Contraceptive Hormones Ended Seizures in Dravet Patients, Case Report Says

Ana Pena, PhD avatar

by Ana Pena, PhD |

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Two teenage girls with Dravet syndrome became seizure-free after starting contraceptive hormonal therapies containing synthetic estrogen and progesterone, according to a recent case report.

The girls had begun taking a birth control pill (patient 1) or received a contraceptive implant (patient 2) at the ages of 12 and 14, respectively. Shortly after  they stopped having seizures, which had been recurrent since the girls were 6 months old.

The case report, “Seizure Freedom in Patients with Dravet Syndrome with Contraceptives: A Case Report with Two Patients,” was published in the journal Neuropediatrics.

Patient 1, who at the time of publication was 16, has remained seizure-free for more than three years, while patient 2, 15, has been seizure-free for more than one year.

Both patients had mutations in the sodium channel gene SCN1A and a history of refractory epilepsy, resistant to several antiepileptics, either alone or in combination, including valproate, potassium bromide, topiramate, stiripentol and clobazam.

Patient 1 started taking birth control pills with a combination of ethinylestradiol, a synthetic estrogen, and dienogest, a synthetic derivative of progesterone, to control excessive menstrual bleeding.

The patient’s mother reports that the girl became seizure-free from the first day of taking the hormone therapy, and in the following three years no further seizures occurred.

The correlation between seizures’ ending and oral contraceptives became apparent when, at age 15, the pill was replaced by an intrauterine device (contraceptive coil). Within one week after discontinuing the pill, the girl experienced a convulsive seizure.

Patient 2 received a skin implant that released etonogestrel — a synthetic estrogen — at age 14, after which she did not experience any more seizures. The same girl later started taking oral pills of ethinylestradiol and levonorgestrel to regulate menstrual bleeding. However, drugs these were not involved in the seizures’ discontinuance.

While estrogen is described as an agent that promotes convulsions, progesterone and its derived molecules, are known anticonvulsants.

The antiepileptic effect of progesterone is attributed to its conversion by cells into other derivatives that activate the GABA(A) receptors, which are important signaling molecules of the nervous system. Once activated, they can have anxiolytic, sedative, muscle relaxation, and anticonvulsant effects.

A biosimilar of these derivatives, ganaxolone, has showed promising results to treat uncontrolled seizures in adults and in children with rare types of epilepsy.

“It is unclear whether the observed effect of these contraceptives containing synthetic progesterone derivatives may be specific for the Dravet syndrome,” researchers noted.

Pills containing only progesterone have long been taken by women with epilepsy, but reports of a relevant seizure reduction have not been available so far.

For now, the researchers say they cannot advocate prescribing a contraceptive for treating epilepsy because of  their known side effects. However, further studies will be important as the choice of a contraceptive may have a positive effect on seizure control.