A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women

Vivian Brache, Ruth Merkatz, Narender Kumar, Cristian Jesam, Heather Sussman, Elena Hoskin, Kevin Roberts, Mohcine Alami, Deshawn Taylor, Aidelis Jorge, Horacio Croxatto, Ellen Lorange, Daniel R. Mishell, Regine Sitruk-Ware

Resultado de la investigación: Article

  • 5 Citas

Resumen

Objective This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. Methods This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Results Eighteen participants were randomized; 16 completed the study. Median NES Cmax values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. Conclusion While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods.

IdiomaEnglish
Páginas289-297
Número de páginas9
PublicaciónContraception
Volumen92
Número de edición4
DOI
EstadoPublished - 1 oct 2015

Huella dactilar

Ovulation Inhibition
Cross-Over Studies
Estradiol
Gels
Ovulation
Ethinyl Estradiol
Corpus Luteum
Contraceptive Agents
ST 1435
Abdomen
Pharmacokinetics
Hemorrhage
Safety
Skin

Keywords

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynaecology

    Citar esto

    Brache, Vivian ; Merkatz, Ruth ; Kumar, Narender ; Jesam, Cristian ; Sussman, Heather ; Hoskin, Elena ; Roberts, Kevin ; Alami, Mohcine ; Taylor, Deshawn ; Jorge, Aidelis ; Croxatto, Horacio ; Lorange, Ellen ; Mishell, Daniel R. ; Sitruk-Ware, Regine. / A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women. En: Contraception. 2015 ; Vol. 92, N.º 4. pp. 289-297.
    @article{4f5b3b2b80ef4101a3c05b052393a30c,
    title = "A dose-finding, cross-over study to evaluate the effect of a Nestorone{\circledR}/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women",
    abstract = "Objective This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95{\%} of cycles. Methods This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Results Eighteen participants were randomized; 16 completed the study. Median NES Cmax values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7{\%}) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. Conclusion While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods.",
    keywords = "Contraception, Estradiol, Nestorone, Transdermal gel",
    author = "Vivian Brache and Ruth Merkatz and Narender Kumar and Cristian Jesam and Heather Sussman and Elena Hoskin and Kevin Roberts and Mohcine Alami and Deshawn Taylor and Aidelis Jorge and Horacio Croxatto and Ellen Lorange and Mishell, {Daniel R.} and Regine Sitruk-Ware",
    year = "2015",
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    doi = "10.1016/j.contraception.2015.05.011",
    language = "English",
    volume = "92",
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    Brache, V, Merkatz, R, Kumar, N, Jesam, C, Sussman, H, Hoskin, E, Roberts, K, Alami, M, Taylor, D, Jorge, A, Croxatto, H, Lorange, E, Mishell, DR & Sitruk-Ware, R 2015, 'A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women' Contraception, vol. 92, n.º 4, pp. 289-297. https://doi.org/10.1016/j.contraception.2015.05.011

    A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women. / Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R.; Sitruk-Ware, Regine.

    En: Contraception, Vol. 92, N.º 4, 01.10.2015, p. 289-297.

    Resultado de la investigación: Article

    TY - JOUR

    T1 - A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women

    AU - Brache, Vivian

    AU - Merkatz, Ruth

    AU - Kumar, Narender

    AU - Jesam, Cristian

    AU - Sussman, Heather

    AU - Hoskin, Elena

    AU - Roberts, Kevin

    AU - Alami, Mohcine

    AU - Taylor, Deshawn

    AU - Jorge, Aidelis

    AU - Croxatto, Horacio

    AU - Lorange, Ellen

    AU - Mishell, Daniel R.

    AU - Sitruk-Ware, Regine

    PY - 2015/10/1

    Y1 - 2015/10/1

    N2 - Objective This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. Methods This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Results Eighteen participants were randomized; 16 completed the study. Median NES Cmax values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. Conclusion While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods.

    AB - Objective This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. Methods This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Results Eighteen participants were randomized; 16 completed the study. Median NES Cmax values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. Conclusion While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods.

    KW - Contraception

    KW - Estradiol

    KW - Nestorone

    KW - Transdermal gel

    UR - http://www.scopus.com/inward/record.url?scp=84941736465&partnerID=8YFLogxK

    U2 - 10.1016/j.contraception.2015.05.011

    DO - 10.1016/j.contraception.2015.05.011

    M3 - Article

    VL - 92

    SP - 289

    EP - 297

    JO - Contraception

    T2 - Contraception

    JF - Contraception

    SN - 0010-7824

    IS - 4

    ER -