Reproductive endocrine dysfunction is common in men with epilepsy.77-80 The most common dysfunction is hyposexuality, which is present in one-third to two-thirds of all men with TLE.79 Rarely, hypersexuality is observed.79,80 Both impotence with normal libido and global hyposexuality with decline in both libido and potency are seen.78,79
Hyposexuality is often a cause of great concern to men with epilepsy and may cause marital difficulties. It is often treatable, so its recognition is important.
The pathogenesis of sexual dysfunction in men with temporal lobe epilepsy (TLE), as in women, is likely to involve a number of factors:
In lesional TLE, the underlying pathologic process may be important. In cases of TLE secondary to neoplasm, for instance, hyposexuality has been noted to precede the onset of seizures by several months.78
The effects of AEDs on reproductive functioning in men occur in all epilepsy types. Because limbic structures may be directly affected by TLE, hyposexuality may be more commonly seen in TLE than in other types of epilepsies.80 It may improve with AED treatment even if it involves higher AED dosing.78,80
Sexual behavior is controlled by the sexually dimorphic regions of the hypothalamus and the amygdala82-the same regions that regulate reproductive endocrine physiology. Alteration in the function of these structures by ictal or interictal epileptiform discharges may affect both the behavioral and the endocrine aspects of sexual behavior.
Endocrine causes of hyposexuality include:79
Hormonally, sexual behavior in men is promoted by LH and androgens; it is inhibited by prolactin. It has been reported that men with TLE who have reproductive and sexual dysfunction tend to have right-sided lateralization of seizures,83 and increased risk of hypogonadotropic hypogonadism and hyposexuality. More recent reports have not shown this lateralizing relationship, however.84
Epilepsy may alter temporolimbic modulation of the frequency of LHRH and LH pulses in relation to the lateralization of the paroxysmal discharges and thus affect gonadal androgen secretion and androgen-dependent sexual behavior.85
Brain structures such as the amygdala and hippocampus contain androgen receptors, so sexual behavior may depend not only on the serum levels of androgens but also on the responsiveness of these structures to androgens.82 Alterations in these structures by ictal or interictal epileptiform discharges could alter their responsiveness, resulting in hyposexuality or hypersexuality.
Elevated interictal prolactin levels, found in men with complex partial and primary generalized seizures, may also contribute to hyposexuality.86 Chronic hyperprolactinemia is associated with decreased libido and impotence in men who do not have epilepsy.87 Prolactin antagonizes LHRH release from the hypothalamus, with a resulting reduction in LH and FSH secretion. Epilepsy-associated hyperprolactinemia could thus result in hypogonadotropic hypogonadism with associated hyposexuality.
One recent study of the effects of AEDs on reproductive functioning in men included a group of men with TLE that were not taking AEDs. Evaluation of this group allows a clearer picture of the effects of TLE itself on reproductive functioning in men. This group had significantly low free testosterone levels, without an appropriate response from the pituitary to increase testosterone production, as evidenced by a lack of increase in LH levels. These findings indicate that TLE itself affects testicular functioning as well as the central nervous system responsiveness to abnormal free testosterone levels.84
Another study found that all men with epilepsy as a group had a significantly lower percentage of normal sperm than controls, as well as higher rates of abnormal sperm morphology and decreased sperm concentration in general.88 Most men with epilepsy have normal fertility, however,77,81 although isolated cases of infertility have been observed.79
These studies showed effects of AEDs on reproductive parameters in men, but also indicated an effect of epilepsy itself. These alterations in groups of men with epilepsy cannot readily be extrapolated to an individual with epilepsy.
Temporal lobe epilepsy surgery, when it is successful and results in seizure freedom, has been associated with restoration of androgen levels to normal, according to one small series.89 This finding also supports the association between mesial temporal lobe dysfunction and reproductive dysfunction in men with epilepsy.
Many antiepileptic drugs also affect hormonal function and may contribute to hyposexuality. (See Antiepileptic drugs: Effects on male sexuality and reproduction.)
Reviewed and revised May 2004 by Cynthia Harden, MD, Weill Cornell Medical College.
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