June 17, 2025, 12:58 pm | Read time: 6 minutes

Hormonal contraception is considered practical, effective, and largely safe. But does this hold true for long-term use? A new large-scale study from France takes a critical look at the mini-pill containing the active ingredient desogestrel and concludes that prolonged use measurably increases the risk of certain benign brain tumors. In contrast, no increased risk is observed with another commonly used hormone, levonorgestrel.

What Was Investigated and Why?

Meningiomas are tumors that develop from the brain membranes. They are usually benign but can—depending on their location—affect the brain or important nerve structures and may require surgery. Previous studies have shown that high-dose hormonal preparations (such as cyproterone acetate or nomegestrol) can significantly increase this risk.¹

It was previously unclear whether low-dose active ingredients, such as those found in contraceptive pills, pose a risk, especially when taken over many years. The researchers wanted to find out if there is a connection between the two commonly used progestins, desogestrel and levonorgestrel, and operated meningiomas, and whether the duration of use plays a role. This is particularly relevant because desogestrel is very common in Europe—about nine out of ten progestin-only pills contain this active ingredient.²

Study Design and Methods

The study used data from the French health system, which covers nearly the entire population. Between 2020 and 2023, 8,391 women who had undergone brain surgery for a meningioma were identified. These were compared with over 83,000 women without meningioma, matched by age and place of residence.

The use of three different types of pills was examined:

• Mini-pill with desogestrel (75 micrograms)
• Pill with levonorgestrel (30 micrograms)
• Combination pill with levonorgestrel and estrogen

The duration of use was considered: “Short-term” meant up to one year, “long-term” several consecutive years. Other risk factors, such as obesity, endometriosis, or previous use of other hormones, were also included. The goal: to provide realistic, everyday statements about the safety of the preparations.

Relative Risk of Meningioma Increases with Long-Term Use of Certain Mini-Pills

The central finding: Women who had taken the mini-pill with the active ingredient desogestrel continuously for more than five years had a long-term increased risk of developing an operated brain tumor of the “meningioma” type. These are slow-growing tumors that originate from the brain membranes. The study only considered a subset of all meningiomas. Those that were “only” observed or irradiated were not part of the evaluation.

• With short-term use of desogestrel (less than one year), there was no increased risk of a meningioma requiring surgery.
• With 5 to 7 years of continuous use, the risk increased by 51 percent.
• With 7 or more years, the risk was more than double that of non-users.
• The risk disappeared if the use was discontinued more than a year earlier.

The increased risk was particularly noticeable for tumors at the anterior and middle skull base, which are typical sites for hormone-dependent meningiomas. Additionally, the risk was especially high for women who had previously taken other hormones with known risks. For levonorgestrel, whether alone or combined with estrogen, no increased risk was observed, even with longer use.

Number of Affected Individuals Is Low

However, the study also shows that the absolute number of affected individuals remains very low. According to the researchers’ calculations, 67,300 women would need to take desogestrel over a long period to cause one additional tumor case. For use over five years, it would be 17,300 women per case.

What Is the Significance of the Results?

For most women, the results are not a cause for concern, but a reason to be more conscious about using the pill. According to the study, those who take the mini-pill with the active ingredient desogestrel for only a few years do not need to worry about an increased risk of brain tumors. Younger women (under 45 years) also have no increased risk with typical use.

The results are important for:

• Women who have taken desogestrel for many years,
• Women over 45 years, whose basic risk for meningiomas increases with age, and
• Women who have previously used other hormones with known risks.

In such cases, it should be regularly assessed whether continuing use is advisable or if alternatives are possible. For levonorgestrel, which is included in many combination pills, there is no cause for concern according to the study, regardless of the duration of use.

Study Classification and Possible Limitations

The study is scientifically sound, large-scale, and based on real health data, making it particularly meaningful. However, there are some limitations:

• Only women with operated meningiomas were recorded—smaller, untreated tumors were not considered.
• The reasons for use (such as contraception or endometriosis) were not documented.
• Combination preparations with desogestrel were not considered, as they are rarely prescribed in France.
• It is possible that some women did not take the prescribed pill regularly, which tends to underestimate the risk.

Despite these limitations, the results are clear: Only desogestrel showed an increased risk with very long use. Levonorgestrel, on the other hand, remains safe from today’s perspective—an important signal for many women.

Increased Risk Also with Depo Shot–Class Action Against Pfizer in the U.S.

While the new study focuses on desogestrel, another hormonal contraceptive is making international legal headlines: the Depo-Provera shot with the active ingredient medroxyprogesterone acetate. A previous BMJ study showed that women had more than a fivefold increased risk of meningiomas with long-term use.³

In the U.S., a class action lawsuit is currently underway against the pharmaceutical company Pfizer because the U.S. package insert for the shot does not include a corresponding warning, unlike in the EU. The allegation: The company did not sufficiently inform patients about the risk. In total, around 400 individual lawsuits are part of the wave of litigation. A hearing is scheduled for the end of May. The case exemplifies the importance of transparent risk warnings for hormonal contraceptives—not only medically but also legally.⁴

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Conclusion

Women over 45 who have taken or are taking desogestrel for many years have a pronounced risk of developing a benign brain tumor. However, this is not only due to the active ingredient but also to the naturally increasing basic risk for meningiomas with age. The mini-pill remains a safe and effective contraceptive method for most women, but regular benefit-risk assessment becomes more important with long-term use. According to the study, combination preparations with levonorgestrel remain unremarkable. The key is: The individual situation matters, and open consultation with doctors is essential.