To assess the effect of transdermal estrogen substitution on the hypothalamic-pituitary-adrenal (HPA) axis responsiveness/sensitivity and the impact of the antrophometric characteristics on these parameters, 20 postmenopausal women seeking treatment for the relief of postemenopausal symptoms were studied. They received transdermal 50 microg/d estradiol for 12 weeks (estrogen replacement therapy [ERT]). Patients were classified as low waist-to-hip ratio (WHR) (peripheral fat distribution women; n = 12) and high WHR (central fat distribution women; n = 8) according to the cut-off value of 0.85. Plasma hormone and lipid concentration were assessed at baseline and after 12 weeks of treatment. Results were compared with a group of 8 placebo-treated patients who served as controls. Corticotropin (ACTH) and cortisol (F) were expressed as fasting values, area under the curve (AUC), and time course over 90 minutes after corticotropin-releasing hormone (CRH) intravenous (IV) bolus (1 microg/kg body weight [BW]). Adrenal sensitivity to CRH stimulus was expressed as time course over 90 minutes and AUC of the F/ACTH molar ratio. The plasma F levels in response to ACTH stimulation did not change after ERT; however, a highly significant improvement of adrenal sensitivity was observed (P <.01). In fact, estrogen treatment significantly decreased the amount of ACTH produced after CRH stimulation, both as absolute time course and AUC (P <.01). No significant change was observed in controls. Considering body fat distribution, the high WHR group showed higher ACTH (P <.01), lower F/ACTH values, and superimposable F plasma values compared with the low WHR group. Estrogen treatment induced a significant ACTH reduction after CRH (P <.01) only in the high WHR group, whereas cortisol response was similar in both groups both before and after treatment. A significant negative correlation was found between WHR and adrenal sensitivity before treatment. ERT significantly improved adrenal sensitivity only in the low WHR group (P <.01). These data suggest that different mechanisms can prevail in the control of the HPA axis in menopause. Estrogens could exert different effects on the hypothalamic-pituitary axis, as well as on adrenal function, and these changes seem to be partially dependent on the pattern of body fat distribution.
Adipose Tissue Administration, Cutaneous