The Link Between Hormones and Meningiomas
Meningiomas are typically benign brain tumors originating from the meninges. They are more common in women, and their growth can accelerate during pregnancy, suggesting a hormonal link. This connection is supported by the fact that meningioma cells often have progesterone receptors. Studies have shown an association between long-term, high-dose exposure to synthetic progestogens and an increased risk of these tumors. Health agencies in various regions have issued warnings about certain medications. It is important to note that the risk is primarily linked to specific, high-potency synthetic progestogens, not all hormonal medications.
Medications with Established High Risk
Large studies have identified several progestogen medications that significantly increase the risk of meningiomas, especially with prolonged, high-dose use. The risk increases with both the dose and duration of treatment.
Cyproterone Acetate (CPA)
High-dose cyproterone acetate (CPA), used for conditions like hyperandrogenism, is strongly associated with increased risk. French studies show a dose-dependent risk, with cumulative doses over 60 grams significantly increasing the risk. Discontinuing CPA has been shown to stabilize or shrink tumors in many cases.
Medroxyprogesterone Acetate (MPA)
Injectable medroxyprogesterone acetate (MPA), known as Depo-Provera, has also been linked to a higher meningioma risk, particularly with over one year of use. US studies found increased risk with injectable MPA compared to other contraceptives. Legal cases have arisen regarding failure to warn about this risk.
Other High-Risk Progestogens
Other progestogens associated with increased risk include Nomegestrol Acetate (NA), Chlormadinone Acetate (CMA), Medrogestone, and Promegestone, particularly with prolonged exposure.
Lower-Risk or Unassociated Hormonal Therapies
Not all hormonal therapies increase meningioma risk.
Examples of Lower-Risk Hormonal Therapies:
- Oral, intravaginal, and percutaneous progesterone
- Dydrogesterone
- Levonorgestrel Intrauterine Systems (IUS)
- Spironolactone
- Combined Oral Contraceptives (COCs) have conflicting or inconclusive evidence, suggesting a much lower risk than potent progestogens.
Risk Comparison of Associated Hormonal Medications
The table below summarizes the meningioma risk associated with various hormonal medications based on recent research.
| Drug (Primary Use) | Risk Level | Notes on Association |
|---|---|---|
| Cyproterone Acetate (CPA) | High (Dose-Dependent) | Strong association with high cumulative dose. Risk reduces significantly upon discontinuation. |
| Medroxyprogesterone Acetate (MPA) (e.g., Depo-Provera injection) |
Increased | Link established with long-term use (>1 year), with some studies showing a fivefold increase in risk. |
| Nomegestrol Acetate (NA) | Increased | Associated with higher risk, especially with prolonged use. |
| Chlormadinone Acetate (CMA) | Increased | Linked to higher incidence of meningioma, particularly with long-term use. |
| Medrogestone | Increased | Prolonged use (>1 year) increases intracranial meningioma risk. |
| Promegestone | Increased | Associated with excess risk with prolonged use. |
| Micronized Progesterone (Oral/Intravaginal) |
Not Increased | No significant association found with meningioma risk. |
| Levonorgestrel (IUS) | Not Increased | No excess risk associated with hormonal intrauterine systems. |
Other Risk Factors and Management
Besides medication, other meningioma risk factors include age, female gender, genetic conditions like NF2, radiation exposure, and obesity.
For patients on high-risk progestogens who develop a meningioma, stopping the medication may stabilize or shrink the tumor, potentially avoiding surgery or radiation. However, patients must consult their doctor before stopping any medication. Regular monitoring with MRI is often recommended for those on prolonged, high-dose progestogen therapy.
Conclusion
Evidence confirms a link between certain high-potency synthetic progestogen medications and an increased meningioma risk. High-dose cyproterone acetate, injectable medroxyprogesterone acetate (Depo-Provera), nomegestrol acetate, and chlormadinone acetate pose the highest risk, especially with long-term use. This is likely due to the stimulation of progesterone receptors on meningioma cells. Many other hormonal therapies, like micronized progesterone and levonorgestrel IUDs, do not show this risk. Patients and clinicians should be aware of these specific risks, and informed decision-making, monitoring, and considering alternative treatments are crucial. For patients who develop meningiomas on these drugs, stopping the medication is a key strategy that can lead to tumor stabilization or regression.
