Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea

OBJECTIVE: Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and β-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. STUDY DESIGN: Corticotropin-releasing hormone, vasopressin, and β- endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. RESULTS: Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and β-endorphin levels were lower in women with functional hypothalamic amenorrhea. CONCLUSIONS: In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal- fluid corticotropin-releasing hormone, vasopressin, or β-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.