LGS girls’ 1st period doesn’t change seizure frequency, study finds
Small study finds seizures, medication use increase with age
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Little is known about the onset of menstuation and seizure burden in girls with LGS. (Photo by iStock)
The onset of menstruation does not appear to affect seizure frequency in girls with Lennox-Gastaut syndrome (LGS), although seizures may become more frequent through adolescence, a small U.S. study suggested.
After accounting for age, researchers found that menarche — a girl’s first menstrual period — was not associated with higher odds of having more frequent seizures. Instead, each additional year of age was significantly associated with 16% higher odds of more frequent seizures.
The number of antiseizure medications also increased with age and was significantly higher after menarche, even after accounting for age. The researchers said the study results suggest “a gradual worsening of epilepsy over adolescence,” the researchers wrote.
“These data provide important information regarding the clinical course of LGS, which may aid in both medical management and in anticipatory guidance for families as their children enter adolescence,” they wrote.
The study, “The effects of menarche on seizure burden in Lennox-Gastaut syndrome,” was published in Epilepsy & Behavior.
Hormonal changes and seizures
Hormonal changes associated with puberty can affect seizures. Estrogen is generally thought to make seizures more likely, while progesterone may have the opposite effect. In up to one-third of women with epilepsy, hormonal fluctuations during the menstrual cycle are associated with changes in seizure frequency, a pattern known as catamenial epilepsy.
But little is known about how menarche, the final step in pubertal development, affects seizure burden specifically in girls with LGS, a severe form of epilepsy that typically begins in childhood and is marked by several types of treatment-resistant seizures.
To investigate, researchers reviewed medical records from girls with LGS treated at C.S. Mott Children’s Hospital, part of Michigan Medicine, between 2013 and 2023.
Of 49 girls with a documented age at menarche, which occurred at a mean age of 13, 22 also had neurological records available from before menarche and were included in the final analysis. Their records were reviewed yearly between ages 5 and 21, when available, to track seizure type and frequency and the number of anti-seizure medications used.
At first glance, menarche appeared to be associated with worsening seizures. After menarche, participants had significantly higher odds, by 67%, of moving into a more frequent seizure category, such as from monthly to weekly seizures.
However, that association was no longer statistically significant after researchers accounted for age. Instead, each additional year of age was significantly associated with 16% higher odds of moving into a more frequent seizure category.
The pattern was also apparent over the course of follow-up. At the first recorded visit, when participants’ mean age was 6.1, some 27% had daily seizures. By the final recorded visit, at a mean age of 19.1, 73% had daily seizures.
In comparison, daily seizures were reported in 32% at the last visit before menarche and 36% at the first visit afterward.
Nonmotor and generalized tonic-clonic seizures were significantly more frequent after menarche, but neither association remained significant after accounting for age. Older age itself was significantly associated with more frequent tonic and generalized tonic-clonic seizures.
Medication use showed a somewhat different pattern. Menarche was associated with a significant increase in the number of antiseizure medications used, with an estimated 1.04 additional medications after menarche. After accounting for age, the increase remained significant, at an estimated 0.43 additional medications.
Antiseizure medication use also increased significantly with age, by an estimated 0.08 medications for each additional year. The estimated mean number of medications rose from 1.79 at age 5 to 3.06 at age 15.
It is unclear why medication use increased after menarche despite no independent increase in seizure frequency. The researchers noted that their broad seizure-frequency categories may have missed smaller changes. For example, an increase from one to five seizures per week would still have been classified as weekly. Doctors also may have intensified treatment in anticipation of seizures worsening around menarche.
The researchers cautioned that the study was small, conducted at a single center, and based on a retrospective review of medical records. Menarche also represents only one point in puberty, a gradual process, meaning the analysis may have missed more subtle effects of hormonal changes on seizures.
Still, the findings suggest “that worsening of seizures over time is not directly caused by a single hormonal change but may be related to ongoing changes throughout adolescence,” the researchers wrote.
Further prospective studies with larger sample sizes are needed to more fully assess the effects of puberty on seizure burden in LGS, as well as to further characterize the long-term outcomes for patients with LGS,” the team concluded.
