Certain progestins have been associated with an increased risk of meningioma. The FAMHP reminds healthcare professionals of measures to minimise the risk of meningioma associated with these progestins.
A meningioma is an intracranial tumour that is in most cases benign. As it grows, it can compress neurological structures, causing symptoms such as headaches, visual impairments and epileptic seizures, sometimes requiring surgical intervention. Several factors have been implicated in meningioma formation, including sex hormones.
Meningioma and hormone treatments: what do the latest studies tell us?
Since 2019, successive epidemiological studies carried out by EPI-PHARE have demonstrated a risk of meningioma associated with various progestins: cyproterone, nomegestrol, chlormadinone, medrogestone, promegestone and medroxyprogesterone.
These studies have shown that the risk of meningioma associated with these progestins increases with dose, duration of treatment and patient age.
More recently, EPI-PHARE published results on the risk of meningioma in women exposed to a progestin when using oral contraception. The potential risk of meningioma had not previously been assessed with the specific use of these oral contraceptives. The study shows no increased risk of meningioma for women using contraception containing levonorgestrel alone or combined with ethinylestradiol.
On the other hand, it brings to light a very slight increase in risk for contraceptives based on desogestrel 75 µg alone during prolonged use in women over 45.
PRAC risk minimisation measures
For each active substance (or combination of active substance ), the European pharmacovigilance committee (PRAC) of the European Medicines Agency (EMA) continuously evaluates available data, particularly post-marketing data, including retrospective cohort studies conducted by EPI-PHARE.
To date, the PRAC has taken risk minimisation measures for the following progestins: cyproterone, nomegestrol, chlormadinone, medroxyprogesterone and dydrogesterone (in combination with estradiol).
To minimise the risk of meningioma, the PRAC recommends that:
• medicines containing these progestins should be contraindicated in patients presenting with a meningioma or a history of meningioma;
• patients are monitored for follow-up and detection of meningiomas in accordance with clinical practice;
• if a meningioma is diagnosed, treatment should be permanently discontinued.
These recommendations vary according to the dose and nature of the progestin. For each speciality, please refer to the summary of product characteristics (SmPC) and the product information leaflet, which have been adapted accordingly.
The SmPCs mention in particular that high cumulative doses can be reached with prolonged use (several years) or over a shorter period with high daily doses.
They also specify that the risk of meningioma may decrease after discontinuation of treatment.
For certain medicines, Direct Healthcare Professional Communications (DHPCs) have also been sent out.
In summary
The confirmed risk of meningioma associated with certain progestins requires regular reassessment of their suitability, in order to limit exposure. If a meningioma is discovered, discontinuation of the medicine is recommended in order to verify the - highly probable – hypothesis of stabilisation or even reduction of tumour volume after discontinuation of treatment.
Recommendations from Belgian scientific societies on the management of meningiomas and sex hormone therapy have recently been published.
The risk of meningioma is not yet known with certain progestins, but it cannot be ruled out, including for those used in low doses over the long term as oral contraceptives.
For progesterone, on the other hand, after review of the available data, including case-control studies, no causal association with meningioma risk has yet been established by the PRAC.
Reporting of adverse reactions
Healthcare professionals and patients are encouraged to report suspected adverse reactions on www.notifieruneffetindesirable.be.
Specialties concerned
The following specialties are listed in the FAMHP medicines database:
• cyproterone acetate
• nomegestrol acetate
• chlormadinone acetate
• medrogestone: not marketed in Belgium
• promegestone: not marketed in Belgium
• medroxyprogesterone acetate
• levonorgestrel
• desogestrel 75 µg
• dydrogesterone + estradiol
• progesterone
Contact
ADR@fagg-afmps.be