Hypothalamic amenorrhea: evidence for a central derangement of hypothalamic-pituitary-adrenal cortex axis activity

OBJECTIVE: To evaluate the activity of the hypothalamic-pituitary-adrenal axis (HPA) in patients with hypothalamic amenorrhea. PATIENTS, PARTICIPANTS: Amenorrheic women with a history of emotional stressful events and eumenorrheic women as control group were studied. DESIGN: Pulsatile cortisol (F) secretion over a 4-hour period of time and plasma F responses to various neuroendocrine tests (naloxone, fenfluramine, corticotropin-releasing hormone [CRH], adrenocorticotropic hormone) were investigated. RESULTS: Women with hypothalamic amenorrhea showed a F secretory pattern higher than normal women. In addition, the lack of naloxone or fenfluramine-induced release of F and a blunted F response to CRH test were observed. CONCLUSION: The increased activity of HPA in patients with hypothalamic amenorrhea is associated with an impaired activity of some central pathways (opioids and serotonin), suggesting multiple alterations in the hypothalamic control of pituitary-adrenal axis in amenorrheic women.