YongMei Huang1, Jeffrey T Jensen2, Vivian Brache3, Leila Cochon3, Alistair Williams4, Maria-José Miranda5, Horacio Croxatto6, Narender Kumar1, Heather Sussman1, Elena Hoskin1, Marlena Plagianos1, Kevin Roberts1, Ruth Merkatz1, Diana Blithe7, Regine Sitruk-Ware8. 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.
RCT Entities:
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.
Authors: Robert M Brenner; Ov D Slayden; William H Rodgers; Hilary O D Critchley; Rebecca Carroll; Xiao Jing Nie; Kuni Mah Journal: Hum Reprod Date: 2003-06 Impact factor: 6.918