Research carried out by the Cleveland Clinic in the United States found that although rare, there was a higher meningioma risk in women who used the Depo-Provera contraceptive for four or more years, or who started having it after the age of 31, than those who used other contraception.
Medpage Today reports that while cases were rare, the brain tumour occurred more frequently among women who used depot medroxyprogesterone acetate (Depo-Provera) versus other forms of contraception, the team said after their analysis of more than 10m women.
Compared with women who did not use hormonal contraception, women who used depot medroxyprogesterone acetate had a relative risk (RR) of 2.43 (95% CI 1.77-3.33) for meningioma, according to Varun Kshettry, MD, of the Cleveland Clinic, and co-authors.
Meningioma risk was limited to women with more than four years of exposure to depot medroxyprogesterone acetate, or who started using it after 31, Kshettry and colleagues reported in JAMA Neurology.
Oral medroxyprogesterone acetate also was associated with meningioma compared with controls, but the risk was smaller (RR 1.18, 95% CI 1.10-1.27). The number needed to harm was 1 152 women for depot medroxyprogesterone acetate, and 3 020 women for oral medroxyprogesterone acetate.
No increased risk of meningioma diagnosis was found with any other contraceptive, including combined oral contraceptives, intrauterine devices (IUDs), progestin-only pills, or subdermal implantable contraception.
Meningiomas are the most common primary brain tumour, arising from the membranes surrounding the brain and spinal cord and usually benign.
A 2024 study in France had suggested an increased risk of meningioma associated with injectable medroxyprogesterone acetate.
“However, that study was limited due to overall low usage of depot medroxyprogesterone in that country,” Kshettry told MedPage Today. “In the United States, depot medroxyprogesterone is more commonly used, so we sought to investigate the association of this progestin with meningioma formation in the American population.”
The findings may be helpful in “the risk-benefit discussion, particularly for patients who might be at increased risk of meningioma due to other risk factors like neurofibromatosis type 2, prior cranial radiation history, and family history of meningioma”, Kshettry added.
Meningioma is the only intracranial tumour with a clear predominance in women, with increasing incidence after puberty, observed Gilles Reuter, MD, PhD, of Centre Hospitalier Universitaire de Liège in Belgium, and Britta Wandschneider, MD, PhD, of UCL Queen Square Institute of Neurology in London.
“More than 60% of meningiomas express progesterone receptors. In known meningioma cases, tumour size increases in periods of higher oestradiol and progesterone serum levels, such as during years of childbearing potential, pregnancy, and peripartum,” Reuter and Wandschneider wrote in an accompanying editorial.
“Histopathologically, there is a higher proportion of progesterone receptor expression during these periods, underscoring a plausible biological relationship of sexual hormones and meningioma evolution,” they added.
Kshettry and co-authors studied 10 425 438 women in the US TriNetX database that included 68 healthcare organisations, analysing data about those who used medroxyprogesterone acetate and other progestins from December 2004 to December 2024.
The main outcome was meningioma diagnosis.
Only females were evaluated, and all ages were included to account for early contraception initiation. Those with prior meningiomas to the initiation of the treatment were excluded.
The analysis was based on women who used only one of the following: depot medroxyprogesterone acetate, oral medroxyprogesterone acetate, combined oral contraceptives, IUDs, progestin-only pills, or subdermal implantable contraceptives.
IUD use was assessed for three subgroups: copper IUD, 52 mg levonorgestrel-releasing IUD, and 13.5/19.5 mg levonorgestrel-releasing IUD. Women who did not use any of these progestins were included as controls.
A total of 88 667 women with a mean age of 26.2 years who used depot medroxyprogesterone acetate were matched with an equal number of controls. Groups were matched on age, race and ethnicity, neurofibromatosis, history of pregnancy or breast cancer, history of radiation exposure, and body mass index.
After propensity score matching, the incidence of meningioma diagnosis for the depot medroxyprogesterone acetate group was 7.39 per 100 000 patient-years; for the control group, it was 3.05. The attributable risk associated with depot medroxyprogesterone acetate was 0.00087, with an attributable risk percentage of 59%.
There was no significant increase in meningioma risk in any non-medroxyprogesterone acetate group after propensity score matching. Compared with controls, there was a statistically decreased RR of meningioma diagnosis in the combined oral contraceptive (RR 0.74), IUD (RR 0.87), and 52 mg levonorgestrel-releasing IUD (RR 0.79) groups.
The analysis relied on insurance codes to identify patients and included only some potential confounders of meningioma risk, Kshettry and co-authors acknowledged.
The findings are observational, they added, and more work is needed to shed light on the biological mechanism underlying progesterone exposure and meningioma growth.
Medpage Today article – Brain Tumour Risk Rises With Birth Control Shot (Open access)
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