Prolonged use of certain progestogen hormone drugs, including a common injectable contraception, is associated with an increased risk of developing intracranial meningioma tumors. Out of 108,366 women, 18,061 with a mean age of 57.6 had intracranial surgery for meningioma during the selected period and were used as the case group. Each case was matched to five controls (90,305 total) with the same birth year and area of residence. The researchers examined various administration routes of progestogen exposure, including intravaginal, percutaneous, intramuscular, and oral progesterone, dydrogesterone with or without estrogen, hydroxyprogesterone, promegestone, medrogestone, the injectable contraceptive medroxyprogesterone acetate, dienogest with or without estrogen, and intrauterine systems of levonorgestrel. The first mode was exposure to the progestogen of concern. The second mode was an exposure to high doses of at least one of the three progestogens already known to increase the risk of meningiomas, such as chlormadinone acetate, nomegestrol acetate, and cyproterone acetate. The third mode was the absence of exposure to any progestogen (used as the reference for the analyses). The study found long-term use of promegestone, medrogestone, and the injectable contraceptive medroxyprogesterone acetate increased the risk of developing an intracranial meningioma. However, researchers found no increased risk of meningioma for progestogens used for less than a year, progesterone, dydrogesterone commonly used for miscarriages, and levonorgestrel intrauterine systems such as Skyla and Mirena that slowly release the hormone into the uterus. Even though most are not cancerous, meningiomas can cause potentially debilitating symptoms, such as confusion, seizures, personality changes, hearing loss or ringing in the ears, compression of adjacent brain tissue, neurological deficits, and muscle weakness. Because of this, surgery is usually the first line of treatment. Although meningiomas are rare before the age of 35, there are recognized risk factors, including being female, intracranial exposure to ionizing radiation, neurofibromatosis type 22, and prolonged exposure to high doses of the three recognized progestogens known to cause meningiomas: cyproterone acetate, chlormadinone acetate, and nomegestrol acetate. “The most likely explanation is that the exposure [to progestogens] accelerates growth in very small meningiomas that would never present clinically to tumours that required surgery. This is plausible as many
Women are diagnosed with meningioma which are asymptomatic when scanned for other symptoms, and most meningiomas have progesterone receptors and can be driven by progesterone,” he said. Dr. Evans also said this would explain the increased incidence of meningiomas in women diagnosed with tumors in adulthood despite boys being at higher risk of developing a meningioma than girls. NF2-related schwannomatosis is a genetic disorder that results in the growth of benign tumors along the nerves and in the skull. Cyproterone acetate is a steroid used in anti-androgen therapy to lower levels of testosterone in the body. It is also used in combination with ethinyl estradiol to treat women with severe acne and symptoms of androgenization. Depo-Provera is the fourth most prevalent contraceptive in the world, with an estimated 74 million users. In the
United States alone, there were more than 2 million prescriptions for the injectable contraceptive in 2020, and more than one in five sexually active
American women reported having used the contraception. The authors of the BMJ paper suggest that the number of meningiomas attributable to the progestogen found in Depo-Provera may be “potentially high” in countries with a large number of people using the contraceptive. Additionally, medroxyprogesterone (non-acetate) is used orally at lower doses in some countries, “notably the US,” for which no data currently exists on the risks of developing meningioma.