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

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.

Author information

1
Population Council, Center for Biomedical Research, New York, NY, USA.
2
Department of Obstetrics & Gynecology, Oregon Health and Science University, Portland, OR, USA.
3
Profamilia, Santo Domingo, Dominican Republic (DR).
4
University of Edinburgh; Royal Infirmary of Edinburgh; 51 Little France Crescent, Edinburgh EH16 4SA, UK.
5
Instituto Chileno de Medicina Reproductiva (ICMER), Santiago, Chile.
6
Universidad Andres Bello, Santiago, Chile.
7
Contraceptive Discovery and Development Branch, NICHD, Bethesda, MD, USA.
8
Population Council, Center for Biomedical Research, New York, NY, USA. Electronic address: regine@popcbr.rockefeller.edu.

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.

KEYWORDS:

Contraception; Endometrium; Pharmacodynamics; Ulipristal acetate; Vaginal ring

[Indexed for MEDLINE]
Free PMC Article

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