Taking certain common contraceptive hormones for a year or more is associated with an increased risk of developing a brain tumor that requires surgical removal, according to a new study. The findings highlight the need for women to review their contraceptive medications regularly.
Progestogens are synthetic hormone medications that mimic a female’s natural sex hormone, progesterone. They’re most used in hormonal birth control and menopausal hormone therapy, either alone or in combination with estrogens, another group of sex hormones, but can also be used to treat conditions such as endometriosis and polycystic ovary syndrome.
A newly published study by French researchers is the first to associate the extended use of certain progestogens and an increased risk of a brain tumor called intracranial meningioma, which accounts for 40% of primary tumors of the central nervous system. While benign, the tumor, which grows from the membranes that surround the brain and spinal cord, can impinge on these structures, necessitating surgical removal.
Researchers from the French National Agency for Medicines and Health Products Safety (ANSM) examined data from 108,366 women, 18,061 of whom had brain surgery to remove an intracranial meningioma between 2009 and 2018. The data was drawn from the French National Health Data System (SNDS) and each case was matched to five controls for year of birth and area of residence. The researchers examined the association between select progestogens and meningioma incidence.
Although some of the progestogens studied are used in France (promegestone) or in only a few countries (medrogestone), others (progesterone, levonorgestrel, hydroxyprogesterone, and medroxyprogesterone) are widely used worldwide. This article has used the most common brand names, but it may not include all of them.
After accounting for potentially influential factors, the researchers found that prolonged use – for one year or more – of 150 mg medroxyprogesterone acetate (Depo-Provera) injection was associated with a 5.6-fold increased risk of intracranial meningioma requiring surgery. Prolonged use of 5 mg oral medrogestone (Colprone) was associated with a 4.1-fold increased risk, and 0.125 mg/0.5 mg oral promegestone (Surgestone) had a 2.7-fold increased risk. There appeared to be no such risk associated with using these progestogens for less than a year. There was no observable increased risk for progesterone (Prometrium, Utrogestan, Endometrin), dydrogesterone (Femoston), or the widely used levonorgestrel-releasing intrauterine devices (IUDs), regardless of the dose they contain.
There was an excess risk for women taking chlormadinone acetate (Belara, Gynorelle, Lutéran, Prostal), nomegestrol acetate (Lutenyl, Naemis, Zoely), and cyproterone acetate, which is unsurprising considering they’re known to increase meningioma risk. No conclusions could be drawn about dienogest (Lafamme, Natazia, Qlaira) or hydroxyprogesterone (Delalutin, Proluton, Makena) because of the small number of women receiving these drugs.
This was an observational study, so it can’t establish cause and effect. The researchers acknowledge that the SNDS database lacked information on all the clinical details and indications for which progestogens were prescribed. They also couldn’t account for a genetic predisposition to meningioma and exposure to high-dose radiation, a risk factor for the condition.
Nonetheless, because medroxyprogesterone acetate is estimated to be used by 74 million women worldwide as a means of birth control, the number of attributable meningiomas may potentially be high.
The study’s findings highlight the need for women to review their contraceptive medication with their doctor regularly.
“The release of these findings should … be a timely reminder to women to review their contraceptive needs periodically to make sure they are still using the best product available for them,” said Gino Pecoraro, associate professor of obstetrics and gynecology at the University of Queensland and practicing OB-GYN.
They may also encourage more women to switch to using contraceptive-releasing IUDs, suggests Susan Evans, a gynecologist and associate professor at the University of Adelaide.
“This information will further speed the changing preference from oral hormonal medications to intrauterine devices,” Evans said. “The Kaiser Family Foundation in the United States found that IUD use increased from 2% to 14% of contraceptive use, while oral contraceptive use fell from 31% to 22% over the period 1995-2017.”
This study considered only a 150 mg dose of medroxyprogesterone acetate. As the drug is rarely used in France, further studies in other countries that use it more broadly are urgently needed to assess the associated meningioma risk to understand the dose-response association better.
The study was published in the journal The BMJ.