EPILEPSY IN WOMEN AND IT’S

RELATIONSHIP TO MENSTRUAL CYCLE

Adefani Tia A
201810401011057
Background
 Epilepsy is a neurological disorder marked by
sudden recurrent episodes of sensory disturbance,
loss of consciousness, or convulsions, associated with
abnormal electrical activity in the brain.
 Occurs in both sexes, at all ages, especially in
childhood, adolescence and increasingly in ageing
populations
 While the incidence of epilepsy is slightly higher in
men, there is a trend of female predominance
during the 5 years of life
 More than 1.1 million women of childbearing age
with epilepsy  estrogen and progesterone may
be related
Literature Review
Definition

 Epilepsy is defined as a disturbance of brain

function caused by the periodic occurrence of
discharge electrical charge excessive and irregular
by brain cells suddenly, so that the acceptance and
delivery of impulses is disrupted
Epilepsy In Women

Catamenial Pregnancy
epilepsy

Breastfeeding Menopause
Catamenial Epilepsy
Definition
 Catamenial epilepsy is defined as a pattern of
seizures that changes in severity during particular
phases of the menstrual cycle, where in ;
- estrogens  proconvulsant
- progesterone  anticonvulsant
Epidemiology
 Epilepsy affects an estimated 7 million people in
India and 50 million worldwide  40% are women
 Catamenial epilepsy  70% of women with
epilepsy
 Reports  up to 50% WWE in the menarche
present worsening of seizures through menstrual
cycle
Relationship Between Epilepsy And The
Menstrual Cycle

Menstrual
Epilepsy
cycle
Catamenia
epilepsy

Catamenial epilepsy is believed to occur secondarily to the

neuroactive properties of endogenous steroid hormones and
the natural cyclic variation in their serum levels throughout the
menstrual cycle.
Diagnosis
 The diagnosis of catamenial epilepsy is established
by careful assessment of menstrual and seizure
diaries and characterization of cycle type and
duration.
 Pathophysiology

 It is known that estrogen and progesterone have important

effects on neuronal development and plasticity in
widespread cerebral and brainstem regions, through their
capacity to regulate synthesis, release, and transport of
neurotransmitters.
 Effects of Estrogens

 Estrogens have proconvulsant and epileptogenic

properties in humans.
 In human studies  a positive correlation has been found
between seizure susceptibility and the
estrogen/progesterone ratio, with a peak in the
premenstrual and preovulatory periods and a decline
during the midluteal phase.
 The periovulatory catamenial exacerbation has been attributed to
the midcycle surge of estrogen that is relatively unopposed by
progesterone until early luteal phase.
 The neuroprotective activity of estrogens was then
confirmed by several subsequent studies. Estrogen causes
a decrease in the verge of seizures due to estrogen as
GABA inhibitors
Effects of Progesterone

 In animal models  progesterone has been found to decrease

spontaneous and induced epileptiform discharges.
 In clinical studies  Seizures decrease in the mid-luteal phase
when serum progesterone levels are high, and increase
premenstrually when there is a fall in progesterone levels and
serum progesterone/estrogen ratio
Pathophysiology
 Azetazolamide
Azetazolamide has been used empirically for years for
the treatment of refractory epilepsy and catamenial
epilepsy
 Benzodiazepine
Such as clonazepam and clobazam are broadspectrum
antiseizure agents.
- Clonazepam highly useful in the therapy of absence
and myoclonic seizure
- Clobazam  effective agent for the treatment of
catamenial epilepsy
 Hormonal Therapy
Because progesterone has mainly been shown to have
anticonvulsant effect  natural progesterone may be used
to treat this cases
Natural progesterone
- taken orally 100 – 200 mg, 2-3x/day

- Side effects : breaktrhough bleeding, amenorhhea

- Antiseizure therapy  its metabolic conversion to

neurosteroid, principally pregnanolone.
 Ganaxolone
- Patients received oral ganaxolone (300 mg/day) starting
on day 21 of the menstrual cycle and continuing through
the third full day following the beginning of menstruation.
- Effective for catamenial epilepsy and doesnt expose
patient to the risk of hormonal side effect
Epilepsy In Pregnancy
Epilepsy In Pregnancy
 During pregnancy  concern arise because of the
potential harm to both WWE and neonates
 The use of AEDs increases the risk of fetal
malformation ;
Valproat  neural tube defect 1% to 2%
Carbamazepine  0,5% to 1%
 Advised for women with epilepsy in pregnancy:
- Take 5 mg/day of folic acid prior to conception
and continue until at least the end of first trimester
- Use a single dose with minimal anti-convulsants, in
doses 3-4 times/day, especially during the first 3
months of pregnancy
- Take vit.k 10-20 mg/day/oral to decrease
neonatal haemorrhage
Breastfeeding in Women With Epilepsy
Breastfeeding in Women With Epilepsy

 In general, there are limited safety data for spesific

AEDs during lactation

Safe

Moderately safe

Possibly hazardous
 Safe AEDs
1. Phenytoin
- highly protein-bound in plasma and has a low degree of
penetration into breastmilk
- adverse effects  mothers were using phenytoin in
combination with other AEDs
2. Valproate
- high degree of plasma protein-binding

3. Carbamazepine
- moderately high degree of proteinbinding in plasma
 Moderately safe
1. Lamotrigine
- 55% protein-bound in maternal plasma and penetrates

into breastmilk in moderate amounts

- Lamotrigine is compatible with breastfeeding, but the
child should be monitored for rash, poor suckling, and
drowsiness. Infant serum levels should be measured if
side effects are suspected
2. Topiramate
- A case report of a breastfed infant whose mother was

treated with topiramate describes diarrhoea and

reduced weight gain, probably caused by topiramate
exposure via breastmilk
3. Gabapentin
- has a low molecular weight and minimal protein
binding in plasma.
-
 Possibly hazardous AEDs
1. Phenobarbital
- Due to an extremely long half-life and low degree of

protein-binding in neonates, phenobarbital has the

potential to accumulate during breastfeeding
2. Benzodiazepines
Epilepsy in Menopause
Epilepsy in Menopause
 The effects of epilepsy on the menopause and the
effects of the hormonal changes of the menopause
on epilepsy cannot be reliably predicted.
 Women with epilepsy are at increased risk of bone
demineralisation, especially if they are receiving a
hepatic enzyme-inducing AED (phenobarbitone,
phenytoin, and carbamazepine), which can
accelerate vitamin D metabolism
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