Men and women with epilepsy are believed to be at high risk for sexual dysfunction, although the precise frequency with which sexual dysfunction occurs in epilepsy (and other chronic neurologic illnesses) is not known. However, a number of social and biologic variables that could negatively impact sexual behavior in people with epilepsy have been identified. These include low self-esteem, mood and anxiety disorders, a disruption to central nervous system regions mediating sexual behavior, and disturbances of hypothalamic, pituitary, and gonadal hormones. Sexual dysfunction in people with epilepsy can serve as a model to aid in understanding the neurobiology of sexual behavior. Most important, recognition of sexual deficits in this patient population is necessary for effective treatment to be developed and delivered.

Sexual behavior can be considered as comprising two main components—desire and arousal.⁴ Sexual desire refers to the willingness to engage in sexual behavior when given an appropriate sexual stimulus. In animals, this is evaluated as willingness to engage in sexual activities when given a receptive mate. In humans, sexual desire is equated with libido or sexual drive. Sexual desire reflects the individual’s psychological health, cultural expectations, and past sexual experiences and requires salient sexual stimuli. Hormones are also required to support sexual desire, including the gonadal sex steroids—estrogen, progesterone, and especially testosterone—as well as hormones of the pituitary, including the gonadotropins—luteinizing hormone (LH) and follicle-stimulating hormone (FSH)—and prolactin. In nonprimate mammals, the hypothalamic hormone gonadotropin-releasing hormone is required to maintain sexual desire.

The second component of the sexual response is defined as sexual arousal. This is strictly defined as the capacity to respond to an appropriate sexual stimulus with a series of stereotyped vascular, neural, and muscular responses. A normal physiologic sexual response requires an intact, functioning cerebral cortex, brainstem, spinal cord, and autonomic nervous system including the sympathetic and parasympathetic divisions. Genital structures must be anatomically and functionally normal. The physiologic sexual response also requires that the hormone milieu include adequate levels of gonadal steroids.

Sexual arousal is characterized by nonspecific physiologic arousal and by a series of stereotyped events in genital tissue, as first described by Masters and Johnson.³⁴ The male sexual response cycle begins with the excitement phase. A sexual stimulus elicits increases in heart and respiratory rates, blood pressure, and skin vascularity. Vasocongestion begins in the penis, eventually with attainment of erection and rigidity. This response is mediated by the parasympathetic branch of the autonomic nervous system and depends on sacral nerves 2, 3, and 4. When vasocongestion is maximal, the plateau phase begins and is then maintained for a variable period. The plateau phase terminates with orgasm, mediated by the sympathetic nervous system and by sacral nerves 2, 3, and 4. The resolution phase follows orgasm and is a refractory period during which no amount of sexual stimulation can elicit physiologic arousal. The refractory period is variable and tends to increase with age.

The sexual arousal cycle in women is quite similar to that in men. An excitement phase is characterized by generalized physiologic arousal and by vaginal vasocongestion and myotonia, which depends on the parasympathetic nervous system and sacral nerves 2, 3, and 4. Following the plateau phase, orgasm occurs, mediated by somatic and sympathetic nerves. The physiologic events of orgasm include rhythmic 0.8-second contractions of the pelvic floor, uterus, and fallopian tubes. In women, the refractory period is short, permitting multiple orgasms.

Regions of the cerebral cortex that mediate sexuality include the medial frontal lobe, structures within the circuit of Papez, limbic tissues, the hypothalamus, and distinct regions of the brainstem. Stimulation of the septum, the circuit of Papez, including the dorsolateral tegmentum of the midbrain, the medial orbital gyrus,³³ and the hippocampus,³² stimulates erections in primates, whereas ablative lesions in the medial forebrain bundle, the hypothalamus, and the dorsolateral tegmentum of the midbrain markedly depress or even eliminate erections and other sexual behaviors.^13,19 Lesions to the medial temporal lobe bilaterally result in the Kluver-Bucy syndrome, which is characterized by uninhibited sexuality.³⁰

The amygdala appears to be critical in mediating sexual and emotional behavior. The amygdala is rich in estrogen and androgen receptors, as well as endocannabinoid, opiate, and catecholamine receptors, all of which affect sexual behavior.⁴⁶ Bilateral amygdala ablation causes sexual dysfunction as well as disruption in other social behaviors.^19,55 Amygdala lesions are also associated with reproductive dysfunction in animals, including aspermatogenesis, anovulatory menstrual cycles, and polycystic ovaries.⁵⁶

Cortical representation of sexual behavior is not well understood in humans. One study in patients implanted with intracranial electrodes, however, reported that erections were elicited by stimulation in the circuit of Papez.²¹ Sexual orgasm was associated with high-frequency rhythmic discharges in the hippocampus, whereas chemical stimulation of the hippocampus reproduced feelings of pleasurable sexual sensation.²⁰ The cerebral cortex, particularly limbic structures, also influences sexual behavior by modulating the hypothalamic-pituitary-gonadal axis. The amygdala, a region of limbic cortex, contains two distinct nuclear groups that are reciprocally connected with the hypothalamus. The corticomedial nuclear group relays excitatory impulses to the hypothalamus, increasing the
release of hypothalamic trophic hormones. The basolateral nuclear group has an inhibitory effect on the release of these same trophic hormones. The cerebral neocortex also is directly connected with the hypothalamus, modulating the release of trophic hormones. In nonhuman mammals, gonadotropin-releasing hormone (GnRH) from the hypothalamus supports mating behavior.⁴⁰ In all mammals, GnRH acts on the pituitary to influence the release of the gonadotropins LH and FSH. The pituitary hormones LH, FSH, and prolactin affect sexual behavior. Elevated pituitary prolactin is associated with reduced libido and with impotence.⁸ The pituitary gonadotropins LH and FSH may have direct effects on the cerebral cortex to support normal sexual behavior.

The gonadotropins stimulate the release of gonadal sex steroid hormones. The gonadal steroids—estrogen and progesterone in women and testosterone in men—exert positive and negative feedback at every level of the cortical–hypothalamic–pituitary axis. In addition, high-affinity receptors for all sex steroids are extensively distributed within the amygdala and other limbic tissues, thereby affecting hypothalamic functions.^42,43,47,52 Any disturbance to the cerebral cortex and to limbic structures could theoretically disrupt the dynamic relationship among the hormones of this neuroaxis. Finally, the dynamic equilibrium of the endocrine axis can be disturbed by medications, including many antiepileptic medications, that enhance or reduce the hepatic metabolism of steroid hormones.

Sex steroid hormones are required for normal sexual desire and arousal. Sexual desire appears to be supported by androgens in both men and women. Normal physiologic sexual arousal in males requires the support of androgens, although a relatively profound androgen deficiency is required before sexual arousal fails. In fact, at least 20% of castrates continue to maintain normal sexual potency. Testosterone and another androgen, dehydroepiandrosterone sulfate, contribute and may be essential to sexual desire in women. Estrogens appear to support the vaginal vasocongestive response associated with the first phase of the sexual response cycle.³⁶

Sexual dysfunction, most often described as global hyposexuality, has been reported in people with epilepsy since 1956.¹⁸ Disorders of desire and of arousal, typically impotence, have been described in 30% to 60% of men with epilepsy.^7,27,44,53 Interviews with 97 men with chronic epilepsy¹⁶ found that 21% had never experienced sexual intercourse despite having had the opportunity to do so, and at least one third of sexually active patients had difficulty achieving and maintaining an erection or ejaculating. Sexual deviancy appears rarely in this population, and hypersexuality was found in only 1% of patients evaluated in one study.⁵³

Deficits in women have not been as well described. By self-report, there is a high incidence of dyspareunia, vaginismus, and arousal insufficiency.³⁸ One third of women with epilepsy described themselves as dissatisfied with their overall sexual function, in contrast to a community prevalence of 8%. More subtle differences in sexual desire are appreciated in some women with epilepsy. One inventory, inviting subjects to imagine and rate their degree of arousal and of anxiety in response to a number of sexual activities, found that sexual arousal was similar in women with localization-related and primary generalized (presumed genetic) epilepsies, but that women with localization-related epilepsy imagined they would experience significantly more anxiety in sexual situations.

Sexual deficits may vary by culture. In Egypt, a psychosexual history obtained in 700 women patients of an outpatient epilepsy clinic found that 18% had sexual disorders, including inhibited desire and arousal.¹² Only 29% of epileptic women in a Scandinavian outpatient clinic complained of dysfunction, which was no different than the rate for healthy controls.²⁹

Two studies have evaluated physiologic sexual function in people with epilepsy. Fenwick et al.¹⁵ assessed nocturnal penile tumescence in men with epilepsy. The patients were divided into two groups—one with relatively low testosterone levels and one with higher testosterone levels. Nocturnal penile tumescence over two nights of monitoring was diminished and disorganized in the low-testosterone group relative to the high-testosterone group. Procedural difficulties of the study included the lack of measurement of rigidity and the relatively arbitrary division into high- and low-testosterone groups. The low-testosterone group did not have a testosterone reduction that would routinely be associated with sexual dysfunction.

Stimulus-induced physiologic sexual arousal was evaluated in men and women with localization-related epilepsy of temporal lobe origin and compared with that in similarly aged controls.³⁹ In this protocol, genital vasocongestion in response to erotic video stimuli was assessed by noninvasive devices. The genital blood flow response, corresponding to the excitement phase of the sexual arousal cycle, was significantly diminished in the men and women with epilepsy. Moderate subjective sexual arousal was reported by all subjects—both those with and those without epilepsy—suggesting that the men and women with epilepsy experienced a disorder of arousal rather than a disorder of desire.

There are a number of potential mechanisms by which sexuality may be disturbed in people with epilepsy. Psychosocial deficits, such as restricted social opportunities and poor self-esteem, limit the opportunity for normal sexual interactions. Poor disease acceptance is associated with sexual dysfunction in other chronic illnesses and may contribute to impaired sexuality in epilepsy.²⁹ Depression is common in persons with epilepsy and is associated with loss of sexual desire as well as arousal deficiencies. However, physiologic mechanisms may be more relevant than psychological variables. Disruption of cortical regions mediating sexual behavior, either by fixed lesions or by epileptiform discharges, could influence sexual desire and arousal. Changes in hormones supporting sexual behavior occur in epilepsy because of seizures and antiepileptic drugs. Antiepileptic drugs have direct effects on cortical regions mediating sexuality and may also cause sexual dysfunction by secondary effects on reproductive hormones.

Psychosocial disability can adversely impact sexuality in men and women with epilepsy. Individuals with epilepsy are susceptible to poor self-esteem. Recurrent seizures may lead to a sense of vulnerability and helplessness, impairing the capacity to form healthy, nurturing relationships. Having epilepsy may limit social development, particularly for patients with frequent seizures who have restricted access to usual educational and occupational experiences. Finally, sexual behavior may be negatively reinforced if sexual feelings are a component of the seizure. Many patients are also concerned that sexual activity will precipitate a seizure, particularly those whose seizures are sometimes triggered by hyperventilation or physical exertion.