Home > Blog > Nextstellis


Nextstellis is the newest birth control pill that was FDA-approved in April 2021. It is different than currently available birth control pills because it contains a new estrogen: estetrol. (Most other pills contain ethinyl estradiol as the estrogen – more details below). Nextstellis also contains a progestin, drospirenone, which is in other currently available products. The use of estetrol is new and can be made from plants. In the North American Phase III trial where 1524 women were tested, Nextstellis had shown to be effective in preventing pregnancies and patients had less than a 2% occurrence of unscheduled bleeding.1 With perfect use, Nextstellis is 98% effective at preventing pregnancy for females between the age of sixteen and fifty compared to other oral contraceptives that usually are only 91% effective.

Although not proven yet, there is strong evidence that shows this new type of estrogen may cause less risks impacting the breast tissue. A study was done that showed the use of estetrol had a 100 times weaker effect on breast tissue production than estradiol in live mice and in lab conducted human cells.3 Along with potentially being better for people’s bodies, Nextstellis is also more environmentally friendly by leaving less of a long-term trace of chemicals in marine life.4

Safety Precautions

Safety concerns with Nextstellis are similar to other birth control pills that contain ethinyl estradiol. Women should not take Nextstellis if they have a high risk of thrombotic diseases or have a history of certain cancers. Nextstellis also should not be taken in patients suffering from gallbladder, liver disease or renal issues. Lastly, women should consult their doctor about abnormal vaginal bleeding before taking this drug. Nextstellis has a black box warning for women over the age of 35 who smoke; serious and possibly fatal events, such as a stroke, heart attack, and more could occur if the drug is used while smoking. The risk of these serious events increases with the amount of nicotine used and the age of the patient. The risk is even greater for females who use nicotine with diabetes, obesity, dyslipidemia, and hypertension. 1 Nicotine containing products include a range from cigarettes, chewing tobacco, cigars, e-cigarettes, hookah tobacco, nicotine replacement therapy, and juuls.

If high blood pressure occurs, the patient should monitor periodically and discontinue if levels persist outside of normal parameters. Additionally, patients should discontinue Nextstellis if migraines are new, persistent, and severe to the patient. Anyone with pre-diabetes and diabetes should monitor their blood glucose levels, and anyone with high cholesterol should consider a different birth control. 1 Talk with your Nextstellis prescriber about any other side effects that are being experienced to see if therapy needs to be discontinued.

Side Effects

Nextstellis could be less effective in patients who are obese. Consult your Nextstellis prescriber about the specific medications and supplements you are taking to ensure that any drug interactions are avoided. The most common side effects that have occurred while taking Nextstellis include bleeding menstrual irregularities. Mood disturbances have also been common in some patients which include irritability, anxiety, insomnia, panic disorder, restlessness, and suicidal ideation. Other side effects that can occur for patients taking Nextstellis, include acne flare ups, endocrine and metabolic issues like breast enlargement, breast sensitivity, and high levels of potassium. Headaches, weight gain, premenstrual cramps, pelvic discomfort and decreased sex drive or loss of sex drive could also occur. 4 Overall, these side effects are very similar to other oral contraceptives on the market. Due to the way the body utilizes and breaks down this drug, side effects are less likely to occur with Nextstellis in comparison to other oral contraceptives contraceptives.

Unique Features

While there are many options on the market for birth control, Nextstellis has unique features that distinguishes it from other contraceptives. First, the active ingredient is estetrol and drospirenone, whereas most other contraceptives contain ethinyl estradiol and drospirenone. The selective actions of estetrol can lead to fewer side effects, in addition to providing a contraceptive option for women who are unable to tolerate ethinyl estradiol. There also are animal studies that show estetrol caused fewer changes to the breast tissue.2 This research shows that there is a lower risk of causing breast cancer when compared to previous birth control pills that had ethinyl estradiol instead of estetrol.2 Lastly, estetrol is beneficial because it is less likely to contribute to water pollution and harm to the environment. This drug is made through a plant-based procedure, unlike other estrogens. Estrogens like ethinyl estradiol are not metabolized well, leading to build up in the body. Once ethinyl estradiol is excreted in the urine, and it ends up in bodies of water where marine life lives, it can lead to damage of the marine life’s growth and ability to reproduce. Whereas estetrol can be decomposed more quickly which is more environmentally friendly to marine life. When estetrol is excreted in the urine is far less toxic than ethinyl estradiol. Levels as low as 1 ng/L of ethinyl estradiol in fish environments can be far more harmful than levels of 32,000 ng/L of estetrol. The toxins from ethinyl estradiol in the water can effect fish’ reproductive health. These effects include reduced testicular growth, development of ova-testes in males, reduced egg production, delayed maturation, and the population ratio skewed towards females. 3

In conclusion, Nextstellis is a recent FDA approved oral contraceptive that offers women another alternative for birth control. Nextstellis’ active ingredient is estetrol which is unique compared to other combination oral contraceptives. Studies have proven its effectiveness, and while not stated in the current package insert, date are emerging a potential for fewer side effects, like risks affecting the breast tissue and irregular bleeding than older forms of oral contraceptives. Overall, Nextstellis is a safe and effective method for birth control.


    1. NEXTSTELLIS® (DRSP/E4): Now Available for Pregnancy Prevention. https://www.nextstellis.com/. Accessed June 25, 2021.
    2. Grandi G, Chiara Del Savio M, Lopes da Silva-Filho A, Facchinetti F. Estetrol (E4): the new estrogenic component of combined oral contraceptives. Taylor & Francis. https://www.tandfonline.com/doi/full/10.1080/17512433.2020.1750365. Published April 7, 2020. Accessed June 25, 2021.
    3. Mithra Pharmaceuticals. “E4 Paves the Road towards a Revolutionary Era of Environmental FRIENDLY MEDICINES.” GlobeNewswire News Room, Mithra Pharmaceuticals, 10 Jan. 2020, www.globenewswire.com/news-release/2020/01/10/1968775/0/en/E4-Paves-the-Road-Towards-a-Revolutionary-Era-of-Environmental-Friendly-Medicines.html.
    4. Nextstellis (Drospirenone and Estetrol) [package insert]. U.S Food and Drug Administration website. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/214154s000lbl.pdf. Accessed April 2021.

About the Authors

Kayla Mitzel, PharmD Candidate 2023, is currently in her second year of pharmacy school at Midwestern University College of Pharmacy – Downers Grove

Athina Herrera Ng, PharmD Candidate 2023, is currently in her third year of pharmacy school at Midwestern University College of Pharmacy-Downers Grove.

Reviewed by Brooke Griffin, PharmD, BCACP.