Certain hormone drugs linked to increased brain tumour risk

Prolonged use of certain progestogen hormone drugs is associated with an increased risk of developing a type of brain tumour known as an intracranial meningioma, according to a study published in The BMJ by French researchers.

Progestogens are similar to the natural hormone progesterone, and are widely used for gynaecological conditions such as endometriosis and polycystic ovary syndrome, as well as in menopausal hormone therapy and contraceptives. Meningiomas, meanwhile, are rare, mostly non-cancerous tumours in the layers of tissue (meninges) that cover the brain and spinal cord. Factors such as older age, female sex and exposure to three high-dose progestogens (nomegestrol, chlormadinone and cyproterone acetate) are already known to increase the risk of meningioma — but there are many other progestogens for which the risk of meningioma associated with their use has not been estimated individually.

To address this knowledge gap, researchers set out to evaluate the real-life risk of intracranial meningioma requiring surgery in women associated with use of several progestogens with different routes of administration. They used data from the French National Health Data System (SNDS) for 18,061 women (average age 58) who underwent intracranial meningioma surgery from 2009–18, matching each case to five control women without intracranial meningioma (total 90,305) by age and area of residence.

The progestogens examined were progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest and levonorgestrel intrauterine systems. For each progestogen, use was defined as at least one prescription in the year before hospital admission or within 3–5 years for levonorgestrel intrauterine systems. Use of at least one of the three high-dose progestogens known to increase the risk of meningioma in the three years before hospital admission was also recorded to minimise bias.

After taking account of other potentially influential factors, prolonged use (a year or more) of medrogestone was associated with a 4.1-fold increased risk of intracranial meningioma requiring surgery; prolonged use of medroxyprogesterone acetate injection was associated with a 5.6-fold increased risk; and prolonged use of promegestone was linked to a 2.7-fold increased risk. There appeared to be no such risk for less than one year of use of these progestogens.

As expected, there was also an excess risk of meningioma for women exposed to chlormadinone acetate, nomegestrol acetate and cyproterone acetate, all of which are known to increase the risk of meningioma. There was no excess risk found for progesterone, dydrogesterone or hormonal intrauterine systems — regardless of the dose of levonorgestrel they contained — while no conclusions could be drawn about dienogest or hydroxyprogesterone, as the number of exposed individuals was too small.

The researchers acknowledged that their study was observational, and so can’t establish cause and effect; that the SNDS database lacked information on all the clinical details and medical indications for which progestogens are prescribed; and that they were not able to account for genetic predisposition and exposure to high dose radiation. Furthermore, as noted by expert commentator Professor Paul Pharoah from Cedars-Sinai Medical Center, “a fivefold increase in a rare disease is still a rare disease”, and so a small increase in risk should be considered in relation to the benefits provided by the medication. However, given that medroxyprogesterone acetate is estimated to be used for birth control by 74 million women worldwide, the researchers believe the number of attributable meningiomas may be potentially high, and that further studies are urgently needed to gain a better understanding of this risk.

Image credit: iStock.com/Nemes Laszlo