Abstracts

RATIONALE: Seizures worsen during perimenarche in up to one third of girls, possibly because of associated reproductive hormonal changes. Estrogens promote and progesterone inhibits seizures. For several years from the beginning of sexual maturation until ovulation begins, the ovaries secrete estrogens but not progesterone. Exposure to estrogens in the absence of progesterone may exacerbate seizures. Progesterone treatment may be beneficial. Natural progesterone has not been previously tried in perimenarche. We report the effect on seizures and the safety and tolerability of long term treatment with progesterone in two girls with perimenarcheal seizure exacerbation.
METHODS: Two anovulatory girls with partial seizure exacerbation during Tanner stage 3 of sexual development received progesterone 100 mg b.i.d. cyclically or continuously for 9 and 10 months in an open label study. Seizures were counted prospectively for 3 and 7 month long baseline periods and during treatment. Other AEDs did not change during progesterone treatment. Serum levels of estradiol, progesterone, LH, FSH, prolactin and TSH were checked before and after 8 months of treatment. Growth chart, Tanner stage of sexual development and reproductive endocrine side effects were evaluated prospectively on monthly basis.
RESULTS: [underline]Case 1:[/underline] A 15 year old girl with [dsquote]double cortex[dsquote] and refractory partial seizures starting at one year of age. Seizures increased from 2-3/day to 20/day at the age of 13, during Tanner stage 3. At 15, she had not undergone menarche and was in Tanner stage 4, without an endocrinopathy. Progesterone 100 mg b.i.d. 14 days each calendar month was added to her AEDs. Seizures decreased to 3/week. Menarche occurred after 7 months of treatment, at the age of 16.
[underline]Case 2:[/underline] A 15 year old girl with lifelong refractory temporal lobe seizures due to perinatal hemorrhage. Seizures increased after menarche at the age of 9, during Tanner stage 2. She developed endometriosis aged 11. At 14 years, she reached Tanner stage 3. Progesterone 100 mg b.i.d. continuously was added to her AEDs. Average number of seizure days fell from 2.5 to 1.7/month, although the average monthly seizure count was unchanged at 7.5.
[underline]Comment[/underline]: Neither girl has had any adverse effects on sexual or skeletal development, nor any other side effects, with highest trough and peak progesterone levels of 29.9 and 65.9 ng/ml (pre-treatment levels 0.4-0.6 ng/ml). Both girls are continuing with the treatment.
CONCLUSIONS: Long term treatment with natural progesterone was safe and well tolerated. Suggestion of seizure improvement in these two cases warrants further exploration of progesterone as adjunctive treatment in girls with perimenarcheal seizure exacerbation.