Evidence for a Causal Role of Low Energy Availability in the Induction of Menstrual Cycle Disturbances During Strenuous Exercise Training

Abstract

It is not uncommon for female athletes to develop reproductive dysfunction in the form of oligoamenorrhea or luteal-phase defects. Warren has postulated that negative energy balance is responsible for suppressed reproductive function, and both prospective and cross-sectional studies have lent support to this concept. The present longitudinal study assessed the role of low energy availability in the development and reversal of exercise-induced amenorrhea in adult female cynomolgus monkeys. The animals were trained to run on a standard human-size treadmill, ensuring adequate ventilation. The goal was for them to run 2 hours a day for 7 days a week, with a 3-minute break after each 30-minute exercise period. Eight animals became amenorrheic, with no menses for at least 100 days and low, unchanging levels of LH, FSH, estradiol, and progesterone. Running distance averaged 12.3 km daily over the period of 7 to 24 months. The first study sought to show whether increased energy intake is able to reverse exercise-induced amenorrhea. This should be the case if energy utilization itself is the primary cause. Overfeeding increased daily energy intake by about 58%. Body weight increased significantly and there were substantial rises in levels of gonadotropins and estradiol. Two of the four overfed monkeys recovered reproductive function very rapidly and two, more slowly. The former animals had higher average energy intake during overfeeding. Calories consumed during overfeeding correlated significantly and negatively with the number of days to the LH surge. A second experiment examined the relation between changes in plasma levels of triiodothyronine (T 3 ), an index of energy availability, and altered reproductive function during and after exercise-induced amenorrhea. In these eight animals, body weight and caloric intake did not change significantly during training or when amenorrhea developed. Gonadotropin levels declined significantly over time. When the animals were amenorrheic, T 3 levels remained quite stable during training but decreased by about one fifth when amenorrhea developed. Reversal of amenorrhea in the overfed animals was associated with a rise in circulating T 3 levels. These findings, obtained in a prospective study, are strong evidence that low energy availability-created by regular vigorous exercise, gives rise to exercise-induced amenorrhea. Other factors associated with exercise do not seem to contribute to suppressed reproductive function in this setting.