Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training

Cross-sectional and short-term prospective studies in humans support the co ncept that low energy availability, and not other factors associated with e xercise, causes the development of exercise-induced reproductive dysfunctio n. To rigorously test this hypothesis, we performed a longitudinal study, e xamining the role of low energy availability on both the development and th e reversal of exercise-induced amenorrhea, using a monkey model (Macaca fas cicularis). Eight adult female monkeys developed amenorrhea (defined as abs ence of menses for at least 100 d, with low and unchanging concentrations o f LH, FSH, E2, and P4) after gradually increasing their daily exercise to 1 2.3 +/- 0.9 km/d of running over a 7- to 24-month period. Food intake remai ned constant during exercise training. To test whether amenorrhea is caused by low energy availability, four of the eight amenorrheic monkeys were pro vided with supplemental calories (138-181% of calorie intake during amenorr hea) while they maintained their daily training. All four monkeys exhibited increased reproductive hormone levels and reestablished ovulatory cycles, with recovery times for circulating gonadotropin levels ranging from 12-57 d from the initiation of supplemental feeding. The rapidity of recovery wit hin the reproductive axis in a given monkey was directly related to the amo unt of energy that was consumed during the period of supplemental feeding ( r = -0.97; P < 0.05). Repeated measurements of plasma Ts concentrations, a marker of cellular energy availability, revealed a tight correlation betwee n the changes in reproductive function and T-3 levels, such that T-3 signif icantly decreased (27%) with the induction and significantly increased (18% ) with the reversal of amenorrhea (P < 0.05). These data provide strong evi dence that low energy availability plays a causal role in the development o f exercise-induced amenorrhea.