Changes of opioid modulation of the hypothalamo-pituitary-adrenal axis in patients with severe premenstrual syndrome.

To assess the function of the hypothalamus-pituitary-adrenal axis in patients with severe premenstrual syndrome (PMS) 28 patients and 14 asymptomatic controls were studied during the mid- to late-luteal phase of the menstrual cycle. The response of plasma cortisol to both high-dose naloxone and corticotropin-releasing hormone (CRH) was assessed. Naloxone stimulated a significant cortisol release in controls whereas it was otherwise almost absent in patients. CRH stimulated a greater release of cortisol in patients than in controls. Fifteen patients met criteria for either current anxiety and/or mood disorders. The cortisol secretion after both naloxone and CRH stimulations was similar for PMS patients with or without psychiatric disorders. These data indicate that endogenous opioids modulate the activity of the hypothalamus-pituitary-adrenal axis. Irrespective of the concomitant presence of menstrual migraine or psychiatric disorder, such control is altered in patients with severe PMS because of the possible hyposensitivity of opiate receptors. The hyperresponsiveness to CRH may be the consequence of the reduced inhibition that endogenous opioids tonically exert on HPA axis.