Endometrial safety of an oral contraceptive containing estradiol valerate and dienogest

Abstract

Johannes Bitzer1, Susanne Parke2, Thomas Roemer3, Marco Serrani21University Hospital of Basel, Women's Clinic, Basel, Switzerland; 2Global Clinical Development, Bayer HealthCare Pharmaceuticals, Berlin, Germany; 3Head of the Department of Gynecology and Obstetrics, Evangelist Hospital Cologne-Weyertal, Cologne, GermanyBackground: The purpose of this study was to investigate the endometrial safety of an oral contraceptive containing estradiol valerate/dienogest (E2V/DNG) administered as an estrogen step-down and progestogen step-up regimen in women of reproductive age (18–50 years), using histological assessment of endometrial biopsy samples.Methods: Endometrial biopsies were taken in a subset of healthy women who took part in a multicenter, open-label, noncomparative study assessing the contraceptive efficacy and safety of an E2V/DNG oral contraceptive. In each 28-day cycle, women received E2V 3 mg on days 1–2, E2V 2 mg/DNG 2 mg on days 3–7, E2V 2 mg/DNG 3 mg on days 8–24, E2V 1 mg on days 25–26, and placebo on days 27–28. Women underwent endometrial biopsy between days 12 and 19 of the cycle, both at screening and at cycle 20 (or at the final examination).Results: Of the 283 women who underwent an endometrial biopsy at screening, 218 underwent a follow-up biopsy at cycle 20. At screening, abnormal biopsy results, both classified as ‘simple hyperplasia without atypia’, were seen in two women, who were withdrawn from the trial. At cycle 20, there were no abnormal findings of endometrial hyperplasia or malignancy, and 80.9% of women had atrophic, inactive, or secretory endometrium.Conclusion: After 20 cycles of treatment, an oral contraceptive containing E2V and DNG is safe and effective to transform the endometrium into a secretory/inactive or atrophic status, and exhibits no deleterious effects on endometrial histology in women aged 18–50 years.Keywords: estradiol valerate, dienogest, endometrial safety, oral contraceptive