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

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• 作者：Gö ; ran Samsioe ; Vladimir Dvorak ; Andrea R. Genazzani ; Bernd Hamann ; Jorma Heikkinen ; Alfred O. Mueck ; Jacek Suzin ; Fern ; o T. Kawakami ; Alberto Ferreira ; Dongming Sun ; et al.
• 关键词：Endometrial safety ; Estradiol ; Norethisterone ; Transdermal patch
• 刊名：Maturitas
• 出版年：2007
• 出版时间：20 June 2007
• 年：2007
• 卷：57
• 期：2
• 页码：171-181
• 全文大小：205 K

文摘

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 μg and NETA 125 μg; applied every 3–4 days) or oral E2/NETA (E2 1 mg 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 μg) provided adequate endometrial protection in postmenopausal women when evaluated according to CPMP/CHMP criteria, achieved a high rate of amenorrhea, and was well tolerated.