Minimized estradiol absorption with ultra-low-dose 10 μg 17β-estradiol vaginal tablets

Methods Fifty-eight women received either 10 mu g or 25 mu g estradiol vaginal tablets, administered once daily for 2 weeks, followed by twice-weekly dosing for 10 weeks. Blood samples were taken over 24 h at baseline (day -1) and days 1, 14, 82 and 83. Estradiol (E2), estrone (E1) and estrone sulfate (E1S) levels were quantified by gas chromatography-mass spectrometry (GCMS) and assessed by the average plasma concentration from time 0 to 24 h (C-ave) derived from the area under the curve within 24 h (AUC((0-24))) divided by 24 h. Results Mean C-ave values were 9.39 and 19.84 pg/ml on day 1, 6.56 and 18.29 pg/ml on day 14, and 4.64 and 9.41 pg/ml on day 83 for the 10 mu g and 25 mu g doses, respectively. After 12 weeks, E1 and E1S levels were slightly higher with the 25 mu g dose and in the same range with the 10 mu g dose, as compared to baseline. Conclusions During 12 weeks' administration, 10 mu g vaginal tablets resulted in at least 50% lower mean estradiol concentrations than with the 25 mu g dose within 24 h after dosing. Administering the 25 mu g dose, mean E2 levels during the first 2 weeks exceeded the published reference range for postmenopausal women using the GCMS method, while, with the 10 mu g dose, mean E2 levels remained in that range from the beginning, indicating minimized estradiol absorption.