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

10 Citas (Scopus)

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.

Idioma originalEnglish
Páginas (desde-hasta)289-297
Número de páginas9
PublicaciónContraception
Volumen92
N.º4
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

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.
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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",
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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

C2 - 26032952

AN - SCOPUS:84941736465

VL - 92

SP - 289

EP - 297

JO - Contraception

JF - Contraception

SN - 0010-7824

IS - 4

ER -