title: Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women.
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.
  
  
  METHODS
  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%).
  
  
  CONCLUSIONS
  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.affiliation: Biomedical Research Department, Profamilia, Santo Domingo 10401, Dominican Republic. vbrache@gmail.com
authors.forename: Vivian
authors.initials: V
authors.lastname: Brache
authors.forename: Regine
authors.initials: R
authors.lastname: Sitruk-Ware
authors.forename: Alistair
authors.initials: A
authors.lastname: Williams
authors.forename: Diana
authors.initials: D
authors.lastname: Blithe
authors.forename: Horacio
authors.initials: H
authors.lastname: Croxatto
authors.forename: Narender
authors.initials: N
authors.lastname: Kumar
authors.forename: Sushma
authors.initials: S
authors.lastname: Kumar
authors.forename: Yun-Yen
authors.initials: YY
authors.lastname: Tsong
authors.forename: Irving
authors.initials: I
authors.lastname: Sivin
authors.forename: Anita
authors.initials: A
authors.lastname: Nath
authors.forename: Heather
authors.initials: H
authors.lastname: Sussman
authors.forename: Leila
authors.initials: L
authors.lastname: Cochon
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Miranda
authors.forename: Verónica
authors.initials: V
authors.lastname: Reyes
authors.forename: Anibal
authors.initials: A
authors.lastname: Faundes
authors.forename: Daniel
authors.initials: D
authors.lastname: Mishell
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D003274:Contraceptive Devices, Female / Q000009:adverse effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008598:Menstruation / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D009649:Norpregnadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006080:Ovarian Follicle / Q000187:drug effects; D034445:Ovulation Inhibition / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D006727:Hormone Antagonists; D009649:Norpregnadienes; D011980:Receptors, Progesterone; C555622:ulipristal acetate