Millions of women around the world who use certain hormone drugs for contraception and to manage conditions such as endometriosis may be at increased risk of rare, usually benign, brain tumors, researchers say.
Scientists have found that long-term use of certain progestogen medications is linked to an increased risk of meningiomas, which are tumors (usually non-cancerous) that form in tissues around the brain.
But while the risk of meningioma was higher in women who took the medication for more than a year, one leading expert said the finding should not worry past or current users because the increased risk remains “extremely small”.
Progestogens are similar to the natural hormone progesterone. They are used in contraceptives, for gynecological conditions such as endometriosis and polycystic ovary syndrome, and in hormone replacement therapies used during menopause.
A handful of high dose progestogens are already known to increase the risk of meningioma, but in the latest study published in the BMJResearchers at France’s National Agency for Medicines and Health Products Safety examined 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 require surgical removal. The tumors are rarely life-threatening, but the surgery involved carries risks, especially for brain structures near the tumors, 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 underwent surgery to remove intracranial meningiomas between 2009 and 2018. By comparing each case with five healthy, matched controls, the researchers found that long-term use – meaning more than 12 months – of three progestogens was associated with an increased risk of meningioma requiring surgery.
Two oral pills, medrogestone and promegestone, have been linked to a 4.1 and 2.7 times greater risk of meningioma respectively; and medroxyprogesterone acetate, a contraceptive injection sold as Depo-Provera, was linked to a 5.6 times higher risk. Because the study is observational, it cannot prove that the hormones cause the tumors. 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 cooperation with regulatory agencies, we are updating product labels and patient information leaflets with appropriate wording.”
Writing in the journal, the researchers call for more studies on the safety of the hormones, especially injectable medroxyprogesterone acetate. The injections are rarely used in the UK and the rest of Europe, but 74 million women worldwide receive them, meaning “the number of attributable meningiomas could potentially be high”, they write.
Prof Paul Pharoah, a cancer epidemiologist who spent 20 years at Cambridge University studying hormone-related cancers before setting up a laboratory at Cedars-Sinai Hospital in California, said there were many different types of progestogens and no link with meningioma was not found. for those commonly used in the United Kingdom.
“Women who use the commonly used contraceptive pills or hormone replacement therapy do not have an increased risk of getting meningioma,” says 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, around four in every thousand 30-year-old women will be expected to develop a meningioma by the age of 80. If medroxyprogesterone acetate is used for more than a year, the risk increases about fivefold, as the BMJ study suggests, that figure will rise to 20 out of every thousand.
“The risk of meningioma is extremely small,” Pharoah said. “If I was currently using Depo-Provera because of the benefits of a long-acting injectable contraceptive, I would continue to do so. In short, current or former users of Depo-Provera need not worry about their very small risk of meningioma.”
