This study aimed to evaluate the effects of changes in sex hormones occurring during the menstrual cycle on the redox balance and lipid peroxidation in normal human endometrial cells. Forty women, ages 21-41 yr, who were admitted to the Department of Gynecology and Obstetrics of the University of Bari for routine checkups or were treated for benign uterine disease, underwent endometrial biopsy and venipuncture. On the basis of histological examination, patients were allocated as follows: 10 in the early proliferative phase, 12 in the late proliferative phase, 8 in the early secretory phase, and 10 in the late secretory phase. LH, FSH (immunoradiometric essay), estradiol (E2), and progesterone (P(4)) (RIA) were determined in plasma samples. On the endometrial specimens, total glutathione (GSH), oxidized GSH (GSSG), malondialdehyde, and GSH peroxidase activity (GSH-Px) were determined. Significant cycle-dependent changes in endometrial GSH-Px (P < 0.0001), GSH (P < 0.001), and GSSG as a percentage of GSH (P < 0.0001) were observed. Malondialdehyde did not show significant differences. A linear regression model correlating sex hormone changes with redox indexes was performed. A significant positive correlation was observed between E2 and GSH-Px (r = 0.74; P = 0.0001), E2 and GSSG, as percentage of total (r = 0.84; P < 0.0001); a negative correlation was found between E2 and GSH (r = -0.57; P = 0.0001). No significant correlation was found between P(4) or FSH and oxidative balance. LH was found to be correlated with GSH-Px (r = 0.66; P = 0.0001) and GSSG as percentage of GSH (r = 0.5; P < 0.001). We conclude that the hormonal pattern is involved in maintaining the optimal redox balance in endometrium, mainly through modulation of GSH level and metabolism.