Exercise and Infertility

Exercise is a well-recognized approach to the enhancement of general health and well-being. In contradistinction to the beneficial effects of exercise, there is increasing evidence that heavy exercise may have detrimental consequences in female athletes. When exercise is started during adolescence, athletes have increased ovulatory dysfunction reflected as menstrual irregularity. It is well recognized that long distance runners, swimmers, dancers and other competitive female athletes have varying degrees of menstrual dysfunction. Menarche (onset of menses) may be delayed by as much as 3 years and these women have more menstrual abnormalities in adulthood than their non-athlete peers. Menstrual dysfunction is usually a reflection of abnormal folliculogenesis and ovulation. Consequently, female athletes and others engaging in heavy physical exercise are often subfertile.

Female participation in high school athletics has increased 800% in the last 30 years. Menstrual abnormalities have subsequently increased. One study evaluating cross country runners found that 23 percent of these women reported irregular menstrual cycles. Interestingly, 19 percent of these cross country runners reported previous eating disorders. As many as 40 percent of female triathletes have menstrual dysfunction. As many as two thirds of runners who have menstrual periods have short luteal phases or are anovulatory. The extent to which exercise related infertility exists has been underestimated because of a lack of attention to anovulatory cycles in female athletes.

Although the pathophysiology of exercise induced amenorrhea and infertility remains to be elucidated, some common themes have emerged. The preponderance of the evidence indicates that the condition is influenced by modulators of the hypothalamic-pituitary-ovarian axis. Gonadotropin releasing hormone (GnRH) is a peptide hormone that is synthesized and released by the hypothalamic portion of the brain. GnRH causes the release of both follicle stimulating hormone (FSH) and luteinizing hormones (LH) from the anterior pituitary gland. FSH and LH are the primary hormones that control ovarian function. Disturbances within the hypothalamic-pituitary-ovarian axis alter the pattern and quantity of FSH and LH release resulting in abnormal ovarian function often reflected as abnormal menses. Central inhibition of GnRH can be discerned in some female athletes even before there is perceptible evidence of menstrual irregularity. This is a very important observation in view of the fact that not all of these athletes will exhibit overt menstrual irregularities. There appear to be three primary modulators of exercise-induced infertility: a critical level of body fat, energy expenditure, and stress.

The onset and regularity of menstrual function necessitates maintaining body weight above a critical level, and therefore, above a critical amount of body fat. A loss of body weight in the range of 10 to 15% of normal weight for height represents a loss of about one third of body fat which will result in abnormal menstrual function. This concept is recognized as the "critical weight hypothesis". The proportion of body fat is also very important to maintain normal menstrual function. It has been estimated that approximately 22 percent body fat is necessary to maintain normal menstrual function. This body fat criterion is not completely accurate; nevertheless, the concept is valid and remains useful to illustrate the concept. Competitive female athletes have about 50% less body fat than the non-competitor and less than the 22 percent required for normal menstrual function. Fat is converted to lean body mass during exercise. As a result, there may be no discernible change in total body weight in the athlete.

Energy availability is defined as dietary energy intake minus energy expenditure. Low energy availability appears to be the factor that impairs reproductive function. Restrictive eating behaviors practiced by girls and women in sports or physical activities that emphasize leanness are of special concern. Differential physiological mechanisms controlling energy balance are closely linked to fertility. Metabolic status is transmitted to the brain via peripheral (e.g. leptin, insulin, and ghrelin) and central (e.g. neuropeptide Y., melanocortin, and orexins) metabolic fuel detectors. When oxidizable fuel is scarce, these detectors function to inhibit the release of gonadotropin releasing hormone and luteinizing hormone, thereby prompting alteration of ovarian function and reproductive cyclicity.

Infertility can result when resources are abundant, but food intake fails to compensate for increased energy demands. Examples of these conditions in women include anorexia nervosa and exercise-induced amenorrhea. Caloric restriction caused by under-nutrition or over-exercise is increasingly common, and has significant health consequences such as hypothalamic amenorrhea and infertility. Several observations provide further evidence of the tight association between energy balance and reproduction. For example, fifty-three percent of female triathletes were found to be in caloric deficit, forty-seven percent had a fat deficit, forty percent had a protein deficit in one study. These findings highlight the importance of metabolic imbalance in female athletes.

Exercise represents a physical stress that challenges homeostasis. Stress and stress hormones play a profound role in the etiology of the onset of menstrual dysfunction in female athletes. Adrenocorticotrophic hormone (ACTH), corticotrophin releasing hormone (CRH), adrenal steroids and cathecholamines are increased in female athletes. Endogenous opiates are thought to decrease GnRH secretion and, thus, the release of LH and FSH for ovarian stimulation. Abnormal luteinizing hormone pulse frequency has been observed in high performance female athletes. When the stressor (heavy exercise) is removed, menstrual function returns to normal. For example, dancers experience the return of normal menstrual function during periods of rest. This observation implies that abnormal ovarian function associated with the stress of exercise is a reversible endocrine metabolic phenomenon. The degree of reversibility is unknown, although general experience indicates that the majority of women regained ovulation upon decreasing the stress of exercise and correction of caloric intake.

Historical and physical evidence should lead the clinician to suspect exercise or dietary related ovulatory dysfunction in patients with a history of heavy exercise. Abnormal ovulatory function associated with heavy exercise is usually reversible, providing that there are no other underlying neuroendocrine causes for the problem. The prognosis for return of normal menstrual function and pregnancy is excellent with early recognition, and simple weight gain will often reverse the state of amenorrhea. Nutritional counseling should be an integral part of the treatment plan. Full weight recovery and restoration of metabolic balance can lead to reversal of ovulatory dysfunction. A multidisciplinary treatment team should include the physician or other health care professional, a registered dietitian, and, for athletes with eating disorders, a mental health practitioner. When pregnancy is desired, reduction in the amount of exercise and weight gain should be recommended, or induction of ovulation may be pursued. It is important for the clinician to realize that suboptimal ovulatory function may exist in female athletes with regular menstrual cycles and that routine hormone testing may not detect subtle changes in the patterns of hormone secretion. Advanced assisted reproductive techniques may be necessary depending on the severity of the patient's ovulatory dysfunction.