A population study in Denmark that was recently published in JAMA confirmed an association between progestogens in hormonal contraceptives and meningiomas, the most common brain tumour in adults – but the experts say the absolute risk for most progestogens is very low, reports Healthed.
The case‑control study drew on Denmark’s linked national health registers, allowing researchers to analyse prescription histories, cancer diagnoses and demographic data.
From a background population of more than 3m women aged 15-59, the authors identified 2 606 meningioma cases. After excluding those with previous use of selected hormones (including all women with a prior HRT prescription), prior cancer, or recent immigration, 1 473 cases and 14 717 matched controls were included.
The study grouped progestogens by route of administration and dose, including combined oral contraceptives, progestogen‑only pills, high‑ and low‑dose levonorgestrel IUDs and injectable medroxyprogesterone.
Several progestogen-containing contraceptives were associated with a small increased risk of meningioma, but the number needed to harm varied greatly depending on the specific progestogen used and the age group.
“Medroxyprogesterone showed the highest risk with relatively low numbers needed to harm, whereas all combined oral contraceptives, oral progestogen-only contraceptives, and IUDs had relatively high numbers needed to harm, especially among the youngest women,” the authors noted.
The highest risk was seen in the oldest women, as well as those who had exposure within the past year.
Prescribing change warranted?
Dr Alex Polyakov, Clinical Associate Professor from the University of Melbourne’s Faculty of Medicine and Medical Director of Genea Melbourne, said that for most types of progestogens, the increase in risk is very small.
“For combined pills and Intra-Uterine Devices (IUDs), the absolute excess risk is negligible and shouldn’t change clinical practice,” he added.
However, the study found risk was highest with medroxyprogesterone injections (odds ratio of 4.55 (95% CI 2.19-9.45)).
“I’d caution against reading this paper as a mandate to start switching women off their contraception. It gives us no validated high-risk profile, and honestly, the more useful question isn’t ‘which patient?’ but ‘which drug?’” Polyakov said
“The answer to that is unambiguous: depot medroxyprogesterone. An odds ratio above four, numbers needed to harm an order of magnitude worse than anything oral, and the French and US data, have been saying the same thing for a while now. Where there’s a sensible alternative, that’s the one I’d think hard about.
“Everything else is a matter of weighing. A woman with a known or previously treated meningioma is the obvious case to steer away from these agents – we know withdrawal can shrink these tumours. Age matters too, because the absolute risk climbs in older women, as does long intended duration and a history of the high-dose progestogens we already worry about.”
Putting it in perspective
Polyakov said it was important to emphasise the risk is about current or recent use.
“The risk applies to women using these drugs now or recently, and it disappears within about five years of stopping. So, when your patient who took the pill in her 30s phones in a panic, you can tell her, truthfully, that she’s carrying essentially at no residual risk,” he said.
“There will be some panic as these headlines write themselves. Meet it with reassurance, not the prescription pad.
“For the combined pill and the levonorgestrel coil, the risk is real but tiny, and it sits against benefits we too easily forget to mention: no unwanted pregnancies, less ovarian and endometrial cancer, lighter and less painful periods. Put simply, the added meningioma risk is smaller than her chance of dying on the drive to your surgery.”
Pregnancy also increases the risk
Dr Gino Pecoraro, an Associate Professor of Obstetrics and Gynaecology at the University of Queensland and past President of the National Association of Specialist Obstetricians and Gynaecologists, agreed that it’s crucial to help patients maintain perspective.
“Meningioma occurs in roughly one in 10 000 people, with women having roughly double the rate that men do. It is well known that meningiomas grow during pregnancy and if extra progesterone is given, but decrease in size once the pregnancy is completed or progesterone withdrawn.
“It is important to point out that a pregnancy in the preceding year also increases the risk of meningioma and carries other potential risks.
“Pregnancy in Australia carries a maternal mortality rate of 6.6 per hundred thousand, while the Australian five-year survival rate after meningioma diagnosis is greater than 90%.”
Non-progestogen-containing contraceptive options including barrier methods and copper-containing IUDs may be considered for women who are concerned about the association between progestogens and meningioma, Pecoraro added.
Study details
Contraceptive progestogens and incident meningioma
Nicklas Hasselblad Lundstrøm, Mette Hjorslev Knudgaard, Michael Skaarup Pedersen et al.
Published in JAMA Network Open on 2 July 2026
Abstract
Importance
Meningioma is a known adverse reaction of high-dose progestogens, but evidence regarding the risk associated with progestogens used as contraception is limited.
Objective
To examine whether different progestogens used as hormonal contraception are associated with increased risk of meningiomas.
Design, Setting, and Participants
This nested case-control study conducted over a 25-year study period from 1 January 2000, to 31 December 2024, is a Danish nationwide population-based register study, which included 3m females aged 15 to 59. Meningioma cases were identified, and for each case, 10 controls were matched on age, birthplace, and marital status and randomly selected from the cohort if considered eligible on the day of the case’s meningioma diagnosis. Data were analysed from 10 July 2025 to 12 May 2026.
Exposure
Use of progestogens was identified in the registers by date of dispensing or procedural records and grouped by route of administration and active substance. Exposure time was determined by redeemed daily doses or product duration. If a female switched to a different product or became pregnant, her exposure time was changed to the new exposure. The females included were allocated to their most recent use, defined as the exposure closest to the matching date.
Main Outcomes and Measures
The main outcome was incident meningioma and was identified in the Danish National Cancer Register using validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses and International Classification of Diseases for Oncology, Third Edition codes.
Results
A total of 1 473 cases and 14 717 controls with a median age of 48 (IQR, 42-53 years) were included in the nested cohort. For combined oral contraceptives, the estimated odds ratios (ORs) for the association between use of progestogens and meningioma were 1.61 (95% CI, 1.00-2.59) with cyproterone, 1.66 (95% CI, 1.31-2.10) with desogestrel, 1.58 (95% CI, 1.05-2.37) with drospirenone, 1.44 (95% CI, 1.17-1.77) with gestodene, 1.40 (95% CI, 1.12-1.76) with levonorgestrel, 1.38 (95% CI, 0.77-2.47) with norethisterone, and 1.04 (95% CI, 0.70-1.54) with norgestimate. For oral progestogen-only contraceptives, the ORs were 1.73 (95% CI, 1.17-2.56) with desogestrel and 0.95 (95% CI, 0.57-1.57) with norethisterone. For injectable medroxyprogesterone, the OR was 4.55 (95% CI, 2.19-9.45). For intrauterine devices (IUDs) with high-dose levonorgestrel, the OR was 1.58 (95% CI, 1.28-1.94), and for IUDs with low-dose levonorgestrel, the OR was 1.14 (95% CI, 0.59-2.22). Exposure within the past year was associated with the highest risk.
Conclusions and Relevance
In this case-control study conducted using data from the entire Danish population, recent use of the contraceptive progestogens cyproterone, desogestrel, drospirenone, gestodene, levonorgestrel, injectable medroxyprogesterone, and high-dose IUD was associated with increased risk of meningioma. These findings are considered relevant information for the treated women and the prescribing physicians.
JAMA Network Open article – Contraceptive Progestogens and Incident Meningioma (Open access)
Healthed article – Progestogens in contraceptives linked to brain tumour risk (Open access)
See more from MedicalBrief archives:
Long-term contraceptive pill use tied to tumour risk – French study
High doses of hormone drug linked to meningioma risk – Meta-analysis
Prolonged use of some hormone drugs tied to tumour risk