Abstracts

Aromatase inhibition has been used to treat men with epilepsy who have decreased libido and sexual dysfunction, since it decreases circulating estradiol and increases testosterone. Estrogen in the brain is generally proconvulsant in animal models and testosterone is anticonvulsant when its[apos] physiologic conversion to estradiol via aromatase is blocked. Therefore, we explored the possibility that aromatase inhibition could improve seizures in men with epilepsy as well. In this pilot study, anastrazole was used in an open-label, add-on manner in men with intractable partial epilepsy after a 4 week prospective baseline. Two seizures per month was the minimum baseline rate to enroll in the study. Subjects meeting criteria then started the FDA-approved dose of 1 mg per day. The main outcome variable was seizure frequency over a 12 week treatment period compared to the 4 week baseline. Androgenic adverse effects, sexual functioning and libido were monitored using subject interview and the ASEX scale. Results are available for seven out of ten enrolled subjects. Six men have completed the study; four completed 12 weeks of treatment. Two of the six chose to discontinue prior to 12 weeks of treatment due to no seizure improvement, but not due to side effects.
The subjects[apos] ages range from 26-51 years (median 40 years). Subjects took 1-3 standard AEDs throughout the study; one subject also had the VNS on during the study. Details of the seven subjects including seizure localization, initial monthly seizure count, and seizure and hormone changes on treatment are in the Table.
No subject had low baseline testosterone levels; initial testosterone levels ranged from 338-831 ng/dL (median=414, mean=506 ng/L) and tended to increase throughout the study (see Table for percent increase). The greatest increases in FSH occurred in subjects with the greatest seizure reduction.
No change in AED levels or libido was found during anastrazole treatment compared to baseline. No CNS side effects were reported. [table1] Add-on anastrazole in this open-label pilot study in men with intractable partial epilepsy produced seizure frequency decrease of clinically important magnitude in some subjects. Few side effects occurred and AED levels were not altered. Increases in FSH levels may be a marker for seizure improvement, indicating a favorable effect of aromatase-inhibition on CNS reproductive hormone levels. (Supported by AstraZeneca International)