Project

Nestorone®/Estradiol Transdermal Gel Contraception

Researchers at the Population Council are developing, in collaboration with Antares Pharma, a novel contraceptive that is absorbed through the skin and may result in fewer side effects than currently available hormonal contraceptives.

The Issue

While several contraceptive methods have been developed for short- and long-term protection against pregnancy, women’s needs differ and may change over the course of their lifetime. Having access to a variety of contraceptive options allows women to choose the method best suited to their needs.

The Progress

The Population Council developed a contraceptive gel that can be absorbed through the skin of a woman's abdomen. The gel contains the progestin Nestorone® and estradiol, a form of estrogen, that is identical to the estrogen made by a woman’s body. Previous research indicates that the transdermal use of a natural estrogen (such as estradiol) may result in fewer side effects than experienced with ethinyl estradiol currently used in oral contraceptives.

The idea of a Nestorone transdermal gel was initially proposed by Horacio Croxatto, a Chilean researcher and member of the Population Council’s International Committee for Contraception Research. He demonstrated that Nestorone, a non-androgenic progestin, could be readily absorbed through the skin. The Nestorone gel was initially created at the Council’s Center for Biomedical Research, and the Council is collaborating with Antares Pharma to continue developing and testing the combined formulation.

Phase 1 and 2 studies of the gel have been conducted in clinical trials in Chile, the Dominican Republic, and the United States. These studies confirmed Nestorone’s ability to safely and effectively suppress ovulation at low doses. An Investigational New Drug (IND) application was submitted to the FDA in 2008, and outcomes from the Phase 2 dose-finding study were used to support registration of a new patent. Early research findings have indicated that the Nestorone/estradiol gel is well tolerated with no serious adverse events, which may increase a woman’s ability and desire to continue using the method. Furthermore, women using Nestorone experience fewer side effects, such as acne, weight gain, and altered cholesterol levels—effects that may be observed by women who use other common progestins as a form of contraception. Future Phase 3 studies are planned in the United States and Europe to demonstrate the safety and efficacy of the gel in preventing pregnancy, and are expected to enroll approximately 2,300 women. 

The Impact

If approved by regulatory authorities, Nestorone/estradiol gel would be the first-of-its-kind transdermal contraception using the natural estrogen estradiol.

The use of estradiol—which closely resembles natural estrogen—combined with a non-oral delivery system may have the potential to minimize safety factors related to oral hormonal contraceptives that use ethinyl estradiol. For instance, by using the skin as the site of delivery, the combination of estradiol with Nestorone in a gel may help bypass the liver (and help prevent toxicity/safety concerns), while still suppressing ovulation. Nestorone may also appeal to women who prefer a method that can be used inconspicuously, since the gel is invisible after application. 

Experts (4)

  • Régine Sitruk-Ware Distinguished Scientist, Center for Biomedical Research
  • Ruth Merkatz Director, Clinical Development, Center for Biomedical Research
  • Narender Kumar Senior Scientist, Center for Biomedical Research
  • Elena Hoskin Senior Research Associate, Center for Biomedical Research