Study Links Several Progestogen Contraceptives to Rare Meningioma Risk, Reinforcing Individualized Patient Counseling

Use of several progestogen-containing contraceptives was associated with an increased risk of meningioma in a large nationwide Danish study, adding to growing evidence that the association extends beyond injectable depot medroxyprogesterone acetate (DMPA) to include certain oral contraceptives and high-dose levonorgestrel intrauterine devices (IUDs).¹

Published in JAMA Network Open, the nested case-control study analyzed nationwide registry data from approximately 3 million women aged 15 to 59 years in Denmark between 2000 and 2024. Investigators identified 1473 women diagnosed with meningioma and matched them with 14,717 controls to evaluate whether individual progestogen-containing contraceptives were associated with incident meningioma.¹

Although meningioma is the most common primary intracranial tumor in adults, approximately 90% are benign. However, depending on their size and location, they may cause seizures, cognitive impairment, focal neurologic deficits and require surgery or radiation therapy.¹

Highest Relative Risk Observed With Injectable DMPA

Among the 12 progestogen formulations evaluated, 8 demonstrated statistically significant associations with meningioma. DMPA showed the strongest association, with an odds ratio (OR) of 4.55 (95% CI, 2.19-9.45) compared with nonusers.¹

Investigators also observed significantly increased odds of meningioma among users of oral desogestrel (OR, 1.73), desogestrel-ethinyl estradiol (OR, 1.66), cyproterone (OR, 1.61), drospirenone (OR, 1.58), high-dose levonorgestrel IUDs (OR, 1.58), gestodene (OR, 1.44), and levonorgestrel-containing oral contraceptives (OR, 1.40).¹

Risk was greatest among current users or those who had used these contraceptives within the previous year. Encouragingly, investigators found that the excess risk generally disappeared 5 years after discontinuation of the contraceptive.¹

Despite the elevated relative risks, the investigators emphasized that the absolute risk remained low. Numbers needed to harm varied substantially depending on the specific contraceptive and patient age, with injectable medroxyprogesterone demonstrating the lowest numbers needed to harm, particularly among older women.¹

Findings Support Individualized Risk-Benefit Discussions

The findings add to an expanding body of literature evaluating hormonal therapies and meningioma risk. Previous observational studies have similarly demonstrated an increased risk with DMPA, prompting updates to product labeling and professional guidance.^2,3

Importantly, the current findings should not be interpreted to mean that hormonal contraceptives broadly cause brain tumors. Rather, they reinforce the importance of individualized counseling when selecting contraceptive therapy. Similar to discussions surrounding menopausal hormone therapy and breast cancer risk, clinicians must consider differences in hormone formulation, dose, route of administration, duration of therapy, and patient-specific risk factors before making treatment decisions.^4,5

Biologically, the association is considered plausible because progesterone receptors are expressed in up to 87% of meningiomas, and previous studies have observed tumor growth during pregnancy or exogenous progesterone exposure, with regression following hormone withdrawal.¹

Pharmacists Play an Important Role in Shared Decision-Making

Sonia Amin Thomas, PharmD, BCOP, AFMCP, INHC, vice chair and professor of pharmacy practice at Philadelphia College of Osteopathic Medicine School of Pharmacy and clinical oncology specialist pharmacist at Wellstar Health System, said the study primarily reinforces existing evidence rather than signaling a dramatic shift in clinical practice.

"These findings support the current evidence that other progesterone-containing products carry the same risk," Thomas said in an interview with Pharmacy Times. "However, the DMPA findings also indicate that the risk depends on the type of progestogen, the dose, and the administration route."

Thomas emphasized that pharmacists should help patients understand the distinction between relative and absolute risk.

"Emphasize to patients that the absolute risk is very low and should be individualized based on patient risk factors and other conditions," she said.

When counseling patients, Thomas said clinicians should continue weighing contraceptive benefits alongside potential risks.

"Like everything in medicine, a risk-benefit ratio needs to be calculated for each patient based on the advantages of use and their risk factors," Thomas said. "I think the findings will increase awareness and reinforce what we already know; however, it is important to individualize care for every patient based on their needs and other conditions. It will strengthen individualization when it comes to contraception."

The authors concluded that the findings provide clinically relevant information for both prescribers and patients but should be interpreted within the context of the rarity of meningioma and the well-established benefits of effective contraception.¹

REFERENCES

1. Hasselblad Lundstrøm N, Hjorslev Knudgaard M, Skaarup Pedersen M, Schougaard Christiansen ML, Wessel Skovlund C. Contraceptive Progestogens and Incident Meningioma. JAMA Netw Open. 2026;9(7):e2622603. Published 2026 Jul 1. doi:10.1001/jamanetworkopen.2026.22603

2. Roland N, Neumann A, Hoisnard L, et al. Use of progestogens and the risk of intracranial meningioma: national case-control study. BMJ. 2024;384:e078078. Published 2024 Mar 27. doi:10.1136/bmj-2023-078078

3. US Food and Drug Administration. Depo-Provera CI (medroxyprogesterone acetate injectable suspension) prescribing information. Revised December 2025. Accessed July 7, 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2025/020246s074lbl021583s045lbl.pdf

4. National Cancer Institute. Menopausal Hormone Therapy and Cancer. Updated September 25, 2023. Accessed July 7, 2026. https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/mht-fact-sheet

5. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333. doi:10.1001/jama.288.3.321