An ongoing lawsuit in the United States alleges that Pfizer failed to warn users of potential risks linked to the Depo-Provera birth control injection, and their increased chances of developing meningioma – or brain tumours, reports NBC News.
The complaint has also been raised by several women in South Africa, all of whose lives have been disrupted by the devastation of meningioma.
In the latest case in the US, for years, Robin Phillip (45) suffered from what she thought were migraines. But today she bears a scar that runs along the side of her head – the result of two craniotomies – after the discovery of an intracranial meningioma.
She said it wasn’t until early 2018 that she learned her headaches were a symptom of something more serious. She nearly crashed on the drive to the emergency room, blinded by pain, she added.
“The nurse said, ‘OK, what’s your pain from 1 to 10?’ I said 11, 12,” Phillip said. “They put me in the chair, and I don’t remember anything after that.”
Phillip awoke later to shocking news: she had an intracranial meningioma – a tumor of the lining of the brain, and needed emergency surgery.
After the procedure, Phillip lost vision in her left eye and had to re-learn how to walk.
Unable to work, she lost her apartment and moved in with her mother until she could get back on her feet.
Today, she believes her birth control is to blame. For nearly 30 years, stopping only when she had her two children, she used Depo-Provera – the progestin shot given every three months.
She’s one of more than 1 000 women suing manufacturer Pfizer, alleging it knew more about the risks and failed to warn users.
Pfizer has moved to have the suit dismissed, arguing the case is pre-empted by a Food and Drug Administration (FDA) decision, and says it stands behind the safety and efficacy of Depo-Provera.
According to the Centres for Disease Control and Prevention (CDC), one in four sexually active women in the United States have used Depo-Provera. Black women use it at nearly double the national rate.
Meningiomas are usually not cancerous, but they can be harmful, depending on their size and where they grow. Phillip’s tumour was pressing on her optic nerve, causing vision problems.
Recent research
In recent years, several studies have shown a possible link between Depo-Provera use and an increased risk of developing meningioma.
One of them, published last month in JAMA Neurology, linked medroxyprogesterone acetate (MPA), the drug in Depo-Provera, with a twofold increase in risk for meningioma. The risk was greatest in women who used the contraceptive for more than four years or started after the age of 31.
Another one in 2024 published in The BMJ and based on French data, found a five-fold increase in risk for meningioma for long-term Depo-Provera users.
Doctors caution that the studies are observational, meaning they can’t prove the medication caused the tumours.
Dr David Raleigh, a radiation oncologist who specialises in brain tumours and who is the chair of meningioma research at the University of California-San Francisco’s Department of Radiation Oncology, said female sex hormones – progesterone in particular – are linked to meningioma. (Progestin, the hormone in Depo-Provera, is a synthetic version of progesterone.)
Meningiomas are the only brain tumours that are more common in women than in men, he added.
Still, Raleigh said that doesn’t necessarily mean progesterone is causing a meningioma to form. “All of the available data suggest that progesterone is fuel on the fire,” he said.
“Progesterone didn’t necessarily start the fire, but the available data suggest that it’s like dumping gas on it.”
He said the recent studies linking Depo-Provera to meningioma give him pause.
“Those of us in the business often recommend that patients with meningioma avoid hormone replacement therapy, use non-hormone-based means of contraception, if possible, and to be cautious with pregnancy and fertility planning because of these very well-documented associations,” he said. “These new studies only amplify those concerns and considerations.”
The overall risk of developing meningioma remains small: about 39 000 meningiomas are diagnosed each year in the US.
“Overall, meningioma is not common. This is not a type of tumour we see very often,” said Dr Colleen Denny, an OB-GYN at NYU Langone Health. “The likelihood of having one as a Depo user is incredibly low. But it’s just that it’s incredibly, incredibly low for people who don’t use Depo.”
The American College of Obstetricians and Gynaecologists (ACOG) published a response to The BMJ study urging caution, saying that, “according to the study, five out of 10 000 women using medroxyprogesterone acetate may possibly develop meningioma compared with one out of 10 000 women not using the medication”.
“The risk that they’re finding is incredibly small,” said Dr Nisha Verma, senior adviser for reproductive health policy for advocacy at ACOG. “I think it is a consideration we can talk to patients about, among all of the considerations they go through.”
Denny said: “Uterine cancer is a lot more common than meningioma, and Depo reduces your risk of uterine cancer. So how do you balance that? It’s complex, and it often depends on the individual patients.”
Phillip says even that small risk would have been too much for her.
“If I would have [known] from the start, I would have never took that shot,” she said.
The lawsuit
Phillip is one of more than 1 000 women suing Pfizer, alleging that it failed to warn them about the risk.
“These women all have meningiomas. Many have surgery, some have radiation, and they’ve all had their lives greatly impacted,” said Ellen Relkin, a lawyer representing Phillip and some of the other plaintiffs.
Phillip’s lawsuit points to several studies dating as far back as 1983 showing a link between progesterone and meningioma. The lawsuit says that those studies created an “unassignable duty to investigate” and that Pfizer should have studied the risks associated with Depo-Provera sooner.
“Defendants wilfully, wantonly, and intentionally conspired, and acted in concert, to ignore relevant safety concerns and to deliberately not study the long-term safety and efficacy of Depo-Provera, particularly in chronic long-term users,” the complaint says.
Verma, of ACOG, said hormonal birth control is well-studied before it hits the market.
“Birth control methods that are commercially available have been studied extensively before becoming available to the public, and so we’ve studied every type of birth control. We’ve looked at safety measures,” she said. “We have guidelines that do intensive reviews of all of the data and help us support patients in what methods may be safer for them.”
In a statement to NBC News, Pfizer said it stands behind the “safety and efficacy of Depo-Provera”.
In a court filing last month, it asked a judge to dismiss the case, saying it became aware of the risks of meningioma associated with Depo-Provera in 2023 and submitted an application to the FDA to add a warning to the drug’s label. The application also requested adding warnings to two pills containing much lower doses of MPA.
The FDA denied that request, according to the filing.
The FDA declined a request for comment. In its denial letter to Pfizer, which is included in company’s filing, it said: “The findings of the available observational studies alone do not support the addition of a warning on meningioma risk to medroxyprogesterone acetate (MPA)-containing products.”
A spokesperson for Pfizer told NBC News that because of the FDA’s denial, federal law pre-empts the company from changing the warning label on Depo-Provera.
Relkin, Phillip’s lawyer, said Pfizer had enough information to study the possible risks associated with Depo-Provera on its own before 2023 and accused it of making an “overbroad and half-baked” effort to warn patients by submitting an application to add a warning label to every medication containing MPA.
“Depo-Provera is 150 milligrams. Three, four times a year, a very high dose,” Relkin said.
“There are low-dose, 2.5 and 5 mg pills, where there are no data showing they cause a problem.”
“The dose makes the poison,” she added. “By asking to change the label for all, they were inviting a rejection.”
Pfizer denied the accusation in its court filing. “If FDA truly thought a meningioma warning were necessary for some products (and not others) … FDA could have ‘promptly’ communicated to Pfizer,” it wrote.
Changes abroad
Outside the United States, however, changes have been made to Pfizer’s label.
The European Medicines Agency added meningioma as a “possible side effect” of drugs with high doses of medroxyprogesterone acetate last year, and Pfizer also communicated that risk to doctors in the European Union.
Canada’s label for the drug, updated last year, includes meningioma in its “warnings and precautions” section, stating that “meningiomas have been reported after long-term administration of progestins, including medroxyprogesterone acetate”.
In January, South Africa’s drug regulatory agency also recommended updating the drug label for MPA to include meningioma risk – this after a number of women in the country had suffered the trauma of brain tumours.
Phillip’s lawsuit alleges that Pfizer knew of the potential risk years before those changes overseas were made, however, citing a 2006 Canadian drug label that lists meningioma as one of the “Post-Market Adverse Drug Reactions” – adverse events that are reported after a drug has already been approved.
The 2006 label notes that “the nature of post-marketing surveillance makes it difficult to determine if a reported event was actually caused by Depo-Provera.”
“Just because something happened associated in time with something, it doesn’t mean that one thing caused the other,” said Dr Janet Woodcock, a former FDA principal deputy commissioner. “It’s in a company’s best interest to put everything on there, because then if they’re sued, they’d say, ‘Well, it was in the fine print’.”
Woodcock, who isn’t involved with the lawsuit, noted the FDA typically has the final word on drug labels.
According to its court filings, Pfizer resubmitted its application to the FDA in June.
“FDA has still not approved any meningioma warning, and Pfizer’s renewed request remains pending,” the filing said.
Relkin said an earlier warning would have changed everything for Phillip and her other clients.
After her surgery in 2018, Phillip continued to take Depo-Provera. Her doctors were unable to remove the entire tumour in 2018, and she needed a second operation in 2022, followed by radiation treatment from 2022 to 2024.
Even still, doctors weren’t able to remove the entire tumour because of how close it is to her optic nerve.
Phillip says she continued taking Depo-Provera until she saw posts on social media last year about the studies linking the drug to meningioma.
Last month, she had her first set of brain scans since she went off the drug. She said her radiologist told her that the meningioma is shrinking.
See more from MedicalBrief archives:
Despite HIV risk, withdrawing Depo-Provera could increase maternal mortality
SA women allege Pfizer knew about contraceptive tumour risk
Birth control jab linked to higher brain tumour risks – large US analysis
Prolonged use of some hormone drugs tied to tumour risk