Endometrial safety of ultra-low-dose Vagifem 10 μg in postmenopausal women with vaginal atrophy

Abstract

Objective The objective of the study was to evaluate the endometrial safety of a 10 μg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women.

Methods A total of 336 healthy, non-hysterectomized, postmenopausal women (age 59.5 ± 6.16 years, 9.4 ± 5.9 years from last menses) were treated with a 10 μg estradiol vaginal tablet for 12 months (once daily for 2 weeks and then twice weekly for 50 weeks). Endometrial histology was analyzed at baseline and at the end of the trial.

Results Of the 336 enrolled subjects, 292 (86.9%) completed the 52-week study. All 336 subjects received an endometrial biopsy at baseline, and 283 had biopsy results at week 52, when 258 out of the 283 biopsy samples were classified as ‘atrophic’ or ‘inactive’ endometrium. There were 21 with ‘no tissue’ despite a repeat biopsy attempt to obtain endometrial tissue, one had insufficient tissue with endometrial thickness >4 mm, one was ‘weakly proliferative’ and two revealed polyps. No cases of endometrial hyperplasia or endometrial cancer were reported. The mean endometrial thickness decreased from 2.04 mm (n = 334) from study start to 1.94 mm (n = 293) after 52 weeks, and the estradiol levels remained at the low postmenopausal level.

Conclusions After 12 months of treatment with the 10 μg estradiol vaginal tablet, there was no suggestion of endometrial stimulation and no cases of endometrial hyperplasia or cancer reported. This study provides reassuring data on the endometrial safety of treatment with the 10 μg estradiol vaginal tablet for 1 year in a large group of postmenopausal, non-hysterectomized women with vaginal atrophy.

Key words:

• ULTRA-LOW-DOSE ESTRADIOL
• ENDOMETRIAL SAFETY
• VAGINAL THERAPY
• VAGINAL ATROPHY
• HORMONE REPLACEMENT THERAPY
• HORMONE THERAPY

Acknowledgements

The authors gratefully acknowledge the assistance of the Vagifem study group, their staff, clinical trial personnel and the subjects for participating in the study. The authors would also like to acknowledge the statistical analysis provided by Pei-Ling Chiu and Anjun Cao.

Principal Investigators

R. Aabø, M. Andresen, B. Arentoft, P. Attila, S. M. Axelsen, O. Chevallier, R. Chmel, S. Christau, P. Colnat, S. Damm, E. Darnis, V. Dvorak, D. Elia, E. Ingelhammar, O. Halonen, E. Hellberg, L. Kambjerre, L. Karinen, P. Krahulec, E. P. Lingman, T. Lunde, J. Mäkinen, P. Mares, A. Martan, L-Å. Mattsson, M. Moyal, T. Naessen, S. Pál, G. Péter, S. Piippo, T. K. Sándor, A-L. Simpanen, A. Skrivanek, H. H. Solbakken, T. Sørdal, A. Vedsted-Jakobsen, M. Veholmen, N. Willumsen, M. Wojtasinska, A. Zandjani and M. Zoltán.

Conflict of interest  Dr L. Ulrich has received speaker's fees from Novo Nordisk and from Organon Schering Plough (now merged with Merck & Co.). Dr T. Naessen has received speaker's fees and a research grant from Novo Nordisk. Dr D. Elia has received an honorarium as a Novo Nordisk trial investigator. Dr J. A. Goldstein is employed by Novo Nordisk Inc. in Princeton, NJ, USA. Dr M. Eugster-Hausmann is employed by Novo Nordisk Femcare AG in Zurich, Switzerland.

Source of funding  Financial support for this study was provided by Novo Nordisk A/S, Bagsvaerd, Denmark. Statistical and editorial support was provided by Novo Nordisk Inc, Princeton, NJ, USA. Novo Nordisk Inc. (Tulay T. Cushman) provided the first draft text for the Methods and Results sections, facilitated co-operation between authors and assisted in proof-reading and language correction.