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: Contribución a una revistaArtículo

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 originalInglés
Páginas (desde-hasta)289-297
Número de páginas9
PublicaciónContraception
Volumen92
N.º4
DOI
EstadoPublicada - 1 oct 2015

Áreas temáticas de ASJC Scopus

  • Medicina reproductiva
  • Ginecología y obstetricia

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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, D. R., & 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, 92(4), 289-297. https://doi.org/10.1016/j.contraception.2015.05.011