Background and aims: This study aimed to determine whether there is an adrenomedullin (AM)-mediated protective effect of postmenopausal estroger/progestin therapy (HRT) against cardiovascular disorders. Methods: A total of 22 post-menopausal women without hysterectomy undergoing postmenopausal symptoms (aged 43-52) were treated with conjugated equine estrogen (0.625 mg/die) plus medroxyprogesterone acetate (2.5 mg/die) for six months. The flow velocity of the right middle cerebral artery [measured as resistance index (RI) and pulsatility index (PI)], plasma levels of adrenomedullin and endothelin-1 (ET-1), mean baseline ratio of AM to ET-1, and lipid profiles were assessed before and after HRT. Results: A statistically significant difference was found for triglycerides, total cholesterol, AM/ET-1 ratio and right middle cerebral artery PI (p < 0.05), without any significant differences in HDL, LDL, AM, ET-1, systolic blood pressure, diastolic blood pressure, a right middle cerebral artery RI (p > 0.05) between pre- and post-HRT. Conclusions: Adrenomedullin may be added to other vasoactive peptides as a new potential candidate for HRT-mediated vascular protection. The ratio of AM/ET-1 vs AM or ET-1 alone may be a useful biological marker of this protection.