PMID- 17317046
OWN - NLM
STAT- MEDLINE
DCOM- 20070726
LR  - 20131121
IS  - 0378-5122 (Print)
IS  - 0378-5122 (Linking)
VI  - 57
IP  - 2
DP  - 2007 Jun 20
TI  - One-year endometrial safety evaluation of a continuous combined transdermal 
      matrix patch delivering low-dose estradiol-norethisterone acetate in 
      postmenopausal women.
PG  - 171-81
AB  - OBJECTIVE: To evaluate the safety and endometrial protection of low-dose 
      transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) 
      in terms of post-treatment incidence of endometrial hyperplasia/cancer after 1 
      year of treatment in postmenopausal women with intact uteri. METHODS: Patients 
      were randomized to receive either transdermal E2/NETA (delivering daily doses of 
      E2 25 microg and NETA 125 microg; applied every 3-4 days) or oral E2/NETA (E2 1mg 
      and NETA 0.5 mg; given daily) in this open-label study. The primary variable was 
      the incidence of endometrial hyperplasia/cancer based on endometrial biopsies; 
      secondary variables included vaginal bleeding/spotting patterns, patch adhesion, 
      safety and tolerability. RESULTS: Six hundred and seventy-seven patients were 
      randomized (507 in the transdermal group and 169 in the oral group; one did not 
      receive study drug) and >80% completed the study. There were no cases of 
      endometrial hyperplasia or cancer in either group and the upper limit of the 
      one-sided 95% confidence interval in the transdermal group was 0.85%. Over time, 
      both treatments were associated with a decreasing frequency of spotting/bleeding 
      days. The overall incidence of adverse events (AEs) was comparable in both 
      groups, and the majority was mild-to-moderate in intensity. Breast tenderness was 
      the most frequently reported AE (transdermal 19.9% versus oral 28.4%). AEs 
      related to the gastrointestinal system were more frequent with oral E2/NETA, and 
      episodes of spotting and bleeding were more frequent with transdermal E2/NETA. 
      Local skin tolerability of the transdermal matrix system was good. CONCLUSIONS: 
      Transdermal E2/NETA (25 and 125 microg) provided adequate endometrial protection 
      in postmenopausal women when evaluated according to CPMP/CHMP criteria, achieved 
      a high rate of amenorrhea, and was well tolerated.
FAU - Samsioe, Goran
AU  - Samsioe G
AD  - Department of Obstetrics and Gynaecology, Lund University Hospital, Lund, Sweden. 
      goran.samsioe@med.lu.se
FAU - Dvorak, Vladimir
AU  - Dvorak V
FAU - Genazzani, Andrea R
AU  - Genazzani AR
FAU - Hamann, Bernd
AU  - Hamann B
FAU - Heikkinen, Jorma
AU  - Heikkinen J
FAU - Mueck, Alfred O
AU  - Mueck AO
FAU - Suzin, Jacek
AU  - Suzin J
FAU - Kawakami, Fernando T
AU  - Kawakami FT
FAU - Ferreira, Alberto
AU  - Ferreira A
FAU - Sun, Dongming
AU  - Sun D
FAU - Arguinzoniz, Miguel
AU  - Arguinzoniz M
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20070220
PL  - Ireland
TA  - Maturitas
JT  - Maturitas
JID - 7807333
RN  - 4TI98Z838E (Estradiol)
RN  - T18F433X4S (Norethindrone)
SB  - IM
MH  - Administration, Cutaneous
MH  - Aged
MH  - Drug Therapy, Combination
MH  - Endometrium/drug effects/pathology
MH  - Estradiol/*administration & dosage/adverse effects
MH  - *Estrogen Replacement Therapy
MH  - Female
MH  - Hot Flashes/*drug therapy/pathology
MH  - Humans
MH  - Middle Aged
MH  - Norethindrone/*administration & dosage/adverse effects
MH  - Postmenopause
MH  - Treatment Outcome
EDAT- 2007/02/24 09:00
MHDA- 2007/07/27 09:00
CRDT- 2007/02/24 09:00
PHST- 2006/07/03 00:00 [received]
PHST- 2006/12/19 00:00 [revised]
PHST- 2007/01/02 00:00 [accepted]
PHST- 2007/02/24 09:00 [pubmed]
PHST- 2007/07/27 09:00 [medline]
PHST- 2007/02/24 09:00 [entrez]
AID - S0378-5122(07)00025-4 [pii]
AID - 10.1016/j.maturitas.2007.01.001 [doi]
PST - ppublish
SO  - Maturitas. 2007 Jun 20;57(2):171-81. doi: 10.1016/j.maturitas.2007.01.001. Epub 
      2007 Feb 20.