UC Davis

INTRODUCTION:: A new contraceptive vaginal system (CVS) for 13 cycles of use has been developed that releases a daily mean of segesterone acetate (SA) 0.15 mg and ethinyl estradiol (EE) 0.013 mg. We evaluated endometrial safety during use of the SA/EE CVS for up to 13 cycles. METHODS:: In this multicenter, open-label, phase 3 study, 2308 women used the SA/EE CVS on a 21-day in/7-day out regimen for up to 13 cycles. Women could choose to participate in an endometrial safety sub-study at 5 study sites. Three blinded pathologists histologically examined endometrial biopsies at screening, at cycle 6 in the first 25 women reaching 6 cycles, and at the end of study (cycle 12/13) or early study termination in the remainder. Women with endometrial hyperplasia or cancer at baseline were excluded. We evaluated histologic changes in women with both screening and follow-up biopsies. RESULTS:: Of the 156 women who participated, 83 had follow-up biopsies. Pathologists identified no cases of endometrial hyperplasia or carcinoma at cycle 6 (n=24), cycles 12/13 (n=30) or other end of therapy times (n=29). The most frequent histologic diagnoses were atrophic/inactive or secretory: atrophic/inactive (29%, 27% and 28%, respectively), secretory (29%, 37%, and 45%, respectively), proliferative (17%, 7%, and 21%, respectively), mixed (17%, 10% and 3%, respectively), menstrual (4%, 7%, and 0%, respectively), or insufficient/no tissue (0%, 10%, and 3%, respectively). CONCLUSION:: Use of the SA/EE CVS for up to 13 cycles did not result in any unexpected endometrial safety effects based on endometrial histology.