title: [Androgens and epilepsy].
abstract: Nowadays there are increasing experimental and clinical data indicating an important role of an endocrine system (especially its neuroendocrine part and sex hormones) in the pathogenesis of epilepsy. The relationships between patomechanisms of epilepsy and activity of hypothalamo-pituitary-ovarian axis in animals and humans are quite well recognized but the role of male sex hormones, i.e androgens, in seizure susceptibility processes is less known. Epidemiological data clearly show that adrogens-related disorders occur more frequently in epileptic men than in general male population. Usually, they appear in the form of hypogonadism associated with low levels of plasma free testosterone and with low excretion of its 17-ketosteroid metabolites in the urine. Reproductive and sexual disorders can be attributed to hypogonadism. Androgen abnormalities in epileptics men are often affected by chronically used anti-epileptic drugs. Antiepileptic drugs, particularly classical ones, substantially modify bioavailability of androgens and can inhibit the activity of hypothalamo-pituitary-testicular axis, and--in a consequence--aggravate hypogonadism. Since neuroactive androgens cross the blood-brain barrier and modify seizure susceptibility, changes in their plasma concentrations can affect the course and clinical outcome of epilepsy. Effects of testosterone on seizures seem to depend on its different metabolic pathways. Aromatization of testosterone leads to formation of 17beta-estradiol that is believed to have proconvulsive activity. Activation of 5alpha-reductase pathway leads to formation of ketosteroid metabolites, primarily andosterone and etiocholanolone that demonstrate the ability to prevent convulsions in majority of animal studies. Recently, it has been shown that androsterone enhances the antiepileptic activity of phenobarbital, carbamazepine, and gabapentin in animal model of epilepsy. Antiepileptic activity of testosterone and its metabolites encourage further investigation of androgens as promising candidates for treatment of epilepsy in men with androgens-related disorders.
authors: Katedra i Zakład Farmakologii Doświadczalnej i Klinicznej, Uniwersytet Medyczny, Lublin.
authors: Tomasz
authors: T
authors: Mróz
authors: Katarzyna
authors: K
authors: Mróz
authors: Piotr
authors: P
authors: Tutka
mesh_terms: D000728:Androgens / Q000097:blood*; D000738:Androsterone / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D015897:Comorbidity; D004357:Drug Synergism; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D007006:Hypogonadism / Q000097:blood* / Q000453:epidemiology*; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism; D017678:Sex Distribution; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D000927:Anticonvulsants; D013739:Testosterone; D000738:Androsterone