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

Resultado de la investigación: Article

  • 17 Citas

Resumen

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.

IdiomaEnglish
Páginas565-574
Número de páginas10
PublicaciónContraception
Volumen90
Número de edición6
DOI
EstadoPublished - 1 dic 2014

Huella dactilar

Female Contraceptive Devices
Progesterone Receptors
Contraception
Estrogens
Contraceptive Agents
Ovulation Inhibition
Research
Ovulation
Hemorrhage
Levonorgestrel
Therapeutics
ulipristal acetate
Progestins
Clinical Trials
Hormones
Safety

Keywords

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynaecology
    • Medicine(all)

    Citar esto

    Huang, Yongmei ; Jensen, Jeffrey T. ; Brache, Vivian ; Cochon, Leila ; Williams, Alistair ; Miranda, Maria José ; Croxatto, Horacio ; Kumar, Narender ; Sussman, Heather ; Hoskin, Elena ; Plagianos, Marlena ; Roberts, Kevin ; Merkatz, Ruth ; Blithe, Diana ; Sitruk-Ware, Regine. / 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. En: Contraception. 2014 ; Vol. 90, N.º 6. pp. 565-574.
    @article{ee276651490b488380564012a6a13b1d,
    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. 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",
    author = "Yongmei Huang and Jensen, {Jeffrey T.} and Vivian Brache and Leila Cochon and Alistair Williams and Miranda, {Maria Jos{\'e}} and Horacio Croxatto and Narender Kumar and Heather Sussman and Elena Hoskin and Marlena Plagianos and Kevin Roberts and Ruth Merkatz and Diana Blithe and Regine Sitruk-Ware",
    year = "2014",
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    language = "English",
    volume = "90",
    pages = "565--574",
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    Huang, Y, Jensen, JT, Brache, V, Cochon, L, Williams, A, Miranda, MJ, Croxatto, H, Kumar, N, Sussman, H, Hoskin, E, Plagianos, M, Roberts, K, Merkatz, R, Blithe, D & Sitruk-Ware, R 2014, '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, vol. 90, n.º 6, pp. 565-574. https://doi.org/10.1016/j.contraception.2014.08.006

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

    En: Contraception, Vol. 90, N.º 6, 01.12.2014, p. 565-574.

    Resultado de la investigación: Article

    TY - JOUR

    T1 - A randomized study on pharmacodynamic effects of vaginal rings delivering the progesterone receptor modulator ulipristal acetate

    T2 - Contraception

    AU - Huang, Yongmei

    AU - Jensen, Jeffrey T.

    AU - Brache, Vivian

    AU - Cochon, Leila

    AU - Williams, Alistair

    AU - Miranda, Maria José

    AU - Croxatto, Horacio

    AU - Kumar, Narender

    AU - Sussman, Heather

    AU - Hoskin, Elena

    AU - Plagianos, Marlena

    AU - Roberts, Kevin

    AU - Merkatz, Ruth

    AU - Blithe, Diana

    AU - Sitruk-Ware, Regine

    PY - 2014/12/1

    Y1 - 2014/12/1

    N2 - 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.

    AB - 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.

    KW - Contraception

    KW - Endometrium

    KW - Pharmacodynamics

    KW - Ulipristal acetate

    KW - Vaginal ring

    UR - http://www.scopus.com/inward/record.url?scp=84910671630&partnerID=8YFLogxK

    U2 - 10.1016/j.contraception.2014.08.006

    DO - 10.1016/j.contraception.2014.08.006

    M3 - Article

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    SP - 565

    EP - 574

    JO - Contraception

    JF - Contraception

    SN - 0010-7824

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