FULL-LENGTH ORIGINAL RESEARCH

Contraceptive practices of women with epilepsy: Findings

of the epilepsy birth control registry
*Andrew G. Herzog, *Hannah B. Mandle, *Kaitlyn E. Cahill, *Kristen M. Fowler,
†W. Allen Hauser, and ‡Anne R. Davis

Epilepsia, 57(4):630–637, 2016

doi: 10.1111/epi.13320

Dr. Andrew G.
Herzog is professor of
neurology at Harvard
Medical School and
director of the
Neuroendocrine Unit at
Beth Israel Deaconess
Medical Center.
SUMMARY
Objective: To report the contraceptive practices of women with epilepsy (WWE) in
the community, predictors of highly effective contraception use, and reasons WWE
provide for the selection of a particular method.
Methods: These cross-sectional data come from the Epilepsy Birth Control Registry
(EBCR) web-based survey regarding the contraceptive practices of 1,144 WWE in the
community, ages 18–47 years. We report demographic, epilepsy, and antiepileptic drug
(AED) characteristics as well as contraceptive use. We determined the frequency of
use of highly effective contraception use, that is, methods with failure rate <10%/year,
and conducted binary logistic regression analysis to determine predictors of highly
effective contraception use. We report frequencies of WWE who consult various health
care providers regarding the selection of a method and the reasons cited for selection.
Results: Of the 796 WWE at risk of unintended pregnancy, 69.7% use what is generally
considered to be highly effective contraception (hormonal, intrauterine device [IUD],
tubal, vasectomy). Efficacy in WWE, especially for the 46.6% who use hormonal con-
traception, remains to be proven. Significant predictors of highly effective contracep-
tion use are insurance (insured 71.6% vs. noninsured 56.0%), race/ethnicity (Caucasian
71.3% vs. minority 51.0%), and age (38–47, 77.5%; 28–37, 71.8%; 18–27, 67.0%). Of the
87.2% who have a neurologist, only 25.4% consult them regarding selection of a
method, although AED interaction is cited as the top reason for selection.
Significance: The EBCR web-based survey is the first large-scale study of the contra-
ceptive practices of WWE in the community. The findings suggest a need for the devel-
opment of evidence-based guidelines that address the efficacy and safety of
contraceptive methods in this special population, and for greater discourse between
neurologists and WWE regarding contraception.
KEY WORDS: Contraception, Epilepsy, Seizures, Women, Epidemiology.

Family planning and contraception are important consid-
erations for women of reproductive age. They present par-
Accepted December 23, 2015; Early View publication February 15,
2016.
*Harvard Neuroendocrine Unit, Beth Israel Deaconess Medical Center,
Boston, Massachusetts, U.S.A.; †Gertrude H. Sergievsky Center, Mailman
School of Public Health, Columbia University, New York, New York,
U.S.A.; and ‡Department of OBGYN, Columbia University Medical
Center, New York, New York, U.S.A.
Address correspondence to Andrew G. Herzog, Harvard Neuroen-
docrine Unit, Beth Israel Deaconess Medical Center, 422 Worcester Street,
Suite 303, Wellesley, MA 02481, U.S.A. E-mail: aherzog@bidmc.harvard.
edu
Wiley Periodicals, Inc.
© 2016 International League Against Epilepsy
ticular challenges for women with epilepsy (WWE).
Specifically, antiepileptic drugs (AEDs) have teratogenic
effects.1–3 Reproductive steroids have neuroactive properties
that can modulate neuronal excitability and seizure thresh-
olds.4,5 Some AEDs have reciprocal interactions with contra-
ceptive hormones that may affect the efficacy of both AEDs
and hormonal contraception.6–13 Despite the importance of
these issues, there has been little formal study of the contra-
ceptive practices of WWE in the community and the decision
making process that goes into the selection of a method.14
The Epilepsy Birth Control Registry (EBCR), a web-
based survey and educational site, gathers data regarding
the following: (1) the contraceptive practices of WWE in

630

Key Points
• Largest study of contraceptive practices of women
with epilepsy (WWE) in the community
• Despite being at higher risk of having offspring with
fetal malformations, 30.3% of WWE do not use highly
effective contraception
• Almost one-half of the WWE use hormonal contracep-
tion which is considered highly effective but has yet to
be proven so in WWE
• Insurance, race/ethnicity and age are significant demo-
graphic predictors of the use of highly effective con-
traception
• Only a minority, 25.4%, of the WWE consult their
neurologist in the selection process
the community; (2) the decision making process; (3) the
impact of various contraceptive methods on seizures, strati-
fied by AED type; (4) frequencies and reasons for discontin-
uation of various contraceptive methods; (5) frequencies of
unintended pregnancy on various contraceptive methods,
stratified by AED type; and (6) rates of folic acid use and
factors that determine its use. Herein, we report the contra-
ceptive practices of WWE in the community, identify fac-
tors that may predict the use of highly effective
contraceptive methods, list the healthcare providers WWE
consult in the contraceptive decision making process and
the reasons WWE provide for the selection of a particular
method.
Methods
Subjects
The cross-sectional data come from the first 1,144
WWE who completed the EBCR web-based survey. We
utilized an online survey methodology to reach a large
cross-section of WWE in the community as a first step to
characterize the contraceptive practices of WWE. Individ-
uals were directed to the survey from a wide assortment
of referral sources such as epilepsy organization websites,
social media, Internet searches, and study brochures
posted in hospital and community clinics. Participation in
the study required that women be of reproductive age,
between 18 and 47 years, and report a diagnosis of epi-
lepsy. Women younger than the age of 18 were excluded
because of the difficulty in ascertaining the consent of
minors and their guardians online.
This study was approved by the Western Institu-
tional Review Board as well as the Columbia Univer-
sity Medical Center Institutional Review Board.
Participants provided online consent before completing
the survey.
631
Contraceptive Use by Women with Epilepsy
Data collection and definitions
The study was carried out between 2010 and 2014. The
first three questions of the survey screened individuals for
eligibility. Those who identified themselves as women
between 18 and 47 years and answered affirmatively to hav-
ing the diagnosis of epilepsy were directed to complete the
remainder of the 40-question survey. Individuals who did
not meet these criteria were excluded from the remainder of
the survey and directed to the EBCR website educational
material. The survey gathered demographic, epilepsy, AED,
reproductive, and contraceptive data.
Demographic data included age, race, ethnicity (Hispanic
or non-Hispanic), education (completion of high school,
some college, baccalaureate degree, or advanced degree),
household income in United States dollars (0–25,000,
25,000–60,000, 60,000–100,000, or >1,000,000), type of
health insurance (none, commercial, or government), and
geographic location (region of the United States: northeast,
southeast, midwest, west, southwest, or country outside of
the United States).
Participants classified their seizures as generalized con-
vulsive, complex partial, and simple partial on the basis of
descriptions of each category provided in the question. The
participants provided the names and daily dosages of cur-
rent AEDs. We categorized AED treatment as none,
monotherapy, or polytherapy. We grouped AEDs into six
categories based on their effects on enzymatic metabolism:
(1) no AED; (2) enzyme-inducing AEDs (EIAEDs), which
included phenobarbital, phenytoin, carbamazepine, oxcar-
bazepine, and topiramate >200 mg daily; (3) glu-
curonidated AEDs (GluAEDs), which included only
lamotrigine; (4) non–enzyme-inducing AEDs (NEIAEDs),
which included levetiracetam, zonisamide, gabapentin,
topiramate in dosages ≤200 mg daily, lacosamide, cloba-
zam, pregabalin, and tiagabine; (5) enzyme-inhibiting
AEDs (InhAEDs), which included only valproate; and (6)
mixed categories. Note, valproate was listed in the InhAED
category, although it is also partially glucuronidated. When
there was a combination of an AED that affected enzymes
and a NEIAED, the combination was listed by the category
that affected enzymes. If the combination comprised two or
more categories that affect enzymes, it was listed as mixed
category.
The WWE were designated at risk of unplanned preg-
nancy if they were currently heterosexually active, not preg-
nant or seeking pregnancy and denied previous
hysterectomy or nonsurgical infertility. The categories and
subcategories of current contraception were as follows: (1)
none, (2) withdrawal, (3) barrier (condom, diaphragm), (4)
systemic hormonal (oral contraceptive pill [OCP]–combi-
nation or progestin only, hormonal patch, vaginal ring,
implanted progestin, depomedroxyprogesterone), (5)
intrauterine device (IUD–progestin or copper), (6) tubal
ligation, and (7) partner with vasectomy. Highly effective,
that is, <10% per year failure rate with typical use,
Epilepsia, 57(4):630–637, 2016
doi: 10.1111/epi.13320
632
A. G. Herzog et al.

contraception included systemic hormonal methods, IUD, pants. Table 1 presents demographic frequencies for the
tubal ligation, and vasectomy. EBCR WWE in the United States, and compares these fre-
We explored the decision making process in terms of the quencies with those for U.S. general population statistics.
healthcare professionals seen during the year prior to taking Overall, the EBCR population was proportionally younger
the survey, the healthcare professionals who were consulted and better educated but with less household income than
regarding selection of a contraceptive method and the top women in the general population.15,16 Racial/ethnic minori-
three reasons for selection of a method. We generated the ties are substantially underrepresented in the survey. The
list of reasons from the most frequently reported unstruc- regional distribution of the WWE who completed the EBCR
tured responses during an initial trial period for the survey. survey in the United States differs only marginally from the
These reasons were (1) convenience, (2) AED interaction,
(3) cost, (4) sexually transmitted infection prevention, (5)
cycle regulation, (6) pelvic pain, (7) effectiveness, (8) side Table 1. Demographic characteristics of the women
effects, and (9) other. with epilepsy in the Epilepsy Birth Control Registry in the
United States
Statistical analysis
EBCR population General
We report descriptive statistics as frequencies and per- N = 1,000 WWE in the % (95% confidence population
centages for demographic, seizure, AED, and contraceptive United States interval) %
variables and means  standard deviations (SDs) for con- Age
tinuous variables (SPSS, version 23). We report frequencies 18–27 51.1 (47.7–54.0)* 33.4
and percentages for the healthcare providers seen during the 28–37 37.6 (34.8–40.7)* 31.8
year before the survey; healthcare providers consulted 38–47 11.3 (9.4–13.3)* 34.8
Race
regarding the selection of a contraception method and rea-
White 91.3 (89.2–92.9)* 74.8
sons for selection of the method. We compared proportions Minority 8.7 (7.1–10.8)* 25.2
among grouped data within the EBCR using chi-square Ethnicity
analysis and means using t-tests. We used bootstrapping to Hispanic 8.1 (6.4–9.9)* 16.3
determine ≥95% confidence intervals (CIs) for EBCR sur- Non-Hispanic 91.9 (90.1–93.6)* 83.7
Education
vey estimates of frequencies in the population of WWE for
No high school diploma 2.0 –
the purpose of comparison with other populations. We High school diploma 14.3 –
report the 95% CI for EBCR frequencies and two-tailed p- Some college 34.6 –
values for the comparisons of proportions. We carried out Associates degree 10.4 –
binary logistic regression analyses to explore predictors of Baccalaureate degree 26.1 –
Advanced degree 12.6 –
highly effective contraception use among WWE at risk.
Education (age: 25+, N = 680)
Demographic predictor factors in the analysis were age, No high school diploma 1.3 (0.6–2.2)* 11.4
race/ethnicity, education, household income, and insurance. High school diploma 12.4 (9.9–14.9)* 29.4
In a separate analysis, we explored seizure type and AED Some college 27.2 (24.0–30.6)* 17.0
category as predictors. We carried out chi-square analysis to Associate degree 11.2 (8.7–13.6) 10.8
Baccalaureate degree 30.0 (26.7–33.4)* 20.2
test for independence between the categories of contracep-
Advanced degree 17.9 (15.1–20.9)* 11.2
tion and the categories of AED in use. Household income
0–25,000 39.8 (36.7–42.8)* 24.7
25–60,000 32.2 (29.4–35.2) 31.9
Results 60–100,000 18.2 (15.7–20.8)* 21.5
>100,000 9.8 (8.0–11.7)* 21.9
Demographic, seizure, and antiepileptic drug
Regional location
characteristics of the EBCR population Northeast 26.7 (24.0–29.3)* 20.4
Referral sources for the 1,144 subjects were Facebook Southeast 23.1 (20.5–26.0) 25.6
(43%), the Epilepsy Foundation/epilepsy.com (32.9%), Midwest 22.5 (20.0–25.2) 21.7
Internet research (4.5%), neurologist (4.4%), and other West 17.9 (15.5–20.2)* 20.3
Southwest 9.8 (7.9–11.9)* 12.0
(12.9%, with each comprising <2%); 3.6% provided no
Insurance
response. None 10.5 (8.7–12.3)* 13.1
Of the 1,144 WWE, 1,000 resided in the United States Medicare 9.2 (7.2–11.0)* 13.6
and 144 were international (United Kingdom [52], Ireland Medicaid 14.4 (12.4–16.7) 15.0
[27], Canada [24], South Africa [11], Australia [9], New Commercial 65.9 (63.0–68.8)* 55.8
Zealand [4], other [one from each of 10 other countries], WWE, women with epilepsy; EBCR, Epilepsy Birth Control Registry.
location outside United States unknown [4]). There was no *p < 0.05 level of statistical significance for comparison of the proportions
in the general population with the confidence intervals of the proportions in
significant difference in age, race, education, or household the EBCR; **p < 0.01; ***p < 0.001.
income between the United States and international partici-
Epilepsia, 57(4):630–637, 2016
doi: 10.1111/epi.13320
 633
Contraceptive Use by Women with Epilepsy

regional distribution of the general population.17 Of the alone or in combination. The frequencies were remarkably
1,000 EBCR WWE in the United States, 89.5% (87.5–91.4) similar for WWE at risk and not at risk. Therefore, the data
had health insurance, which is a little greater than the 86.9% are combined. Of note, among the five most commonly used
for women 18–65 years in the general population, AEDs for all of the WWE, valproate made up a greater per-
p < 0.05.18 centage of all AEDs for non-U.S. subjects versus U.S. sub-
The majority, 59.5%, of the WWE reported having gener- jects (20.9% vs. 8.4%, [v2 = 21.653, d.f. = 1, p < 0.001]),
alized convulsive seizures during the year before the survey, whereas topiramate made up a greater percentage for U.S.
whereas 40.8% reported complex partial and 28.4% simple subjects (17.3% vs. 9.3%, [v2 = 7.226, d.f. = 1,
partial seizures. Complex partial seizures were the most sev- p = 0.007]). With regard to combinations, the two AEDs
ere seizure type in 20.3% and simple partial in 20.0%. Only that were in most common use individually, lamotrigine and
7.7% of WWE were seizure-free. Seizures occurred less levetiracetam, also formed the most frequent combination
than annually in 39.1% of WWE and less than monthly in (16.4%).
51.7%.
The 1,144 WWE reported the current use of 1,693 AEDs. Contraceptive practices of women with epilepsy in the
AEDs were used as monotherapy (54.7%) or polytherapy community
(39.7%); 5.6% used no AED. Table 2 lists the frequencies Of the 1,144 WWE in the study, 69.6% (95% CI 67.0–
of AEDs by categories and by individual AED type used 72.2%) were designated at risk of unplanned pregnancy.
The 796 WWE at risk reported the current use of 1,017 con-
traceptive methods. Only 2.0% (0.8–2.3%) used no contra-
ception. There were no significant differences in the
Table 2. Antiepileptic drugs used by women with frequencies of use of the various categories of contraception
epilepsy in the Epilepsy Birth Control Registry between U.S. and international participants. Therefore, the
Percent of
Antiepileptic drug Number Percent of AEDs WWE
categoriesa N = 1,693 N = 1,693 N = 1,080
Enzyme-inducing 279 25.8
Glucuronidated 343 31.8 Table 3. Contraceptive categories and methods used by
Non–enzyme-inducing 321 29.7 women with epilepsy at risk of unplanned pregnancy
Enzyme-inhibiting 79 7.3 Contraceptive categories, Percent of
Mixed 58 5.4 combinations listed by Number WWE at risk
Antiepileptic drugs used more effective method N = 796 N = 796
alone or in combination
Lamotrigine 419 24.7 38.8 Systemic hormonal 371 46.6
Levetiracetam 352 20.8 32.6 Barrier 185 23.2
Topiramate 185 10.9 17.1 IUD 135 17.0
Carbamazepine 121 7.1 11.2 Withdrawal 38 4.8
Valproate 111 6.6 10.3 Tubal ligation 32 4.0
Zonisamide 102 6.0 9.4 Vasectomy 18 2.3
Oxcarbazepine 77 4.5 7.1 No method 16 2.0
Clonazepam 54 3.1 5.0 Percent of
Lacosamide 53 3.1 4.9 Contraceptive methods contraceptive Percent of
Phenytoin 47 2.8 4.4 used alone or in Number methods WWE at risk
Pregabalin 35 2.1 3.2 combination N = 1,020 N = 1,020 N = 796
Clobazam 24 1.4 2.2
Gabapentin 24 1.4 2.2 Male condom 302 29.6 38.0
Phenobarbital 11 0.6 1.0 Combined OCP 261 25.6 32.8
Tiagabine 10 0.6 0.9 Withdrawal 130 12.7 16.4
Primidone 10 0.6 0.9 Progestin IUD 96 9.4 12.1
Other 58 3.4 5.4 DMPA 48 4.7 6.0
Copper IUD 39 3.8 4.9
AEDs, antiepileptic drugs. Tubal ligation 32 3.1 4.0
Each of the AEDs listed in the category of “Other” comprises <0.5% of all Ring 29 2.8 3.6
AEDs.
a
AED categories: Enzyme-inducing AEDs (phenobarbital, phenytoin, carba-
Implanted progestin 18 1.8 2.3
mazepine, oxcarbazepine, and topiramate in dosages >200 mg daily); glu- Vasectomy 18 1.8 2.3
curonidated AEDs (lamotrigine only), non–enzyme-inducing AEDs Progestin OCP 16 1.6 2.0
(levetiracetam, zonisamide, gabapentin, and topiramate in dosages up to No method 16 1.6 2.0
200 mg daily; lacosamide, clobazam, pregabalin, and tiagabine), enzyme-inhi- Diaphragm 10 1.0 1.3
biting AEDs (valproate only and mixed [AED combinations are listed under Hormone patch 5 0.5 0.6
the category that is known to affect hormone metabolism, e.g., carba-
mazepine + levetiracetam are listed under “Enzyme-inducing AEDs” ; carba- WWE, women with epilepsy; OCP, oral contraceptive pill; DMPA, depo-
mazepine + valproates are listed as “Mixed.”]). medroxyprogesterone; IUD, intrauterine device..

Epilepsia, 57(4):630–637, 2016

doi: 10.1111/epi.13320
634
A. G. Herzog et al.
data were combined. Table 3 lists the frequencies of contra-
ception use by categories and individual contraceptive
methods used alone or in combination. When used in combi-
nation, the category is listed under the generally more effec-
tive method. Almost half, 46.6%, used systemic hormonal
OCPs, hormonal patch, vaginal ring, progestin implant, or
depomedroxyprogesterone); 53.4% used nonhormonal con-
traception (withdrawal, barrier, IUD, tubal ligation, or part-
ner with vasectomy). Approximately one quarter of the
WWE, 28.3%, reported the use of contraceptive methods in
combination. Of these, the most frequent combinations, that
is, ≥10% of all combinations, were OCP plus barrier
(32.9%), barrier plus withdrawal (23.6%), and OCP plus
withdrawal (12.4%).
The majority, 69.7% (64.4–72.8%), of the 796 WWE at
risk used what are generally considered to be highly effec-
tive contraception methods. Of note, 30.3% of the WWE in
the EBCR survey did not use methods that are considered
highly effective. Significant demographic predictors for
effective contraceptive use were insurance (p = 0.003),
race/ethnicity (p = 0.007), and age cohort (p = 0.015).
Education and income were not significant. The OR for
highly effective contraception use with no insurance
(56.0%) versus insurance (71.6%) was 0.484 (95% CI
0.301–0.779). The OR for racial/ethnic minorities (51.0%)
versus Caucasians (71.3%) was 0.437 (0.238–0.801). The
proportional rate of highly effective contraception use
increased progressively by age cohort (p = 0.015). In com-
parison to the 18–27 cohort (67.0%), the rate of highly
effective contraception use was greater for the 28–37 cohort
(71.8%, OR 1.360, 95% CI 0.959–1.929; p = 0.084) and
more so for the 38–47 cohort (77.5%, OR 2.270, 95% CI
1.255–4.105; p = 0.007). Seizure type and AED category
were not significant predictors. Contraceptive category,
however, did differ by AED category (v2 = 40.054,
d.f. = 6, p = 0.021). Most notably, WWE taking EIAEDs,
which have reciprocal interactions with hormonal contra-
ception6,9–13 used hormonal contraception significantly less
often than WWE taking NEIAEDs, which are known not to
interact pharmacologically with hormonal contraception
(53/169 [31.4%] vs. 86/181 [47.5%], v2 = 9.524, d.f. = 1,
p = 0.002).19 In contrast, WWE taking lamotrigine, another
AED that has reciprocal interactions with contraceptive hor-
mones,7,8,13 used hormonal contraception at a frequency
that is similar to women taking NEIAEDs (96/187 [51.3%]
vs. 86/181 [47.5%], v2 = 0.538, d.f. = 1, p = NS). WWE
taking EIAEDs also used IUDs more frequently than WWE
taking other categories of AED. These are the specific com-
parisons for IUD use by AED categories: EIAED versus
NEIAED (49/195 [25.1%] vs. 34/237 [14.3%], v2 = 8.013,
d.f. = 1, p = 0.005); EIAED versus GluAED (49/195
[25.1%] vs. 36/243 [14.8%]; v2 = 7.357, d.f. = 1,
p = 0.007); EIAED versus InhAED (49/195 [25.1%] vs. 4/
49 [8.2%]; v2 = 6.629, d.f. = 1, p = 0.01).
Epilepsia, 57(4):630–637, 2016
doi: 10.1111/epi.13320
Decision making process in contraception selection
The great majority, 71.4%, of the 796 WWE at risk
reported having a healthcare visit with their primary care
physician or nurse practitioner during the year preceding the
survey; 61.4% saw their gynecologist and 87.2% saw their
neurologist/epileptologist. Almost one-half (44.4%) of the
796 WWE at risk consulted their gynecologist regarding the
selection of a contraceptive method. Fewer consulted their
neurologist/epileptologist (25.4%) or primary care/nurse
practitioner (22.2%). The top single reason listed for selec-
tion of their contraceptive method was AED interaction
(31.8% of the 796 WWE at risk), followed by efficacy
(17.3%), convenience (14.6%), cycle regulation (10.1%),
and side effects (6.5%). Cost was listed as most important
by only 4.5%. Listed among the top three reasons most fre-
quently was AED interaction (55.3% of the 796 WWE at
risk), followed by efficacy (55.0%), convenience (48.8%),
cycle regulation (29.5%), and cost (20.8%) (Table 4). Hor-
monal contraception users listed cycle regulation (50.0%)
more often than convenience (44.1%).
Discussion
The first goal of the EBCR survey was to obtain a repre-
sentative sampling of the contraceptive practices of WWE
in the community. The web-based methodology offered the
advantage of ready and wide-reaching access to large-scale
sampling of WWE, which is consistent with the goal. The
methodology, however, introduced biases that require con-
sideration in extrapolating the findings to WWE in general.
For example, although the regional distribution of EBCR
enrollment across the United States approximated that of
the 2010 U.S. Census figures, the EBCR participants were
disproportionately younger and better educated than women
of similar age range in the general population, consistent
Table 4. Top reasons for selection of a contraception
method
% of WWE
Reasons included at risk selecting a
among top three Frequencies % of all reasons method
reasons of the reasons N = 2,212 N = 796
AED interaction 431 19.5 55.3
Efficacy 429 19.4 55.0
Convenience 381 17.2 48.8
Side effects 281 12.7 36.0
Cycle regulation 230 10.4 29.5
WWE, women with epilepsy.
The five most frequently cited reasons listed among the top three reasons
for selection of a contraceptive method by women with epilepsy at risk of
unplanned pregnancy are presented in descending order. The frequencies of
reasons are presented as percentages of all reasons cited for selection of
contraceptive methods and as percentages of all WWE at risk who selected a
contraceptive method.

with greater Internet access by younger and better educated
people in the general population.20 In comparison to WWE
in general, the EBCR attracted a disproportionately higher
frequency of WWE who were actively having seizures. The
7.7% who were seizure-free in the EBCR is much lower
than the 63% found by Kwan and Brodie to be seizure-free
for at least 1 year,21 and the 60–70% figure that is usually
quoted for WWE in general.22 The frequencies of use of the
various types of AEDs by WWE in the EBCR population,
however, were similar to those found for women of child-
bearing age in the Neurodevelopmental Effects of
Antiepileptic Drugs (NEAD) study.23
The EBCR found that 30.3% of WWE at risk do not use
highly effective contraception despite the higher risks that
WWE have for offspring with congenital malformations.
Moreover, the efficacy of methods that are regarded as
highly effective in the general population remains to be pro-
ven in WWE. This point is particularly pertinent for the
large proportion of WWE (46.6%) who use systemic hor-
monal forms of contraception, which may interact with a
number of AEDs to compromise efficacy. Contraceptive
efficacy, stratified by AED category, in the EBCR popula-
tion will be the focus of another report.
In the absence of previous large-scale studies of the con-
traceptive practices of WWE, we present findings in the
general population as a framework for discussing the possi-
ble effects of epilepsy and AEDs on contraceptive practices
versus the confounding effects of sampling bias resulting
from the different methodologies of ascertainment in the
two populations. The ultimate goal is to develop a survey
method that will be more representative of the experiences
of WWE in general.
Among the contraceptive methods, we find that the great-
est disparity between comparably aged women in the EBCR
survey (18–37 years) and the general population household
interviews (14–35 years) is in the frequency of sterilization,
that is, irreversible contraception using tubal ligation or
partner with vasectomy, which is much higher in the general
population (18.3% vs. 6.4%).24 A number of biases in the
web-based survey methodology may contribute to this dis-
crepancy. WWE who have had sterilization, that is, irre-
versible contraception, may not be captured by the survey
because sterilized women may be less inclined to seek
further contraceptive information. Young women,
18–27 years, who make up the majority (51.1%) of EBCR
participants, are less likely to use sterilization.24 On the
other hand, minorities, who are greatly underrepresented in
the EBCR, are more likely to use sterilization.24 This may
apply to WWE as well. In an inner city clinic study by Davis
et al. (2008)25 that included a substantially greater minority
(Hispanic) representation than the EBCR (31.8% vs. 7.2%),
17.2% of the 58 WWE who reported their method of contra-
ception used sterilization. This rate is much closer to the
18.3% reported in the general population than the 6.4% in
the EBCR.
635
Contraceptive Use by Women with Epilepsy
Another notable disparity between the EBCR and the
general population among comparably aged women is the
greater use of IUD in the EBCR (17.4% vs. 6.3%).24 IUD
use is overrepresented, even if only reversible contraception
is considered (18.6% vs. 7.7%).24 Although the use of long-
acting, reversible contraception is increasing,26,27 the most
recent general population rate for 2011–2013 (9.3%) is still
substantially lower than for the EBCR.28 The greater use of
IUDs by WWE in the EBCR could be related to sampling
bias but could also reflect, at least in part, the lack of interac-
tion between IUDs and AEDs.29 This possibility is sup-
ported by the substantially and significantly greater use of
IUDs by WWE who take an EIAED (25.1%) as compared to
WWE who take any of the other categories of AEDs among
which use ranges between 8.2% and 14.8%. AED interac-
tion was reported as the top reason for selection of IUD,
more so than for any other category of contraception (IUD
53.4%, barrier 47.7%, withdrawal 22.2%, and hormonal
18.2%).
OCP use, in contrast, comprised a lower proportion of
reversible contraception use in comparably aged WWE in
the EBCR versus the general population (37.6% vs.
46.0%),24 and more so among WWE on EIAEDs (22.9%) as
compared to WWE on NEIAEDs (41.1%). This may be
related to the widely known pharmacologic interactions
between EIAEDs and OCPs.6,9–12 In contrast, WWE on
lamotrigine, which also has reciprocal interactions with
contraceptive hormones,7,8,13 use OCPs with a frequency
that is similar to that of NEIAEDs (42.7% vs. 41.1%). One
possible explanation might be that EIAEDs reduce serum
contraceptive hormonal concentrations more than GluAED
(lamotrigine), which might result in a greater chance of con-
traceptive failure.6–13 On the other hand, this explanation
ignores the finding that hormonal contraception can lower
lamotrigine levels more than EIAED levels and that the low-
ering of lamotrigine levels has been associated clinically
with exacerbation of seizure frequency.30 This can be coun-
tered by an increase in lamotrigine dosage, which compen-
sates for the drop in serum level, but consideration still
needs to be given to the substantial differences in levels on
active and inactive pills unless OCP use is converted to con-
tinuous active pill use which, in turn, can be complicated by
breakthrough bleeding. OCP use was even lower as a pro-
portion of reversible contraception in the Davis et al. study
(16/48, 30.0% vs. 37.6% [34.1–41.1%], p < 0.001) in which
more WWE used EIAEDs (30.0% vs. 25.8% [23.2–28.4],
p < 0.01).25
Insurance (insurance 71.6% vs. no insurance 56.0%),
Caucasian race (Caucasian 71.3% vs. minority 51.0%), and
older age (18–27 years, 67.0%; 28–37, 71.8%; 38–47,
77.5%) were significant predictors of highly effective con-
traception use. These predictors are consistent with general
population findings.24 Women in the general population
with insurance have a greater rate of highly effective contra-
ception use than women without insurance (78.4% vs.
Epilepsia, 57(4):630–637, 2016
doi: 10.1111/epi.13320
636
A. G. Herzog et al.
70.8%).24 Caucasian women use highly effective contracep-
tion more often than minorities (Caucasian 91.3% vs. His-
panic 80.8%, black 85.9%, and Asian 62.6%).24 Highly
effective contraception use increases progressively from
20- to 24-year-old cohort (66.6%) to the 40- to 44-year-old
cohort (76.6%).24 As in the EBCR, education level showed
little difference between the no high school diploma
(87.3%) and graduate degree (88.3%) levels of education.24
Only 25.4% of the EBCR WWE at risk consulted their
neurologist regarding the selection of a contraceptive
method, although 87.4% had a neurologist/epileptologist
and AED interaction was identified among the top three rea-
sons for selection of a method by 55.3%. The American
Academy of Neurology has formally recognized the impor-
tance of counseling WWE of reproductive age regarding the
special concerns that may apply to them in relation to con-
traception and pregnancy and included the discussion of
these reproductive issues as a clinical quality measure.31–34
The Centers for Disease Control and Prevention35 and the
American Academy of Neurology31–34 have also provided
healthcare providers with authoritative guides for prescrib-
ing contraceptives to WWE. These guides, however, are
based largely on pharmacologic interactions between con-
traceptive methods and AEDs. Large-scale clinical data
regarding the actual efficacy and seizure safety of contra-
ceptive practices with typical use by WWE in the commu-
nity have been lacking. This clinical experience is the focus
of the EBCR project and upcoming publications regarding
the (1) effects of various methods of contraception, strati-
fied by AED type, on seizures; (2) adverse reasons that
WWE in the community cited for discontinuation of contra-
ceptive methods; (3) rates of unintended pregnancies; (4)
pregnancy outcomes; and (5) folic acid use and its determi-
nants. The development of epidemiologic, as well as phar-
macologic, evidence-based guidelines for safe and effective
contraception use for WWE should provide a more solid
basis and greater incentive for the neurologist/epileptologist
to engage WWE in the discussion of this topic.
Conclusions
The EBCR survey finds that the majority of WWE at risk,
69.7%, use what is generally considered to be highly effec-
tive contraception; 30.3% of WWE at risk do not use highly
effective contraception despite the higher risks that WWE
have for offspring with congenital malformations. More-
over, the efficacy of methods that are regarded as highly
effective in the general population remains to be proven in
WWE. This point is particularly pertinent for the large pro-
portion of WWE, 46.6%, who use systemic hormonal forms
of contraception, which may interact with a number of
AEDs to compromise efficacy. The EBCR findings with
regard to contraceptive efficacy will be the focus of another
report. Insurance, race/ethnicity, and age are significant
demographic predictors for the use of highly effective
Epilepsia, 57(4):630–637, 2016
doi: 10.1111/epi.13320
contraception. Only a minority, 25.4%, of the WWE consult
their neurologist in the selection of a contraceptive method,
although 87.4% have a neurologist/epileptologist and AED
interaction is identified among the top three reasons for
selection of a method by 55.3% of WWE at risk.
Acknowledgments
We acknowledge the programming support provided by Mr. Dan Man-
dle for the setup and maintenance of the web-based survey, as well as the
assistance with data management provided by Ms. Jane Dreske. We
acknowledge the generous support of the Epilepsy Foundation and Lund-
beck.
Disclosure of Conflict of
Interest
Dr. Herzog was the principal investigator on this research that was sup-
ported by grants from the Epilepsy Foundation and Lundbeck. Mr. Mandle,
Mr. Cahill, and Mr. Fowler received salary support from the grants. Dr.
Hauser receives grant support from the CDC. Dr. Davis has no relevant dis-
closures. We confirm that we have read the Journal’s position on issues
involved in ethical publication and affirm that this report is consistent with
those guidelines.
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