Systemic lupus erythematous (SLE) is an autoimmune disease that induces chronic inflammation of the major body systems. This disease induces autoantibodies production, causing immune complex formation and deposition in tissue, which result in inflammation and multi-organs damage. Among the common SLE complications is the development of lupus nephritis (LN) in which inflammation and damage to the kidneys occur. In the current study we aimed to evaluate the effect of administrating pulse therapy on LN patients during ovulation period (period of high estrogen level) in menstruating patients and during full moon period in non-menstruating group. This was a one year prospective cross-sectional study, included 101 LN female patients in the reproductive age attended Nephrology Department, Assiut University Hospital. They was divided into; Group A (menstruating group) that was subdivided into; Group A1: included 36 patients received pulse therapy during ovulation, Group A2: included 15 patients served as controls and received pulse therapy during any time (n=15). Group B (non-menstruating) that was subdivided into; Group B1: included 35 patients received pulse therapy during moon period, and Group B2: included 15 patients served as controls and received pulse therapy during any time. Patient’s response was evaluated to determine the best time for receiving the pulse therapy. In menstruating women, the degree of reduction in blood urea nitrogen (P=0.033, after three months of follow up), protein/ creatinine ratios (P=0.016, after two months of follow up, and P=0.005, after three months of follow up), and increase in hemoglobin level (P=0.006, after two months of follow up, and P=0.016, after three months of follow up) were significantly higher among patients who received pulse therapy during the period of ovulation. In non-menstruating women, receiving pulse therapy during full moon period enhanced and augmented its effect. In conclusion, estrogen hormone may play a major role in the female predominance of autoimmune disease, particularly systemic lupus erythematous.