Millions of women around the world who use certain hormone drugs for contraception and to manage conditions such as endometriosis may have a raised risk of rare, usually benign, brain tumours, researchers say.

Scientists found that prolonged use of certain progestogen medications was linked to a greater risk of meningioma, which are tumours (usually noncancerous) that form in tissues around the brain.

But while the risk of meningioma was higher in women who took the medications for more than a year, one leading expert said the finding should not worry past or present users because the elevated risk remained “extremely small”.

Progestogens are similar to the natural hormone progesterone. They are used in contraceptives, for gynaecological conditions such as endometriosis and polycystic ovary syndrome, and in hormone replacement therapies used during the menopause.

A handful of high dose progestogens are already known to raise the risk of meningioma, but in the latest study published in the BMJ, researchers at France’s National Agency for Medicines and Health Products Safety investigated eight more commonly used forms of the hormone.

Most meningiomas are not usually cancerous and grow slowly, but because they can put pressure on the brain they often need surgical removal. The tumours are rarely life-threatening, but the surgery involved carries risks, not least to brain structures near the tumours, which can sometimes be damaged.

Using data from the French national healthcare system, the researchers identified 18,061 women, with an average age of 58, who had surgery between 2009 and 2018 to remove intracranial meningiomas. By comparing each case with five healthy, matched controls, the researchers found that prolonged use – meaning more than 12 months – of three progestogens was associated with a greater risk of meningioma that needed surgery.

Two oral pills, medrogestone and promegestone, were linked to a 4.1 and 2.7-fold greater risk of meningioma respectively; and medroxyprogesterone acetate, a contraceptive injection sold as Depo-Provera, was linked to a 5.6-fold higher risk. Because the study is observational, it cannot prove that the hormones cause the tumours. No excess risk was found for progesterone, dydrogesterone, or widely used hormonal intrauterine systems.

In a statement, Pfizer, the manufacturer of Depo-Porvera, said: “We are aware of this potential risk associated with long-term use of progestogens and, in collaboration with regulatory agencies, are in the process of updating product labels and patient information leaflets with appropriate wording.”

Writing in the journal, the researchers call for more studies into the safety of the hormones, particularly injectable medroxyprogesterone acetate. The injections are rarely used in the UK and the rest of Europe, but 74 million women globally receive them, meaning “the number of attributable meningiomas may be potentially high”, they write.

Prof Paul Pharoah, a cancer epidemiologist who spent 20 years at the University of Cambridge studying hormone-related cancers before setting up a lab at the Cedars-Sinai hospital in California, said there were many different types of progestogens and no association with meningioma was found for those commonly used in the UK.

“Women taking the commonly used birth control pills or hormone replacement therapy are not at increased risk of meningioma,” said Pharoah, who was not involved in the French study. “It is important that women do not stop using their birth control pills without consulting their doctor.”

Based on UK cancer data registries, about four in every thousand 30-year-old women would be expected to develop a meningioma by the age of 80. If using medroxyprogesterone acetate for more than a year increases the risk about fivefold, as the BMJ study suggests, that figure would rise to 20 in every thousand.

“The risk of meningioma is extremely small,” Pharoah said. “If I were currently using Depo-Provera because of the advantages of a long-acting injectable contraceptive I would continue to do so. In short, current or previous users of Depo-Provera do not need to worry about their very small risk of meningioma.”

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