Reduce Meningioma Risk: Effective Measures

Between 2019 adn 2023, 95 % drop in treatment initiations from 18,000 per month to approximately 1,000.Pla2na / iStock / Getty images Plus / via Getty Images

Résumé

The Gis epi-Phare scientific interest group publishes a study evaluating the impact of the risk reduction measures of meningioma in patients exposed to chlormadinone (Luteran) acetate or nomestrol acetate (Lutenyl).

Since 2019, the number of prescriptions of these progestins has decreased by 97 %, due to the treatment stops and a reduction in initiations. The number of patients was less than 10,000 in 2023.

While brain mRI exams in exposed population have increased since 2021, the number of intracranial meningomes surgery attributable to treatment wiht chlormadinone or nomestrol has largely decreased, divided by 10 in 5 years.

These results show the positive effect of the measures implemented in France from 2020. However, the authors raise points of vigilance, in particular in the event of postponements to other progestins, including deogestrel or medrogestone, for which a lower risk of meningioma is identified.

URecent pharmacoepidemiological study of the scientific interest group GIS EPI-Phare shows the positive impact of the reduction measures implemented in France as 2019, to reduce the risk of meningioma in patients treated by chlormadinone (5 mg or 10 mg) or Nomestrol (3.75 mg or 5 mg).

The results highlight[[1, 2]:

• a drastic decrease in the use of acetates chlormadinone and nomégestrol (respectively Luteran and Lentenyl) since 2020
• A significant reduction in the number of meningiomas operated in the population of women exposed to these two progestins.

much fewer women on chlormadinone or nomestrol

The analysis of the GIS EPI-Phare is based on data from the National Health Data System (SNDS) over the period from 2010 to 2023.

After a slight and progressive decrease between 2010 and 2018,there is a collapse of the prescriptions of the progestogen Chlormadinone and Nomestrol from 2019 (cf. Illustration 1), year in which the first alerts relating to the risk of meningioma were issued (cf. Our article of February 12, 2019).

Between 2019 and 2023:

• The monthly use was reduced by 97 %, from more than 262,000 users in 2019 to 8,800 in 2023;
• Treatment initiations fell 95 %, from almost 18,000 per month in 2019 to around 1,000 per month in 2023.

This brutal fall is observed in all age groups.

Illustration 1 – Monthly number of users of Cyproterone, Chlormadinone Acetate and Nomestrol between 2010 and 2023 (According to figure A of[[2])

Note that in 2025, there are no more chlormadinone specialties, alone, marketed in France and only only two specialties of nomestrol, alone, remain available in pharmacies (LUTENYL 5 mg and NOMEGESTROL VIATRIS 5 mg).

Less meningioma surgeries in an increased context

The Epi-phare study shows above all a massive drop in the number of intracranial meningomes surgery attributable to the acetates of chlormaudinone and nomestrol:

• 90 % drop or a number of surgeries divided by 10 in 5 years (2018-2023): 152 women in 2018 against 15 in 2023.

This drop is all the more remarkable as the screening of a meningiom in the exposed population has developed, in accordance with the monitoring recommendations in force for the exposed population and initiated in 2020 (cf.nos articles of June 18, 2020, January 13, 2021 et of July 13, 2021). In 2023, 22 % of women exposed more than 1 year to progestins carried out a brain surveillance MRI, against only 5 % in 2019. Imaging examinations (MRI) have increased by:

• 15 % in women treated over 1 year old, compared to the period prior to 2021;
• 35 % in women treated over 5 years.

As a reminder, the ANSM recommends carrying out a brain MRI for anyone after one year of treatment when it requires being prosecuted.

According to the authors, “About 150 interventions of intracranial neurosurgery are thus avoided each year” thanks to these monitoring measures and an earlier diagnosis (cf. Illustration 2).

Illustration 2 – Number of meningiomas operated annually for women in France according to the exhibition in the previous year to the acetate of ChlormaDinone, Nomestrol and Cyproterone (2010-2023) (According to Figure B of[[2])

Postponement, cumulation, surveillance: the points of vigilance raised by the authors

For the authors, the decrease in meningioma surgery attributable to chlormadinone acetate and/or nomestrol is explained by 4 factors:

• the Decrease in prescriptionsand thus the use of these progestins;
• increased Treatment stops ;
• the earlier detection meningiomas before the symptomatic stage;
• and the dissemination of recommendations Neurosurgeons to favor surgical abstention in the event of exposure to macrodotic progestins, coupled with clinical-radiological monitoring.

If the assessment of risk reduction measures appears globally positive,the authors of the EPI-Phare report underline Vigilance points and elements to deepen:

• Risk related to postponement towards other progestins at risk of known meningioma subsequently (medogestone, Déogestrel – cf. Our article of July 2, 2024) or at risk not studied to date (diénogest). Among the 210,976 women who stopped their treatment with acetate from Chlormadinone or Nomestrol after November 2020 and in the 38 months which followed, 39 % of them took another progestin, versus 28 %of those who had stopped their treatment before November 2020. The main medicines identified in postponement are deogestrel (16 %),medrogestone (4 %),Diénogest and the progesterone (cf. Illustration 3) ;
• taken into account of the cumulative dose During life and its consequences for all progestins (in patients to which progestins have been prescribed successively);
• a surveillance still shy: the non-realization of a brain MRI is more critically important in women more than 50 ans Compared to women under the age of 30, even though age is a determining factor of meningioma.

Illustration 3 – Drugs used to replace chlormadinone and nomestrol [[2]

Navigating the Shifting Landscape of Progestin Prescriptions: Beyond Chlormadinone and Nomestrol

The critically important decline in surgeries related to chlormadinone and nomestrol, a consequence of reduced prescriptions and increased patient awareness, presents a complex possibility. While the immediate risk appears mitigated, vigilance is crucial in understanding the long-term implications of these changes. The Epi-Phare study highlights the potential for unintended consequences, particularly concerning the choice of alternative progestins and the importance of long-term monitoring.

The data underscores a clear shift in prescribing patterns. When considering the choice of alternative progestins, the study suggests a need to understand the nuances of each progestin’s risk profile. While some, like desogestrel and medrogestone, are considered to have a lower associated risk of meningioma compared to chlormadinone and nomestrol, this does not equate to zero risk. The authors’ concerns indicate that the overall cumulative exposure to progestins throughout a woman’s life is a critical factor. This suggests that even progestins with lower individual risk profiles might contribute to a higher overall risk if used over extended periods or in combination with other progestins.

Furthermore, the study’s findings reveal that the crucial aspect of brain surveillance with MRI is not consistently implemented. The study shows lower rates of MRI scans amongst those aged 50 and older. This is concerning given that advanced age is an important risk factor for meningioma advancement. This indicates a need for targeted dialog and more consistent adherence to screening recommendations. The benefits of early detection are well documented, and ensuring optimal screening requires active engagement from healthcare providers and patients alike.This requires heightened awareness and proactive steps from both patients and doctors about how to handle the use of progestins.

The shift in prescribing practices presents multiple challenges and questions to be addressed:

• Long-term Safety Data: There is still a need for long-term safety data on the alternative progestins being used, including updated risk assessments for less-studied drugs, like dienogest.
• individualized Risk Assessment: Patient-specific risk factors should play a bigger role in assessing the optimal progestin choice. This should include factors like age, detailed medication history, and family history.
• Enhanced Patient Education and Communication: Patients should be better informed about the specific risks associated with all progestins and the importance of adhering to monitoring guidelines
• Proactive Monitoring: It may be necesary to increase the proactive measures of brain MRI in higher risk groups.

while the measures implemented in France have shown a success in reducing meningioma surgeries associated with chlormadinone and nomestrol, the long-term implications of these changes require continuing vigilance. A proactive approach that focuses on assessing the thorough risk profile of each patient and incorporating personalized monitoring plans, educating patients, and monitoring the cumulative effect of progestin usage is essential. This requires continued research, increased collaboration between healthcare providers, and an unwavering commitment to patient safety.