Counseling on complex contraceptive dilemmas

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Table 1

Table 2

As ob/gyns, we find ourselves taking care of women with complex medical conditions that impact their reproductive health decision-making. Office visits for family planning present an opportunity to talk to patients about their fertility desires and to review safe and effective birth control options, while also discussing risks of pregnancy with a given medical condition or while taking certain medications. According to the American College of Obstetricians and Gynecologists (ACOG), counseling around pregnancy should include optimizing control of chronic medical conditions prior to conception.¹

Download the full US Medical Eligibility Criteria chart

One important resource available to us is the Centers for Disease Control and Prevention (CDC) U.S. Medical Eligibility Criteria for Contraceptive Use (US MEC), which provides guidance on use of contraceptive methods for a wide range of medical conditions, such as hypertension, renal disease and seizure disorder, and addresses potential medication interactions.² Categories 1 and 2 indicate that a contraceptive method is safe and without restrictions for the specific medical condition and the advantages of the method generally outweigh any theoretical risks, respectively. Category 3 suggests that the theoretical or proven risks of the contraceptive method outweigh the benefits. Category 4 means that there is an unacceptable risk to the patient with use of the contraceptive method. The full US MEC chart is available for download or purchase at and an easy-to-use mobile application is available in the Apple or Google Play Store. 
 

Women with epilepsy
Epilepsy is a neurologic disorder that affects about 1.5 million women in the United States and is characterized by seizures that temporarily disrupt brain function. Antiepileptic drugs (AEDs) are the treatment mainstay.³

AEDs and pregnancy
Exposure to AEDs in the first trimester is associated with an increased risk of fetal malformation. Valproate is associated with neural tube and cardiac fetal malformations. Phenobarbital exposure in pregnancy increases risk of cardiac malformations. Both lamotrigine and levetiracem appear to be safe in pregnancy.⁴ The American Academy of Neurology recommends 0.4 mg of folic acid supplementation for women with epilepsy (WWE) who want to become pregnant.⁵

Epilepsy and contraception
Limited data are available with regards to use of contraception in women with epilepsy. One recent international survey of reproductive–aged women with epilepsy found that the most common AEDs were lamotrigine and levetiracem. Almost half of women with epilepsy used a hormonal contraceptive method (46.6%) and 17% used an intrauterine device (IUD).⁶

Case 
Elaina, a 25-year-old G0, presents to discuss birth control. Her medical history is complicated by a history of a seizure disorder that is well-controlled on an antiepileptic medication. Otherwise, Elaina’s medical history is significant for a bicornuate uterus. As a teenager, she used a birth control implant, but she had it removed following a skin infection with methicillin-resistant Staphylococcus aureus at the insertion site.  Elaina is planning to become married in 6 months and would like to become pregnant shortly after her wedding.

What potential concerns are there in choosing a contraceptive method for Elaina, considering her AED use?

A. Change in kidney function
B. Decrease in contraceptive effectiveness
C. Liver toxicity
D. Increased thromboembolism risk

Answer: B

In helping a patient like Elaina choose a contraceptive method, an ob/gyn needs to balance medical history, medication use, and fertility desire. While the contraceptive implant and intrauterine devices are generally recommended in women with epilepsy, Elaina’s history of complication with an implant and bicornuate uterus, in combination with wanting to conceive in the next year make these unsuitable choices. Likewise, because the injectable progestin, depot medroxyprogesterone acetate (DMPA) can delay fertility for up to 1 year, you would not recommend this option.⁷ Given those restrictions, the choices for this patient are combined hormonal contraception and progestin-only pills (POPs). 

It is important to clarify Elaina’s antiepileptic medication use in order to appropriately counsel her because significant drug interactions exist between contraceptive steroids and AEDs. These drug interactions can occur in either direction, where some AEDs may
decrease serum contraceptive hormone level, thus decreasing contraceptive effectiveness and increasing the risk for unintended pregnancy and some hormonal contraceptive methods may lower serum levels of AEDs, thereby increasing the frequency of seizures. 

AED/contraception interactions

Enzyme inducers
Several AEDs are characterized as enzyme-inducers (Table 1) , meaning that they enhance metabolism of contraceptive steroids, and may impact counseling and medical decision-making around contraception for WWE.⁸ The epilepsy foundation provides helpful information about enzyme-inducers for patients and providers.⁹ As a result, the US MEC indicates that in women who use enzyme-inducer AEDs, both combined hormonal contraception and POPs are category 3, reflecting that the risks outweigh the benefits of use. Finally, data suggest that topiramate decreases serum levels of ethinyl estradiol among combined hormonal contraceptive users and the US MEC recommends against use of estrogen-containing methods for topiramate users.¹⁰ The etonogestrel implant is a progestin-only implant that is considered safe in women who take enzyme-inducing AEDs, however, the US MEC classifies it as Category 2 due to some concerns about decreased contraceptive effectiveness. 

Lamotrigine
Use of estrogen-containing contraceptives by women who take lamotrigine is concerning because the drugs are metabolized in the same pathway. As a result, estrogen-containing methods decrease the concentration of lamotrigine and may reduce seizure control in WWE. This drug interaction can be overcome by increasing lamotrigine concentrations.⁸ Additionally, we recommend a monophasic estrogen-containing pill and using the method continuously (skipping placebo pills or hormone-free weeks) to minimize changes in serum concentrations of lamotrigine. We recommend a team-based approach between the obstetrician-gynecologist, neurologist, and patient to provide patient education and so that dose adjustments can be appropriately made to meet fertility goals while maintaining good seizure control.

Contraceptive methods without drug-drug interactions
Both copper and levonorgestrel intrauterine devices are considered safe in WWE regardless of which antiepileptic drug they use. The progestin injectable is considered safe in women with epilepsy and is listed as Category 1 by the US MEC. Due to the high progestin levels, the injectable is not thought to be susceptible to enzyme-inducer activity. The etonogestrel implant is safe for women with epilepsy and more information needs to be collected on the effects of enzyme-inducers on efficacy. 

Choosing the best method
Ultimately, you must consider the pros and cons of each contraceptive method for Elaina (Table 2). Both combined hormonal contraception and POPs remain ideal options, given her future plans for pregnancy and medical history. If Elaina is taking an enzyme-inducing drug, you can recommend a higher-dose combined hormonal contraceptive pill (50 ug ethinyl estradiol) or one that contains a higher-dose, long-acting progestin (levonorgestrel, desogestrel).¹¹ However, you would not recommend using combined hormonal contraception with concurrent lamotrigine use without consultation with her neurologist. If Elaina is not taking an enzyme-inducing drug, both combined hormonal contraceptive methods and POPs are safe.  It is important to counsel her that POPs need to be taken each day within a 3-hour window and are associated with irregular menstrual bleeding. Her visit today is a good opportunity to discuss safety of AEDs in pregnancy and to provide preconception counseling. 

References:

• ACOG Committee Opinion No. 762: Prepregnancy Counseling. Obstet Gynecol. 2019;133(1):e78-e89.

• Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR. Recomme rep. 2016;65(3):1-103.

• Epilepsy Fast Facts.  https://www.cdc.gov/epilepsy/about/fast-facts.htm. Accessed 1/2/2019, 2019.

• Bromley RL, Weston J, Marson AG. Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children. JAMA. 2017;318(17):1700-1701.

• Harden CL, Meador KJ, Pennell PB, et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73(2):142-149.

• Herzog AG, Mandle HB, Cahill KE, Fowler KM, Hauser WA, Davis AR. Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry. Epilepsia. 2016;57(4):630-637.

• Paulen ME, Curtis KM. When can a woman have repeat progestogen-only injectables--depot medroxyprogesterone acetate or norethisterone enantate? Contraception. 2009;80(4):391-408.

• O’Brien MD, Guillebaud J. Contraception for women taking antiepileptic drugs. J Fam Plann Reprod Health Care. 2010;36(4):239-242.

• Epilepsy foundation: Contraception. https://www.epilepsy.com/living-epilepsy/women/all-women/contraception. Accessed January 2019. 

• Rosenfeld WE, Doose DR, Walker SA, Nayak RK. Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia. 1997;38(3):317-323.

•  Allen RH, Cwiak C. Contraception for the Medically Challenging Patient. New York, New York. Springer Publishing Company. 2014: 135-14