Weight Loss and Dieting Weight loss can cause amenorrhea even if weight does not decrease below normal. Loss of 10% body mass in 1 year is associated with amenorrhea. Some but not all of these women have an underlying eating disorder. Prognosis is good for the return of menses if the patients recover from the weight loss. Dieting without weight loss and changes in diet can lead to amenorrhea (114).
Exercise In patients with exercise-induced amenorrhea, there is a decrease in the frequency of GnRH pulses, which is assessed by measuring a decreased frequency of LH pulses. These patients are usually hypoestrogenic, but less severe alterations may cause minimal menstrual dysfunction (anovulation or luteal phase defect). The decrease in GnRH pulsatility can be caused by hormonal alterations, such as low levels of leptin or high levels of ghrelin, neuropeptide Y and corticotrophin-releasing hormone (120). Runners and ballet dancers are at higher risk for amenorrhea than swimmers (121). It was previously suggested that a minimum of 17% body fat is required for the initiation of menses and 22% body fat for the maintenance of menses (122). Studies suggest that inappropriately low caloric intake during strenuous exercise is more important than body fat (123). Higher-intensity training, poor nutrition, stress of competition, and associated eating disorders increase an athlete’s risk for menstrual dysfunction (124). Osteoporosis may result in stress fractures during training and lifelong increased fracture risk. Stress fractures most commonly occur in the weight-bearing cortical bone such as the tibia, metatarsal, fibula, and femur. These athletes may fail to reach peak bone mass and have abnormal bone mineralization.
Stress Stress-related amenorrhea can be caused by abnormalities in neuromodulation in hypothalamic GnRH secretion, similar to those that occur with exercise and anorexia nervosa.
Excess endogenous opioids and elevations in CRH secretion inhibit the secretion of GnRH (115). These mechanisms are not fully understood but appear to be the common link between amenorrhea and chronic diseases, pseudocyesis, and malnutrition.
Obesity Most obese patients have normal menstrual cycles, but the percentage of women with menstrual disorders increases for women with obesity compared with women of normal weight. The menstrual disorder is more often irregular uterine bleeding with anovulation rather than amenorrhea. Obese women have an excess number of fat cells in which extraglandular aromatization of androgen to estrogen occurs. They have lower circulating levels of sex hormone–binding globulin, which allows a larger proportion of free androgens to be converted to estrone. Excess estrogen creates a higher risk for endometrial cancer for these women. The decrease in sex hormone–binding globulin allows an increase in free androgen levels, which initially are eliminated by an increased rate of metabolic clearance. This compensatory mechanism diminishes over time, and hirsutism can develop. Frequently, these patients are classified as having PCOS. Alterations in the secretion of endorphins, cortisol, insulin, growth hormone, and IGF-1 may interact with the abnormal estrogen and androgen feedback to the GnRH pulse generator to cause menstrual abnormalities.