Special issues pertaining to women and epilepsy
By
Dr. George Morris
Historically epilepsy, or recurring seizures, is a
common illness in both genders. Recurring seizures occur in between 0.8 and 1.2% of the
American public, regardless of gender. A frequent problem is that research excludes
women as research candidates, limiting the information available
concerning epilepsy in women. There do appear to be certain
specific situations in women's epilepsy uniquely different than that of
men.
Some of the differences in the nature of seizures
in women require different attention in counseling women with epilepsy. Presentations concerning women in epilepsy generally divide into 4 categories:
-
The
effects of various stages of reproductive life and epilepsy's
effect on the stages of reproductive life
-
Women's health as it relates
to the effects of epilepsy and the treatment of epilepsy
-
Contraception
and conception
-
Pregnancy
In years past, such
presentations on women's issues with respect to epilepsy would have been
restricted to pregnancy alone. It has become increasingly clear that
many additional elements in epilepsy require specific attention when
dealing with the female patient.
Epilepsy and reproduction
The first area we generally discuss women patients
is epilepsy and reproductive life. When we talk about the reproductive
life of a woman, we speak specifically about the various stages including
puberty, the onset of menstrual periods known as menarche, perimenopause
and menopause. Each of these stages is fairly specific and may have
differential types of effects when each occurs.
Puberty and the onset of the menstrual cycle is
potentially one of the least studied portions of reproductive life. This stage involves predominantly children, and few publications actually
exist addressing whether the relationship between epilepsy and
the onset of the menstrual cycle exists. It is very common to hear
that the onset of their seizures occurred around the time of the onset
of their menstrual cycle in women. No study has been performed looking
at the relationship between these events, but authors have looked at
girls with epilepsy and not identified an effect of epilepsy on the
onset of the menstrual cycle.
Two publications do address
if epilepsy affects menarche. One author strongly recommends
eliminating medications before menarche if possible. An additional
study of a large number of children sees no effect of epilepsy on the
puberty development cycle. They strongly recommend that any child
who is not experiencing normal development of sexual differentiation be
evaluated for a cause. Epilepsy has never been shown to produce a
delay or acceleration of this process.
Much more study has gone into the periods known as perimenopause and menopause. Menopause is the stage of the reproductive
life when hormones that control reproduction decrease with fewer menstrual
cycles. The onset of menopause is not immediate, and the period
immediately prior to menopause with many menstrual irregularities is perimenopause. Perimenopause
is associated with cycles that are of irregular length and decreasing
hormonal levels. Perimenopause is
also associated with instability in the blood vessel system that causes
individuals to experience a phenomenon referred to as hot flashes.
No
effect of epilepsy on perimenopause and menopause has been discovered. Significant studies of the effects of perimenopause and menopause on the
seizure frequency are available. One study reported by Dr. Harden of
Cornell University suggests that the period of perimenopause is
significantly associated with an increase in seizure frequency in a
group of patients he followed. Women
experienced an increase in their seizures compared to the earlier
portions of their life. Menopause was associated with a
significant reduction in seizures. Approximately 1/2 of
patients during the menopausal period reported that their seizures were
significantly less than earlier in their life.
This study reported that women experiencing an
increase during their perimenopausal stage were the same group of
individuals experiencing a reduction during their menopause. This group
also had increases in their seizures during their menstrual cycle earlier
in life. This group appeared to have seizure increases when exposed to
hormone replacement therapy. Hormone replacement therapy involves the
taking of estrogens to attempt to replace the normal secretion of estrogen
in the body to diminish some of the side effects and symptoms that are
associated with the onset of perimenopause. Hormones are generally known
to be estrogen-like substances and the traditional treatment is the
medication Premarin.
Women also experience seizures associated with
their regular menstrual cycles. The menstrual cycle is associated with an
increasing frequency of seizures. Between 15 - 70% of women have
increased seizures during their menstrual flow. Originally referred to as catamenial epilepsy, it is now obvious this increase is not as unique a
condition as was once anticipated. Depending on how rigidly one defines catamenial epilepsy, as having all seizures occur 3 days prior to or
following the menstrual flow vs. having a majority of seizures
occur during this time, the frequency of catamenial epilepsy is estimated
to be as high as 70%.
So, the majority of women report the majority of
their seizures occurred during their menstrual flow. Research suggests
that estrogen has an important role in the seizure process. It balances with a
2nd hormone known as progesterone. The varirations
of these hormones produce the menstrual cycle and a cycle of seizure
frequency.
Estrogen is a well-known proconvulsant substance
which can be used to actually induce seizures when placed directly on the
surface of the brain. Progesterone serves in an opposite function to
actually reduce the tendency of the brain to experience seizures. Several
studies have been done looking at compounds which affect these hormones
and the affect that they may have on seizures. A well known agent used to
increase the fertility of women, Clomiphene was described by a physician
at Harvard University, Dr. Herzog, as improving seizure frequency.
Dr. Herzog looked at the administration of
progesterone as a treatment for epilepsy. He used a 200mg tablet 3 times a day and was able to see significant reductions
in seizures in nearly 70% of the patients who attempted the use of the
medicine. No significant side effects were seen, and Dr. Herzog reported
that the majority of patients remained on the medication for periods of up
to 3 years experiencing more than 50% reductions in their seizures.
Further study is ongoing.
The addition of extra medications during the
menstrual cycle is used in catamenial seizures. Systematic studies of
this approach have not been completed, but antecedotal attempts at
increasing of patient's current medication while adding a 2nd
medication have been undertaken. Historically, the use of Acetazolamide
has been considered a treatment for women who experience this form of
seizure. Significant studies do not exist and no controlled trials
of this approach exist as well.
Epilepsy, bone health and sexuality
The next potion of the discussion with women who
experience epilepsy is that of health issues as they surround
the presence of epilepsy. Two categories are covered: bone health and sexuality. Bone health is
important because women have a
predisposition to develop osteoporosis. Osteoporosis, or thinning
of the density of the bone, can be associated with an increased chance
of breakage of bone and can lead to significant disability from broken
bones in the back and limbs. The effects of epilepsy on sexuality
appear to reduce general satisfaction and produce negative emotional and
physical effects.
For a long time bone health has been an issue in
the treatment of epilepsy. Some medications haven been identified
as being associated with poor bone maintenance and it was
assumed seizure medications blocked the vitamins that are responsible for
bone health, such as vitamin D. Recently it appears that there is a more
complex relationship that may exist.
Several
anticonvulsants such as Tegretol, Depakote and Dilantin have been
associated with reduced bone development, and additional studies have
shown that vitamin D levels do not appear to be fundamentally involved
in the process of bone strength. While it is yet unproven, it has
been suggested that the effects of anticonvulsants may be to modify the
influence which estrogen has on the bones. Areas of research in
this problem are currently underway.
Sexuality has been reported to be influenced by
epilepsy and by the medications potentially that are used in the
treatment of epilepsy. Women were originally noted to have a lower
fertility rate when experiencing seizures. This phenomenon was
also noted in men but appeared to become normal in men who married, while
in women fertility rates remained low. Dr. Morrell investigated
the nature of sexual satisfaction in women who were experiencing
epilepsy. Using a questionnaire, she gathered significant
information to suggest that there were elevations in anxiety and
discomfort associated with the sexual act in women with epilepsy when
compared to a control group.
Surveys are easily criticized as being reflective
of an individual's perception of their situation, and Dr. Morrell was
able to similarly study physical effects associated with sexuality and
epilepsy. Dr. Morrell measured increases in blood flow in the
genital area associated with viewing erotic material. She
was able to show that individuals with epilepsy experienced significant
reductions in physiological changes associated with sexual stimulation
which occurred in both men and women. While the specific causes of
this phenomenon are unclear, it is definitely an area of some
considerable interest and potentially plays a role in a higher
infertility rate in women who experience seizures.
Conception and contraception
The 3rd area which is unique in women with
epilepsy is conception and birth control. Birth control can definitely be affected as many seizure medications
lowering the effect of birth control pills (BCP). Medications that
potentially can effect BCPs include Phenobarbital, Dilantin, Tegretol, Carbatrol, Gabitril and Topamax. Drugs which are not
associated with these effects include Depakote, Neurontin and Lamictal.
This interaction between BCPs and seizure drugs is not one that is well
appreciated by many medical practitioners. A survey conducted by Dr.
Krauss at John Hopkins University attempted to identify what knowledge
physicians had concerning the effects of seizure medications on BCPs. He
determined there was a very low knowledge about interactions between
seizure drugs and BCPs. Unplanned pregnancies occur if BCPs are impaired
by seizure medications. His study showed that no obstetricians and only
4% of neurologists surveyed knew the effects of the most commonly used
seizure medications on BCPs.
Conception is also significantly impacted by
epilepsy. The effects are different with different types of
epilepsy. The presence of lower conception rates in epilepsies of
the temporal lobe have been described. Effects from of epilepsy
are a likely altering of the secretion of hormones regulating fertility. Further research is necessary in this area to further show these
effects.
In addition, there appears to be an increased
frequency of a condition known as Polycystic Ovary Syndrome. This
condition involves the formation of fluid filled cysts in the ovaries. These fluid-filled cysts are the remnants of normal cystic growth in the
ovaries, but if they enlarge and stay enlarged, they can hamper the
ability of the ovary to secrete eggs and produce fertility. Polycystic
Ovary Syndrome can lead to infertility. It has been associated with some
forms of epilepsy and has been suggested to be related to an antiseizure
drug, Depakote. While these effects are still under study, physicians are
carefully, currently considering the use of and effects of Depakote on
women's fertility.
Finally, pregnancy is potentially modified by
epilepsy and epilepsy modified by pregnancy. Studies have
suggested that epilepsy itself does not appear to be significantly
modified, although some women do experience increases or decreases in their seizures,
while for others seizure frequency is stable.
Several issues come up regarding pregnancy and
epilepsy. These include the safe use of seizure medications during pregnancy and precautions during pregnancy.
Probably the most common of these concerns is
seizure medication use during pregnancy. This issue has always been
studied in ways that fail in providing important information. That
important information, of course, being the safety of seizure medications
for the developing fetus. Several medications have been both historically
and repeatedly shown to have negative effects on the fetus. Medications
such as Dilantin, Carbatrol or Depakote have been associated with an
increase in major malformations and carry a warning that they should
only be used when absolutely necessary. The remainder of seizure
medications carry a warning of potential harm but no clear studied
effects that recommend that they not be used.
Currently a large scale study is underway at
Harvard University in
attempts to document how safe seizure medications. Unfortunately
this study does not have significant numbers of women whose pregnancy was
exposed to new seizure medications, so it leaves great holes
in our knowledge about the safe use of seizure medications. Some pregnancy
registries have been undertaken by governments in Europe or by the
pharmaceutical sponsors themselves. Lamictal has a significant number of
patients (greater than 400) exposed to their medication and no pattern
of specific seizure malformation has been seen.
Additional, careful registries of all
pregnancies reported are available for medications including Neurontin,
Topamax and Trileptal, but all of the numbers of exposures are below what
is believed to be an important threshold number of 400 patients and
hopefully in the years to follow these reports will be completed and
these medications safety profiles can be established.
Seizures themselves appear to have an effect on
the developing fetus but few studies have been able to identify how many
seizures produce a specific risk. When studied in a specific
Chinese population, women experiencing more frequent seizures tended to
have more fetal abnormalities, but this same group of women were also
exposed to more seizure medications. The more medications that a
woman takes, the more likely they are to experience a fetal malformation.
These gloomy reports of increased fetal
abnormalities need to be taken into context. While no negative
outcome is acceptable, the normal population experiences human
malformations at a rate of approximately 0.5%. An overall
increase in this frequency occurs on the order of between 3 and 5 times. This, in context, means that 95 - 97% of pregnancies in women on
anticonvulsant agents happen without major malformations. Importantly, this risk to human development must be put in perspective.
Finally the period of delivery and the management
of seizure medications can be of some additional difficulty. Seizure
medications often change the body's ability to eliminate them. As
pregnancies advance, both kidney and liver functions are altered. Women
experience increases in the quantity of blood within their blood stream,
as well as increases in the activities of their livers. Some medications,
such as Tegretol and Lamictal, can have dramatic swings in blood
concentrations during pregnancy. These seizure medications
generally need to be monitored much more frequently, anywhere from
monthly to weekly when these changes occur. At the time of
delivery, supplementation with vitamin K to avoid bleeding difficulties
is also often necessary.
All women need to have folate supplementation
during pregnancy. Women with epilepsy have been described as benefiting
from ongoing folate supplementation, so as to provide a good folate level
prior to conception.
These issues cover many areas pertaining to women
and epilepsy and what makes their situation unique. There are
potentially many others that may come up, but these cover many of the
traditionally identified areas. If they apply, these should be
part of the discussion that each woman has with the physician treating
her epilepsy.
For more information about epilepsy surgery, see
Frequently Asked
Questions.
|
