._How_Does_Reduced_Energy_Availability_Affect_Hormonal_Control_of_Female_Reproduction__How_Are_Hormonal_Changes_Related_to_Energy_Intake_

Much research has been done on the effects of reduced energy availability on hormonal control of female reproduction. One study analyzed groups of male and female rats divided into three different diet groups for over six months. The first group had a normal diet and acted as the control, the second group had a 20 to 40 percent caloric restriction (CR), and the third group underwent intermittent fasting (IF). The females in the 40 percent CR group were emaciated, ceased cycling, began showing endocrine masculinization, had a heightened stress response, increased spontaneous activity, improved learning and memory, and maintained elevated levels of circulating brain-derived neurotrophic factor (Martin et al). They concluded that lowering body weight caused elevation of corticosterone levels, thus suggesting a heightened activation of the hypothalamic-pituitary-adrenal axis. They also noted reduced gonad size and elevated testosterone levels in accordance to the ceased cycling. Rats in the 40 percent CR group also showed enhanced performance in cognitive testing. All of these alterations in physiology and behavior suggest that the female is preparing herself for survival in an environment that is scarce in food. Evolutionarily, women are more sensitive to these changes because they must obtain food not only for themselves, but for their offspring as well. Thus, the body goes into a survival mode that diverts energy from reproductive processes and focuses them toward increasing the chance of survival (Martin et al). Another study done in 2006 aimed to understand the hormonal effect that limited energy availability had on female reproduction. They analyzed women with ceased ovulation who were underweight or performed strenuous exercise. These women showed lower levels of LH, leptin, and estradiol. They also had gonadotropin pulses at too low of frequencies to maintain antral follicular development until ovulation. To confirm this, the women were injected with LH to restore the levels to normal. In just 2 weeks, LH pulse frequency was increased and antral follicles became enlarged toward normal. They concluded that the reduced ability to maintain female menstruation occurred after 10 to 15 percent loss of normal body weight and was due to changes in gonadotropin-releasing hormone secretion and dopaminergic/opioid systems (ESHRE 2006). Yet another study done in 2006 describes the effects of reduced energy availability on female reproduction by focusing on an extreme case of this, in amenorrhea in anorexia nervosa. Amenorrhea in anorexia nervosa occurs when the altered release of hypothalamic gonadotropin-releasing hormone causes hypothalamic hypogonadism. The gonadotropins released by the anterior pituitary gland in this axis are LH and FSH and are much lower than normal in anorexia nervosa patients. FSH and LH control the formation of estradiol and ovarian estrogen, resulting in patients with amenorrhea having low estrogen levels as well. Estrogen functions in follicular maturation, but those with extreme energy deprivation show levels typical of pre-pubertal stage (Wolfe 2006). One final hormone that may influence female reproduction is leptin. Typically, leptin (a 146-aa protein) acts as an adipocyte-derived factor that notifies the brain on body fat accumulation, and may also respond acutely to negative energy balance. Leptin stimulates the hypothalamic-pituitary-thyroid axis and inhibits the hypothalamic-pituitary-adrenal axis. At low levels, leptin decreases the activity of the thyroid gland and increases activity of the adrenal gland, leading to hypothyroidism and hypercortisolism. Both of these signals tell the body to go into survival mode (Moneleone et al 2004). ESHRE Capri Workshop Group. Nutrition and reproduction in women. Human Reproduction Update, Vol.12, No.3 pp. 193–207. 31 Jan 2006. Martin, Bronwen; Pearson, Michele; Kebejian, Lisa; Golden, Erin; Keselman, Alex; Bender, Meredith; Carlson, Olga; Egan, Josephine; Ladenheim, Bruce; Cadet, Jean-Lud; Becker, Kevin G.; Wood, William; Duffy, Kara; Vinayakumar, Prabhu; Maudsley, Stuart; Mattson, Mark P. Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess. Endocrinology. 148: 9. 4318-4333. Monteleone, MD, Palmiero; DiLieto, MD, Antonio; Castaldo, MD, Eloisa; Maj, MD, PhD, Mario. Leptin Functioning in Eating Disorders. CNS spectrums. 9: 7. 523-529. Jul 2004. Wolfe, Barbara E. Reproductive Health in Women with Eating Disorders. JOGNN Clinical Issues. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 34: 2. 9 Mar 2006.