Long-term progestin use increased the risk of developing meningioma
A case-control study by French scientists has shown that long-term use of medrogestone, medroxyprogesterone and promegestone, which are used as contraception and therapy for gynecologic diseases and breast neoplasms, increases the risk of intracranial meningioma. Meanwhile, intrauterine systems with levonorgestrel had no effect on this risk. The results of the study are published in The BMJ.
Tumors made from cells in the spider dura mater are called meningiomas. They are usually slow-growing benign tumors that can compress the substance of the brain and lead to neurological damage; therefore, they require surgical treatment. The incidence of meningiomas increases with age; other recognized risk factors for meningioma development include female sex, intracranial exposure to ionizing radiation, neurofibromatosis, and long-term use of high doses of three potent progestagens: cyproterone, chlormadinone, and nomegestrol.
The association between female sex hormones, particularly progesterone, and intracranial meningioma is biologically well established. Progesterone receptors are present in more than 60 percent of meningiomas, and it has been observed that the volume of these tumors increases during pregnancy and decreases after delivery. However, to date, no significant association has been found between exogenous female hormones and meningioma risk when hormonal contraceptives (either combined or progestogen-only pills) are used. In addition, data on hormone replacement therapy during menopause are also conflicting.
A research team led by Noémie Roland from the French National Agency for the Safety of Medicines and Health Products tried to assess the real risk of intracranial meningioma in connection with long-term progestins with different routes of administration. The list of drugs studied included progesterone, hydroxyprogesterone, didrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest and levonorgestrel.
A total of 108366 women were included in the study from 2009 to 2018, of which 18061 women in the main group were compared with 90305 women in the control group. Among them, data from 15162 women in the study cohort and 75810 women in the control group were used to analyze intrauterine systems and copper IUDs using 52 milligrams of levonorgestrel; the effects of IUDs with 13.5 milligrams of levonorgestrel were also investigated.
Researchers found no statistically significant association between taking progesterone (in any form) and didrogesterone and the risk of surgery for intracranial meningioma. However, an increased risk of meningioma development was associated with the use of medrogestone (odds ratio 3.49), medroxyprogesterone acetate (OR 5.55), and promegestone (OR 2.39). The analysis showed that, on average, women had been taking these drugs for more than three years.
The excess risk of meningioma development was higher with long-term medrogestone, medroxyprogesterone acetate, and promegeston than with short- and long-term exposure combined. Meanwhile, doctors found no tumor malignancy among patients who received medrogestone, medroxyprogesterone acetate, or promegeston. Researchers also found no increased risk of meningioma development when using hormonal intrauterine systems with levonorgestrel.
According to the scientists, further studies are needed to assess the risk of meningioma development when using different hormonal drugs at different dosages. They expect to detect a dose-response relationship to identify the safest doses of the drugs.