Efficacy and tolerability of fully transdermal hormone replacement in sequential or continuous therapy at two doses of progestogen in postmenopausal women.
OBJECTIVE
Two randomized open-label studies were performed to evaluate fully transdermal hormone replacement therapy (HRT) with oestradiol (E2) and norethisterone acetate (NETA) in postmenopausal women.


METHODS
Both hormones were delivered by transdermal matrix patches changed twice weekly. Subjects received E2, 50 microg/day and NETA, 170 microg/day or 350 microg/day, either continuously or sequentially. A one-year study (13 cycles of 28 days), including a reference regimen of transdermal E2 and sequential oral progestogen, was followed by a continuation study for a further year in 367 women.


RESULTS
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 scheduling of bleeding around the end of the progestogen phase. The continuous regimens were associated with irregular bleeding, which was rarely severe, and a gradually increasing incidence of amenorrhoea. With sequential or continuous therapy, bleeding was less severe at the lower dose of progestogen than at the higher dose. No endometrial hyperplasia was detected by biopsy in any treatment group. One serous endometrial carcinoma and one endometrial adenocarcinoma were detected. An endometrial thickness >5 mm did not predict the presence of hyperplasia at biopsy. Hormone-related adverse events were typical of those expected for HRT and dermal tolerability of the patches 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.
Ylikorkala
O
O
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, PO Box 140, 00029 HYKS, Helsinki, Finland. olavi.ylikorkala@huch.fi
Rozenberg
S
S
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D019584:Hot Flashes / Q000188:drug therapy; D006801:Humans; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome
D004338:Drug Combinations; D008055:Lipids; D011374:Progesterone; D004958:Estradiol