S69-1 Mechanisms Underlying Variable Susceptibility to Functional Hypothalamic Amenorrhea: Clinical Implications

Program: Symposia
Session: S69-Functional Hypothalamic Amenorrhea: Special Topics
Clinical
Tuesday, June 18, 2013: 7:30 AM-9:00 AM
Presentation Start Time: 7:30 AM
Room 134 (Moscone Center)
Mark E Wilson*
Emory University, Atlanta, GA
Talk Description:

Functional hypothalamic amenorrhea (FHA) is thought to result from chronic exposure to psychosocial stressors and is often co-morbid with other clinical problems, including metabolic abnormalities. A number of models using nonhuman primates have been employed to better understand the stressors that contribute to the emergence of FHA, possible mechanisms that mediate these effects, and interventional strategies to alleviate these stress-induced disorders. Like women, the FHA phenotype in monkeys is characterized by sustained periods of anovulation or a preponderance of short luteal phase cycles. Despite having persistently low levels of ovarian estradiol secretion, evidence suggests that the resulting hypogonadotropism may be due to hypersensitivity to estradiol negative feedback inhibition. Together the studies show the stressors responsible for this phenotype are sustained and unpredictable and produce a dysregulation of the stress-hormone axis as well disrupted serotonergic signaling. Indeed, antagonism of stress hormone signaling in the brain restores LH pulsatility. Furthermore, reduced energy intake, analogous to disrupted eating in women with FHA, is likely a contributing factor to this stress-induced reproductive compromise, as increasing caloric intake through dietary manipulations normalizes LH secretion. Finally, similar to data from women, behavioral interventions that alleviate stress rescue ovarian function in monkeys. These translational models also provide the opportunity to identify genetic and behavioral factors that provide resilience to the neurobiological insults caused by chronic stress exposure, thereby helping to explain why some women are more vulnerable to stress-induced infertility.

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