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

YongMei Huang, Jeffrey T Jensen, Vivian Brache, Leila Cochon, Alistair Williams, Maria-José Miranda, Horacio Croxatto, Narender Kumar, Heather Sussman, Elena Hoskin, Marlena Plagianos, Kevin Roberts, Ruth Merkatz, Diana Blithe, Regine Sitruk-Ware

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalContraception
DOIs
Publication statusPublished - 12 Aug 2014

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