New research links popular hormonal drugs to brain tumors

A recent study indicates a significant increase in the risk of developing intracranial meningioma associated with prolonged use of certain progestins, hormones commonly used in women’s health. This first-of-its-kind study, using data from the French National Health Database, highlights the need for further research due to the potential implications for global health, given the extensive use of these medications .

This is the first study to evaluate the risk associated with widely used progestins.

Prolonged use of certain progestin hormone medications has been linked to a higher risk of intracranial meningioma, a type of brain tumor, according to a French study published recently in The BMJ.

Researchers say this study is the first to assess the risk associated with progestins used by millions of women worldwide, and that further studies are urgently needed to better understand this risk.

Progestins are similar to the natural hormone progesterone, which is widely used to treat gynecological conditions such as endometriosis and polycystic ovarian syndrome, as well as in menopausal hormone therapy and contraceptives.

Meningiomas are mostly noncancerous tumors located in the layers of tissue (meninges) that cover the brain and spinal cord. Factors such as older age, female gender, and exposure to three high-dose progestins (nomegestrol, chlormadinone, and cyproterone acetate) are already known to increase the risk of meningioma.

But there are many other progestins for which the risk of meningioma associated with their use has not been estimated individually.

Study methodology

To address this knowledge gap, researchers set out to evaluate the actual risk of intracranial meningioma requiring surgery in women associated with the use of multiple progestins with different routes of administration.

They used data from the National Health Information System (SNDS) on 18,061 women (average age 58) who underwent surgery for intracranial meningioma between 2009 and 2018.

Each case was matched to five control women without intracranial meningioma (90,305 in total) by year of birth and area of ​​residence.

The progestins examined were progesterone, hydroxyprogesterone, dydrogesterone, medrogesterone, medroxyprogesterone acetate, promegestone, dienogest, and levonorgestrel for intrauterine systems.

For each progestin, use was defined as at least one prescription in the year before hospital admission or within 3 to 5 years for levonorgestrel intrauterine systems.

Use of at least one of three high-dose progestins known to increase meningioma risk during the 3 years before hospital admission was also recorded to minimize bias.

After accounting for other potentially influential factors, prolonged (one year or more) use of medrogestre was associated with a 4.1-fold increased risk of intracranial meningioma requiring surgery. Prolonged use of medroxyprogesterone acetate injection was associated with a 5.6-fold increased risk, and prolonged use of promegestone was associated with a 2.7-fold increased risk.

Observations and conclusions

There appears to be no such risk for less than a year of use of these progestins.

As expected, there was also an excess risk of meningioma in women exposed to chlormadinone acetate, nomegestrol acetate, and cyproterone acetate, all of which are known to increase the risk of meningioma.

However, the results showed no excess risk of meningioma for progesterone, dydrogesterone, or the widely used hormonal intrauterine systems, regardless of the dose of levonorgestrel they contained.

No conclusions could be drawn regarding dienogest or hydroxyprogesterone because the number of people exposed was too small.

This is an observational study so cannot establish cause and effect, and the authors acknowledge that the SNDS database lacked information on all the clinical details and medical indications for which progestins are prescribed. They were also unable to take into account genetic predisposition and exposure to high-dose radiation.

However, they say, given that medroxyprogesterone acetate is estimated to be used for birth control by 74 million women worldwide, the number of attributable meningiomas could be potentially high.

Further studies using other data sources are urgently needed to better understand this risk, they conclude.

Reference: “Use of progestins and risk of intracranial meningioma: national case-control study” by Noémie Roland, Anke Neumann, Léa Hoisnard, Lise Duranteau, Sébastien Froelich, Mahmoud Zureik and Alain Weill, March 27, 2024, BMJ.
DOI: 10.1136/bmj-2023-078078