A dose-finding, cross-over study to evaluate the effect of a transdermal Nestorone®-estradiol (NES/E2) gel on ovulation suppression and assess acceptability in healthy ovulating women
Presentation at American Society for Reproductive Medicine 66th Annual Meeting, Denver, 23-27 October
Merkatz,Ruth B.; Sitruk-Ware,Regine; Mishell,Daniel R.,Jr.; Brache,Vivian; Taylor,DeShawn; Gaete,Cristian Jesam
Publication date: 2010
Evaluate the effect of NES/E2 transdermal gel delivery on ovulation suppression and assess acceptability in healthy, ovulating women.
A Phase II, dose-finding, cross-over study to evaluate effects of NES/E2 transdermal gel in three different doses in 18 women in Chile, the Dominican Republic, and the United States.
Materials and methods
Women received three doses of NES/E2 gel over seven months. Gel was applied to the abdomen; doses were: high (4.5mg NES/1.5mg E2), medium (3.0mg NES/1.0mg E2), and low (1.5mg NES/0.5mg E2). 10 percent of steroid doses are absorbed after transdermal application. There was one lead-in cycle prior to first application of gel. Between each dose regimen, recovery of ovulation was documented before the next dose was tested (measured by transvaginal ultrasounds and serum progesterone levels). Serum E2 was measured to assess residual endogenous levels and exogenous therapy. An acceptability interview was administered at trial's end with open-ended questions.
All doses of NES/E2 gel showed ovulation suppression. The low dose, although able to suppress ovulation, did not completely suppress follicle growth, as reflected by high levels of serum E2 (endogenous and exogenous). High-dose gel led to NES/E2 hormone levels above target. Medium-dose gel led to stable E2 levels within mid-follicular range and low numbers of large follicles indicating good ovarian suppression and was selected for future studies as the lowest effective dose. There was minimal breakthrough bleeding during three weeks of use. Acceptability study results revealed participants found the gel easy to use, to remember, and with few side effects. No negative effects were reported from subjects' partners.
The concept of a transdermal contraceptive using Nestorone, a potent progestin close to progesterone, and natural estrogen (Estradiol) showed promising results and may represent a safe, effective, acceptable hormonal method of contraception. Additional studies are required in larger populations. Supported by: Population Council; Antares Pharma Inc.