Pharmacokinetics of percutaneous estradiol: a crossover study using a gel and a transdermal system in comparison with oral micronized estradiol

Abstract

The pharmacokinetics of three transdermal estradiol (E2) replacement regimens were studied following establishment of steady-state dynamics. Oestrogel 3.0 mg, Oestrogel 1.5 mg, and Estraderm transdermal delivery system 4 mg (0.05 mg/day) were administered for 14 days each to 15 postmenopausal volunteers, with a 14-day washout period between each regimen. The percutaneous E2 pharmacokinetics were compared with an oral micronized E2 preparation. Venous samples were obtained at 0, 1, 2, 4, 8, 12, and 24 hours on 3 sequential days 11 days after initial application of the Oestrogel and the transdermal delivery system, and at the same times after oral E2 ingestion. All three percutaneous regimens provided nearly constant serum E2 and estrone (E1) levels throughout their use. The mean serum E2 levels were 102.9 +/- 39.9, 68.1 +/- 27.4, and 41.1 +/- 13.5 pg/mL for Oestrogel 3.0 mg, Oestrogel 1.5 mg, and Estraderm, respectively. Oral E2 resulted in a mean serum E2 level of 114.0 +/- 65.2 pg/mL with marked peak and nadir values. The E1/E2 ratio was comparable with all three percutaneous regimens (1.08-1.33) and was significantly lower than that found with oral Estrace (5.05).