Long-term use of contraceptive pills may double the risk of developing brain cancer, according to a new study.

Scientists say that taking hormonal contraception, particularly progesterone-only methods, for five years more than doubles the chance of developing glioma, a rare type of brain cancer which affects roughly five in 100,000 people.

Researchers used health data from Denmark to compare 317 women diagnosed with glioma and 2,126 who were free of the disease. The scientists evaluated females, aged 15 to 49 years old. According to the Danish study, women who had used an oral contraceptive or hormone-releasing intra-uterine device were 50 percent more likely to develop brain cancer than those who had not.

The difference in risk almost doubled for women who had used contraceptives for five years or more compared with women from the general population with no history of brain tumor, with a 90 percent increase. When taken for five years or more, progestin-only contraceptives increased the risk almost threefold, with a 2.4 times higher risk than the control group. In terms of type of brain cancer, the risk was greatest for glioblastoma multiforme, the most aggressive type of primary brain cancer.

Lead researcher, Dr. David Gaist from Odense University Hospital and University of Southern Denmark noted that it is important to keep the increase in risk in context. Only five out of 100,000 Danish women between the ages of 15 and 49 develop glioma each year, and this number includes women who take contraceptives.

The progesterone hormone is known to increase proliferation of high-grade glioma cells called astrocytomas in the laboratory. Additionally, it is thought to raise levels of growth factors, natural substances that stimulate cell growth. However, the scientists said that it was impossible to come to a conclusion regarding how progesterone-containing contraceptives may influence brain cancer development.