Cardioprotective mechanism in females during reproductive phase is unclear. New perspective explains cardioprotective function of progesterone. Progesterone, the intermediary metabolic product in synthesis of steroid hormones, with t/2 of 30 min, stimulates respiratory center inducing respiratory alkalosis in turn lowers plasma ionic calcium. This results in decreased blood coagulability and cardiac contractility along with smooth muscle relaxation. Vascular smooth muscle relaxation, leading to generalized vasodilatation causes better tissue perfusion resulting in diminished erythropoietin, and erythrocyte count. This reduces blood viscosity and afterload on the heart. Cardiac contractility remains balanced due to opposing influences of decreased plasma ionic calcium and raised basal body temperature. On sudden withdrawal of progesterone, as during premenstrual, postpartum and postmenopausal periods, cardioprotective changes are reversed. The awareness helps to build better body buffer system, aiming to correct acid-base imbalance, during expected fluctuations of progesterone.