Meningioma and progestogens

Meningiomas are, in most cases, low-grade intracranial tumours (1):

• a systematic review found that
  • vast majority of meningiomas express progesterone receptors in almost three-quarters of cases
  • the proportion of cases in which progesterone receptors are present is greater in some situations:
    • 1. female gender;
    • 2. the period of genital activity in women;
    • 3. during pregnancy or postpartum;
    • 4. under hormonal treatment
  • presence of progesterone receptors is associated with significantly more favorable prognostic factors
    • grade 1 meningiomas express progesterone receptors in more than three-quarters of cases
    • grade 3 meningiomas express progesterone receptors in less than 20%
    • recurrent meningiomas express significantly less progesterone receptors

A French study of 18,061 cases matched to 90,305 controls found prolonged use (≥one year) of medrogestone, medroxyprogesterone acetate, and promegestone increased the risk of intracranial meningioma. No excess risk found for progesterone, dydrogesterone, or levonorgestrel IUS:

• for injectable medroxyprogesterone acetate, the excess risk of meningioma was 9 exposed cases /18,061cases (0.05%) versus 11 exposed controls/90,305 controls (0.01%), odds ratio 5.55 (95% CI 2.27 to 13.56)
• prolonged use of medrogestone (5 mg, oral), medroxyprogesterone acetate (150 mg, injectable), and promegestone (0.125/0.5 mg, oral) was found to be associated with an excess risk of intracranial meningioma

A dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with the progestin cyproterone acetate (CPA) has been established (3):

• CPA-associated meningiomas seem to be mainly located in the anterior and middle skull base, are more likely to be multiple, may harbour P1K3CA mutations in up to one-third of cases, and are more common with a longer duration of treatment

Advice from the NHS Specialist Pharmacy Service states (4):

• medicines containing high doses, when used for contraception or non-oncological indications, are contraindicated in patients with meningioma or with a history of meningioma
• if a meningioma is diagnosed in a patient treated with high doses medroxyprogesterone acetate, treatment must be stopped
• if a meningioma is diagnosed in an oncological patient treated with high doses medroxyprogesterone acetate, the need to continue the treatment should be carefully reconsidered, on a case-by-case basis taking into account individual benefits and risks
• patients treated with high doses medroxyprogesterone acetate should be monitored for signs and symptoms of meningioma in accordance with clinical practice

Reference:

1. Agopiantz M, Carnot M, Denis C, Martin E, Gauchotte G. Hormone Receptor Expression in Meningiomas: A Systematic Review. Cancers (Basel). 2023 Feb 3;15(3):980.
2. Roland N, Neumann A, Hoisnard L, Duranteau L, Froelich S, Zureik M et al. Use of progestogens and the risk of intracranial meningioma: national case-control study BMJ 2024; 384 :e078078 doi:10.1136/bmj-2023-078078
3. Hage M et al. Estrogen and Progesterone Therapy and Meningiomas, Endocrinology, Volume 163, Issue 2, February 2022, bqab259, https://doi.org/10.1210/endocr/bqab259 (https://doi.org/10.1210/endocr/bqab259)
4. NHS Specialist Pharmacy Service (September 13th 2024). Medroxyprogesterone: increased risk of meningioma with high doses and after prolonged use.