Prolonged use of some hormone therapies may increase risk for brain tumors
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Key takeaways:
- Prolonged use of medroxyprogesterone acetate injection associated with a 5.6-fold increased risk.
- Use of progestogens for less than 1 year appeared to have no increased risk.
The prolonged use of certain progestogen hormone drugs — such as medrogestone, medroxyprogesterone acetate and promegestone — increased the risk for developing intracranial meningioma, according to data published in The BMJ.
This study, which researchers believe is the first of its kind to determine potential risk of progestogens use, are widely used by women across the globe for gynecologic conditions, such as endometriosis and polycystic ovary syndrome, as well as in menopausal hormone therapy and contraceptives.
“Although the risk [for] meningioma was already known for three progestogens, this study is the first to assess the risk associated with progestogens that are much more widely used for multiple indications, such as contraception,” Noémie Roland, MD, PhD, of EPI-PHARE Scientific Interest Group, Saint-Denis, France, and researchers wrote. “This population-based study shows an association between the prolonged use of medrogestone (5 mg), medroxyprogesterone acetate injection (150 mg), and promegestone (0.125, 0.25, 0.5 mg), and a risk [for] intracranial meningioma requiring surgery.”
Background, methods
Meningiomas account for approximately 40% of primary tumors of the central nervous system, according to study background. With a link between female sexual hormones and intracranial meningioma being biologically plausible, researchers conducted an observational population-based study to assess potential risk for such meningiomas with the use of selected progestogens.
The study included 108,366 women (mean age, 57.6 years), 18,061 of whom lived in France and had intracranial surgery for meningioma between Jan. 1, 2009, and Dec. 31, 2018, comprised the case group. Cases were matched to five controls (n = 90,305) based on year of birth and area of residence.
The study included selected progestogens, specifically progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel.
For each progestogen, researchers defined use as at least one dispensation within the year before the index date (within 3 years for 13.5 mg levonorgestrel intrauterine systems and 5 years for 52 mg).
Results, next steps
Analyses showed excess meningioma risk in exposed cases compared with exposed controls with use of medrogestone [42 (0.2%) vs. 79 (0.1%); OR = 3.49 (95% CI, 2.38-5.1)], medroxyprogesterone acetate [9 (0.05%) vs. 11 (0.01%); OR = 5.55 (95% CI, 2.27-13.56)] and promegestone [83 (0.5%) vs. 225 (0.2 %); OR = 2.39 (95% CI, 1.85-3.09)].
Excess risk appeared to be driven by prolonged use, typically of at least 1 year. Data showed no additional risk for developing intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems.
Furthermore, researchers could not draw any conclusions concerning dienogest or hydroxyprogesterone due to the small number of individuals receiving these drugs.
Researchers observed highly increased risk for meningioma in exposed cases compared with exposed controls for cyproterone acetate [891 (4.9%) vs. 256 (0.3%); OR = 19.21 (95% CI, 16.61-22.22)], nomegestrol acetate [925 (5.1%) vs. 1,121 (1.2%); OR = 4.93 (95% CI, 4.5-5.41)], and chlormadinone acetate [628 (3.5%) vs. 946 (1.%); OR = 3.87 (95% CI, 3.48-4.3)], which researchers used as positive controls for use.
Researchers determined that the prolonged use of medrogestone, medroxyprogesterone acetate and promegestone exhibited increased risk for intracranial meningioma, with the use of injectable medroxyprogesterone acetate being particularly important due to its use in contraceptives.
Study investigators reported a 4.08-fold increased risk for intracranial meningioma requiring surgery associated with prolonged use of at least 1 year of medrogestone.
Prolonged use of medroxyprogesterone acetate injection appeared associated with a 5.6-fold increased risk, and prolonged use of promegestone appeared linked to a 2.7-fold increased risk. Researchers observed no such risk for use of less than 1 year.
Due to the study’s observational nature, researchers stated no cause and effect can be determined, but that further studies are needed due to the high use of medroxyprogesterone among women globally.
“Worldwide, in 2019, 3.9% of women of childbearing age were using injectable contraception (medroxyprogesterone), that is, 74 million users, but figures vary widely between world regions (from 1.8% in high-income countries to 8.7% in low-income countries),” researchers wrote. “Further studies are also needed to assess the meningioma risk with the use of medroxyprogesterone acetate, which, in this study, was considered at a dose of 150 mg and corresponded to a second-line injectable contraceptive that is rarely used in France.
“Studies from countries with a broader use of this product, which, furthermore, is often administered to vulnerable populations, are urgently needed to gain a better understanding of its dose-response association,” they added.
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