title: Aromatase inhibition, testosterone, and seizures.
abstract: The effect of testosterone on brain excitability is unclear. The excitatory aspect of testosterone's action in the brain may be due to its conversion to estrogen via aromatase. We report herein a 61-year-old man with temporal lobe epilepsy and sexual dysfunction due to low testosterone levels. Use of an aromatase inhibitor, letrozole, normalized his testosterone level and improved his sexual functioning. Letrozole, in addition to standard antiseizure medication, was also associated with improved seizure control. This was sustained and, further, was associated with seizure exacerbation after withdrawing letrozole, and subsequent seizure improvement after restarting it. During the course of treatment, his serum testosterone level increased, sex hormone-binding globulin decreased (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels increased, while serum estradiol levels remained undetectable. Letrozole may, therefore, have produced a central alteration in the testosterone/estrogen ratio, thereby impairing estrogen-mediated feedback control of the pituitary, resulting in the observed increase in circulating LH and FSH levels. This experience suggests that aromatase inhibitors should be further investigated as a beneficial treatment modality for male patients with epilepsy.
authors.affiliation: Department of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Medical College of Cornell University, New York, NY, USA. clharden@med.cornell.edu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Harden
authors.forename: Neil J
authors.initials: NJ
authors.lastname: MacLusky
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects*; D004833:Epilepsy, Temporal Lobe / Q000097:blood / Q000188:drug therapy*; D007172:Erectile Dysfunction / Q000097:blood / Q000188:drug therapy; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D000077289:Letrozole; D000077287:Levetiracetam; D007989:Libido / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011788:Quality of Life; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D047072:Aromatase Inhibitors; D009570:Nitriles; D012738:Sex Hormone-Binding Globulin; D014230:Triazoles; D013739:Testosterone; D000077287:Levetiracetam; D004958:Estradiol; D000077289:Letrozole; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D010889:Piracetam