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

Contraception. 2014 Dec;90(6):565-74. doi: 10.1016/j.contraception.2014.08.006. Epub 2014 Aug 12.


Objective: To determine whether a 3-month contraceptive vaginal ring (CVR) delivering ulipristal acetate (UPA) can inhibit ovulation in 90% of cycles.

Study design: 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.

Conclusion: 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.

Implications: 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.

Keywords: Contraception; Endometrium; Pharmacodynamics; Ulipristal acetate; Vaginal ring.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Contraception / methods*
  • Contraceptive Agents, Female / administration & dosage*
  • Contraceptive Agents, Female / adverse effects
  • Contraceptive Agents, Female / blood
  • Contraceptive Agents, Female / pharmacology
  • Contraceptive Devices, Female*
  • Endometrium / drug effects
  • Female
  • Humans
  • Norpregnadienes / administration & dosage*
  • Norpregnadienes / adverse effects
  • Norpregnadienes / blood
  • Norpregnadienes / pharmacology
  • Ovarian Follicle / drug effects
  • Ovarian Function Tests
  • Ovary / drug effects
  • Ovulation / drug effects
  • Ovulation Inhibition / drug effects
  • Receptors, Progesterone / administration & dosage
  • Receptors, Progesterone / drug effects
  • Uterine Hemorrhage / drug therapy
  • Vagina / drug effects
  • Young Adult


  • Contraceptive Agents, Female
  • Norpregnadienes
  • Receptors, Progesterone
  • ulipristal acetate