Progestogen-Only Pill Linked to Small Increase in Brain Tumor Risk

A commonly prescribed contraceptive pill, desogestrel, has been linked to a slight increase in brain tumor risk when used for several years, according to new multi-institutional research from France.

The research, published in The BMJ, found no increased risk with levonorgestrel.

Do contraceptive pills increase brain tumor risk?

Intracranial meningiomas are common brain tumors. Although they are often not cancerous, depending on where they grow, they can cause serious problems and sometimes require surgery. These tumors are more likely to develop in older women, and several risk factors are already known, such as age, sex and past exposure to certain hormonal drugs called progestogens.

A handful of these progestogens, including cyproterone acetate, medroxyprogesterone acetate and nomegestrol acetate, among others, have been linked to a higher risk of meningioma when used at high doses or for long periods. But the picture is less clear for other progestogens found in widely used contraceptives, like desogestrel and levonorgestrel. Most earlier studies didn’t separate out different progestogens or look at how risk changes with duration or recency of use.

Desogestrel dominates the progestogen-only pill market in countries like France and the UK, contributing to ~ 90% of sales. If there is a risk tied to long-term use, especially in older women or those with a history of using other high-risk progestogens, it is essential for public health to understand.

The researchers wanted to know whether taking desogestrel or levonorgestrel, either alone or in combination with estrogen, is linked to a higher chance of developing intracranial meningioma.

Long-term desogestrel use linked to higher meningioma risk

The team ran a national case–control study using data from France’s health insurance system. It included nearly all women in the country who had surgery for an intracranial meningioma between 2020 and 2023, with a total of 8,391 cases. Each of the women were matched to 10 controls – women the same age and from the same region who hadn’t had meningioma – making 83,910 controls in total.

The researchers looked at the use of 3 types of oral contraceptives: desogestrel 75 µg (a progestogen-only pill), levonorgestrel 30 µg and levonorgestrel combined with estrogen. For each, they examined short-term use, under a year, and prolonged use, up to seven years.

They found desogestrel was linked to a small but measurable increase in risk, but only with long-term use. Women who used desogestrel for 5–7 years had 51% higher odds of needing meningioma surgery than non-users, which jumped to more than double for use over 7 years.

There was no added risk for short-term use, and the risk disappeared if the drug had been stopped for more than a year. The risk was greater in women over 45 and in those whose tumors were in the front or middle of the skull base. It was also higher if the woman had previously used one of the older high-risk progestogens.

There was no increased risk at all for levonorgestrel, whether taken alone or with estrogen, regardless of how long it had been used.

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The team estimate that 67,000 women would need to use desogestrel for 1 woman to require surgery for meningioma, which would drop to 17,000 if use continues for over 5 years.

What these findings mean for women using desogestrel or levonorgestrel

The findings are reassuring for women using levonorgestrel, which showed no increased risk of intracranial meningioma, even after long-term use. However, for desogestrel, while the risk is still low, using it continuously for over five years appears to increase the chance of needing surgery for a meningioma. For these women, stopping desogestrel and switching to monitoring may help avoid surgery. 

“It is already common knowledge that stopping cyproterone, nomegestrol, chlormadinone, promegestone, medroxyprogesterone or medrogestone precludes the need for surgery,” said Dr. Gilles Reuter, a neurosurgeon at the University Hospital of Liège, in a BMJ editorial. “Now we know that stopping desogestrel may also avoid unnecessary potentially harmful treatments.”

“While it identifies a small increased risk of intracranial meningioma associated with long-term use of desogestrel oral contraceptives, it’s vital to stress that this is a correlation, not proof of causation,” Dr. Karen Noble, the director of research, policy and innovation at Brain Tumour Research told the Science Media Centre (SMC).

“These results do not give any reasons for women using progestogens to panic,” Dr. Mangesh Thorat, an honorary reader in Wolfson Institute of Population Health, Queen Mary University of London and consultant breast surgeon at Homerton University Hospital, also told the SMC.

Reference: Roland N, Kolla E, Baricault B, et al. Oral contraceptives with progestogens desogestrel or levonorgestrel and risk of intracranial meningioma: national case-control study. BMJ. 2025;389:e083981. doi:10.1136/bmj-2024-083981

This article is a rework of a press release issued by the BMJ Group. Material has been edited for length and content