BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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%). CONCLUSION: 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.
BACKGROUND: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. STUDY DESIGN: 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. RESULTS: 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%). CONCLUSION: 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.
Authors: Ian S Fraser; Edith Weisberg; Vivian Brache; Francisco Alvarez; Rebeca Massai; Daniel R Mishell; Dan Apter; Judi Gale; Yun Yen Tsong; Irving Sivin Journal: Contraception Date: 2005-07 Impact factor: 3.375
Authors: F Lakha; P C Ho; Z M Van der Spuy; K Dada; R Elton; A F Glasier; H O D Critchley; A R W Williams; D T Baird Journal: Hum Reprod Date: 2007-07-03 Impact factor: 6.918
Authors: George L Mutter; Christine Bergeron; Liane Deligdisch; Alex Ferenczy; Mick Glant; Maria Merino; Alistair R W Williams; Diana L Blithe Journal: Mod Pathol Date: 2008-02-08 Impact factor: 7.842
Authors: Lyndsey R Buckner; Erma Z Drobnis; Molly S Augustine; Lynette K Rogers; Jill Akers; Patricia D Mott; Thomas J Hope; Alison J Quayle; Danny J Schust Journal: PLoS One Date: 2019-05-16 Impact factor: 3.240