But Australian experts have been quick to point out that the risk of developing meningioma is still very low.
Birth control options containing progestogens have been linked to a higher risk of meningioma, according to a new Danish study.
Previous research has established an association between several high-dose progestogens and an increased risk of meningioma, the most common type of intracranial tumour in adults.
To explore whether progestogen-containing contraceptives are also associated with an increased risk of meningioma, a team of Danish researchers undertook a nested case-control study using data from a series of national, population-based registries over a 25-year period.
Their findings, published in JAMA Network Open, suggests that recent use of certain progestogen birth control options could be linked to an increased risk of meningioma.
“The risk of meningioma may extend beyond high-dose progestogens and medroxyprogesterone injections to include some contraceptive progestogens, including high-dose intrauterine devices with levonorgestrel,” said the researchers.
Researchers identified 1473 women between the ages of 15 and 59 with a validated diagnosis of meningioma from the National Cancer Register. These women had not redeemed a prescription for hormone replacement therapy, an antiandrogen medication, or infertility hormones prior to their diagnosis, nor had they previously been diagnosed with cancer.
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These cases were compared to 14,717 control women from the broader Danish population. Each case was matched to 10 different controls based on age at the time of cancer diagnosis, where they were born, and their marital status.
The median age of women in both groups was 48 years (interquartile range 42-53 years). Forty-eight percent of control women had experienced one or more births, compared to 45% of controls.
Data on hormonal contraceptive use was primarily sourced from the Danish National Prescription Register. Progestogens were grouped as oral products (where progestogen-only and combined oestrogen-containing oral contraceptives were considered separately) or hormone intrauterine devices (where high dose [52mg] and low dose [13.5mg and 19.5mg] were considered separately). The duration of progestogen use and time since progestogen exposure were divided into four categories: less than one year, one year to five years, five or more years, or no use.
When compared to non-users of progestogen-containing contraceptives and adjusting for parity, the use of several oral contraceptives were associated with an increased risk of meningioma: the oestrogen-containing norethisterone (odds ratio and 95% confidence interval 1.66 [1.31-2.10]), drospirenone (1.58 [1.05-2.37]), gestodene (1.44 [1.17-1.77]), and levonorgestrel (1.40 [1.12-1.76]), as well as the progestogen-only desogestrel (1.73 [1.17-2.56]).
In contrast, the combined oral contraceptives cyproterone (1.61 [1.00-2.59]), norethisterone (1.38 [0.77-2.47]), and norgestimate (1.04 [0.70-1.54]), as well as the progestogen-only norethisterone (0.95 [0.57-1.59]), were not associated with meningioma risk.
Beyond the oral contraceptives, injectable medroxyprogesterone (4.55 [2.19-9.45]) and high-dose levonorgestrel (a hormonal IUD; 1.58 [1.28-1.94]) also displayed an increased risk of developing meningioma. There was no association between low-dose intrauterine levonorgestrel and meningioma risk.
The associations between progestogen use and meningioma risk were greater in women who were currently using hormonal contraceptives or who had used hormonal contraceptives in the previous year. The increased risk typically disappeared after five years of not using progestogen-containing contraceptives.
The researchers also reported that women who were pregnant in the year preceding their meningioma diagnosis also had an increased risk of meningioma.
“Given the pronounced increase of progesterone during pregnancy, the frequent expression of progesterone receptors in meningiomas, and the consistently higher incidence observed among women, a pregnancy-related effect is biologically plausible and has been described in the literature over several decades, although not confirmed in larger epidemiological studies,” wrote the researchers.
Associate Professor Alex Polyakov, a Clinical Associate Professor in the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne, said the increase in the risk of meningioma was “negligible and shouldn’t change clinical practice”.
“The number of women who need to take these compounds to develop one extra meningioma runs from the hundreds of thousands into the millions per year of use, and these numbers are most reassuring in younger women. To put it in perspective, the chance of dying on our roads is about 1 in 20,000. The chance of dying from a meningioma is less than 1 in 500,000,” he said in a statement.
Associate Professor Gino Pecoraro OAM, a practising obstetrician and gynaecologist from Queensland, described the findings as “interesting” but emphasised that preventing unwanted pregnancies is a major health issue.
“Pregnancy in Australia carries a maternal mortality rate of 6.6 per hundred thousand, while the Australian five-year survival rate following meningioma diagnosis is greater than 90%,” the past president of the National Association of Specialist Obstetricians and Gynaecologists told media.
“Prescribers should certainly be aware of the association between progestogen exposure and meningioma and also of non-progestogen-containing contraceptive options, including barrier methods and copper-containing IUDs should this association be of concern to the woman.
“This is further evidence of the importance of appropriate contraceptive consultations addressing risks and benefits of various means of contraception, taking place between prescribers and women, prior to writing a script or making a recommendation.”
The researchers acknowledged the possibility that their methods could have led to an underestimation of the risk of meningioma following progestogen use.
“Some women may have had their long-acting reversible contraception removed before the end of the recommended use period. If they did not switch to another hormonal contraceptive or became pregnant, their subsequent time would still be allocated to this exposure category, even though they were not exposed anymore,” they wrote.
