Increased vasopressin and adrenocorticotropin responses to stress in the midluteal phase of the menstrual cycle

Accumulating evidence indicates that gonadal steroids modulate functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which has been closely li nked to the pathophysiology of anxiety and depression. However, the effect of the natural menstrual cycle on HPA axis responsivity to stress has not b een clearly described. In nine healthy women, metabolic and hormonal respon ses to treadmill exercise stress during the early follicular phase of the m enstrual cycle, when gonadal steroid levels are low, were compared with res ponses in the midluteal phase of the cycle, when both progesterone and estr ogen levels are relatively high. Exercise intensity was gradually increased over 20 min to reach 90% of each subject's maximal oxygen consumption duri ng the final 5 min of exercise. Basal plasma lactate, glucose, ACTH, vasopr essin, oxytocin, and cortisol levels were similar in the two cycle phases. However, in response to exercise stress, women in the midluteal phase had e nhanced ACTH (P < 0.0001), vasopressin (P < 0.01), and glucose (P < 0.001) secretion. These findings suggest that relatively low levels of gonadal ste roids during the early follicular phase of the menstrual cycle provide prot ection from the impact of stress on the HPA axis.