A New, Potentially Safer Birth Control Pill

Andrew M. Kaunitz, MD


April 30, 2021

On April 16, 2021, the US Food and Drug Administration approved Nextstellis, a new oral contraceptive (OC) that combines a novel estrogen, estetrol, with the well-known progestin drospirenone. (Full disclosure: The University of Florida receives research funding from the manufacturer, and in past years I have been a consultant to the company.) The new OC contains 14.2 mg of estetrol and 3 mg of drospirenone, the same amount of drospirenone found in other, commonly prescribed OCs.

Almost all currently prescribed OCs are formulated with ethinyl estradiol, a synthetic and highly potent estrogen. In contrast to ethinyl estradiol, estetrol is naturally occurring, and the estetrol used in the new OC is produced from a plant source. An earlier clinical trial found that an OC formulated with estetrol and drospirenone had substantially less impact on coagulation markers than an ethinyl estradiol-drospirenone or an ethinyl estradiol-levonorgestrel OC.

Recent phase 3 clinical trials conducted in North America and in Europe have found that the estetrol-drospirenone combination OC has contraceptive efficacy comparable with that of current OCs and is well tolerated, having a bleeding profile similar to familiar, current OCs. In the phase 3 trials, the new estetrol-drospirenone OC had minimal impact on triglyceride, cholesterol, or glucose levels.

When prescribed to appropriate candidates, OCs are a safe contraceptive option for millions of women. The main safety concern with combination estrogen-progestin OC use relates to a higher risk for venous thromboembolism (VTE), which underscores the importance of not prescribing combination estrogen-progestin OCs, patches, or rings to women at elevated baseline VTE risk.

It is possible that this new estetrol-drospirenone OC is less likely to increase VTE risk than are conventional OCs formulated with ethinyl estradiol. VTEs are uncommon events in OC users; thus, the potential safety advantage of this new estetrol-drospirenone pill over older formulations will not become clear until postmarketing epidemiologic studies can compare VTE risk with the estetrol OC vs an ethinyl estradiol OC in large populations of women.

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