The Issue
There are current gaps in the contraceptive method mix for overweight women, women with sensitivities or contraindications to ethinyl estradiol, and women who smoke cigarettes due to associated safety risks with synthetic estrogens. Globally, nearly half (44%) of adult women are overweight and between 5 and 6% smoke. Despite this prevalence, most contraceptive research excludes women with higher body mass indexes (BMIs) and smokers. This lack of research in the scientific literature, combined with known higher risks of adverse neonatal and maternal outcomes, can raise challenges for clinicians when making contraceptive recommendations and women choosing their preferred method.
Many currently available hormonal contraceptive options are made with ethinyl estradiol, a synthetic estrogen that has been associated with an increased risk of a venous thromboembolism (VTE). For women with higher BMI, the risk of VTE while using an ethinyl estradiol-based method is 5–8 times that of women with a higher BMI not using an ethinyl estradiol-based method. However, this risk is still lower than that associated with unintended pregnancy and the postpartum period. Postpartum women also have limited options for contraception, as they are often advised against using hormonal methods containing ethinyl estradiol due to its effect on milk production or composition. These gaps represent a need to explore new, user-controlled methods of contraception with better safety profiles to expand contraceptive choice.
The Progress
Researchers at the Population Council’s Center for Biomedical , in partnership with Duchesnay Pharmaceutical Group, are developing a 3-month intravaginal contraceptive ring using Nestorone®, a potent progestin, designed for all women of reproductive age in need of contraception. This woman-controlled vaginal ring provides a regular bleeding profile and does not require refrigeration or insertion by a skilled health care provider, thus providing greater autonomy to users who could insert and remove the ring themselves. The ring is expected to have an improved-side effect profile, minimized effects on bone density, and a rapid return to fertility. Further, Nestorone is not orally active and would therefore be safe to use among breastfeeding mothers.
The Council plans to file an investigational new drug application for the Nestorone-only contraceptive vaginal ring to the United States Food & Drug Administration (FDA) and conduct a phase 2 dose-finding study to select the optimal ring to advance.
The Impact
The Nestorone-only ring would be a safe option for heavy women (with no body mass index restrictions), cigarette smokers, and women with sensitivities to synthetic estrogen or who are at risk for blood clots. Further, in 2023, the United States FDA approved the first ever progestin-only contraceptive pill (OPill®) to become available over-the-counter based on the exceptional safety profile. Now that this precedent has been set, it is possible that the Nestorone only ring could be considered for over-the-counter access, expanding prescription-free, low-cost contraceptive options for women in the United States.
