Efficacy and tolerability of fully transdermal hormone replacement in sequential or continuous therapy at two doses of progestogen in postmenopausal women

Objectives: Two randomized open-label studies were performed to evaluate fu lly transdermal hormone replacement therapy (HRT) with oestradiol (E-2) and norethisterone acetate (NETA) in postmenopausal women. Methods: Both hormo nes were delivered by transdermal matrix patches changed twice weekly. Subj ects received E-2, 50 mug/day and NETA, 170 mug/day or 350 mug/day, either continuously or sequentially. A one-year study (13 cycles of 28 days), incl uding a reference regimen of transdermal E-2 and sequential oral progestoge n, was followed by a continuation study for a further year in 367 women. Re sults: All regimens were highly and equally effective in the prevention of hot flushes. The fully transdermal regimens were associated with beneficial changes in the lipid profile. The sequential regimens provided effective s cheduling of bleeding around the end of the progestogen phase. The continuo us regimens were associated with irregular bleeding, which was rarely sever e, and a gradually increasing incidence of amenorrhoea. With sequential or continuous therapy, bleeding was less severe at the lower dose of progestog en than at the higher dose. No endometrial hyperplasia was detected by biop sy in any treatment group. One serous endometrial carcinoma and one endomet rial adenocarcinoma were detected. An endometrial thickness > 5 mm did not predict the presence of hyperplasia at biopsy. Hormone-related adverse even ts were typical of those expected for HRT and dermal tolerability of the pa tches was good. Conclusions: Fully transdermal sequential or continuous HRT is effective and well tolerated in postmenopausal women. The lower dose of NETA may be preferable, because it confers adequate endometrial protection at a lower dose of progestogen. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.