Variability of midcycle estradiol positive feedback: evidence for unique pituitary responses in individual women

In women the preovulatory estradiol (E2) level must reach a peak concentration and dose (strength and duration) to initiate the LH surge. The variability of the surge-initiating serum E2 level in individual women from cycle to cycle, however, has not been studied. Accordingly, we studied 24 normally ovulating women longitudinally during a total of 221 menstrual cycles (range, 4-17 cycles/woman). In those women we measured periovulatory serum E2 and LH concentrations daily from 3 days before the LH peak to the day after the LH peak. The mean peak E2 concentration was 343 pg/mL, and the mean E2 dose (concentration X time) was 979 pg/mL. When the values in individual women were compared between women by components of variance analysis of variance, the differences were significant (concentration, P less than 0.01; dose, P less than 0.005), indicating that individual women have discrete and characteristic responses to E2 positive feedback. When E2 peaks and doses from initial cycles were compared with subsequent cycles by regression analysis, there were strong positive correlations (peak: r = 0.47; P less than 0.001; dose: r = 0.60; P less than 0.001). Of the total group variance in mean E2 peak and mean dose, 67% of the peak and 54% of the dose variance resulted from an individual woman's cycle to cycle variability, while 33% of the peak and 46% of the dose variance was attributable to differences among the women's responses to positive feedback. We conclude that individual women have characteristic and predictable periovulatory E2 production, leading to a LH surge which is maintained from cycle to cycle; and approximately two thirds of the total variance in mean peak E2 concentration (67%) and approximately half the variance in mean dose (54%) are the result of cycle to cycle biological variability around this characteristic periovulatory pattern of E2 production.