Effects of a novel estrogen-free, progesterone receptor modulator-contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women
Brache,Vivian; Sitruk-Ware,Regine; Williams,A.; Blithe,Diana; Croxatto,Horacio B.; Kumar,Narender; Kumar,Sushma; Tsong,Yun-yen; Sivin,Irving; Nath,Anita; Sussman,Heather; Cochon,Leila; Miranda,Maria Jose; Reyes,Veronica; Faundes,Anibal; Mishell,Daniel R.,Jr.
Contraception 85(5): 480-488
Publication date: 2012
Progesterone receptor modulators (PRMs) delivered by contraceptive vaginal rings provide an opportunity for development of an estrogen-free contraceptive that does not require daily oral intake of steroids. The objective of this proof-of-concept study was to determine whether continuous delivery of 600-800 mcg of ulipristal acetate (UPA) from a contraceptive vaginal ring could achieve 80% to 90% inhibition of ovulation.
This was a prospective, controlled, open-labeled, multicenter international trial to examine the effectiveness and safety of this prototype vaginal ring. Thirty-nine healthy women, 21-40 years old and not at risk of pregnancy, were enrolled at three clinic sites. Volunteers participated in a control cycle, a 12-week treatment period and a post-treatment cycle. Pharmacodynamic effects on follicular function and inhibition of ovulation, effects on endometrium, bleeding patterns and serum UPA levels were evaluated.
Mean UPA levels during treatment were nearly constant, approximately 5.1 ng/mL throughout the study. Ovulation was documented in 32% of 111 "4-week treatment cycles." A correlation was observed between serum UPA and degree of inhibition of ovarian activity. There was no evidence of hyperplasia of endometrium, but PRM-associated endometrial changes were frequently observed (41%).
In this study, the minimum effective contraceptive dose was not established. Further studies are required testing higher doses of UPA to attain ovulation suppression in a higher percentage of subjects.