0.011 g/cm2; 95% CI: -0.021, -0.001 g/cm2; 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 g/cm2; time main effect P = 0.004). Conclusions: 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 (∼352 kcal/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.