How Do Seizures Affect Reproductive Endocrine Function In

Reproductive endocrine dysfunction is common in men with epilepsy.45-48 Hyposexuality, the most common clinical finding, is often a cause of great concern and, not infrequently, of marital difficulties. Its recognition is thus important, particularly because it is often treatable.

Hyposexuality is present in one-third to two-thirds of all men with TLE.47 Causes include hypogonadotropic hypogonadism (about 25%), hypergonadotropic hypogonadism (about 10%), and hyperprolactinemia (about 10%).47 Reproductive dysfunction may be confined to the patient's sexuality with reproductive potential remaining normal. Unlike women with epilepsy, men with epilepsy have mostly normal fertility,33,45 although isolated cases of infertility have been observed.47 In most epileptic men with sexual dysfunction, the dysfunction is hyposexuality; rarely is hypersexuality observed.47,48 Both impotence with normal libido and global hyposexuality with decline in both libido and potency are seen.46,47

The pathogenesis of sexual dysfunction in epileptic men, as in epileptic women, is likely to be multifactorial. Alteration of temporal lobe function by an underlying pathologic lesion, alteration of temporal limbic structures by ictal or interictal discharges, associated neuroendocrine changes, and medication effects may all play a part.

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.46

Although several AEDs can cause hyposexuality (a detailed discussion follows), epilepsy-related alteration of limbic structures may be directly involved. Thus, hyposexuality is commonly seen in TLE but not in other types of epilepsies,48 may occur in patients with untreated TLE,47 and may improve with AED treatment even if it involves higher AED dosing.46,48

Sexual behavior is controlled by the sexually dimorphic regions of the hypothalamus and the amygdala43—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.

Hormonally, sexual behavior is promoted by LH and androgens in men and women and by estradiol in women; it is inhibited by prolactin. Men with TLE who have reproductive and sexual dysfunction tend to have right-sided lateralization of seizures,49 reduced LH pulse frequency compared with men with left-sided TLE (unpublished personal observation), and increased risk ofhypogonadotropic hypogonadism and hyposexuality. Thus, 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. Moreover, this behavior may depend not only on the serum levels of androgens but also on the responsiveness to androgens by brain structures such as the androgen receptor-containing amygdala and hippocampus.43 It is possible that alterations in these structures by ictal or interictal epileptiform discharges could alter the responsiveness to androgens, resulting in hyposexuality or hypersexuality.

In addition, elevated prolactin levels may also be a contributing factor to hyposexuality in epileptic men. Chronic hyperprolactinemia in nonepileptic men is associated with decreased libido and impotence.3" Men with both complex partial and primary generalized seizures have increased prolactin levels interictally.3' 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.

The effects of AEDs on sexuality and the evaluation of hyposexuality are discussed later, in the section on AED effects on hormonal function.

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