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Increased Vasopressin and Adrenocorticotropin Responses to Stress in the Midluteal Phase of the Menstrual Cycle

Department of Psychiatry, Weill Medical College, Cornell University (M.A., C.R.), New York, New York 10021; Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health (C.R.), Bethesda, Maryland 20892; and Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences (E.G., P.D.), Bethesda, Maryland 20814

Address all correspondence and requests for reprints to: Dr. Margaret Altemus, Box 244, Weill Medical College, Cornell University, 1300 York Avenue, New York, New York 10021. E-mail: maltemus{at}mail.med

Abstract

Accumulating evidence indicates that gonadal steroids modulate functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which has been closely linked to the pathophysiology of anxiety and depression. However, the effect of the natural menstrual cycle on HPA axis responsivity to stress has not been clearly described. In nine healthy women, metabolic and hormonal responses to treadmill exercise stress during the early follicular phase of the menstrual cycle, when gonadal steroid levels are low, were compared with responses in the midluteal phase of the cycle, when both progesterone and estrogen levels are relatively high. Exercise intensity was gradually increased over 20 min to reach 90% of each subject’s maximal oxygen consumption during the final 5 min of exercise. Basal plasma lactate, glucose, ACTH, vasopressin, oxytocin, and cortisol levels were similar in the two cycle phases. However, in response to exercise stress, women in the midluteal phase had enhanced ACTH (P < 0.0001), vasopressin (P < 0.01), and glucose (P < 0.001) secretion. These findings suggest that relatively low levels of gonadal steroids during the early follicular phase of the menstrual cycle provide protection from the impact of stress on the HPA axis.

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