Pharmacokinetics of continuous once-a-week combination 17β-Estradiol/Low- or high-dose levonorgestrel transdermal delivery systems in postmenopausal women.

Two open-label, randomized, two-period, crossover studies were performed to determine the safety, delivery rates, and pharmacokinetic properties of a combination estradiol (E2)/levonorgestrel (LNG) transdermal delivery system (TDS). Study 1 enrolled 24 postmenopausal women who received a single TDS containing 4.4mg E2 and 1.39mg of LNG (E2/LNG Low) or E2 0.050mg/24hours TDS and 0.090mg LNG oral tablet. Study 2 enrolled 44 postmenopausal women who received either E2/LNG Low or TDS containing 4.4mg E2 and 2.75mg LNG (E2/LNG High) weekly for a period of 4 weeks. E2, estrone (E1), LNG, and sex hormone-binding globulin (SHBG) serum concentrations were determined. Overall, both E2/LNG TDS were well tolerated and had excellent adhesion properties. The average daily delivery for E2/LNG Low was 0.045mg for E2 and 0.0132mg for LNG. Following weekly delivery of E2/LNG Low or High for 4 weeks, the combination of E2 with two different strengths of LNG did not alter the pharmacokinetic profile of E2. SHBG, total cholesterol, and triglycerides concentrations significantly decreased compared to baseline. Both E2/LNG Low and High TDSs were well tolerated and provided continuous drug delivery over 7 days supporting the benefits of the transdermal route of administration in optimally delivering hormonal therapy.