One-year endometrial safety evaluation of a continuous combined transdermal matrix patch delivering low-dose estradiol-norethisterone acetate in postmenopausal women

Göran Samsioe, Vladimír Dvořák, Vladimir Dvorak, Andrea R. Genazzani, Bernd Hamann, Jorma Heikkinen, Alfred O. Mueck, Jacek Suzin, Fernando T. Kawakami, Alberto Ferreira, Dongming Sun, Miguel Arguinzoniz
Maturitas · 2007 · vol. 57(2) , pp. 171–181 · doi:10.1016/j.maturitas.2007.01.001 · PMID:17317046 · W2057973830
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This study evaluated the endometrial safety of a continuous transdermal patch delivering low-dose estradiol and norethisterone acetate over one year in postmenopausal women.

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Abstract

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.

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MeSH descriptors

Estradiol Estrogen Replacement Therapy Hot Flashes Norethindrone Administration, Cutaneous Aged Drug Therapy, Combination Endometrium Endometrium Endometrium Estradiol Estradiol Female Hot Flashes Hot Flashes Humans Middle Aged Norethindrone Norethindrone Postmenopause

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