Is Depo Provera (medroxyprogesterone acetate) safe for patients with meningioma?

Depo-Provera and Meningioma: Safety Considerations

Direct Recommendation

Depo-Provera (medroxyprogesterone acetate) should be avoided in patients with existing meningiomas and discontinued if a meningioma is diagnosed during use, as progestin exposure is associated with increased meningioma risk and accelerated tumor progression. 1, 2

Evidence-Based Rationale

Progestin-Meningioma Connection

• Progestin is known to increase the risk for meningioma and is associated with enrichment of PIK3CA mutations, according to the European Association of Neuro-Oncology. 1

• Approximately 76% of meningiomas express progesterone receptors (PR), making them hormonally responsive tumors. 1, 3

• Progesterone-only contraception specifically demonstrates a shorter progression-free survival in premenopausal women with WHO Grade I meningioma (18 months vs. 32 months for combination/estrogen-only contraception, p = 0.038). 2

• The recurrence rate is significantly higher with progesterone-only contraception (33.3% vs. 19.6% for other hormonal contraceptives). 2

Clinical Evidence of Tumor Growth

• Clinical onset during pregnancy occurred in three patients and tumor growth during contraceptive progesterone therapy was documented in two patients in a surgical series of premenopausal women. 4

• A case report documented meningioma development after therapy with medroxyprogesterone acetate in a patient being treated for renal carcinoma. 5

• Medroxyprogesterone acetate binds competitively to meningioma progesterone receptors, with mean PR values significantly decreased (15.6 fmol/mg protein vs. 54.9 fmol/mg protein in untreated tumors). 6

Guideline Recommendations

• Testing for PR expression as a basis for antihormonal treatment is discouraged for clinical routine and should only be considered in clinical trials (ESCAT IVA), per the European Association of Neuro-Oncology. 1, 3

• A phase III trial failed to show benefit of the PR inhibitor mifepristone on failure-free or overall survival of unresectable meningioma, indicating that blocking progesterone receptors does not reverse tumor growth. 1, 3

• Brain MRI screening for meningioma should be performed in females with LAM receiving progestative drugs or planned to receive such treatment, according to the European Respiratory Society. 1

Clinical Algorithm for Management

For Patients Without Known Meningioma:

1. Screen for neurological symptoms (persistent headaches, vision changes, seizures) before initiating Depo-Provera. 7

2. Consider baseline brain MRI in patients with risk factors for meningioma (prior cranial radiation, neurofibromatosis type 2, family history). 1

3. Choose alternative contraception if any meningioma risk factors are present—consider copper IUD, estrogen-containing contraceptives (if not contraindicated), or barrier methods. 4

For Patients With Known Meningioma:

1. Discontinue Depo-Provera immediately regardless of tumor grade or treatment status. 4, 2

2. Avoid all progesterone-only contraceptives including oral progestins, implants, and progesterone-releasing IUDs. 4, 2

3. Transition to non-hormonal contraception (copper IUD, barrier methods) or estrogen-containing methods if no contraindications exist. 4

4. Monitor with serial MRI according to neurosurgical recommendations, typically every 3-6 months initially. 1

For Patients Who Develop Meningioma While on Depo-Provera:

1. Stop Depo-Provera immediately—do not wait for the next scheduled injection. 4

2. Obtain neurosurgical consultation for treatment planning (observation, surgery, or radiation). 1

3. Document the temporal relationship between Depo-Provera use and meningioma diagnosis for risk assessment. 2

Critical Pitfalls to Avoid

• Do not continue Depo-Provera in patients with meningioma based on the rationale that "most meningiomas are benign"—the progesterone exposure accelerates progression regardless of grade. 2

• Do not assume combination oral contraceptives carry the same risk—the evidence specifically implicates progesterone-only formulations, not estrogen-containing products. 8, 2

• Do not rely on progesterone receptor status to guide contraceptive decisions, as testing for PR expression is not recommended for clinical decision-making outside trials. 1, 3

• Do not use mifepristone or other antiprogestins as a strategy to allow continued Depo-Provera use, as phase III trials showed no clinical benefit. 1, 3

Nuances in the Evidence

While some older studies suggested no increased risk with hormonal contraceptives in general 8, the most recent and highest-quality evidence specifically identifies progesterone-only contraception as problematic 2. The 2018 study demonstrating shortened progression-free survival with progesterone-only contraception represents the most clinically relevant data, as it directly examined recurrence outcomes rather than just initial tumor development. 2

The European Association of Neuro-Oncology's 2025 guideline explicitly states that progestin increases meningioma risk, providing the strongest guideline-level evidence against Depo-Provera use in this population. 1