What is a Meningioma?
Meningiomas are the most common primary brain tumor, accounting for approximately 40% of all primary brain tumors in the United States [1]. These tumors arise from the meninges—the protective membranes covering the brain and spinal cord. While approximately 95% of meningiomas are benign and have no symptoms, enlarging size and location can cause significant symptoms and may require surgical intervention.[2] Headaches may be a symptom.
Meningiomas occur more frequently in women than men, with a female-to-male ratio of approximately 2:1 across all ages, peaking at over 3:1 in patients during their third to fifth decades of life.[1] This female predominance has led researchers to newly investigate the role of hormonal factors in meningioma development.
Progesterone, PROGESTEGINES and Meningioma Risk
Progesterone Receptor Expression
Approximately 72-75% of meningiomas express progesterone receptors, providing a biological mechanism through which progesterone and synthetic progestins may influence tumor growth.[1][3] This receptor expression varies with tumor characteristics—progesterone receptor positivity is more common in WHO grade I tumors, younger patients, female patients, skull base locations, and meningothelial histology.[4]
Pregnancy and High Progesterone Levels
Progesterone levels in pregnancy are many times greater than any levels in a non-pregnant or a hormonal contraceptve client. The relationship between pregnancy and meningioma risk is complex and somewhat paradoxical. While case reports have described meningioma growth during pregnancy and tumor regression following delivery,[2][5] large population-based studies have not demonstrated an increased risk of meningioma diagnosis during pregnancy or in the first year postpartum.[6]
A Swedish cohort study of over 2.2 million women found that meningiomas were actually less commonly detected during pregnancy than expected (SIR = 0.40; 95% CI 0.20-0.72), and there was no increased risk in the first year postpartum (SIR = 1.04; 95% CI 0.74-1.41).[6] Interestingly, nulliparous women had higher meningioma rates compared to parous women (SIR = 1.73; 95% CI 1.52-1.95), suggesting that pregnancy itself may not increase overall meningioma risk despite the dramatically elevated progesterone levels during gestation.[6]
The accelerated growth of existing meningiomas during pregnancy appears to be related to the 200-fold increase in progesterone levels, which may stimulate growth of hormone-sensitive tumors that are already present.[7] However, this growth stimulation does not appear to translate into an increased incidence of new meningiomas among pregnant women.
FDA has issued an update to the package insert of DMPA regarding meningiomas.
Exogenous Progesterone and Progestins
Gynecologists give progesterones for fertility, for sleep, for control of heavy bleeding, for contraception and menopause treatments. The risk associated with exogenous progesterone varies significantly depending on the specific formulation and route of administration:
With many progesterones out there, and some available since the 1950s, many physicians are surprised to hear of this meningioma question newly posed. Injectable medroxyprogesterone acetate (Depo-Provera) shows the strongest association with meningioma risk among contraceptive progestins, with odds ratios ranging from 5.49 to 5.55 in European studies and a relative risk of 2.43 in a large US cohort.[8][9][1] This risk increases with prolonged use, particularly with exposures exceeding 4 years or initiation after age 31.[1] Again, confusion about what age 31 would have to do with anything physiologic, as it’s not a known cut point for any other physiological issues.
Other high-risk progestins include cyproterone acetate, (OR 19.21), nomegestrol acetate (OR 4.93), chlormadinone acetate (OR 3.87), medrogestone (OR 3.49), and promegestone (OR 2.39).[8] However, cyproterone acetate is not approved in the United States,, and two of these not used in current USA brands, the other two rarely.
Lower-risk or neutral formulations include progesterone, dydrogesterone, and levonorgestrel intrauterine systems, which have not shown increased meningioma risk in large studies.[8] Combined oral contraceptives containing estrogen and progestin generally show either no association or potentially decreased risk.[2][3] And to add further confusion, most DMPA users have used a variety of products over their reproductive life.
The mechanism appears to involve prolonged progesterone receptor stimulation leading to tumor development, particularly in individuals with specific genetic vulnerabilities. Progestin-associated meningiomas harbor PIK3CA mutations in approximately 35% of cases versus only 3% of controls, suggesting a distinct molecular pathway.[1]
Other Known Risk Factors for Meningioma
Radiation Exposure
Prior exposure to ionizing radiation, particularly during childhood, is an established risk factor for meningioma development. This includes therapeutic cranial radiation for other conditions.
Genetic Syndromes
Neurofibromatosis type 2 (NF2) is strongly associated with meningioma development, often presenting with multiple tumors.[1][10] Other genetic conditions including [Li-Fraumeni syndrome](/rare-disease/li-fraumeni-syndrome) also increase risk.[10]
Age and Sex
Meningioma incidence increases with age, with peak incidence in the sixth and seventh decades of life. Female sex is an independent risk factor, with the female predominance most pronounced during reproductive years.[1]
Race and Ethnicity
African American women have an increased risk compared to Caucasian women (OR 2.4), an association that persists in postmenopausal women.[11]
Hormone Replacement Therapy
Postmenopausal hormone replacement therapy has been associated with a modestly increased meningioma risk (RR 1.19-1.79), though the evidence is mixed and the absolute risk increase appears small.[3][12]
Testosterone Therapy
Some studies have linked testosterone treatment to meningiomas, some have not. [15]. Testosterone gets converted into estrogen, and testosterone treatment shouldn’t really alter progesterone levels, so if anything, perhaps protective?
Obesity
Higher body mass index has been identified as a potential risk factor, though the relationship is complex and may interact with hormonal factors.[1] Given rates of obesity as we rise in age, combined with need for effective combination this is a risk factor we cannot ignore.
Protective Factors
Interestingly, pregnancy appears to have a protective effect on lifetime meningioma risk, with the protective effect increasing with number of pregnancies and age at first pregnancy.[11] Smoking has also been associated with decreased meningioma risk in some studies, particularly in premenopausal women (OR 0.6), though this should not be interpreted as a recommendation given smoking’s numerous health risks.[11] This again, very odd, since smokers usually have lower estrogen levels, so you would think if this hormonal link is important we’d expect a higher risk given lower level of protective factor. No data yet on secondary smoke effects, but also, if anything protective?
Clinical Implications
FDA has added this meningioma risk to the package insert of DMPA, As with all medications, assess whether there is risk of discontinuing or changing any hormonal treatments you have selected, and this discussion has to take all of that into consideration. New onset of symptoms, including headaches is something we have always recommended to evaluate. The real risk of DMPA associated meningioma appears very low. A gynecologist would have to treat 1-2 thousand patients to find such a case, and even gynecologists practice for over 50 years haven’t seen a case they know of. Since most of the cases will never need treatment, risk of even acquiring the problem is hard to quantify.
For patients with known meningiomas or those at high risk, progesterone-only contraception should generally be avoided, and alternative contraceptive methods should be considered.[13] The Society of Family Planning and Society of Gynecologic Oncology recommend shared decision-making with patients and their oncologists when hormonal contraception is requested by individuals with a history of meningioma.[2]
For pregnant patients with known meningiomas, a multidisciplinary approach involving neurosurgeons, obstetricians, and other specialists is essential to balance maternal and fetal risks.[5][14]
References
- Depot Medroxyprogesterone Acetate and Risk of Meningioma in the US. Xiao T, Kumar P, Lobbous M, et al. JAMA Neurology. 2025;82(11):1094-1102. doi:10.1001/jamaneurol.2025.3011.
- Society of Family Planning Clinical Recommendation: Contraceptive Considerations for Individuals With Cancer and Cancer Survivors Part 3 – Skin, Blood, Gastrointestinal, Liver, Lung, Central Nervous System, and Other Cancers: Joint With the Society of Gynecologic Oncology. Batur P, Brant A, McCourt C, Schwarz EB, et al. Contraception. 2025;147:110869. doi:10.1016/j.contraception.2025.110869.
- Estrogen and Progesterone Therapy and Meningiomas. Hage M, Plesa O, Lemaire I, Raffin Sanson ML. Endocrinology. 2022;163(2):bqab259. doi:10.1210/endocr/bqab259.
- A Systematic Review and Individual Participant Data Meta-Analysis of Gonadal Steroid Hormone Receptors in Meningioma. Miyagishima DF, Sundaresan V, Gutierrez AG, et al. Journal of Neurosurgery. 2023;139(6):1638-1647. doi:10.3171/2023.3.JNS221838.
- Brain Tumors in Pregnancy: A Review of Pathophysiology, Clinical Management, and Ethical Dilemmas. Tleubergenov MA, Zhamoldin DK, Baymukhanov DS, et al. Cancers. 2025;17(23):3854. doi:10.3390/cancers17233854.
- The Risk of Developing a Meningioma During and After Pregnancy. Pettersson-Segerlind J, Mathiesen T, Elmi-Terander A, et al. Scientific Reports. 2021;11(1):9153. doi:10.1038/s41598-021-88742-2.
- Reproductive Epidemiology of Glial Tumors May Reveal Novel Treatments: High-Dose Progestins or Progesterone Antagonists as Endocrino-Immune Modifiers Against Glioma. Altinoz MA, Ozpinar A, Elmaci I. Neurosurgical Review. 2019;42(2):351-369. doi:10.1007/s10143-018-0953-1.
- Use of Progestogens and the Risk of Intracranial Meningioma: National Case-Control Study. Roland N, Neumann A, Hoisnard L, et al. BMJ (Clinical Research Ed.). 2024;384:e078078. doi:10.1136/bmj-2023-078078.
- Hormonal Contraceptives and the Risk of Meningioma: A Swedish Register-Based Case-Control Study. Tettamanti G, Shu X, Mogensen H, et al. Neuro-Oncology. 2025;:noaf228. doi:10.1093/neuonc/noaf228.
- Pregnancy and Brain Tumors; A Systematic Review of the Literature. Molina-Botello D, Rodríguez-Sanchez JR, Cuevas-García J, et al. Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2021;86:211-216. doi:10.1016/j.jocn.2021.01.048.
- Association of Meningioma With Reproductive Factors. Lee E, Grutsch J, Persky V, et al. International Journal of Cancer. 2006;119(5):1152-7. doi:10.1002/ijc.21950.
- Reproductive and Exogenous Hormone Factors in Relation to Risk of Meningioma in Women: A Meta-Analysis. Qi ZY, Shao C, Huang YL, et al. PloS One. 2013;8(12):e83261. doi:10.1371/journal.pone.0083261.
- Meningiomas in Premenopausal Women: Role of the Hormone Related Conditions. Maiuri F, Mariniello G, Somma T, et al. Frontiers in Oncology. 2020;10:556701. doi:10.3389/fonc.2020.556701.
- Simultaneous Surgical Management of a Giant Tuberculum Sellae Meningioma and Pregnancy-Related Complications: A Case Report and Literature Review. Tleubergenov MA, Ryskeldiyev NA, Baymukhanov DS, et al. Frontiers in Oncology. 2025;15:1576797. doi:10.3389/fonc.2025.1576797.
- Hormonal factors predisposing to the development of meningiomas in men: a case-control study | Journal of Neuro-Oncology
