FSRH CEU Statement: Response to new study by Roland et al (2024). Use of progestogens and the risk of intracranial meningioma: national case-control study.

Posted 28 March 2024

Date: 28 Mar 2024

Type: FSRH Clinical Guidance and Clinical Statements

Meningioma is an uncommon and predominantly benign tumour. Incidence increases significantly with age, the median age at diagnosis being 66 years old. The incidence in patients over 40 is 18.69/100,000 and in patients aged 0-19 is 0.16/100,000. The main risk factors are advanced age and being female. (1)

New evidence

A paper published in the BMJ on the 27th March 2024 looked at the use of progestogens and the risk of intracranial meningioma requiring surgery. This national case-control study included 18,061 women who had intracranial surgery for meningioma (between 1st January 2009 and 31st  December 2018) and 90,305 controls without meningioma, matched for age and area of residency in France. The researchers looked at previous exposure to different types of progestogens in cases and controls. The average age of women in this study was 57.6 years (standard deviation 12.8 years). (2)

What do we know already?

Current FSRH guidelines advise that in general, women can stop using contraception at age 55. Women using depot medroxyprogesterone acetate (DMPA) should in general switch to another method at age 50 years. If a woman does not wish to stop using DMPA, consideration may be given to continuation, providing the benefits and risks have been assessed and the woman informed of the potential risks. (3)

Two statements have been published by the FSRH CEU regarding risk of meningioma in patients using hormonal contraception. In 2020, the MHRA advised that individuals who have had a meningioma should not use any product containing cyproterone acetate. This was due to data from a French cohort study indicating that high dose cyproterone acetate is associated with a significantly increased risk of meningioma. Individuals without meningioma wishing to use cyproterone acetate 2mg with ethinylestradiol for acne/hirsutism should be advised of the increased risk of meningioma, but that risks are likely to be low. (4)

In 2023, the FSRH CEU issued a statement about the risk of intracranial meningioma in users of nomegestrol acetate (NOMAC). In line with advice issued by MHRA, the FSRH advised that Zoely (Estradoil 1.5mg, Nomogestrel acetate 2.5mg) should not be used by individuals who have or have had meningioma. (5)

What does this study add?

The study suggests a link between the prolonged use of medroxyprogesterone acetate (150 mg) and risk of intracranial meningioma requiring surgery.  Out of a group of 18,061 women who had surgery for meningioma, nine women (0.05%) had been exposed to medroxyprogesterone acetate, compared to 11 women (0.01%) out of 90,305 in the control group (women without meningioma). Despite the data being suggestive of a link between the use of medroxyprogesterone acetate and meningioma (odds ratio [OR] 5.55, 95% confidence interval [CI] 2.27 to 13.56), it should be noted that the overall risk of this tumour remains relatively low. Furthermore, the cumulative dose of medroxyprogesterone acetate (mg) was higher in women with the tumour (median 3,609mg) compared to women without the tumour (median 1,575mg).

Consistently with previous findings, the study found an association between use of cyproterone acetate (OR 19.21, 95%CI 16.61 to 22.22) and nomegestrol acetate (OR 4.93, 95%CI 4.50 to 5.41) and an increased risk of meningioma requiring surgery (see table 1).

There was no evidence of association between the use of the levonorgestrel intrauterine devices and the increased risk of meningioma requiring surgery (see table 1). The commonly used progesterone only pill (desogestrel) was not investigated in this study.

How does this affect practice?

The FSRH CEU recommends no significant change to current practice currently but does suggest that this information is included in individual discussions with patients regarding risks and benefits of various contraceptive methods.

Conclusion

This case-control study shows a small increased risk of meningioma in women using certain progestogens. The average age of women in the study was 57.6 and the number of women exposed to medroxyprogesterone acetate was low. The FSRH CEU will continue to monitor the evidence regarding progestogen use and the risk of meningioma.

References

1.       Ogasawara C, Philbrick BD, Adamson DC. Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions. Biomedicines. 2021 Mar 21;9(3):319

2.       Roland N, Neumann A, Haszard L, Duranteau L, Froelich S, Zureik M, Weill A. Use of progestogens and the risk of intracranial meningioma: national case-control study. BMJ. 2024 Mar 27;384:e078078.

3.       FSRH Clinical Guideline: Progestogen-only Injectable (July 2023). Available online https://www.fsrh.org/standards-and-guidance/documents/cec-ceu-guidance-injectables-dec-2014/ 

4.       FSRH CEU Statement: New advice from the MHRA regarding cyproterone acetate: how does this affect prescribing of Co-cyprindiol/Dianette® for acne/hirsutism? (July 2020). Available online https://www.fsrh.org/documents/fsrh-ceu-statement--new-advice-from-the-mhra-regarding/ 

5.       FSRH CEU Statement: New manufacturer/MHRA advice regarding nomegestrol acetate – how does this affect prescribing of Zoely®? (April 2023). Available online https://www.fsrh.org/documents/fsrh-ceu-statement-nomac-meningioma-zoely-april-2023/ 

Table 1. Associations between various progestogens and risk of intracranial meningioma requiring surgery (case control design, 2009-18 Système National des Données de Santé Data)(Roland et al. 2024).

Type of progestogen

Cases

(n=18 061)

Controls

(n=90 305)

Odds ratio (95%Confidence Interval)
Used for contraception in the UK
Cyproterone acetate 891 (4.9) 256 (0.3) 19.21 (16.61 to 22.22)
Medroxyprogesterone acetate 9 (0.05) 11 (0.01) 5.55 (2.27 to 13.56)
Nomegestrol acetate 925 (5.1) 1121 (1.2) 4.93 (4.50 to 5.41)
Levonorgestrel 52 mg IUS* 566 (3.7) 3888 (5.1) 0.94 (0.86 to 1.04)
Levonorgestrel 13.5 mg IUS** 10 (0.2) 48 (0.2) 1.39 (0.70 to 2.77)
Used for other indications or not used in the UK
Medrogestone 42 (0.2) 63 (0.1) 3.49 (2.38 to 5.10)
Promegestone 83 (0.5) 225 (0.2) 2.39 (1.85 to 3.09)
Chlormadinone acetate 628 (3.5) 946 (1.0) 3.87 (3.48 to 4.30)
Progesterone (oral and intravaginal) 329 (1.8) 2149 (2.4) 0.88 (0.78 to 0.99)
Progesterone (percutaneous) 90 (0.5) 503 (0.6) 1.11 (0.89 to 1.40)
Dydrogesterone 156 (0.9) 990 (1.1) 0.96 (0.81 to 1.14)
Spironolactone 264 (1.5) 1473 (1.6) 0.95 (0.84 to 1.09)
Dienogest 3 (0.02) 11 (0.01) Not available***
Hydroxyprogesterone None None Not available

*Cases: 15,162, controls: 75,810

**Cases: 4,048; controls: 20,240

*** Odds ratios involving fewer than six people who were exposed in the cases group are not shown.