The Evidence Room: Depo-Provera, Meningiomas, and Professional Responsibility
The delicate balance of truth and tranquility: providing women with undiluted facts, framed by compassion, understanding and reassurance.
What is Depo-Provera?
Depo-Provera is a contraceptive injection given every three months. It contains depot medroxyprogesterone acetate (dMPA), a synthetic progestin that suppresses ovulation. Approved in the United States in 1992, it is used by about 2% of American women aged 15 to 49 and nearly 68 million women worldwide. For many, its convenience—no daily pill, no implant, no device—has made it attractive.
But convenience is not the same as safety. Recent research has raised serious concerns about a link between dMPA and brain tumors known as meningiomas.
The New JAMA Neurology Study
A landmark study published in September 2025 in JAMA Neurology (Xiao et al., 2025) analyzed data from more than 10 million women across 68 U.S. healthcare systems.
Women using dMPA had a 2.43-fold increased relative risk of being diagnosed with meningioma compared with matched controls.
The risk rose even higher with longer duration:
4–6 years of use: threefold increased risk
More than 6 years: nearly fourfold increased risk
The risk was greatest for women starting after age 31.
The “number needed to harm” was 1,152, meaning that for every 1,152 women using dMPA, one extra case of meningioma may occur.
Other contraceptives—including IUDs, implants, and combined oral contraceptives—showed no increased risk. In fact, some (like combined pills and certain IUDs) were associated with lower meningioma risk.
This is the first large-scale, U.S. population-based cohort study to confirm and extend earlier French and insurance-based case-control studies. The consistency across studies strengthens the evidence that dMPA exposure contributes to meningioma development.
The Lawsuits
Over 1,000 women are now suing Pfizer, the maker of Depo-Provera, alleging that the company knew about tumor risks and failed to warn. These lawsuits focus not just on harm but on lack of transparency.
This is part of a recurring cycle in women’s health: a drug is widely promoted, adverse effects emerge, and then the profession confronts whether patients were truly informed.
ACOG’s Response: Reassurance or Minimization?
The American College of Obstetricians and Gynecologists (ACOG) responded with a statement urging “caution” but stressing that the absolute risk is small: “five out of 10,000 women using medroxyprogesterone acetate may possibly develop meningioma compared to one out of 10,000 women not using the medication.”
Nisha Verma, MD, MPH, a senior ACOG advisor, concluded: “The risk that they’re finding is incredibly small. I think it is a consideration we can talk to patients about, among all of the considerations that patients go through.”
But is this professional responsibility—or minimization?
For the women who do develop meningiomas, which can cause neurological damage and often require neurosurgery, the risk is anything but “incredibly small.” The relative increase is significant, and the clustering of risk in long-term and older users demands attention.
Absolute versus Relative Risk
When doctors talk about risk, we often use two different ways of measuring it: absolute risk and relative risk. These sound like jargon, but the difference is actually easy to understand.
Absolute risk is the raw chance of something happening. For example, if five out of 10,000 women taking Depo-Provera get meningiomas, that means the absolute risk is 0.05%. That’s small.
Relative risk is how much higher the risk is compared to women who don’t take the drug. If only one out of 10,000 women not taking it develops a tumor, but five out of 10,000 do when taking it, that’s a fivefold increase. The relative risk is large, even though the absolute numbers like 2.5% (compared to 0.5%) are small.
Think about it this way:
Imagine you buy a lottery ticket. Your absolute chance of winning is tiny—maybe one in millions. If someone offers you a ticket that doubles your chances, your relative risk of winning has doubled. But your absolute chance is still almost zero.
Or take seatbelts. Without a seatbelt, maybe 40 out of 1,000 people in a crash die. With a seatbelt, maybe 10 out of 1,000 die. At first, “40 out of 1,000” might sound low—after all, 960 out of 1,000 survive. But if you’re the one in that group of 40, it’s not low at all. Seatbelts cut that risk down by 75%. So both the absolute numbers and the relative difference matter.
Patients deserve to hear both numbers. Absolute risk keeps things in perspective and prevents unnecessary fear. Relative risk shows that the increase is real and meaningful. If we only tell patients “the absolute risk is low,” we risk minimizing the seriousness. If we only tell them “the relative risk is five times higher,” we risk scaring them without context.
Informed consent means putting the two together in plain language: “This risk is rare, but it is clearly higher if you use this medication, especially for a long time or at older ages.” That way, patients can make decisions with full understanding—not with half the story.
Professional Responsibility and Informed Consent
The professional responsibility model in obstetric ethics requires physicians to tell the whole truth. Numbers, not adjectives. “Low risk” can be misleading. Patients deserve clarity:
Relative risk doubled to quadrupled depending on duration.
Risk higher in women older than 31 at initiation.
Alternatives exist that show no such association.
John Gregory, the 18th-century physician-ethicist, emphasized honesty and integrity in medical communication. ACOG’s response did not meet that standard. Minimizing findings undermines trust and weakens informed consent.
Lessons for Patients and Clinicians
Ask for numbers. If told “low risk,” ask, “Compared to what? Over how long?”
Duration matters. The risk climbs after four years. Short-term users appear less affected.
Age matters. Women over 31 initiating dMPA face higher risk.
Alternatives exist. Pills, IUDs, and implants show no increased risk.
Insist on transparency. Professional organizations must avoid vague reassurance.
Reflection
The evidence is mounting. Depo-Provera carries a measurable, biologically plausible risk for brain tumors, especially with long-term use. The role of professional bodies is not to soothe but to inform. Women are entitled to the facts, presented without dilution.
The deeper question: When does “reassurance” become dismissal? And if we minimize risks in contraception—used by healthy women for decades—what does that say about our ethical commitment to patient autonomy?