title: A randomized study on pharmacodynamic effects of vaginal rings delivering the progesterone receptor modulator ulipristal acetate: research for a novel estrogen-free, method of contraception.
abstract: OBJECTIVE
  To determine whether a 3-month contraceptive vaginal ring (CVR) delivering ulipristal acetate (UPA) can inhibit ovulation in 90% of cycles.
  
  
  METHODS
  This was a randomized dose-finding parallel group clinical trial. Fifty-five healthy women with normal ovulation at baseline were randomized to receive a low-dose (1500 μg/day) or a high-dose (2500 μg/day) UPA-CVR for two consecutive 12-week treatment periods, followed by a recovery cycle. A subgroup of women received levonorgestrel (LNG) 1.5 mg orally twice (at the end of both 12-week ring periods) or once (at the end of the 24-week treatment). The primary outcome was ovulation suppression assessed by transvaginal ultrasound and hormone levels. Secondary outcomes included endometrial safety and bleeding patterns.
  
  
  RESULTS
  All subjects showed normal ovulation at baseline and recovery. Ovulation suppression was seen in 81.8% (95% CI: 73.3%, 88.5%) and 86.1% (95% CI: 78.1%, 92%) of treatment cycles with low and high-dose, respectively. Benign progesterone receptor modulator associated endometrial changes (PAEC) were seen during treatment; 78.8% at week 24, but resolved at recovery cycle. A few cases of heavy bleeding occurred near the end of the 24-week treatment, but a single dose of LNG every 12 weeks reduced the increase in endometrial thickness during the second treatment period and prevented excessive bleeding.
  
  
  CONCLUSIONS
  The 3-month UPA-CVR may become an effective long-acting, user-controlled estrogen-free contraceptive. The greatest suppression of ovulation was seen with the 2500-μg/day ring.
  
  
  CONCLUSIONS
  The 3-month CVR delivering UPA 2500 μg/day can become an effective user-controlled estrogen-free contraceptive method. Benign PAEC during treatment returns to normal after discontinuation. The prevention of occasional excessive withdrawal bleeding, either by a progestin or by using higher UPA levels to increase follicle suppression may permit prolonged treatment.
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA.
authors.forename: YongMei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Obstetrics & Gynecology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Jensen
authors.affiliation: Profamilia, Santo Domingo, Dominican Republic (DR).
authors.forename: Vivian
authors.initials: V
authors.lastname: Brache
authors.affiliation: Profamilia, Santo Domingo, Dominican Republic (DR).
authors.forename: Leila
authors.initials: L
authors.lastname: Cochon
authors.affiliation: University of Edinburgh; Royal Infirmary of Edinburgh; 51 Little France Crescent, Edinburgh EH16 4SA, UK.
authors.forename: Alistair
authors.initials: A
authors.lastname: Williams
authors.affiliation: Instituto Chileno de Medicina Reproductiva (ICMER), Santiago, Chile.
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Miranda
authors.affiliation: Universidad Andres Bello, Santiago, Chile.
authors.forename: Horacio
authors.initials: H
authors.lastname: Croxatto
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA.
authors.forename: Narender
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Sussman
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Hoskin
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA.
authors.forename: Marlena
authors.initials: M
authors.lastname: Plagianos
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Roberts
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Merkatz
authors.affiliation: Contraceptive Discovery and Development Branch, NICHD, Bethesda, MD, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Blithe
authors.affiliation: Population Council, Center for Biomedical Research, New York, NY, USA. Electronic address: regine@popcbr.rockefeller.edu.
authors.forename: Regine
authors.initials: R
authors.lastname: Sitruk-Ware
mesh_terms: D000328:Adult; D003267:Contraception / Q000379:methods*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D003274:Contraceptive Devices, Female; D004717:Endometrium / Q000187:drug effects; D005260:Female; D006801:Humans; D009649:Norpregnadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects; D010050:Ovarian Function Tests; D010053:Ovary / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects; D034445:Ovulation Inhibition / Q000187:drug effects; D011980:Receptors, Progesterone / Q000008:administration & dosage / Q000187:drug effects; D014592:Uterine Hemorrhage / Q000188:drug therapy; D014621:Vagina / Q000187:drug effects; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D009649:Norpregnadienes; D011980:Receptors, Progesterone; C555622:ulipristal acetate
keywords: Contraception; Endometrium; Pharmacodynamics; Ulipristal acetate; Vaginal ring