What Causes a Meningioma and Who Is Most at Risk?

Meningiomas arise from a tangle of interacting causes rather than a single trigger. Ionizing radiation, certain genetic mutations, hormonal influences, and obesity all raise the risk, with the strongest documented environmental factor being prior radiation exposure to the head. Women develop meningiomas roughly twice as often as men, incidence climbs steeply with age, and non-Hispanic Black individuals face higher rates than non-Hispanic White individuals across every age group. Despite being the most common primary brain tumor, meningiomas remain understudied compared with more aggressive cancers, and the picture of what drives them has shifted considerably in the past decade.

The Genetic Landscape

The most frequent genetic driver behind meningiomas is a change in the NF2 gene on chromosome 22. NF2 encodes a protein called merlin, which acts as a kind of scaffolding at the junctions between cells, helping maintain the signals that tell a cell to stop dividing when it contacts its neighbors. When both copies of NF2 are lost or inactivated, that brake on growth disappears. Lab work has shown that restoring merlin in meningioma cells, whether or not they originally carried an NF2 mutation, slows their proliferation.¹ NF2 alterations are the single most common genetic event in meningioma and correlate with tumor location, histological subtype, and how aggressively the tumor behaves.²

But roughly half of all meningiomas lack NF2 mutations entirely. A landmark genomic analysis of 300 tumors uncovered mutations in TRAF7, a protein involved in triggering cell death, in close to one-quarter of all meningiomas. TRAF7 mutations often appeared alongside either a specific change in the transcription factor KLF4 or an activating mutation in AKT1 that ramps up a cell-growth signaling pathway. A smaller fraction, about five percent of non-NF2 meningiomas, carried mutations in SMO, which activates a different growth-signaling cascade. These non-NF2 tumors looked clinically different: they were almost always benign, showed stable chromosomes, and tended to arise from the middle of the skull base.³ There are still other meningiomas that lack all of these known mutations, pointing to driver genes that haven’t been identified yet.⁴

Radiation Exposure

Ionizing radiation is the single best-established environmental risk factor. Both high-dose and low-dose exposure to the head have been linked to later meningioma development, though the relationship is dose-dependent: higher doses both increase the overall risk and shorten the gap between exposure and tumor appearance.⁵ Much of the evidence comes from people who received cranial radiation as children, whether for leukemia, other brain tumors, or the now-abandoned practice of irradiating the scalp for ringworm. Cranial radiation during childhood is a firmly established risk factor for meningioma later in life.⁶

Even at lower doses, the risk appears elevated, though exactly how much remains harder to pin down. A case report study notes that while intermediate-to-high-dose exposure is well-characterized as a risk factor, the parameters for low-dose radiation-induced meningioma are still being defined.⁷ The practical takeaway is that anyone who received radiation therapy to the head, especially in childhood, should be aware of this long-term risk during routine medical follow-up.

Hormones and the Female Predominance

Meningiomas are roughly twice as common in women as in men, and researchers have long suspected that sex hormones play a role. Many meningioma cells express progesterone receptors. In one study of premenopausal women with meningiomas, half had tumors where 80 percent or more of the cells tested positive for progesterone receptors.⁸ That receptor presence suggests the tumors can respond to hormonal signals, which may help explain why some meningiomas grow faster during pregnancy or in the luteal phase of the menstrual cycle.

More recent work has focused on estrogen receptor beta (ERβ). A molecular analysis found that ERβ expression was significantly higher in tumors from female patients compared with males and was elevated in higher-grade and recurrent meningiomas. The researchers showed that ERβ appeared to promote aggressive behavior by modulating components of the mTOR signaling pathway, a central regulator of cell growth.⁹ This matters because it suggests that the hormone connection is not just about whether tumors form but also about how aggressively they behave once they do.

Progestogen Medications

The hormone connection extends beyond the body’s own hormones. Cyproterone acetate, a high-dose synthetic progestogen prescribed for conditions ranging from severe acne to prostate cancer to transgender hormone therapy, has emerged as a clear pharmacological risk factor. A large French cohort study found that women who used high-dose cyproterone acetate faced roughly six to seven times the rate of meningioma requiring surgery or radiotherapy compared with unexposed women. For those with cumulative doses above 60 grams, the risk jumped even further, to about 22 times that of non-users.¹⁰ An earlier population-based study found a similar pattern, with high-dose users showing about an 11-fold increased risk compared with people who never used the drug.¹¹

A recent systematic review and meta-analysis pooling data across multiple studies put the overall association at about a 12-fold increased odds for cyproterone acetate users. The same review found that depot medroxyprogesterone acetate, a long-acting injectable contraceptive, carried a smaller but still meaningful elevation in risk, with pooled odds roughly two to three times higher than in non-users.¹² The French health authority has already restricted prescribing of high-dose cyproterone acetate in response to this evidence. Low-dose formulations, such as those in common oral contraceptive pills, have not shown the same association.

Who Is Most at Risk by Age, Sex, and Race

Meningiomas overwhelmingly affect adults, with incidence rising steeply after age 40 and peaking in the sixth and seventh decades of life. Children and adolescents accounted for less than one percent of meningioma cases in a large U.S. cancer registry analysis. Unlike adults, pediatric patients showed no female predominance, with a roughly equal male-to-female ratio, and had a higher proportion of spinal tumors.¹³

Race matters too. A large registry study found that non-Hispanic Black individuals face elevated meningioma rates compared with non-Hispanic White individuals starting in young adulthood and persisting through old age. The disparity was more pronounced for higher-grade tumors: in the seventh decade of life, the rate ratio for grade 2 and 3 meningiomas was about 1.57, compared with about 1.27 for grade 1 tumors. The study also found a synergistic interaction between Black race and male sex, meaning non-Hispanic Black men were at particularly elevated risk relative to non-Hispanic White men.¹⁴ The reasons for these racial disparities remain unclear. They may involve genetic susceptibility, differences in environmental exposures, or a combination of both.

Obesity and Metabolic Risk

Body weight is an underappreciated risk factor. A large prospective cohort study reported about a 48 percent increased risk of meningioma among obese individuals compared with those at a normal body mass index.¹⁵ That finding has been reinforced by additional work showing that both BMI and waist-to-hip ratio are significantly associated with meningioma incidence, along with female sex.¹⁶

The mechanism likely loops back to hormones. Adipose tissue produces estrogen through a process called aromatization. More body fat means more circulating estrogen, which, given the hormone-receptor profile of many meningiomas, could plausibly promote tumor growth. Obesity also drives chronic low-grade inflammation and elevates insulin-like growth factor levels, both of which are biologically plausible contributors. None of this means that losing weight will prevent a meningioma, but it adds meningioma to the growing list of tumors for which excess body fat is a modifiable risk factor.

Inherited Syndromes

Meningiomas arising in the context of an inherited genetic syndrome occur almost exclusively with neurofibromatosis type 2, now called NF2-schwannomatosis. This condition follows an autosomal dominant inheritance pattern and results from germline mutations in the NF2 gene. People with NF2-schwannomatosis often develop multiple meningiomas, along with schwannomas and other nervous system tumors.¹⁷ The NF2 gene on chromosome 22 encodes the merlin protein; people born with one faulty copy need only a “second hit” in the remaining copy to lose merlin’s tumor-suppressing function altogether.¹⁸

NF2-schwannomatosis is not the only syndrome to consider. Among patients who present with multiple meningiomas but don’t meet standard NF2 diagnostic criteria, about seven percent were found to carry mutations in SMARCE1, and about five percent had mosaic NF2, meaning the NF2 mutation was present in only some of their cells.¹⁹ These findings suggest that anyone diagnosed with multiple meningiomas should discuss genetic testing with their care team, even if they don’t have obvious signs of a familial syndrome.

Head Trauma and Mobile Phones

Two commonly feared risk factors deserve their own discussion because the evidence runs against popular belief. The idea that a blow to the head can cause a meningioma has persisted for decades, and a meta-analysis of observational studies did find a statistically significant association, with about double the odds of meningioma after a reported traumatic brain injury.²⁰ However, the same authors cautioned that this association likely reflects bias rather than biology: people diagnosed with meningioma may be more likely to recall past head injuries, and surveillance after a head injury may simply detect tumors that were already there. A Mendelian randomization study, which uses genetic variants to test for causation and is less prone to these biases, found no causal relationship between any type of traumatic brain injury and meningioma.²¹ The weight of the evidence currently leans against head trauma as a true cause.

Mobile phone use is another frequent concern. A large prospective cohort study called COSMOS tracked participants for a median of about seven years and found no meaningful increase in meningioma risk with increasing hours of call time. The adjusted hazard ratio per 100 cumulative hours of phone use was essentially 1.0.²² An earlier case-control study similarly found no increased meningioma risk among regular mobile phone users and no dose-response relationship with measures of radiofrequency exposure.²³ The consistency of null findings across study designs makes it unlikely that mobile phones contribute to meningioma risk.

How Pediatric Meningiomas Differ

When meningiomas do appear in children, they are not simply small versions of adult tumors. Molecular profiling shows that pediatric meningiomas cluster separately from adult cases and are characterized by distinct features. While NF2 alterations are frequent in childhood meningiomas, the other common mutations seen in adult tumors, such as those in TRAF7, AKT1, KLF4, and SMO, are typically absent.²⁴ Pediatric meningiomas also show a higher proportion of the clear cell histological subtype, tend to appear in different locations, and are more often associated with germline mutations, meaning the child was born with a predisposing genetic change rather than acquiring it through environmental exposure.²⁵ This distinction has practical implications: a meningioma in a child should prompt a more thorough genetic workup than one discovered in a 60-year-old.

Incidental Meningiomas and Watchful Waiting

A growing number of meningiomas are found by accident on brain imaging done for unrelated reasons like headaches or dizziness. These incidental meningiomas raise a natural question: if you have one, how worried should you be? A prospective study followed incidental meningiomas for up to 12 years and found that while growth was the natural trend, it tended to decelerate after about a year and a half and became statistically insignificant after eight years. About 63 percent of tumors showed a self-limiting growth pattern. Within five years, almost all interventions that would ultimately be needed had already been initiated, and no patient developed symptoms before intervention was offered. More than 40 percent of patients with indolent tumors avoided treatment entirely, and roughly 31 percent of the cohort died of unrelated causes without their meningioma ever becoming a problem.²⁶

A more recent study developed a clinical tool to stratify incidental meningiomas into risk categories. Tumors classified as low risk had a progression rate of only about 4 percent, while medium-risk tumors progressed about 24 percent of the time and high-risk tumors about 52 percent of the time. The five-year progression-free survival across the whole cohort was about 88 percent.²⁷ For people with a small, incidentally discovered meningioma, periodic imaging and clinical follow-up is often the appropriate first step rather than immediate surgery.

What Predicts Recurrence After Surgery

Even among grade 1 meningiomas, which are the least aggressive, recurrence is not rare. The factors that predict it most reliably are how completely the tumor was removed and how fast its cells were dividing. In one analysis, subtotal resection (leaving some tumor behind because of its location near critical structures), posterior fossa location, nuclear atypia, and a high cell proliferation index were all independently associated with recurrence. Patients who had a complete resection but whose tumors had a proliferation index above about 4.5 percent recurred at roughly the same rate as those who had incomplete removal.²⁸ Tumor size and extent of resection were also identified as independent predictors of recurrence in a separate study that built a nomogram for risk stratification.²⁹

This means the pathology report matters enormously. A grade 1 meningioma that was fully removed and showed low proliferative activity has an excellent prognosis. The same grade with incomplete removal or brisk cell division warrants closer surveillance. Patients should ask their neurosurgeon and neuropathologist about both the completeness of resection and the Ki-67 or MIB-1 index to understand where their individual tumor falls on the risk spectrum.

Molecular Subtyping and DNA Methylation

Traditional grading based on what a tumor looks like under the microscope does not always capture how it will behave. Researchers have turned to DNA methylation profiling, a way of reading the chemical marks on a tumor’s genome, to sort meningiomas into more biologically meaningful categories. One study identified four methylation-based subgroups: Malignant, Intermediate, Benign A, and Benign B. Specific mutations tended to cluster within particular methylation groups, with NF2, AKT1, SMO, and TRAF7 mutations each associating with distinct subgroups.³⁰

An earlier landmark analysis identified a methylation subgroup with an unfavorable prognosis that carried complex chromosomal losses, including losses on chromosomes 1p, 6q, 14q, and 18q, all previously flagged as indicators of poor outcome. These methylation signatures correlated with recurrence risk better than traditional histological grading in many cases.³¹ This kind of molecular classification is gradually working its way into clinical practice. For patients with tumors that seem borderline or behave unexpectedly, methylation profiling can provide a more accurate picture of what to expect.

The Tumor Immune Microenvironment

One of the more surprising recent findings is how much the immune cells inside a meningioma influence its behavior. Tumor-associated macrophages, a type of immune cell that infiltrates many solid tumors, show up in large numbers in meningiomas. The trouble is that most of them, more than 80 percent in one analysis, are the “M2” type that actually supports tumor growth rather than fighting it. M2 macrophage density correlated with tumor size, and the balance between tumor-fighting M1 macrophages and pro-tumor M2 macrophages shifted dramatically in higher-grade and recurrent tumors.³²

A larger follow-up study confirmed that high infiltration by pro-tumoral macrophages was an independent predictor of poor survival and actually counteracted the benefits of having tumor-infiltrating lymphocytes, which are ordinarily a good prognostic sign in cancer. The presence of abundant macrophages created an immunosuppressive niche inside the tumor, essentially shielding it from the immune system.³³ This line of research opens the door to immunotherapy strategies targeting the macrophage population, a therapeutic avenue that is still early-stage but could eventually change how aggressive meningiomas are treated.

Where the Cell of Origin Debate Stands

For over a century, textbooks have stated that meningiomas come from arachnoid cap cells, a specific type of cell in the membranes covering the brain. Recent work using advanced techniques like single-cell sequencing and transgenic animal models has started to challenge that assumption, suggesting the cellular origin is more varied and complex than previously believed.³⁴ This might sound like a purely academic question, but identifying the true cell of origin has real consequences for developing targeted therapies. If meningiomas can arise from more than one cell type, treatments designed to exploit the vulnerabilities of one cell type may not work for all patients. The field is still in flux, and the classic “arachnoid cap cell” story is likely to be revised further as more data accumulate.