Decades of Research

Research on the relationship between meningiomas and synthetic progesterone — the main ingredient in Depo-Provera, which prevents ovulation and hinders sperm from reaching the eggs — is extensive.

In the 1930s, an American neurosurgeon noted that women, who have higher progesterone levels than men, are more likely to develop these types of brain tumors than their male counterparts. As early as 1989, scientists found that drugs that block the absorption of progesterone significantly reduce the growth of meningioma cells, and since then, a number of studies have found a link between medications containing synthetic progesterone and the development of these tumors.

In 2024, a large study of more than 18,000 cases of women undergoing surgery for meningiomas found that “prolonged use of . . . [Depo-Provera] . . . was found to increase the risk of intracranial meningioma.” Specifically, the scientists found that use of Depo-Provera was associated with a more than fivefold heightened risk of developing a meningioma that required surgery, and that risk increased further if patients used Depo-Provera for more than a year.

While the majority of meningiomas are benign, they can still impact vital nerves or compress the brain, causing significant disabilities or even becoming life-threatening. Ten to 15 percent of these tumors can be cancerous.

The link between synthetic progesterone and brain tumors is also dose-dependent, meaning the higher the dose, the greater the risk of developing a meningioma. Depo-Provera contains a very high dose of synthetic progesterone compared to other types of contraception, like daily birth-control pills and intrauterine devices.

The science is so robust, in fact, that the scientific committee that monitors the safety of medicines in Europe recommended last year that patients taking high doses of synthetic progesterone be monitored for meningioma symptoms. Drug labels for Depo-Provera in the European Union, United Kingdom, New Zealand, Australia, and Canada also warn about these brain tumors.

Yet, even though Depo-Provera’s US drug label has been updated at least thirteen times since 2003, Pfizer has yet to add a warning to it about the risk of meningiomas. While such a warning could potentially reduce the drugmakers’ liability for adverse effects of the medicine, it could also reduce demand, leading to lower profits.

Finally, in early 2024, in the face of mounting scientific evidence, Pfizer proposed adding a warning to all of its synthetic progesterone products stating that “meningiomas have been reported following long-term administration” of these drugs. But by grouping Depo-Provera with low-dose synthetic progesterone birth-control pills — which have little evidence linking them to meningiomas — the company cast doubt on the connection between brain tumors and the entire class of synthetic progesterone drugs, according to a recent court filing from attorneys representing plaintiffs in the case.

Furthermore, the drugmaker omitted six studies that found significant links between patients taking injectable synthetic progesterone-containing contraception like Depo-Provera and brain tumors. This “deprived [the] FDA of information crucial to assessing Depo-Provera’s meningioma risk,” the filing reads.

FDA regulators subsequently concluded the science did not support such a warning.

“One would assume that if a drugmaker went to [the] FDA and said, ‘Hey, we want to include a warning on this drug label,’ that the manufacturer would submit all evidence to support the warning,” said Aylstock, the attorney who is coleading the litigation. Instead, “Pfizer was able to pick and choose what it gave the FDA.”

“The FDA Said ‘No’”

Now Pfizer is arguing that the FDA’s rejection — and their reasoning that the drugmaker “fully informed the FDA of the justifications for the warning” — preempts the 1,200-plus brain tumor lawsuits it’s facing over Depo-Provera.

Essentially, “Pfizer’s argument is it’s impossible to put a warning on Depo-Provera’s label when the FDA said no,” Alystock explained. If the Florida judge agrees with this argument, it would exempt Pfizer from liability in all lawsuits alleging it failed to adequately warn consumers.

Johnson & Johnson and Eli Lilly are also relying on preemption to fight allegations that they concealed evidence linking their blockbuster antipsychotic drugs, Risperdal and Zyprexa, to breast cancer.

Both medications, which are prescribed to treat conditions like schizophrenia and bipolar disorder, are known to elevate prolactin — a hormone tied to breast development and milk production. Scientists have known about the connection between high prolactin levels and breast cancer since at least the 1970s, and by the 1990s, research had established that certain antipsychotics, including those sold by Eli Lilly and Johnson & Johnson, could trigger dangerous hormone spikes.

Subsequent studies confirmed these risks: Prolactin levels can rise two to threefold in Zyprexa users and up to tenfold in Risperdal users. A 2022 analysis of eleven studies covering nearly 1.5 million people found that antipsychotic exposure is “an independent risk factor for cancer,” with high-dose users up to 39 percent more likely to develop breast cancer than low-dose users.

Right now, a growing number of lawsuits are alleging that Johnson & Johnson and Eli Lilly failed to warn consumers about potential risks from the antipsychotics. But both drugmakers are arguing that their FDA-approved labels shield them from state claims.

For years, the drug labels on Risperdal and Zyprexa downplayed the risk of breast cancer. This January, the FDA added a new warning for all drugs that elevate prolactin levels: “Published epidemiologic studies have shown inconsistent results when exploring the potential association between [abnormally high levels of prolactin] and breast cancer.”

These label changes came after the publication of three studies, which all concluded that Risperdal, Zyprexa, and other prolactin-raising antipsychotics were not linked to increased breast cancer risk. All of these studies, it turns out, were designed and funded by a subsidiary of Johnson & Johnson.

In response to a California lawsuit, both drugmakers pointed to these studies, claiming that the FDA’s findings of “inconsistent” evidence override any state demand for stronger warnings of breast cancer on Risperdal’s and Zyprexa’s labels.

“Our position is [the drugmakers] have an obligation to assess these risks . . . to go to the FDA and request labeling changes,” said Monique Alarcon, an attorney at Wisner Baum, which filed a lawsuit against Eli Lilly and Johnson & Johnson. “But they’ve failed to do that.”

When asked for a comment on the ongoing litigation, a spokesperson for Eli Lilly wrote in an email to the Lever that “Patient safety is Lilly’s top priority.”

“Zyprexa has helped millions of patients with schizophrenia and bipolar I disorder since its FDA approval in 1996, and it was added to the World Health Organization’s List of Essential Medicines in 2023,” the email continues. “We will continue to vigorously defend against these claims.”

Johnson & Johnson did not respond to a request for comment.

“I Don’t Want Any Other Woman to Have My Life”

This is not the first time Pfizer has faced lawsuits over Depo-Provera. In 2021, the pharmaceutical company was ordered to pay nearly $2 million in settlements for failing to warn Canadian consumers about the risk of bone mineral density loss associated with the drug. The medicine now includes a warning on the matter. The current brain tumor claims could lead to significantly larger payouts from the company — if the plaintiff’s attempts aren’t derailed by Pfizer’s preemption move.

Taking Depo-Provera “didn’t just affect my quality of life, it ruined my life,” said Jane Garcia, one of those plaintiffs, who was diagnosed with multiple meningiomas in 2023 after taking the birth control shot for roughly a decade. The tumors are small, the size of erasers, so the doctors are monitoring them to see if they grow. Meanwhile, Garcia suffers from a myriad of debilitating symptoms, including balance issues, blurred vision, and extreme anxiety.

“I’m afraid to go to bed at night because I’m afraid that I’m not going to wake up. I’ll stay awake for days,” she said, wiping away tears. “I think about it all day long. Is it gonna leak, is it growing?”

If the attorneys representing Garcia and other plaintiffs can overcome the question of preemption that currently sits in the Florida court, the chances of being able to show the link between Depo-Provera and meningiomas are high, said Aylstock.

“This case is one of the strongest drug cases we’ve seen in a long time in terms of scientific literature,” Aylstock said.

For the people bringing these cases, though, the fight isn’t just about science and legal arguments — it’s about preventing others from having to go through the same ordeal.

These lawsuits force Pfizer “to be accountable,” said Garcia. “There needs to be awareness. I don’t want any other woman to have my life now.”