Journal of the Neurological Sciences 350 (2015) 7–13

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Review article

Stroke and sexual dysfunction — A narrative review Jong-Ho Park a,b, Bruce Ovbiagele b, Wuwei Feng b,⁎ a b

Department of Neurology, Myongji Hospital, Goyang, South Korea Department of Neurology, MUSC Stroke Center, Medical University of South Carolina, Charleston, SC, United States

a r t i c l e

i n f o

Article history: Received 5 October 2014 Received in revised form 9 January 2015 Accepted 1 February 2015 Available online 7 February 2015 Keywords: Stroke Sexual dysfunction Complication Outcomes Rehabilitation

a b s t r a c t Sexual function is an essential part of quality of life in adults. However, sexual dysfunction (SD) in stroke survivors is a common but under-recognized complication after stroke. It is frequently neglected by patients and clinicians. The etiology of post-stroke SD, which is multifactorial includes anatomical, physical and psychological factors. Complete return of sexual function is an important target for functional recovery after stroke, so clinicians need to be aware of this issue and take a lead role in addressing this challenge in stroke survivors. Accurate diagnosis and prompt treatment of post-stroke SD should be routinely incorporated into comprehensive stroke rehabilitation. This narrative review article, outlines the anatomy and physiology of sexual function, discusses various factors contributing to post-stroke SD, and proposes directions for future research. © 2015 Elsevier B.V. All rights reserved.

Contents 1. 2. 3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . Physiology of the sexual response cycle . . . . . . . . . . . . . Anatomical locations responsible for sexual dysfunction (Table 1) . 3.1. Mesodiencephalolimbic system . . . . . . . . . . . . . 3.2. Cerebral hemisphere, cortex and subcortex (Striatum) . . . 3.3. Cerebellum . . . . . . . . . . . . . . . . . . . . . . 3.4. Anatomical locations responsible for hypersexuality . . . . 4. Sexual dysfunction after stroke. . . . . . . . . . . . . . . . . 4.1. Factors contributing to post-stroke sexual dysfunction . . . 4.1.1. Psychological factors . . . . . . . . . . . . . . 4.1.2. Sociodemographic factors. . . . . . . . . . . . 4.1.3. Physical deficits . . . . . . . . . . . . . . . . 4.1.4. Vascular risk factors . . . . . . . . . . . . . . 4.1.5. Urogenic factors . . . . . . . . . . . . . . . . 4.1.6. Autonomic dysfunction. . . . . . . . . . . . . 4.1.7. Neuroendocrine dysfunction . . . . . . . . . . 4.1.8. Partner factor(s) . . . . . . . . . . . . . . . . 4.1.9. Medications . . . . . . . . . . . . . . . . . . 5. Return of sexual functionality after stroke . . . . . . . . . . . . 6. Conclusions and future research . . . . . . . . . . . . . . . . Source of funding . . . . . . . . . . . . . . . . . . . . . . . . . Disclosures . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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⁎ Corresponding author at: Department of Neurology and Neurosurgery, Medical University of South Carolina, Charleston, SC 29425, United States. Tel.: +1 843 792 3020. E-mail address: [email protected] (W. Feng).

http://dx.doi.org/10.1016/j.jns.2015.02.001 0022-510X/© 2015 Elsevier B.V. All rights reserved.

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J.-H. Park et al. / Journal of the Neurological Sciences 350 (2015) 7–13

1. Introduction

3. Anatomical locations responsible for sexual dysfunction (Table 1)

Stroke is a leading cause of disability that can impair physical, linguistic, cognitive and sexual function [1]. Of all post-stroke disabilities, sexual dysfunction (SD) is considerably under-recognized. SD can present as decreased libido, impotence or inability to ejaculate in males or decreased libido, lack of vaginal lubrication, arousal problems or orgasmic dysfunction in females. Understandably stroke patients are often embarrassed to discuss SD issues with their physicians. Patient reticence and physician ignorance have arguably led to a relative neglect of poststroke SD, thereby limiting our ability to explore underlying mechanisms and identify appropriate therapeutic strategies [2]. Normal sexual function relies on a complex network of central and peripheral nervous system pathways involving autonomic (sympathetic/parasympathetic), spinal, and somatic nervous systems [2]. However, little is known about the impact of stroke on sexual activity or which specific psychological or organic factors contribute to SD after stroke. In this narrative review, we first outline the physiology and anatomical correlations of sexual activity; secondly, we discuss the various factors contributing to post-stroke SD; and finally, we propose directions for future research.

3.1. Mesodiencephalolimbic system

2. Physiology of the sexual response cycle There are three ways that neurobiological systems are involved in sexual response [2,3]: (1) physiologic input systems for inducing sexual arousal, (2) spinal and mesodiencephalolimbic in mediating sexual arousal, and (3) physiologic response in the genital region by sympathetic/parasympathetic nervous system necessary for priming and executing a sexual activity. In males, the neurotransmitters and neuropeptides facilitating penile erections are oxytocin, dopamine, glutamic acid, opioid peptides, hexarelin peptides, and pro-VGF peptides [4]. The paraventricular nucleus (PVN) of the hypothalamus [4] is the most sensitive area for the pro-erectile effect of oxytocin. It projects oxytocinergic neurons to extra-hypothalamic brain areas (e.g., septum, hippocampus, amygdala, ventral tegmental area, medulla oblongata and spinal cord). The PVN is considered as a cardinal integration center between the central and peripheral autonomic nervous systems [5]. During sexual arousal, oxytocin-induced penile erection is mediated by Ca2+ influx into the oxytocinergic neurons in PVN. This causes nitric oxide by activation of nitric oxide-synthase. Nitric oxide in turn leads to the activation of oxytocinergic neurons, which project to extra-hypothalamic brain areas, thereby inducing penile erection and copulatory behavior [4,5]. Oxytocinergic pathways from PVN to extra-hypothalamic brain areas that mediate penile erection are illustrated in Fig. 1. Furthermore, oxytocin also activates mesolimbic dopaminergic neurons. Dopamine released in the nucleus accumbens (NAcc) in turn stimulates neural pathways leading to the activation of incerto-hypothalamic dopaminergic neurons in the PVN involved in erectile function [4]. On the contrary, little is known about precise mechanisms that mediate female sexual response. Male genital apparatus is innervated mainly by pudendal nerves, which contain the primary afferent sensory and motor pathways to the penis, and by cavernous nerves, which contain the primary efferent sympathetic and parasympathetic pathways [5]. Cavernous nerves are innervated by hypogastric nerves, pelvic nerves, and paravertebral sympathetic ganglia chain of the thoracic–lumbar tract (T11–L2) [5]. In males, penile erection is mediated by pelvic parasympathetic activity while ejaculation is controlled by thoracolumbar sympathetic system [6]. In females, sexual stimulation increases blood flow to the vagina resulting in lubrication and erection of the cavernous tissues and clitoris, which are innervated by the pudendal nerve [7]. Sexual function in females proceeds in a more complex and circuitous manner than males and is more vulnerable to psychosocial factors [8].

The thalamus may play a crucial role in penile erection. Jeon et al. investigated the correlation of erectile dysfunction (ED) with stroke lesion(s) in 44 ischemic stroke patients [9]. Thalamic lesions were found to be more associated with ED compared to lesions in other locations. In an fMRI study, the thalamus was bilaterally activated during erection in 10 out of 12 subjects [10]. In another study, eleven healthy heterosexual young volunteers underwent positron emission tomography (PET) to measure increases in regional cerebral blood flow (rCBF). During ejaculation, the mesodiencephalolimbic system, including the ventral tegmental area, lateral central tegmental field, subparafascicular nucleus, and the medial/ventral thalamus recorded the most intense activation [11]. However, another study found no specific activation in the thalamus or hypothalamus to the genital part of the primary somatosensory cortex during sexual intercourse [12]. The NAcc is a part of the mesolimbic system and regulates dopaminedriven pleasure and sexual activity [13]. Studies of NAcc relating to sexual behavior have shown conflicting results. In a study with male rats, bilateral NAcc lesions caused inability to have an erection and intromission [14], but other studies showed only minor impairment of sexual behavior or limited change after NAcc damage [15,16]. Moreover, increased rCBF was not observed in NAcc in a human study [12]. The amygdala was found to be closely associated with ejaculation in human studies [11,17]. Contrary to other limbic system studies, the amygdala seems to have an inverse relationship between euphoric psychological states and amygdala activation during human male ejaculation [11]. 3.2. Cerebral hemisphere, cortex and subcortex (Striatum) The right hemisphere is more likely to play a dominant role in activation/attention of libido and erectile functionality [18,19]. Sexual reaction time is more impaired in right hemispheric stroke than left [19]. In a PET study [12] to measure rCBF during various stages of sexual performance, sexual stimulation of the penis increased rCBF in the posterior insular and adjacent posterior part of the secondary somatosensory cortex of the right hemisphere. In the neocortex, the activated regions were primarily on the right side. The right hemisphere also dominates in sensing emotional stimuli, as a result, right parietal lesions frequently cause hemi-inattention [18] and increase susceptibility to emotional disorders [20,21]. Patients with right hemispheric stroke likely have difficulty in responding to erotic sensations because of sensory and perceptual neglect [22]. Therefore, it is conceivable that right parietal lesions are more closely associated with the development of SD. However, studies are not consistent regarding the laterality of hemispheric lesion and SD. Monga et al. reported that females with right-hemispheric lesions were more likely to experience a decline in sexual function when compared to those with left-hemispheric lesions [23]. Another study suggested that left hemispheric lesions play an important role in post-stroke SD (diminished libido or satisfaction) among male patients [24]. Post-stroke depression occurs more commonly with left hemispheric stroke and is closely related to SD, but these studies failed to show a relationship between the lesion side and SD [25–27]. 3.3. Cerebellum The cerebellum is involved with motor coordination, emotional processing [28] and sexual arousal [17]. Large portions of cerebellum, including deep cerebellar nuclei, vermis, and hemispheres are activated during ejaculation, especially the left side [11]. Jung et al. showed that right cerebellar lesions were associated with ejaculation disorder in a

J.-H. Park et al. / Journal of the Neurological Sciences 350 (2015) 7–13

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Fig. 1. Schematic representation of oxytocinergic neurons in the paraventricular nucleus (PVN) of the hypothalamus in males. Penile erection was mediated by Ca2+ influx into the oxytocinergic neurons in PVN that are linked to extra-hypothalamic brain areas. Facilitatory neurotransmitters and neuropeptides that control penile erection are oxytocin, dopamine, glutamic acid, opioid peptides, hexarelin peptides, and pro-VGF peptides. Nitric oxide-synthase-induced nitric oxide activates oxytocinergic neurons that project to extra-hypothalamic brain areas and genital apparatus, thereby inducing penile erection.

survey of 109 post-stroke male patients [29]. Annoni et al. reported a patient with a left cerebellar infarct who showed emotional blunting and autonomic inability to react differentially to positive and negative external stimuli [30]. The fastigial nucleus in cerebellum is closely connected with hypothalamus, which is responsible for sympathetic/parasympathetic modulation [31].

3.4. Anatomical locations responsible for hypersexuality While hyposexuality is a common occurrence after a stroke, hypersexuality can occur. Increased libido was reported in 10% of 192 stroke patients in one study [26]. Hypersexuality after stroke is commonly associated with temporal lobe lesions [32]. It can also develop after subthalamic or bilateral thalamic infarction [33,34]. Frontolimbic structures may have an important role in sexual behavior as well. Hypersexuality may result from reactive hypermetabolism within the frontolimbic system (basal forebrain, temporal lobes, anterior cingulate, and medial prefrontal cortices) and striatum ipsilateral to the stroke [33].

4. Sexual dysfunction after stroke As summarized in Table 2, post-stroke SD is quite common with a prevalence ranging from 20 to 75%. Majority of study subjects are males. However, SD can occur in either male or female stroke survivors [23–27,35–42]. Clinical presentations of SD for males include decreased sexual activity despite normal function, decreased libido, decreased frequency of coitus, ED and ejaculatory dysfunction. In females, SD is generally exhibited as decreased libido, lack of vaginal lubrication, arousal problems and orgasmic dysfunction [23–27,35–40]. Of note, even in stroke patients with no or mild physical disability, nearly half experienced a decrease in libido, coital frequency, sexual arousal, orgasm and sexual satisfaction [39]. Occasionally, hypersexuality can occur as well [26,32–34].

Table 1 Relevant anatomical locations for sexual activation and function. Anatomical locations Mesodiencephalolimbic area Ventral tegmental area [11]⁎ Lateral central tegmental field⁎[11] Subparafascicular nucleus⁎[11] Ventroposterior, midline, and intralaminar thalamic nuclei⁎ [9–11] Hypothalamus [12] Amygdala†[11,17] Cerebral hemisphere [18–21,38]

Cerebral cortex and subcortex Parietal cortex [11,19] Posterior insula [12] Secondary somatosensory cortex [12] Inf. frontal gyrus [11] Inf. temporal cortex [11] Precuneus [11] Sup. frontal gyrus (small portion) [11] Visual cortex [11] VL putamen [11] Claustrum [11] Cerebellum‡[11,17,28–31]

Side Function(s) prediction Both Both

Orgasm, ejaculation Ejaculation

Both Both

Ejaculation Sexual arousal, erection, sensory experience

Right Left Right

Sexual arousal Ejaculation Activation/attention of libido and erectile function, recognition of emotional stimuli

Right Right Right

Ejaculation, attention, reaction time Sexual arousal Sexual arousal

Right Right Right Left

Ejaculation Ejaculation Ejaculation Ejaculation

Both Both Both Left

Ejaculation Ejaculation Ejaculation Sexual arousal, ejaculation, emotional processing, autonomic modulation

VL: ventrolateral. ⁎ The strongest activation area. † Deactivated structure. ‡ Including deep cerebellar nuclei, vermis, and hemispheres.

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Table 2 Summary from studies regarding sexual dysfunctions after stroke. Studies

Subjects (no)

(Mean) Age (y)

Predicting factor(s)

Measures

Prevalence (%)

Korpelainen [26]

192 Pts, 94 spouses

59

↓ Libido, coitus, EF/lubrication, orgasm, and SS

57

Monga [23]

69-M, 68-F

74 (M), 63 (F)

N/A

Depression, Lt. hemisphere lesion

↓ Libido, coitus, EF/lubrication, and orgasm ↓ Libido and EF

Sjögren [25]

113 (78 M, 35 F) 100 (75 M, 25 F) 51

Psychosocial factors (general attitude, fear, inability to discuss, unwillingness), functional disability, spouse Fear for stroke recurrence

NA

↓ Libido, coitus, EF, and ejaculation

64 (M), 75 (F)

Choi-Kwon [27]

70

NA

Psychogenic (performance orientation and sexual stigmatism) Poststroke emotional incontinence

↓ Libido, coitus and EF

Korpelainen [35]

50 (38 M, 12 F) 110 50 M 26 M 106 (63 M, 43 F)

32 to 65

Sensory hemisyndrome, spouse

NA NA NA NA

↓ Cutaneous sensibility, dependent ADL ↓ Prestroke sexual activity Rt. hemisphere lesion Unwillingness, belief in adverse effect of stroke on sexuality

↓ Libido, coitus, EF/lubrication, ejaculation/orgasm, and SS ↓ Coitus ↓ EF ↓ Libido and coitus ↓ Libido, coitus, SA, orgasm, and SS

64

Forsberg-Wärleby [41]

62 (46 M, 16 F) 67 spouses

Stein [42]

38

55.1

Fear, false belief of sexual life only to healthy people, spouse Sensorimotor symptom and low ability in self-care, cognitive/emotional impairments –

44 (↓ Libido), 49 (↓ Coitus), 20 (↓ EF) 28 at 2 months 14 at 6 months 75 NA 50 54 (↓ Libido), 44 (↓ Coitus), 25 (F)/52 (M) (↓ SA), 20 (F)/46 (M) (↓ Orgasm), 29 (SS) 57 (M), 25 (W)

Kimura [24]

Sjögren [36] Hawton [37] Coslett [38] Cheung [39]

Giaquinto [40]

NA

↓ Libido, coitus, EF/lubrication, and ejaculation ↓ Sexual life (at 1 year) Changes in sexual functioning questionnaire

59 (M), 44 (W)

NA 47

M: male; F: female; EF: erectile function; SS: sexual satisfaction; SA: sexual arousal; ADL: activities of daily living; NA: not accessible.

4.1. Factors contributing to post-stroke sexual dysfunction Post-stroke SD is thought to result from multiple factors, both psychosocial (i.e. depression, anxiety, fear of stroke recurrence, loss of self-esteem, role changes) and/or organic (i.e. stroke lesion, comorbidity and medications) [43]. Potential factors related to SDs after stroke are summarized in Table 3 and reviewed as follows. 4.1.1. Psychological factors Psychological factors may affect SD more than physical deficits. Stroke survivors with no or mild physical impairment frequently experienced reduced sexual activity [36]. • Depression: Depression is very common after stroke. It is more likely to contribute to SD than the stroke lesion itself [24,40]. In a study, higher score of Hamilton Rating Scale for Depression after stroke was an independent predictor of SD development for both male and female (OR = 1.55) [24]. Korpelainen et al. also reported that poststroke SD is closely correlated with depression severity [26]. • Fear: Another important factor is fear of stroke occurrence during sexual activity. Sexual intercourse may trigger an acute ischemic stroke [44–46] or rupture of cerebral aneurysm [47] during or after sexual activity, but the risk is very low [45] and unusual [46] as is the case in myocardial infarction [48]. Ischemic stroke triggered by sexual intercourse was reported in several young female patients presenting with paroxysmal embolism (i.e. patent foramen ovale) [44–46]. Fear can also be instigated by sexual partners. Giaquinto et al. evaluated sexual changes one year after stroke with 62 patients, they found that fear by patients' partners also played a substantial role in the reduction of sexual activity [40]. Many partners reported fear of relapse, anguish, lack of excitation or even horror [40]. • Fatigue: It is a common issue that 30–39% of stroke survivors experienced post-stroke fatigue [49–51]. It may result from a combination of an organic brain lesion and psychosocial adjustment after stroke [52,53]. Fatigue is a risk factor for activities of daily living (ADL) dependence and higher case fatality [50]. Right hemispheric stroke is particularly associated with fatigue [53,54]. There are few data on post-stroke fatigue and SD, but fatigue may also contribute to SD

directly or indirectly. Many medications carry the adverse effect of fatigue which can be a contributing factor as well.

4.1.2. Sociodemographic factors Several studies have revealed that age or gender is not independently related to SD occurrence [24,26,27,40]. Additionally, there was no clear correlation with marital status [26], marriage/partnership duration, or educational level [40]. It was suggested that an active sexual life before stroke is a major determining factor for sexual activity after stroke [37]. 4.1.3. Physical deficits Post-stroke physical deficits, such as, hemiparesis/hemiplegia and/ or spasticity may limit appropriate body position and movement, which may contribute to SD. Stroke survivors with hemiparetic limb may experience challenges in embracing, stimulating and engaging in intercourse [22]. Many negative symptoms from post-stroke spasticity—fatigue, limb weakness, and loss of dexterity can also create a challenge for sexual activities [55]. Drooling, pseudobulbar palsy, urinary/bowl incontinence, and other unattractive features can cause intimacy issue [40]. Decreases in intercourse frequency were positively correlated to the degree of physical impairment and levels of dependence in ADL [36]. 4.1.4. Vascular risk factors Vascular risk factors may affect sexual function via endothelial dysfunction and impaired smooth muscle cells in the genital organs. Diabetes, hypertension, dyslipidemia, smoking and obesity are important comorbid factors for ED in stroke patients [56]. ED is very common among patients at high risk for cardiovascular disease [57]. In males, dyslipidemia [high total cholesterol and low high-density lipoproteins (HDL)] is associated with an increased risk of ED [58]. In premenopausal females, dyslipidemia (especially, low HDL and high triglyceride) is significantly associated with SD [59]. Hyperhomocysteinemia is a known risk factor for endothelial dysfunction, and is therefore, a risk factor for ED as well [60]. Furthermore, ED and atherosclerosis share

J.-H. Park et al. / Journal of the Neurological Sciences 350 (2015) 7–13 Table 3 Potential non-lesion factors contributing to post-stroke sexual dysfunction. Factors

Features

Psychological Depression Fear Fatigue(?)

• May be independently linked to SD irrespective of impairment • By organic brain lesion plus psychosocial stress • Right hemispheric stroke-prone

Sociodemographic

• Active sexual life prior to stroke is an important determining factor • Questionable for age, gender, marriage, or education

Physical deficits Hemiparesis or hemiplegia ± spasticity

• Depends on severity of physical impairment and level of dependence in ADL

• May affect endothelial dysfunction and impair Vascular smooth muscle cells in genital organs Diabetes Hypertension Dyslipidemia Smoking Obesity Hyperhomocysteinemia Urogenic Overactive bladder

• Severity correlated with age, male, stroke disability, and white matter hyperintensity

Autonomic dysfunction

• Imbalance of sympathetic hyperactivity and parasympathetic hypoactivity • Highly prevalent in right hemispheric stroke

Neuroendocrine dysfunction

• Inverse relationship between testosterone level and infarct size and stroke outcome

Medications

• Antihypertensive: beta blocker, calcium channel blocker, diuretics • Antipsychotics • Antidepressants: selective serotonin re-uptake inhibitors • Others: phenytoin, ranitidine, cyclobenzaprine, promethazine, meclizine

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serum testosterone levels were significantly lower in stroke patients (vs. control). Both total and free testosterone levels were inversely associated with stroke severity and 6-month mortality at a significant level. Total testosterone was also inversely correlated with infarct size. 4.1.8. Partner factor(s) Sexual activity is a mutual process between two adults. Post-stroke SD can also occur as a consequence of the dissatisfaction from partners (or spouses) with regard to libido, sexual activity, and sexual satisfaction [26,35]. Fear of relapse, anguish, lack of excitation, or even horror (to face a naked disabled partner) may prevent a partner from engaging in sexual activities [40]. Data suggest that spouses of stroke patients with sensorimotor symptom and low ability in self-care or those with cognitive/emotional impairment are less satisfied with their leisure situation, sexual life and partner relationship, particularly at 1 year after stroke. There is a need for better psychological support of spouses/partners, as well of patients, for better overall stroke recovery [41]. 4.1.9. Medications Stroke survivors frequently take several medications to prevent recurrent strokes. Antihypertensive agents can inhibit erections by concomitantly lowering of cavernosal artery pressure. For instance, beta blocker (i.e. metoprolol), calcium channel blocker (i.e. nifedipine), diuretics (i.e. hydrochlorothiazide) can reduce sexual desire and result in ED [22]. Antipsychotic drugs may affect prolactin levels and subsequently influence sexual function. Antidepressants have been shown to promote post-stroke recovery [71] and therefore widely prescribed. However, SD is a common side effect of antidepressants, especially with selective serotonin re-uptake inhibitors. The new agents, such as bupropion and nefazodone are reported to be associated with the lowest risk for SD [72]. Other drugs, which potentially carry the adverse effect of SD, include phenytoin, ranitidine, cyclobenzaprine, promethazine, and meclizine.

ADL: activities of daily living.

5. Return of sexual functionality after stroke similar risk factors, so much so that ED can serve as an independent predictor of peripheral arterial disease [61]. 4.1.5. Urogenic factors Overactive bladder (OAB) is also a disturbing post-stroke complication that affects the daily life of stroke survivors. In a study of 141 stroke patients with OAB, burden of OAB is correlated with advanced age, male, and higher scores of modified Rankin Scale and white matter hyperintensity [62]. OAB is significantly linked with SD (i.e. increased ED, reduced sexual activity, or increased sexual dissatisfaction) [63]. 4.1.6. Autonomic dysfunction Post-stroke SD can be a consequence of imbalance of sympathetic hyperactivity and parasympathetic hypoactivity [64,65]. High prevalent of SD in patients with right-hemispheric stroke might be explained from an autonomic dysfunction perspective. Sympathetic pathways tend to be anti-erectile, whereas sacral parasympathetic pathways are proerectile [66]. Stimulation of the right insular region increases the sympathetic cardiovascular tone, while stimulation of the left insular region activates parasympathetic activity [67]. 4.1.7. Neuroendocrine dysfunction Studies regarding sexual hormone levels in stroke survivors with SD are scarce. Androgen is thought to play a major role in erectile functionality [68]. Halpern et al. showed that salivary testosterone levels positively correlated with the numbers of sexual contacts [69]. Testosterone deficiency is associated with non-specific symptoms including decline in libido, decreased muscle mass, decreased energy, and increased depression. Jeppesen et al. studied the impact of sexual hormone levels in males with ischemic stroke [70]. Mean total and free

The natural recovery trajectory of SDs is not currently well documented. Most studies were based on anecdotal personal interviews, which make it difficult to determine an accurate prognosis. In an interview with 50 males who suffered moderate to severe strokes, most of them had encountered initial difficulties with sexual activities, and two-thirds returned to sexual activity approximately seven weeks after index event [37]. This was accomplished by assuming new sexual position(s) to overcome the physical disabilities [37], but not everyone can resume sexual intercourse [41]. In another study with 38 stroke patients, a majority (71%) identified SD as a “moderate to very important” issue in overall stroke recovery [42]. Regarding recovery, it is important to point out whether or not the couple resumes sexual activity after stroke heavily depends on the frequency of sexual activity prior to stroke [37]. Furthermore, fear was determined as a negative predictor of sexual life because of perception of adverse effect of sexual activity [39]. In reality, the incidence of stroke during or after sexual intercourse appears to be very low [45]. Generally sexual activity may trigger a paradoxical embolism through preexisting patent foramen ovale and cause stroke [44–46]. With regard to counseling, 81% report receiving insufficient information about post-stroke SD, and 60% express a preference for receiving sexual counseling from a physician. A significant proportion of patients (26.5%) want to receive counseling prior to discharge from a hospital or rehabilitation center. In another study, only 10% of patients reported that their physician or psychologist discussed the sexual issues with them during rehabilitation period [73]. Several factors, including time limitations, workplace regulation and embarrassment, prevent the healthcare professionals from discussing sex-related issues [74]. Since counseling on sexual issues is not yet a routine part of hospital discharge or inpatient/outpatient rehabilitation plans, rehabilitation

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guidelines should consider including guidance on counseling on sexual adjustment for patients as well as their spouses [37]. Indeed, it has been recommended that assessment of SD and sexual counseling by medical experts should be integrated into comprehensive stroke rehabilitation [43]. Post-stroke SD is a multifactorial medical issue. Periodic evaluation and tailored treatment by a multidisciplinary team that includes a stroke neurologist, neuropsychologist, and urologist would be ideal [75]. 6. Conclusions and future research Post-stroke SD is likely more prevalent than expected. Post-stroke SD can result from multiple factors. Psychosocial factors are important contributing etiologies, since post-stroke SD can develop even in stroke survivors with little or no physical impairment. However, there is a lack of systematic and organized published data on post-stroke SD — most published studies are based on surveys, questionnaires, or self-report. Studies with objective and quantitative measurements are scarce, thereby limiting the translation of these findings into clinical practice. The natural course of recovery after post-stroke SD is poorly understood. Clinically relevant post-stroke sexual adjustment assessment tools should be developed and SD should be addressed in a multidisciplinary approach. Accurate diagnosis and implementation of SD management as part of comprehensive stroke rehabilitation protocol may enhance the emotional and functional outcome in stroke survivors, which could significantly improve quality of life. Proper identification and timely treatment of vascular risk factors may also reduce the risk of development of post-stroke SD. There is an increasing trend of stroke in middle aged population [76]. Stroke survivors who experience stroke at a young age are frequently left with significant disability that persists during their young adult years and time of peak productivity. It is conceivable that post-stroke SD is an unavoidable quality of life challenge that they may have to face for a long time. This group of patients needs more attention, and future studies should incorporate this age group. Finally, most research of SD and stroke prognosis has focused on male-related SD in both animal and human studies. Future studies focusing on females and young adults deserve substantially more attention. Source of funding None. Disclosures None. Acknowledgment We would like to thank Mr. James Sawers for his generous comments to manuscript. References [1] Haacke C, Althaus A, Spottke A, Siebert U, Back T, Dodel R. Long-term outcome after stroke: evaluating health-related quality of life using utility measurements. Stroke 2006;37:193–8. [2] Pistoia F, Govoni S, Boselli C. Sex after stroke: a CNS only dysfunction? Pharmacol Res 2006;54:11–8. [3] Rowland DL. Neurobiology of sexual response in men and women. CNS Spectr 2006; 11(8 Suppl 9):6–12. [4] Melis MR, Argiolas A. Central control of penile erection: a re-visitation of the role of oxytocin and its interaction with dopamine and glutamic acid in male rats. Neurosci Biobehav Rev 2011;35:939–55. [5] Argiolas A, Melis MR. Central control of penile erection: role of the paraventricular nucleus of the hypothalamus. Prog Neurobiol 2005;76:1–21.

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