Certain progestogens linked to higher brain tumor risk in women, study suggests

By Dr. Chinta SidharthanReviewed by Susha Cheriyedath, M.Sc.Apr 3 2024

In a recent study published in the journal BMJ, a team of French researchers investigated the association between progestogen use and the risk of benign central nervous system tumors such as intracranial meningioma among women.

Study: Use of progestogens and the risk of intracranial meningioma: national case-control study. Image Credit: vitahima / Shutterstock

Background

Meningiomas occur every 9.5 per hundred-thousand-person years in the United States and account for 40% of the central nervous system-associated primary tumors. Although histologically benign and slow-growing, they can cause problems by exerting pressure on adjacent tissue in the brain, requiring surgical intervention to decompress the area. Age is one of the factors that significantly increases the risk of meningiomas, especially after 65 years.

Female sex, neurofibromatosis type 2, and ionizing radiation exposure to the intracranial region are other known risk factors for meningiomas, apart from age. Recent research has also indicated that the long-term use of three progestogens — chlormadinone acetate, nomegestrol acetate, and cyproterone acetate — at high doses can also increase the risk of intracranial meningiomas. Studies have also found meningioma volumes to increase during pregnancy and subsequently decrease in the postpartum phase.

Furthermore, the significant presence of progesterone receptors in meningiomas indicates a biological link between meningioma risk and female sexual hormones, highlighting the need for robust studies on progestogen use and meningioma risk.

About the study

In the present study, the researchers investigated the intracranial meningioma risk associated with numerous progestogens and various administration routes of these progestogens. The progestogen exposures included intravaginal, percutaneous, and oral progesterone, dydrogesterone by itself or with estrogen, hydroxyprogesterone, promegestone, medrogestone, the injectable contraceptive medroxyprogesterone acetate, dienogest by itself or with estrogen, and intrauterine systems of levonorgestrel.

The study also aimed to characterize factors such as age, location of meningioma, and tumor grade for the women included in the case group and determine how many of the meningiomas that were surgically treated could be attributed to the use of one of the progestogens. The data for this case-control study was obtained from France's national health data system.

The study included women of all ages who lived in France and had undergone surgical treatment for intracranial meningioma between 2009 and 2018. The control group included women who matched in the area of residence and birth year with the case group participants. The World Health Organization's anatomical, therapeutic, and chemical classification was used to define progestogen exposure.

The various administration routes assessed in the study were percutaneous, oral, intramuscular, intravaginal, and intrauterine. For progestogens administered via the intravaginal, oral, intramuscular, or percutaneous routes, one dispensation in the year preceding the index date was considered as an exposure, whereas for intrauterine progestogens and levonorgestrel intrauterine systems, an exposure was one dispensation in three or five years preceding the index date, respectively.

The researchers analyzed three modes of exposure to progestogens. The first was exposure to the progestogen of concern. The second was exposure to a high dose of one of the three progestogens already associated with increased meningioma risk (nomegestrol acetate, chlormadinone acetate, and cyproterone acetate) in the three years leading up to the index date. The third mode was the absence of exposure to any of the progestogens. The analysis also included a wide range of medical and sociodemographic factors as covariates.

Results

The results showed that long-term use of promegestone, medrogestone, and the injectable contraceptive medroxyprogesterone acetate was associated with a higher risk of intracranial meningioma. However, short-term use spanning less than a year of any of these progestogens was not found to increase the meningioma risk.

Furthermore, the use of intravaginal, percutaneous, and oral progesterone, dydrogesterone by itself or with estrogen, short—or long-term use of spironolactone, or levonorgestrel intrauterine systems was not associated with any increase in intracranial meningioma risk.

The use of promegestone, medrogestone, and medroxyprogesterone acetate was not found to be linked to the incidence of malignant meningiomas, and the number of cases of intracranial meningiomas that needed surgical treatment that was associated with promegestone, medrogestone, and medroxyprogesterone acetate was significantly fewer than those associated with nomegestrol acetate, chlormadinone acetate, and cyproterone acetate.

Conclusions

To conclude, the findings reported that long-term use of three progestogens — promegestone, medrogestone, and the injectable contraceptive medroxyprogesterone acetate — was found to increase the intracranial meningioma risk in women. However, these progestogens did not increase the risk of malignant meningiomas, and the use of these progestogens for less than a year was not found to increase the intracranial meningioma risk. Additionally, other progestogens such as spironolactone, dydrogesterone, progesterone, or hormonal intrauterine systems were not linked to increased risk of meningiomas.