Abstract
Commentary
This discrepancy and the results of the Talbot et al. study indicate that other elements must be interposed in any link between epilepsy and males with infertility. The Talbot et al. study offered one example: “a significant correlation … between sexual function and indices of anxiety and depression.” Stress, depression, and stigma-induced social isolation impair the ability to attract partners and marry (2,5). Psychosocial stress also may influence the development of hypogonadism, as stress may activate the hypothalamo–pituitary axis, increasing the formation of adrenocorticotropic hormone (ACTH) and endorphin; both of these hormones inhibit gonadotrophin secretion and reproductive function (1,6).
The effect of epileptic discharges on fertility (particularly when abundant) merits consideration. Patients with focal epilepsy are more disadvantaged reproductively than those with primary generalized seizures (7,8). Temporal lobe epileptic discharge likely disrupts hypothalamic functions associated with reproduction, but direct proof of any contribution to male hypogonadism and, therefore, to the loss of male fertility, is lacking. Afferents from the medial amygdaloid nucleus and the amygdaloid–hippocampal area project directly into the medial preoptic area of the hypothalamus—an area principally involved in reproductive functions (9). Electrical kindling of the rat amygdala increased serum testosterone in one study (10). However, the fact that kindled male rats have far fewer seizures than do patients with temporal lobe epilepsy diminishes the value of the kindling model for human male reproductive assessment (11). Of interest, the medial preoptic area also is involved in motivational aspects of male copulatory behavior; thus, lesions of this area may diminish interest and sexual arousal (9).
Enzyme-inducing AEDs (e.g., carbamazepine and phenytoin) decrease BAT in two ways: 1) by suppressing gonadal testosterone synthesis, and 2) by increasing hepatic production of SHBG (1). While the Talbot et al. study confirmed these effects, their finding that BAT levels exceeded the “androgen threshold” for normal sexual function in both patients and controls suggests that, as with most side effects, AED dose exerts a significant influence. Some types of epilepsy and patients with refractory epilepsy require substantially higher AED dosing than others. For example, the percentage of patients who fall into various epilepsy syndromes or subtypes and who have been seizure-free for more than 1 year ranges from over 80% (e.g., idiopathic generalized epilepsy) to between 24 and 54% (e.g., other focal epilepsies) to 3% (e.g., temporal lobe epilepsy, with dual pathology) (12,13). Moreover, enzyme-inducing AEDs generally are preferred by prescribing physicians for focal epilepsies, whereas nonenzyme-inducing AEDs are selected for generalized epilepsies (1416). When combining data on seizure severity and AED preferences, it appears that enzyme-inducing AEDs used at higher doses may underlie the higher incidence of infertility in males with focal seizure disorders (7).
The following provides several epilepsy management implications for male patients with epilepsy:
Establishing whether the seizure disorder is focal or primary generalized, using ictal semiology and one or more EEGs, is important.
Depression is often hidden by men with epilepsy. Judicious enquiry of the patient and those living with him may be required to ascertain a diagnosis.
Probing for the presence of sexual dysfunction through history and physical examination can be helpful.
Reproductive endocrine levels can be measured by determination of the bioactive portions of total BAT and SHBG.
Patients with seizures that originate focally and are intractable can be considered for resective surgery.
If economic, employment, and driving factors permit, an attempt can be made to replace the patient's enzyme-inducing AEDs with nonenzyme-inducing ones.