ABSTRACT
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.
Subject(s)
Contraceptive Agents, Female/pharmacology , Contraceptive Devices, Female , Endometrium/drug effects , Menstruation/drug effects , Norpregnadienes/pharmacology , Ovulation Inhibition/drug effects , Receptors, Progesterone/antagonists & inhibitors , Adult , Biomarkers/metabolism , Cell Proliferation/drug effects , Contraceptive Agents, Female/administration & dosage , Contraceptive Agents, Female/adverse effects , Contraceptive Agents, Female/pharmacokinetics , Contraceptive Devices, Female/adverse effects , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/adverse effects , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Endometrium/cytology , Endometrium/metabolism , Female , Hormone Antagonists/administration & dosage , Hormone Antagonists/adverse effects , Hormone Antagonists/pharmacokinetics , Hormone Antagonists/pharmacology , Humans , Immunohistochemistry , Menstruation/blood , Menstruation/metabolism , Norpregnadienes/administration & dosage , Norpregnadienes/adverse effects , Norpregnadienes/pharmacokinetics , Ovarian Follicle/drug effects , Young AdultABSTRACT
Although classically the antiprogestins have been used for the control of pregnancy diseases and adrenal function, in the medical literature are a plenty of papers about the treatment with progesterone antagonists of leiomyoma, breast cancer, endometriosis and meningioma. The treatment is beneficial or mitigating in greatest number of cases, but they have other different uses than usual like contraception and abortion.