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.