The Antiandrogen Cyproterone acetate : New data suggests possible meningioma risk

Cyproterone acetate may increase risk for meningioma

Cyproterone acetate has been used in some countries as an off-label use for related to androgen sensitivity such as acne, hirsutism, and female pattern hair loss. The drug is not available in all countries.

Many worldwide dermatologists have used the medication in women when other anti androgens (i.e. spironolactone, finasteride) have not proven helpful or can not be used. For treating AGA in women, some dermatologists have prescribed cyproterone 25 mg to 100 mg for 10 days of the menstrual cycle, generally with an oral contraceptive.

New data from Europe has prompted the European Medicines Agency (EMA) this year to recommend limits on how cyproterone acetate is used due to a possible increased risk of a brain tumour know as a meningioma. The EMA states “that medicines with daily doses of 10 mg or more of cyproterone should only be used for androgen-dependent conditions such as hirsutism (excessive hair growth), alopecia (hair loss), acne and seborrhoea (excessively oily skin) once other treatment options, including treatment with lower doses, have failed. Once higher doses have started working, the dose should be gradually reduced to the lowest effective dose.

The risk for meningiomas increases with dose but is highest for doses above 25 mg or more daily and in patients (especially older patients) using the medication for many years. The risk however, appears to be cumulative with total cumulative doses above 3 grams total carrying a 6 fold increased risk and  total cumulative doses between 36-60 grams having an 11 fold increased risk and  total cumulative doses above 60 grams total having a 21 fold increased risk of meningioma.

What are meningiomas?

Meningiomas are the most common intracranial tumours. It has been estimated that about 6 cases are diagnosed per 100,000 people in the general population and the average age is in the mid 60s. Individuals in their 60s and 70s have a 20 fold increase risk of developing meningiomas in general compared to individuals in their teens and 20s. The tumors arise from a special covering of the brain and spinal cord. It is thought that sex hormones may have a role in how meningiomas develop. This is based on findings that 70% of meningiomas express progestogen receptors and 30% express estrogen receptors.

These tumors are usually benign, but when tumors occur in the brain even benign lesions can create issues because of the pressure they exert on other parts of the brain. Patients with meningiomas can exert a variety of symptoms including changes in vision, hearing loss or ringing in the ears (tinnitus), loss of smell, headaches that worsen with time, memory loss, seizures, or weakness in extremities.

Conclusion

I think the recommendations from the EMA will soon find their way around the world in other health bodies given these findings. Cyproterone acetate use in dermatology has a long history in many countries. It can be very effective for many women in treating AGA with some studies suggesting similar effectiveness to spironolactone and other studies suggestive greater effectiveness.

The issue with anti-androgen use in treating hair loss is that doses generally can not be reduced once they prove effective - at least not without causing hair loss. Substitution to other anti-androgen may be helpful for some and introduction of other hair loss therapies may also be helpful.

Dermatology texts and treating guidelines will likely update risks of meningioma in the years ahead.

Reference

Weill A et al. Exposition prolongée à de fortes doses d’acétate de cyprotérone et risque de méningiome chez la femme. Paris: ANSM. 2019 June