Intracranial hypertension (IH) is a serious and potentially disabling neurological condition. This condition is also sometimes called by its older names, benign intracranial hypertension or pseudotumor cerebri. The link between progestin-containing birth control implants, such as Norplant, and IH, has been known for almost 20 years, but this issue started to receive more attention when research linking IH to use of the Mirena IUD was published.
What is Intracranial Hypertension?
Intracranial hypertension develops when the pressure of the cerebrospinal fluid (CSF) is too high in the skull. CSF is produced in the choroid plexus area of the brain and under normal circumstances, flows over the brain and is absorbed into the venous blood system. CSF is produced continuously, so normal CSF pressure in the skull requires a balance between production and absorption of CSF. Although the mechanism behind IH is not well understood, researchers believe it involves a problem with the absorption of CSF in the blood.
The symptoms of IH can vary between individuals, but three of the main symptoms are severe headaches, visual changes (papilledema), and a whooshing noise in the ears (called pulse-synchronous tinnitus). These three symptoms do not all have to be present in IH. The visual changes can result in vision loss or even blindness. Other possible symptoms include sharp pain in the arms, legs, and back, severe neck stiffness, nausea/vomiting, numbness or tingling in hands, feet, and face, depression, exercise intolerance, memory difficulties, and more.
Intracranial hypertension can be acute, in cases of head injury or bleeding in the skull, or chronic, developing more slowly. Chronic IH can occur without an identifiable cause, in which case it is called idiopathic IH, or it can be secondary to an underlying condition or medication use. Conditions that can cause IH include head trauma, stroke and cerebral blood clots, and medications include certain antibiotics, certain types of progestins (synthetic progesterone used in birth control), Accutane, and more.
Anyone can develop IH, regardless of age, gender, or ethnicity, but it is thought that women of child-bearing age are at higher risk, raising the question of how hormones may influence its development. Being overweight has also been identified as a risk factor. The incidence of idiopathic IH overall is 1 in 100,000, but in overweight women of child-bearing age, the incidence is 20 in 100,000. The incidence is increasing for reasons that are unknown, but could potentially be related to the increase in popularity of progestin-secreting IUDs like the Mirena and Skyla.
Intracranial Hypertension and Mirena
The Mirena IUD is designed to deliver a sustained dose of levonorgestrel, a type of progestin, to the lining of the uterus (the endometrium) over a period of five years. Use of the Mirena was found in a research study to increase the risk of developing IH. This study looked at reports of IH associated with Mirena IUD use in the FDA’s Adverse Events Reporting System (FAERS), and found a higher than expected number of reports. And the actual number of cases is likely to be around ten times higher, as the FAERS database is generally acknowledged to underreport the incidence of adverse effects by around 10 fold. The study also examined the risk for IH with the Mirena using a large health care claims database, and compared it to the risk of IH with two oral birth control pills. This part of the study found that the risk was similar for the Mirena and for birth control pills containing the progestin norethindrone, and the risk was lower with birth control pills containing norgestimate. More research is needed to identify the levels of risk with the various types of progestin and delivery systems (IUD vs oral vs implants). However, it is clear from this study that progestins can increase the risk of IH. This study did not address the question of whether the risk was also increased with the Skyla IUD, which also contains levonorgestrel, at a slightly lower dose than in the Mirena IUD.
In 1995, research connecting Norplant, a contraceptive implant containing levonorgestrel, to a higher risk of IH was published; however, in the intervening years, very little published research has investigated and defined this risk more clearly, despite the increased use of levonorgestrel an contraceptive implants, IUDs and birth control pills. There have been occasional case reports connecting birth control use to IH, such as this case of IH developing in a woman two days after the use of emergency contraception containing levonorgestrel, and this case of a woman developing IH after an injection of Depo-Provera (depot medroxyprogesterone acetate).
Systemic Hormonal Effects with Levonorgestrel IUDs
In the U.S., uptake of intrauterine contraceptive devices such as the Mirena and Skyla IUDs has been low relative to other countries—in some parts of Asia, over 40% of contraceptive users choose intrauterine devices, whereas in the U.S., only about 10% of contraceptive users are using IUDs. However, this number is increasing. The Mirena and Skyla IUDs are strongly promoted as having few systemic effects, because the progestin is being delivered locally.
Knowing, however, that Mirena has been linked to IH, a neurological disorder presumably not connected to local delivery of progestin to the uterus, and that Mirena has also been found recently to increase the risk of breast cancer, one must question whether in fact it is true that the effects of the Mirena really are mostly local. In fact, some research has found that the serum concentration of levonorgestrel in women using progestin-secreting IUDs can be similar to or higher than the serum concentration in women using progestin-only oral birth control pills. In addition, the concentration of levonorgestrel in tissues other than the endometrium is also similar between oral progestin users and IUD users (except in the endometrium, where it is much higher in women with an IUD).
Discontinuation rates for Mirena and Skyla IUDs have been reported to be as high as 60%, and the most common reasons for discontinuation are irregular bleeding, pelvic pain, and systemic progestogenic side effects. These systemic effects include depression, mood changes, breast tenderness, weight gain, bloating, headaches, acne, and loss of libido—effects that can be expected with serum concentrations of levonorgestrel similar to those found with oral intake. This high discontinuation rate raises the question of whether healthcare professionals underestimate the incidence of these adverse effects, and whether they are informing women of the possibility of their occurrence.
The awareness of possible systemic effects of hormone-releasing IUDs, as well as the connection to serious diseases such as IH, is extremely important. The reputation of these IUDs as only delivering hormones locally does not seem to be supported by the data. Women should be able to choose their birth control methods with fully informed consent about the full range of possible side effects, and armed with information about what side effects to be alert for and discuss with their doctors. Recognizing the early warning signs of serious adverse effects from birth control use, however, relies on our collective acknowledgement of the fact that these serious side effects can and do occur.
Real Risk Study: Birth Control and Blood Clots
Lucine Health Sciences and Hormones Matter are conducting research to investigate the relationship between hormonal birth control and blood clots. If you or a loved one have suffered from a blood clot while using hormonal birth control, please consider participating. We are also looking for participants who have been using hormonal birth control for at least one year and have NOT had a blood clot, as well as women who have NEVER used hormonal birth control. For more information or to participate, click here.