Bioavailability of estradiol from two matrix transdermal delivery systems: Menorest® and Climara®

Abstract

Objectives: To compare two estradiol transdermal matrix systems with regard to bioavailability, pharmacokinetics and tolerability. Methods: A single centre, open, randomized, comparative cross-over study in 20 healthy postmenopausal women. Menorest® with 3 or 4 days of suggested use and Climara® with 7 days of suggested use (both 50 μg/24 h) were compared at steady state. Two 14-day treatment periods were separated by a 4 week washout. Plasma levels of estradiol were monitored during the second week of each treatment. Tolerability was assessed by open questions and inspection of the application site. Results: There were no differences between the two treatments with regards to AUC, C max, C min, C average or fluctuations of plasma estradiol. T max was significantly shorter for Menorest® than Climara®. C max and C min were significantly higher for the second Menorest® patch during the monitoring period compared to the first. All local reactions were mild and there were three cases of erythema with Menorest® and a total of 21 skin reactions in 15 subjects with Climara®. Systemic tolerability was similar between treatments with eight estrogen-related adverse events in eight subjects (period pains, uterine bleeding, mastodynia, headache and vaginal discharge) with Menorest® and 13 events in ten subjects with Climara®. Conclusions: The bioavailability of estradiol from the two matrix transdermal delivery systems Menorest® and Climara® was similar, but the products were not bioequivalent because T max was significantly shorter for Menorest® than for Climara®. Tolerability of treatment was good for both patches but with a higher number of local reactions and estrogen related adverse events for Climara®.