Jan. 23, 2023
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Sexual dysfunction is common in a variety of neurologic disorders. Symptoms include lack of sexual desire, erectile dysfunction in men, decreased lubrication in women, and disturbances of ejaculation and orgasm. Sexual dysfunction can be the result of a lesion involving neural tissue specifically relevant for sexual responses or lesions in other neural structures more generally involved in control of behavior. The term “hypoactive sexual desire disorder” is used to define a decline in desire for sexual activity, alone or with a partner, associated with personal distress. In this article, the author addresses sexual dysfunction in neurologic disorders and discusses how recognition and adequate management of sexual dysfunction related to underlying neurologic disorders can greatly improve patients’ quality of life.
• Sexual dysfunction may be the presenting symptom of a developing neurologic disease or it may be due to more general effects of a neurologic disorder.
• Sexual dysfunction may manifest as decreased or increased sexual desire, erectile dysfunction in men, decreased lubrication in women, and disturbances of ejaculation and orgasm.
• The history should include details of neurologic disease as well as any past history of endocrine, cardiovascular, psychological, and psychiatric disturbances.
• A detailed neurologic examination will provide better understanding of the underlying neurologic disease.
• Sexual dysfunction can be seen in patients with neurologic disorders localized to the central or the peripheral nervous system.
• The extent of the sexual dysfunction can vary based upon the localization site, natural history, and the age of onset.
• Forebrain areas regulate the initiation and execution of sexual behavior; the medial preoptic area integrates sensory and hormonal signals; and the amygdala and other nuclei play a role in the execution and reward aspects of sexual function.
• Neurophysiological tests can be utilized as direct extensions of the clinical neurologic examination.
Sexual dysfunction in neurologic disease can be classified as relating to primary, secondary, and tertiary factors. Primary factors include those stemming from physiological disturbance of sexual function or pharmacological effects. Secondary factors include those related to sensorimotor, bladder, and bowel disturbances and higher brain dysfunction. Tertiary factors include those related to psychosocial and cultural changes resulting in the disease (52).
Clinical manifestations depend on the underlying etiology from both central and peripheral nervous systems and to some extent on the aging process. Please see Table 1 for neuroanatomical localization, etiology, and laboratory workup:
The neurologic history and examination should remain focused on the details of neurologic disorders having sexual dysfunction. Sexual dysfunction (eg, lack of libido, erectile dysfunction and disturbances of ejaculation, deficient lubrication, dyspareunia, problems with orgasm) is not uncommon in the general population. Men should be asked about erectile function (the occurrence of nocturnal erections, morning erections, and erections evoked by genital, visual, auditory, or psychogenic stimuli) and retrograde ejaculation. Women may report problems with vaginal lubrication or the quality of orgasmic sensations (01; 26).
Central nervous system disorders of the brain.
Cerebrovascular disease. Reduced frequency of intercourse has been reported after stroke and other cerebrovascular disorders. Patients and their partners report that concern about precipitating another stroke leads to a decline in the frequency of intercourse (115; 120). The best predictor of decreased sexual activity in these patients is the degree of dependence in activities of daily living (86; 80). Locked-in syndrome from a lesion involving the ventral pons can occur from a variety of causes, including primary vascular or traumatic injury to the brainstem. Almost two thirds of the patients reported having sexual desire, but only one third maintained sexual relations (91).
Epilepsy. A variety of clinical manifestations can be seen in men and women with epilepsy. Various types of abnormal behavior, hypersexuality, and, most commonly, hyposexuality have been reported, particularly in temporal lobe epilepsy. Sexual phenomena may occur as part of an epileptic seizure, and sexual behavior may change in epileptic patients. Sensations in the genital organs as partial epileptic seizures can be localized to the genital sensory cortical area. Erection and ejaculation may also occur. Sexual automatisms may also occur with frontal lobe lesions (97). In men with temporal lobe damage and epilepsy, desire is sometimes preserved, but erectile function is impaired (58; 45). Menstrual irregularities are common among women with epilepsy (96; 57). Antiepileptic drugs, especially the older agents, may lead to increased estradiol and decreased free testosterone levels in men. The newer anticonvulsants seem to have fewer direct effects on sexuality (44; 15; 145; 164). Variety of sexual dysfunction have been reported in patients using antiepileptic drugs (181). Even though some sexual issues occur more commonly in patients with epilepsy than in the general population, specific predictors are challenging to be identified (71).
Multiple sclerosis. Erectile dysfunction is more common with increasing spinal cord involvement in multiple sclerosis (56; 23). Spontaneous improvement in erectile function sometimes occurs with disease remission. Problems with ejaculation are also seen in combination with erectile dysfunction (166; 43). In a study of patients with multiple sclerosis, Lombardi and colleagues documented notable percentages of blood hormone alterations and sexual dysfunction, but no significant statistical correlations were detected between hormonal status and sexual function (94). In 1 study, Keller and colleagues have revealed an association between erectile dysfunction and prior multiple sclerosis even after adjusting for potential confounders (84). Sexual dysfunction is not just limited to men and should also be considered in women with multiple sclerosis (55).
Neuroendocrine disorders. Decreased libido is the first symptom in most men with small pituitary tumors and hyperprolactinemia. Hypothalamopituitary dysfunction is usually caused by a pituitary adenoma. A decline in serum testosterone levels causes reduced libido and erectile dysfunction. The diagnosis of a pituitary tumor is sometimes not made until a decade after the onset of changes in sexual behavior (119; 100). Endocrine abnormalities are known in opiate users. However, there are still some unanswered questions, including the range of hormones affected and their clinical relevance. In an attempt to look into some of these aspects, a study was done by Trajanovska and colleagues (168). They found no statistically significant results between sexual desire and overall satisfaction. However, in the domains of erectile function and orgasm function, the results were statistically significant. The results reveal that street heroin addicts have almost 4 times as high a level of prolactin compared to the group of methadone maintenance patients. Women with hypoprolactinemia complain of loss of sexual desire compared to those with normal serum prolactin levels (75; 38).
Movement disorders. Sexual dysfunction is seen at any age in patients with Parkinson disease (176). Tremor, muscle rigidity, and bradykinesia may preclude sexual activities. Men with Parkinson disease may have premature ejaculation or an inability to maintain erections or reach orgasm (54; 88). Treatment with levodopa has been shown to induce spontaneous erections in these patients (127). Women with Parkinsonism experience vaginal tightness and dissatisfaction with the quality of their sexual experiences (174; 176). Deep-brain stimulation of the subthalamic nucleus has been utilized for sexual well-being in Parkinson disease (33; 177). Akakin and colleagues have reported hypersexuality after bilateral deep brain stimulation of the subthalamic nucleus for Parkinson disease (04).
Erectile failure is seen as an initial symptom in almost a third of patients with multisystem atrophy (16; 73). Although 10% of patients with Huntington disease (HD) have increased sexual activity, these patients may have difficulty in becoming sexually aroused (118; 18; 161; 178). It remains unclear whether the sexual dysfunction in Huntington disease is caused by the chronic illness itself or by the sociopsychiatric burden related to the illness (137). Erectile dysfunction seems to be 1 of the neglected portions in management of patients with Huntington disease. Male sexual dysfunction is seen in parallel with motor and total patient dysfunction in patients with Huntington disease (85). Neurodegenerative diseases involving α-synucleinopathies can present with a variety of symptoms including sexual dysfunction. Symptoms due to autonomic dysfunction can appear before motor symptom onset, particularly in multisystem atrophy and Parkinson disease (112).
Traumatic brain injuries. Traumatic brain injury can cause a multitude of symptoms, including cognitive impairment, personality change, and sensorimotor disability. This may be accompanied by sexual dysfunction as a consequence of either the cerebral lesion or psychosocial factors. Decreased or increased sexual desire, erectile failure, and retarded ejaculation may occur (87), perhaps in part as a consequence of post-traumatic pituitary dysfunction (02; 17). Klüver-Bucy syndrome with hypersexuality may result from traumatic lesions of bilateral anterior temporal lobes (68; 128).
Dementias. The basis of hypersexual behavior among patients with dementia is not entirely clear. Mendez and Shapira concluded that frontotemporal dementia is uniquely associated with hypersexuality (111). In addition to cognitive impairment with frontal disinhibition, there are alterations in sexual drive, possibly from right anterior temporal-limbic involvement in this disease.
Headaches. Bestepe and colleagues compared the incidence of sexual dysfunction in patients with tension-type headache, patients with migraine, and healthy controls in order to investigate the relationship between sexual dysfunction and the features of headache (22). The study revealed that patients with either migraine or tension-type headache do experience problems in several aspects of sexuality compared with healthy controls. Women treated for primary headaches were found to display a high rate of sexual symptoms and distress. Both migraine and tension-type headache were associated with sexual pain and hypoactive sexual desire disorder, but women with chronic tension-type headache seem to be more prone to develop sexual distress (122).
Disorders of the spinal cord. The male genital reflexes (reflex penile erection and the bulbocavernosus and cremaster reflexes) are abolished or profoundly depressed during the period of spinal shock, and erectile and ejaculatory functions are abolished (65). Although bladder, bowel, and sexual dysfunction often coexist, this is not necessarily the case; sexual function may be preserved in spite of severe neurogenic bladder dysfunction, presumably owing to preservation of the thoracic sympathetic outflow (12; 25). The ability to ejaculate by masturbation or sexual intercourse is impaired in most men with severe spinal cord injuries; consequently, pregnancies caused by such men are rare without medical intervention. The semen of men with spinal cord injuries is characterized by small volume, low sperm count, and low sperm mobility. Reduced fertility cannot, therefore, be completely attributed to ejaculatory dysfunction (28; 139). Given the proximity of the spinal centers controlling bladder, sphincteric, anorectal, and sexual functions, it is not uncommon to see an overlap of symptoms associated with urinary, sexual, and fecal disorders (41). Sexual dysfunction in meningomyelocele depends on the severity of the malformation. Loss of erection and orgasm may be seen along with loss of genital sensations (149; 32). Paraplegic women and their fetuses are at additional risk during pregnancy. The 2 major problems to be considered during delivery are autonomous dysreflexia as well as caesarian section (19).
Neurocutaneous disorders. Neurodermatitis is a well-recognized chronic skin disease. The associated complications are generally non-life-threatening; however, besides producing psychosocial burden and sleep disturbance, neurodermatitis can also lead to sexual dysfunction (10).
Peripheral nervous system and neuromuscular disorders.
Nerve disorders. Diabetes remains the most common cause of polyneuropathy. The most frequent type of neuropathy is the distal symmetric sensorimotor variety, in which small nerve fibers may be involved earlier than large fibers. When accompanied by autonomic involvement, bladder, bowel, and sexual dysfunction can occur (64). Erectile dysfunction is particularly common in diabetic men. Neurogenic erectile dysfunction usually occurs with other signs of neuropathy. Retrograde ejaculation may result from failure of normal closure of the bladder neck by sympathetic activation during ejaculation. In women, the degree of sexual dysfunction correlates with the degree of other diabetic complications (48). Sexual dysfunction in both men and women is reportedly more common with insulin-dependent diabetes (64). Women with familial amyloidotic polyneuropathy are 4 times as likely to have disorders of desire, arousal, orgasm, and sexual dissatisfaction (125).
Autonomic dysfunction, including erectile dysfunction, occurs in other peripheral neuropathies, including those due to infectious agents, chemical toxins, secondary amyloidosis, vitamin B1 deficiency (167), or vitamin B12 deficiency (89), or those who are parainfectious or paraneoplastic. Uremic autonomic neuropathy involves erectile dysfunction in men and reduced desire and lubrication in women (31; 51). Trauma may be the cause of pudendal nerve injury, leading to loss of penile sensation, dysesthesias, pain syndromes, and dribbling ejaculation because of perineal muscle denervation (11; 74). Erectile dysfunction and ejaculatory problems have been reported with some hereditary polyneuropathies including Charcot-Marie-Tooth disease (21) and amyloidotic neuropathies (35). Medication-induced sexual dysfunction (especially that induced by antihypertensives and antidepressants) has been reported to the WHO centers (98).
Chronic pelvic pain (CPP) is often attributed to psychogenic causation. To determine if women with CPP possess a unique psychological profile, Roth and colleagues examined the comparative pain experience, psychological functioning, and marital/sexual satisfaction of women with either CPP or chronic migraine headache (143). Patients with CPP reported greater dissatisfaction with their marriage and greater sexual dysfunction.
Disorders of nerve roots. Erectile dysfunction is present in almost 75% of patients with complete lesions of the cauda equina. However, 25% of remaining patients are still able to achieve an erection. This is thought to be mediated by a sympathetic erectile pathway involving the hypogastric plexus rather than parasympathetic erectile pathways. There are also ejaculatory disturbances, penile sensory loss, paresthesias, dysesthesias, and even pain syndromes. Women report dyspareunia, loss of lubrication, loss of sensation during vaginal intercourse, and difficulties in achieving orgasm (105). Sexual activity may be affected in lumbar disc herniation through different mechanisms (05). Decreased sexual desire and decreased sexual intercourse are the most commonly reported problems. Taking time during examination and giving simple recommendations may improve sexuality and quality of life of the patients.
Muscle disorders. Patients with myotonic dystrophy may have diminished libido, hypogonadism, and erectile dysfunction (104; 126). A study by Antonini and colleagues revealed that myotonic dystrophy patients with hormonal evidence of interstitial failure had a larger cytosine-thymine-guanine (CTG) expansion, longer disease duration, higher grade of disease, and lower erectile function score than eugonadic patients (13). Impotence occurred in 13 of 14 hypogonadic patients with interstitial failure and in 5 of 12 eugonadic patients.
Disorders of anterior horn cells. Sexual activity may be limited in patients with muscle weakness, but men with motor neuron disease are able to achieve erection and ejaculation (79). Sexual relationships remain an important aspect of life for people living with motor neuron disease. The model from the study by Marsden and Botell provides a structured approach to assist in discussions with patients as well as to promote reflection and exchange of knowledge in the multidisciplinary team (102). It is a useful model when addressing issues that are sometimes difficult to discuss. In hereditary neuromuscular diseases like Kennedy syndrome (eg, X-linked bulbospinal muscular atrophy), gynecomastia, testicular atrophy, decreased libido, and erectile dysfunction may occur.
Aging. With normal aging, a variety of changes occur in both men and women. The frequency of intercourse overall is reduced for both men and women. Men have decreased ejaculatory volume as well as sensation of impending ejaculation. In addition, their refractory period after detumescence is prolonged, requiring more time and stimuli to achieve erection and orgasm (144; 78). In women, menopause leads to decreased sexual thoughts, libido, and thinning of the vaginal wall with decreased elasticity and lubrication (30).
Prognosis depends on the underlying etiology. Neurologic complications of sexual activity include benign coital cephalgia and transient global amnesia. The term benign coital cephalalgia refers to a sudden, severe headache at the time of the orgasm. Headache may begin before orgasm and worsen as orgasm approaches. The headache is usually pulsatile and occipital in location and may last from 10 minutes to several hours. Most patients are men in the third or fourth decade (131). The most concerning diagnosis in the differential is subarachnoid hemorrhage or referred pain to the head due to angina pectoris or myocardial infarction. Spontaneous remission is the rule. Short-term prophylaxis with indomethacin or propranolol is recommended (47). Although amyl nitrite can be used to enhance orgasm, phosphodiesterase inhibitors taken for treatment can cause headache as a side effect (53; 24; 130).
Transient global amnesia is seen most commonly in women. Sexual intercourse has been reported among provoking events in both genders (135; 03).
At 2-year follow up, patients who underwent surgical procedures, including fusion or total disc replacement for back pain, were found to have an improvement in their sex lives (20).
A 42-year-old man had a 10-year history of type 1 diabetes. The patient had experienced burning sensations in his feet for the past 6 months. On further exploration, the patient and his wife reported that he had been experiencing erectile dysfunction and had recently started sildenafil. He denied any significant benefit from this medication, but he experienced the side effect of intermittent chest pain. Autonomic studies were performed that revealed normal heart rate variation with Valsalva maneuver and tilt-table testing. However, heart rate response to deep breathing was markedly reduced, and QSART revealed sweat below the 5th percentile from the feet. The patient’s erectile dysfunction was most likely secondary to autonomic dysfunction from diabetes.
Neuroanatomical localization to the central and peripheral nervous systems can produce sexual dysfunction. Please see Table 1 for neuroanatomical localization, etiology, and laboratory workup:
Please see clinical manifestations, etiology, and epidemiology sections for details.
Central nervous system disorders. Epidemiology of some disorders is listed under the clinical manifestations and additional information is mentioned in this section.
Almost half of men have erectile dysfunction after a stroke (08; 80). The prevalence of major sexual dysfunction (decrease in libido and frequency of intercourse) is reportedly significantly greater after right- than left-hemisphere stroke in men with unilateral lesions (36; 93). Involvement of the nondominant hemisphere, especially the parietal lobe, was more often associated with a decline of desire.
Patients with epilepsy, regardless of gender, often report a loss of sexual desire, reduced sexual activity, or inhibited sexual arousal; the prevalence of these complaints varies in different studies (117; 58; 45; 185). Sexual interest is more reduced in patients with right than left temporal lobe epilepsy. Yang and Wang have reported that Topiramate, pregabalin, and gabapentin may cause sexual dysfunction, whereas oxcarbazepine, lamotrigine, and levetiracetam may improve sexual function (181).
Increased sexual arousal in patients with movement disorders has different etiologies and is linked to cultural aspects, deep brain stimulation, or even dopaminergic treatment (165).
Patients with multiple sclerosis, irrespective of the gender, have sexual dysfunction mainly related to spinal cord involvement by the disease; dysfunction is associated with urinary symptoms and lower limb involvement (186; 106). The course and duration of the multiple sclerosis did not predict sexual dysfunction in these patients. However, depression may be a major contributory factor for sexual dysfunction in both men and women with multiple sclerosis (92).
Patients with erectile dysfunction and low serum testosterone level may not have a space-occupying lesion in the hypothalamopituitary region (34).
The mechanisms behind sexual dysfunction in parkinsonian patients are not well understood (154; 169). Multiple system atrophy selectively involves certain autonomic nuclei, including Onuf's nucleus, but it remains unclear why erectile dysfunction is an early symptom in multiple system atrophy (172; 132).
In patients with traumatic brain injury, frontal and temporal lesions seem to result more often in sexual disturbances than do parieto-occipital lesions. In addition, basal frontal and limbic brain injury may lead to inappropriate sexual behavior (153). Yang and colleagues reviewed a comprehensive database to analyze the association of erectile dysfunction and traumatic brain injury in the Asian population (182). They revealed that traumatic brain injury patients have a significantly higher risk of developing erectile dysfunction.
Almost 80% of men with spinal cord injury reported spontaneous erections (97). Latency to orgasm is greater in women with spinal cord injury than in normal subjects (157; 156). Sexual readjustment has been positively correlated with a young age at injury and frequency of sexual intercourse (65; 155).
Fibromyalgia has negative effects on female sexual function that are aggravated by depression (183).
Peripheral nervous system disorders. Erectile dysfunction has been reported in 9% of diabetic men aged 20 to 29 years, rising to 95% of diabetics by 70 years of age. Patients experienced onset of impotence within the first 10 years of their disease in 50% of cases (50; 83). In addition, men with diabetic polyneuropathy have reduced sleep-related erections, diminished penile circumference increase, and lower penile rigidity (72).
Autonomic involvement may lead to erectile dysfunction in Guillain-Barré syndrome (63). Bladder, bowel, and sexual problems may also occur in patients with chronic inflammatory demyelinating polyneuropathy but are less common.
In a group of men with cauda equina lesions of differing causes and variable severity, only 15% reported normal sexual function (133; 105).
Surgical procedures may damage the peripheral autonomic nerves to the genitalia, leading to erectile and ejaculatory dysfunction in men and loss of lubrication in women (90). Erectile dysfunction has also been reported with injection of sclerosing agents to treat hemorrhoids (170).
Prevention depends on control of underlying medical problems.
The differential diagnoses are included in the clinical manifestations section.
Continuous monitoring of nocturnal penile tumescence can be obtained by a rigidometer at various states during the day or night. Testing for nocturnal erections, however, does not reliably distinguish psychological from CNS causes of erectile dysfunction (56). Suspected vasogenic erectile dysfunction may require the testing of penile vasculature (blood pressure and vascular competence) by a urologist. Pharmacotesting may be sufficient for the majority of patients, and invasive tests should be reserved for those in whom surgery is considered (113; 66).
Direct or indirect methods can be used to measure blood-flow changes in the labia and vagina. Noncontrast dynamic MRI can assess female sexual arousal quantitatively (101). The vibration perception threshold on the penis (glans and shaft) in neurologically healthy men is similar to that of the feet, whereas in females this threshold (best measured on the clitoris, labia majora, and perineum) (76) is the same as in the hands. Small-fiber function testing, eg, penile thermal sensation, may be more informative about the neural control of erection (42).
Neurophysiological testing of pudendal nerve function, however, is not more sensitive in diagnosing neuropathy in impotent diabetics than limb nerve conduction studies (171; 172; 67). Methods for assessing sacral or suprasegmental neural lesions include somatic sensory (QST, QSART, dorsal penile neurography, pudendal SSEPs), visceral sensory (SSEPs to proximal urethra/bladder neck, bladder sensitivity testing), somatic motor (EMG, MEPs, sphincter muscle M wave), sacral reflex (bulbocavernous reflex, anal reflex), autonomic (SSR, penile EMG), neurocardiac (HRDB) and cystometric tests.
Cortical-evoked potentials of the dorsal nerve of the clitoris suggest that pudendal somatosensory input is necessary for female orgasmic function (180; 29). Penile EMG, despite some controversy about the source and nature of the signal (151), seems to be a promising investigative technique that has also been applied to the clitoris (103). The lumbosacral sympathetic system may be tested by the SSR from the perineum (and penis). Recordings should be made both in the limbs and perineum so that generalized, localized, somatic, and autonomic neuropathy might be distinguished (09).
Hormone assays may be obtained in patients with sexual dysfunction and symptoms or signs indicating neuroendocrine dysfunction. The hormones to be studied depend on the circumstances (sex, age, and onset and nature of symptoms). Endocrine consultation may be helpful.
The management of sexual dysfunction occurring in the setting of neurologic disease depends on the specific clinical situation and etiology of the process in question. Sexual dysfunction must be part of the overall management of neurologic patients. The treatment of sexual dysfunction requires multidisciplinary teamwork and cooperation among specialists, individual patients, partners, and society. Sexual education, counseling, and specific suggestions about therapeutic methods are important. The management of sexual dysfunction in men is focused on problems with erection, ejaculation, and decreased libido. In women, the focus is on management of decreased libido and anorgasmia. Healthcare providers should be aware of the importance of managing erectile dysfunction in spinal cord-injured men, as it represents a major determinant of their psychological distress, independently of the degree of functional independence impairment (14). Sexual dysfunction after spinal cord injury has a major impact on quality of life and interpersonal relationships for spinal cord–injured men. Akman and colleagues emphasized the need for sexual education and recommended that more attention be given to sexuality after spinal cord injury (06).
Treatment of neurogenic erectile dysfunction. The development of drug treatments by the oral and intracavernous routes has made a dramatic impact in the quality of life for men with erectile failure. Surgical treatment is not the preferred method.
Sildenafil has been first in the group of specific phosphodiesterase-5 inhibitors to be approved for erectile dysfunction. The selective inhibitors of type 5 c-GMP augment the nitric oxide mediated relaxation pathway in penile tissues by increasing available cyclic guanosine monophosphate in the corpus cavernosum (116; 107). It has shown efficacy in treatment for erectile dysfunction in men with diabetes (27; 123), renal transplantation, multiple sclerosis, Parkinson disease (07), spinal cord injury (46), spina bifida (129; 46), and familial amyloidotic polyneuropathy (124). In a literature review done by Lombardi and colleagues, PDE5s represent first-line erectile dysfunction therapy only for spinal cord injury patients, though treatment results through meta-analysis were not possible. Encouraging results are reported for Parkinson and multiple sclerosis patients (95). In men with diabetes mellitus or spinal cord injuries, vardenafil (5 to 20 mg) and tadalafil (2.5 to 20 mg) have been used with similar efficacy (60; 59; 152). Tadalafil also has a longer half-life and is, thus, longer acting (49). Comparative studies done on tadalafil and vardenafil did not reveal a statistically significant difference in effectiveness or satisfaction (141).
Sildenafil can be started at 25 or 50 mg 1 hour before intended sexual activity. Significant effects have been reported between 30 minutes and 4 to 6 hours after taking the medication. Sildenafil can be used repeatedly, and if used once or twice per week, there should be no fear of tachyphylaxis (148; 109). In men with erectile dysfunction after radical prostatectomy, sildenafil is ineffective when a nerve-sparing procedure was not performed on at least 1 side (110; 107).
Phosphodiesterase-5 inhibitors are contraindicated in combination with vasodilator drugs of the nitro type and nitric oxide donors in men with retinitis pigmentosa and hypotension (blood pressure below 90/50 mmHg). The most common adverse events of sildenafil are headache, flushing, and dyspepsia. Temporary color-visual disturbances may occur at doses of 100 mg (148; 110). Recommendations for the use of sildenafil in patients with cardiovascular disease have been published (187). Although no significant increased risk of cerebrovascular events has been reported, there has been in 1 case a temporal association of sildenafil use with a transient ischemic attack and then a stroke (110; 108). In 1 study, there seems to be limited evidence to support sildenafil citrate as an effective treatment for erectile dysfunction in patients with multiple sclerosis. The authors recommend future well-designed, randomized, double-blinded, placebo-controlled trials with long-term duration (179).
Apomorphine, a sublingual alpha2-adrenergic blocker, is another therapeutic option for men with erectile dysfunction. The action is through a dopaminergic effect in the hypothalamus. Doses of 2 to 4 mg are given. Erection occurs within 10 to 25 minutes (61; 140). Nausea is the most common adverse reaction (69; 140).
Among self-injection therapies for erectile dysfunction, prostaglandin E1 (alprostadil) is the preferred drug. Papaverine intrapenile injections have also been used extensively in the treatment of erectile dysfunction in men with spinal cord injury, multiple sclerosis, or other neurogenic conditions. Priapism and prolonged erection were the most common acute complications but were dose-related (114; 146). The effect is very rapid and may last for 2 to 4 hours. Its efficacy in diabetic patients with impotence has been confirmed (70; 134). Local bleeding, pain, and fibrosis may develop in the corpora cavernosa, leading to loss of effectiveness.
Painless priapism of less than 6 hours duration should be treated at first by cooling. Oral treatment with terbutaline may be attempted only when self-injection therapy has resulted in prolonged erections lasting for less than 4 hours. However, the guidelines of the American Urological Association and the European Association of Urology do not recommend any oral or subcutaneous vasoconstricting medication for ischemic erections lasting longer than 4 hours. The initial intervention should be therapeutic blood aspiration with a 19- or 21-gauge needle under sterile conditions (97).
Intraurethral therapy with alprostadil (prostaglandin E1) seems an effective treatment of erectile dysfunction and is preferred compared to intercavernous injections (142). Transdermal nitroglycerin applied on the penis may allow an erection sufficient for vaginal penetration but is not as effective as intracavernous papaverine (138).
Vacuum devices can be utilized to develop rigidity essential for vaginal penetration. Premature loss of rigidity and difficulty in placing and removing the constriction bands are common complaints. The most common complications are bruises, petechiae, and skin edema. Prolonged placement of constriction band over 30 minutes may lead to penile gangrene, severe erosion, and cellulitis (40; 114). Penile prostheses and surgical revascularization are not utilized currently as risk outweighs the benefits.
In patients with sexual function related to diabetes, tadalafil and vardenafil are equally effective and well-tolerated, with no serious side effects (81). Sildenafil can be considered as an effective treatment in patients with Parkinson-emergent erectile dysfunction (147).
Rahimi-Movaghar outlined a step-wise approach in patients with spinal cord injury. Step 1 involves smoking cessation, weight loss, and increasing physical activity. Step 2 is phosphodiesterase type 5 inhibitors such as Sildenafil, intracavernous injections of Papaverine or prostaglandins, and vacuum constriction devices. Step 3 is a penile prosthesis, and Step 4 is sacral neuromodulation (136). When trying to prioritize the management, especially with an overlap symptomatology, the treatment of urinary incontinence and management of anorectal disorders should precede the treatment for sexual complaints (41).
Utilization of oral appliance can help improve the erectile function in patients with obstructive sleep apnea-hypopnea syndrome (184).
Treatment of ejaculatory dysfunction in men with neurologic disorders. Treatment of ejaculatory dysfunction includes nonpharmacotherapy and pharmacotherapy options. Vibratory stimulation may be helpful for anejaculation or anorgasmia. The presence of intact dorsal penile nerves is necessary for orgasm achieved by penile vibratory stimulation (175; 159). In addition, penile vibration has been found to have a significant antispastic effect in men with spinal cord injuries (37). Patients may somewhat respond to problems of retrograde ejaculation with sympathomimetic pharmacological agents such as imipramine, ephedrine, or phenylpropanolamine. If retrograde ejaculation continues, then sperm for inoculation can be retrieved from the bladder. Premature ejaculation may be treated with antidepressants (tricyclic agents such as clomipramine, or SSRIs such as sertraline or paroxetine may be tried) (162; 82; 163). In men with spinal cord injury, when sperm retrieval is wanted, Ibrahim and colleagues have emphasized trying the simple methods of penile vibratory stimulation or electroejaculation prior to some advanced or invasive surgical procedures (77).
Treatment of abnormalities of libido in men with neurologic disorders. Hormonal insufficiency should be corrected in both men and women. Dopaminergic drugs may also be helpful for reduced libido in some instances. For abnormally increased libido, androgen antagonists (cyproterone acetate, medroxyprogesterone acetate) may be effective. In resistant cases, neuroleptics are usually helpful (97). Song and colleagues demonstrated that a sexual rehabilitation intervention program significantly increased sexual satisfaction and frequency of sexual activity (160). The intervention program can be used as a practical guideline for post-stroke sexual rehabilitation. In addition, the findings of this study provide evidence regarding the usefulness of sexual education and counseling on the sexual health of post-stroke patients and their spouses. The exact contribution of patients’ neurologic profile including stroke laterality and severity of their sexual dysfunction remains indecisive; however, sexual rehabilitation needs to be an integrative part of stroke patients’ rehabilitation process at the interdisciplinary level (62).
Treatment of lack of libido and anorgasmia in women with neurologic disorders. Hormone replacement can benefit women with signs of estrogen insufficiency. Vibratory stimulation may be helpful in patients with genital sensory disturbances and in those with weakness or motor disorders. Sildenafil has been tried and well tolerated in women with multiple sclerosis who have a lack of sexual arousal (39; 146). Lubrication was effected, but quality of life did not improve significantly. In women with dysesthetic or painful sensations in the genitalia that are not alleviated by improving lubrication, antiepileptic drugs such as gabapentin, pregabalin, and carbamazepine may be helpful (158).
In addition to the above-mentioned measures, sexual education and counselling has shown benefits to improve the sexuality and quality of life in these patients (173).
At 2-year follow up, patients who underwent surgical procedures, including fusion or total disc replacement for back pain, were found to have an improvement in their sex lives (20).
Proper understanding of women's sexual function requires a detailed awareness about their physical, emotional, and psychosocial states. Sexual dysfunction may occur at any level, and diagnosing such issues begins with careful assessment through a sexual health history (121). Sexual function often decreases during pregnancy, particularly in the third trimester. Reduced sexual activity may persist for up to 6 months following delivery. Breastfeeding, dyspareunia, and postpartum pelvic floor dysfunction were reported as possible causes for the delay in resuming sexual intercourse after childbirth. Awareness in couples about the decline of libido, desire, and orgasm encountered during pregnancy and puerperium may help improve quality of life (150).
No specific information about anesthesia is available with regard to sexual dysfunction in patients with neurologic disorders.
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