Does Depo-Provera (medroxyprogesterone acetate) increase the risk of meningioma?

Medroxyprogesterone Acetate (Depo-Provera) and Meningioma Risk

There is evidence that high-dose progestins, particularly cyproterone acetate, increase the risk of meningioma, but there is insufficient evidence to establish a clear link between Depo-Provera (medroxyprogesterone acetate) and increased meningioma risk.

Evidence on Progestins and Meningioma

High-Dose Cyproterone Acetate (Different from Depo-Provera)

• A strong dose-dependent relationship has been established between cyproterone acetate (a different progestin than medroxyprogesterone acetate) and the risk of intracranial meningiomas 1
• The risk of meningioma with high-dose cyproterone acetate was 6.6 times higher than controls, with risk increasing with cumulative dose 1
• Meningiomas associated with cyproterone acetate tend to be located in the anterior and middle skull base 2

Medroxyprogesterone Acetate (Depo-Provera) Specifically

• Limited direct evidence exists regarding Depo-Provera (medroxyprogesterone acetate) and meningioma risk 3, 4
• A pilot study of five cases found no response of existing meningiomas to treatment with medroxyprogesterone acetate, suggesting it may not stimulate growth of established tumors 4
• Another study found that medroxyprogesterone acetate binds to progesterone receptors in meningioma cells, but its effect on growth rate remained unclear 3

Hormonal Influence on Meningiomas

• Meningiomas have a female predominance, suggesting a potential hormonal influence 2
• 92% of meningioma specimens in one study expressed progesterone receptors, while only 1% expressed estrogen receptors 5
• The relationship between oral contraceptives and meningioma risk appears modest at best, with some studies showing weak associations 5
• Hormone replacement therapy in menopausal patients may be associated with increased risk of meningiomas, though evidence is mixed 2

Risk of Secondary Tumors After Radiotherapy

• Radiotherapy for pituitary tumors has been associated with an increased risk of secondary brain tumors, including meningiomas 6
• In patients with GH deficiency who received radiotherapy for pituitary tumors, the risk of developing meningiomas was 4.06 times higher compared to those who did not receive radiotherapy 6
• Younger age at the time of radiotherapy is associated with higher risk of developing secondary tumors, with risk of meningioma increasing 1.6-fold for every 10 years of younger age 6

Clinical Implications

• While high-dose cyproterone acetate clearly increases meningioma risk, there is insufficient evidence to establish that Depo-Provera (medroxyprogesterone acetate) at contraceptive doses increases meningioma risk 2, 3, 4
• Depo-Provera remains an important contraceptive option for many women, with the CDC classifying it as category 2 (benefits generally outweigh risks) for most women 6
• Depo-Provera is particularly valuable for women who cannot use estrogen-containing contraceptives and those with certain medical conditions 6

Monitoring Recommendations

• Based on current evidence, routine screening for meningiomas in women using Depo-Provera is not indicated 3, 4
• Women with a personal history of meningioma should discuss alternative contraceptive options with their healthcare provider given the theoretical concern about hormonal influences on meningioma growth 2
• Any neurological symptoms such as persistent headaches, vision changes, or seizures should prompt evaluation regardless of contraceptive method 6