Pregnancy, Contraception Data Highlighted in Epilepsy Registry

Women with epilepsy appear to have a significantly greater number of unintended pregnancies than does the general population and cite a wide variety of reasons for discontinuing different contraceptive methods, according to preliminary results from the Epilepsy Birth Control Registry.

In the survey of 350 women with epilepsy, pregnancy was unintended in 125 (86%) of the 146 women who had pregnancies and in 215 (63%) of the 340 total pregnancies. This was significantly higher than the rate of 49% observed in a general U.S. population survey of 7,643 women.


Jeff Evans/IMNG Medical Media

Arielle Saporta (left) and Dr. Andrew G. Herzog

This was surprising to senior study investigator Dr. Andrew G. Herzog, director of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center, Wellesley, Mass. “The epilepsy population, which is thought to have a lower fertility rate [than the general population], nevertheless had the higher unintended pregnancy rate,” he said in an interview.

The frequency of unintended pregnancy differed significantly between various combinations of contraceptive methods and types of antiepileptic drug (AED), and was highest for those who used enzyme-inducing AEDs (EIAEDs) and hormonal birth control such as depot medroxyprogesterone acetate. EIAEDs also proved to be the only significant AED-related reason for stopping contraception, at least for women who were using hormonal birth control.

“There are some reciprocal interactions between antiepileptic drugs and contraceptive hormones, which can compromise both contraceptive efficacy and also seizure control,” Dr. Herzog noted. “We now know that enzyme-inducing and glucuronidated AEDs such as lamotrigine interact with hormonal contraceptives.” For instance, high estrogen levels decrease levels of lamotrigine but increase levels of EIAEDs.

Studies have shown that many women with epilepsy who take hormonal contraceptives also do not know that they can interact with AEDs or that some AEDs have a high teratogenic potential.

“Our goal is to get enough information so that we can develop some meaningful guidelines for safe and effective contraception for women with epilepsy … and also for their health care providers,” Dr. Herzog said. “Neurologists need to be informed and knowledgeable about the interactions between hormones and the antiepileptic drugs, and need to be comfortable in talking to their patients about contraception and these interactions because gynecologists are comfortable in discussing contraception, but they have a limited number of patients with epilepsy, like 1% perhaps.”

The investigators promoted the Epilepsy Birth Control Registry through online advertisements and Facebook as an educational website for epilepsy birth control in which women could get educational material after taking a 30-question survey. It is the first community-based study of contraceptive methods and AED use in women with epilepsy.

Demographic characteristics of the survey respondents, aged 18-47 years, indicated that they were “somewhat younger than the general epilepsy population and somewhat better educated,” Dr. Herzog said at the annual meeting of the American Academy of Neurology.

Respondents reported contraceptive methods including withdrawal, barrier, hormonal, hormonal-depot, and intrauterine device (IUD). AEDs were grouped into enzyme-inducing, non–enzyme-inducing, glucuronidated (lamotrigine), enzyme-inhibiting (valproate), or none.

 

All of the expected frequencies for contraceptive methods and AED categories assumed equal risk of stoppage and unintended pregnancies because no data are available to set expected values. In statistical comparisons, the contraceptive methods and AED categories were adjusted for differences in frequency of their use in the survey population.

Of 408 total stoppages of contraceptives, 214 (53%) were for adverse reasons – not because of a desire to become pregnant, sexual inactivity, or tubal ligation. Participants cited 22 different reasons for stopping their contraceptive method, which the investigators collated into 8 categories: menstrual disorder, increasing seizures, logistical issues related to the method, pregnancy on the method, concerns about the reliability of the method, headache, emotional changes, and concern about AED interaction.

Respondents stopped birth control for an adverse reason most often with depot medroxyprogesterone acetate (56%); followed by hormonal (oral pill, patch, or vaginal ring) (47%); withdrawal (38%); IUD (28%); and barrier (condom or diaphragm) (21%). Frequencies of stoppage for each of the categories of adverse reasons differed significantly between the contraceptive methods, Arielle Saporta, a research assistant in Dr. Herzog’s lab, reported at the meeting.

The reasons for stoppage varied from method to method. For withdrawal and barrier methods, they included reliability and pregnancy (as well as logistical concerns for barrier). Hormonal contraception was stopped over concerns about seizures and menstrual disorder (irregular cycles, heavy menses, or irregular bleeding). Depot medroxyprogesterone acetate was often stopped because of menstrual disorder and logistical reasons. IUDs were discontinued largely because of menstrual disorder.

Among the different types of AEDs, only EIAEDs were significantly associated with a reason for stopping birth control. For example, menstrual disorder as a reason for stopping birth control was significantly associated with use of EIAEDs. Overall, 29% of respondents who used EIAEDs and hormonal birth control cited menstrual disorder as a reason for stopping, which was twice as often as for women not taking AEDs.

An earlier report from the registry showed that 18% of women on hormonal contraceptives had worsening of their seizures, compared with 3% of women on nonhormonal contraceptives.

These results also led some audience members to wonder who was prescribing AEDs to women on unreliable contraceptive methods such as withdrawal. Indeed, only one-fourth of women who completed the survey consulted a neurologist about what contraceptive methods might be most appropriate for their type of epilepsy and treatment. This was a “surprise,” Dr. Herzog said. “Either they don’t think their neurologist know about the topic, or maybe they are correct that [we] don’t know about the topic. And for gynecologists, epilepsy makes up only about 1% of their practice, so it’s not their major focus either.”

The investigators now have 550 completed surveys and hope to get 1,000. They are planning to set up a prospective arm of the study in which patients can check back into the registry every 3 months, which will hopefully provide rates of unintended pregnancy for each kind of contraceptive in terms of woman-years of contraceptive use, which is the standard measurement for contraceptive efficacy.

The registry is funded in part by the Epilepsy Foundation. Dr. Herzog and Ms. Saporta had no relevant disclosures.

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