Endometrial safety of a transdermal sequential estradiol-levonorgestrel combination.
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.


CONCLUSIONS
Estradiol and sequential levonorgestrel administered in a 7-day transdermal matrix patch for 1 year provide endometrial protection.
Sturdee
D W
DW
Department of Obstetrics and Gynaecology, Birmingham Heartlands and Solihull NHS Trust, Solihull Hospital, Lode Lane, Solihull, West Midlands B91 2JL, UK.
van de Weijer
P
P
von Holst
Th
T
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D005858:Germany; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009426:Netherlands; D017698:Postmenopause; D006113:United Kingdom
D004958:Estradiol; D016912:Levonorgestrel