Objective: The aim of this 1-year, randomized, multinational, open-label study was to assess the effect on the endometrium of three dosages of estradiol and sequential levonorgestrel, each administered in a novel 7-day transdermal matrix patch.
Methods: A total of 468 postmenopausal women received patches of 15 cm2 (50 micrograms/day estradiol for 2 weeks followed by 50 micrograms/day estradiol-10 micrograms/day levonorgestrel for 2 weeks), 22.5 cm2 (75 micrograms/day estradiol for 2 weeks followed by 75 micrograms/day estradiol-15 micrograms/day levonorgestrel for 2 weeks) or 30 cm2 (100 micrograms/day estradiol for 2 weeks followed by 100 micrograms/day estradiol-20 micrograms/day levonorgestrel for 2 weeks). Each patch was applied for 7 days.
Results: Endometrial biopsies were taken before and after 1 year of treatment, with final valid biopsy results being obtained in 399 women. There were two cases of endometrial hyperplasia (one in the 22.5-cm2 and one in the 30-cm2 group). All three doses of this 7-day sequential combined estradiol-levonorgestrel transdermal hormone replacement therapy therefore had excellent endometrial safety. The lowest dose, however, was associated with less bleeding and a somewhat different histological pattern, compared with the two higher doses. All three doses provided a high level of patient satisfaction with the bleeding response.
Conclusion: Estradiol and sequential levonorgestrel administered in a 7-day transdermal matrix patch for 1 year provide endometrial protection.