Long-Term Use of Hormone Therapies May Increase Brain Tumor Risk in Women

Long-term use of hormone therapies, such as medrogestone, medroxyprogesterone acetate, and promegestone is associated with an increased risk for intracranial meningioma in women, according to study results published in BMJ.

Researchers conducted a national observational, population-based, case-control study to evaluate the risk for intracranial meningioma associated with the use of certain progestogens (progesterone, hydroxyprogesterone, dydrogesterone, medrogestone,

medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel).

Women of all ages residing in France who underwent surgery for intracranial meningioma between January 2009 and December 2018 were eligible for inclusion and matched 1:5 for birth year and area of residence with patients in a control group. The researchers sourced data from the Système National des Données de Santé. Odds ratios (ORs) for each progestogen meningioma association were calculated using conditional logistic regression.

A total of 108,366 women (mean age, 57.6) were included in the final analysis, with 18,061 women comprising the case group and 90,305 women comprising the control group. Cases steadily increased from 1329 in 2009 to 2069 in 2018. A majority of meningiomas were benign (92.3%), and most of those requiring surgery were primarily located at the base of the skull (55.6%).

The usage of hormone therapies among women in the case group were as follows:

• oral or intravaginal progesterone (1.8%),
• percutaneous progesterone (0.5%),
• dydrogesterone (0.9%),
• medrogestone (0.2%),
• medroxyprogesterone acetate (<0.1%),
• promegestone (0.5%),
• dienogest (<0.1%), and
• spironolactone (1.5%).

No significant association with an increased risk for intracranial meningioma surgery was noted with exposure to oral or intravaginal progesterone, percutaneous progesterone, dydrogesterone, or spironolactone.

An excess risk for meningioma was associated with the use of medrogestone (OR, 3.49; 95% CI, 2.38-5.10), medroxyprogesterone acetate (OR, 5.55; 95% CI, 2.27-13.56), and promegestone (OR, 2.39; 95% CI, 1.85-3.09). This excess risk was driven by prolonged use of any given medication (≥1 year).

A highly increased risk for meningioma was observed in women with positive control exposure to neurofibromatosis type 2 (OR, 18.93; 95% CI, 10.50-34.11), as well as those exposed to cyproterone acetate (OR, 19.21; 95% CI, 16.61-22.22), nomegestrol acetate (OR, 4.93; 95% CI, 4.50-5.41), and chlormadinone acetate (OR, 3.87; 95% CI, 3.48-4.30), which were used as positive controls for use.

Study limitations included the limited number of years of lookback period for the oldest meningioma cases, limited number of progestogens studied, missing data, and potential underestimation of the prevalence of meningiomas attributable to the use of progestogens.

“Future studies should further clarify the association between the duration of use and risk for the progestogens studied, and extend the discussion of meningioma risk to dienogest and hydroxyprogesterone,” the researchers concluded.