Curr Bladder Dysfunct Rep (2014) 9:268–274 DOI 10.1007/s11884-014-0256-5

NEUROGENIC BLADDER (CR POWELL, SECTION EDITOR)

Sexual Dysfunction in Male Spinal Cord Injury Patients Eric M. DeRoo & Matthew J. Mellon

Published online: 18 September 2014 # Springer Science+Business Media New York 2014

Abstract Spinal cord injury (SCI) patients pose complex urologic management challenges. Not only is neurogenic bowel/bladder oversight required of urologists, but also sexual dysfunction as well. These patients with SCI are frequently encountered in clinical practice, but a significant number of physicians are not knowledgeable about the set of guidelines available for clinical management. In this review, we discuss the pathophysiology behind sexual dysfunction and fertility in SCI patients, the thorough clinical evaluation required, and the many treatment options available to this specific patient population.

Keywords Spinal cord injury . Impotence . Sexual dysfunction

Abbreviations SCI Spinal cord injury TLP Thoraco-lumbar pathway CNS Central nervous system LMN Lower motor neuron UMN Upper motor neuron ROS Reactive oxidated species NPT Nocturnal penile tumescence PDE5I Phospho-diesterase 5 inhibitors ED Erectile dysfunction LUTS Lower-urinary-tract symptoms

Introduction Spinal cord injury (SCI) patients pose complex urologic management challenges. SCI patients are often referred to urologists for neurogenic bowel and bladder oversight as well as neurogenic sexual dysfunction. In addition, many of these patients are young males and sexuality/reproduction remains an important priority. Men with SCI are often infertile secondary to erectile dysfunction, ejaculatory dysfunction, impaired spermatogenesis, and poor semen quality [1]. While multiple advances have been made in the evaluation and treatment of resulting neurogenic bowel and bladder, few studies have been conducted involving sexual dysfunction in this patient population. Surveys have shown that one of the biggest concerns of patients with a recent SCI is the evaluation and rehabilitation of sexual function. However, the topic remains one of the last to be approached by physicians. Further, of those physicians who discuss sexual dysfunction with this patient population, few perform diagnostic tests to differentiate the many causes of sexual dysfunction. Even fewer investigate the residual sexual function in these patients and utilize this information in approaches to therapy. This article discusses the pathophysiology behind SCI sexual dysfunction and fertility, the thorough clinical evaluation including subjective and objective measures, and the many treatment options specific to this patient population.

Pathophysiology Erectile Function

iThenticate 5 % E. M. DeRoo : M. J. Mellon (*) Department of Urology, Indiana University, 535 Barnhill Drive, Suite 420, Indianapolis, IN 46202, USA e-mail: [email protected]

Like neurogenic bowel and bladder, the impact of SCI on sexual dysfunction is determined by the level and extent of injury [2]. Erectile function in a male is controlled by two distinct pathways. The first is the sacral pathway which

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involves pudendal and pelvic nerves comprised of S2, S3, and S4. These nerves are both parasympathetic and somatic. This pathway mediates reflexive erections through sensation of the glans, penis, and perineum. The second pathway, otherwise known as thoraco-lumbar pathway (TLP), mediates psychogenic erections and involves hypogastric, sympathic, and pelvic nerves comprised of T11, T12, L1, and L2. This pathway involves erections as a response to non-genital stimulation including; visual, auditory, olfactory, or non-genital tactile sensation. Studies have shown that the majority of SCI patients maintain some form of sexual function due to this dual innervation pathway [3••]. Based on these two pathways, spinal cord injuries can be broken down into four categories: (1) lesions above the two pathways (cranial to T11), (2) lesions between the two pathways, (3) lesions involving sacral pathway, and (4) lesions extending from sacral pathway to cauda equina [3••]. The knowledge of these pathways and lesion categorization will allow the physician to better delineate the level of SCI and differentiate between organic and psychogenic erectile dysfunction. A. Lesions Above the Sacral and Thoraco-Lumbar Pathways Lesions involving the spinal cord above T11 damage the communication between the thoraco-lumbar nerves and higher CNS structures. These patients will likely have impaired psychogenic erections and frequently require direct stimulation of the genital skin to achieve erection suitable for intercourse. Alternatively, the sacral pathway remains uninjured in this patient population and therefore, reflexive erections remain intact. These patients rely on dermal stimulation and perineal reflexes for sexual function. Studies have shown that the majority of patients with high injuries maintain adequate erectile function [4]. B. Lesions Between the Thoraco-Lumbar and Sacral pathways These patients often have the best sexual function due to the fact that the lesion spares communication between higher CNS structures and thoraco-lumbar nerves as well as an intact sacral pathway. These patients therefore maintain erectile function via psychogenic and reflexive stimulation. Close to 100 % of patients with these injuries will maintain erectile function [5]. C. Lesions Involving Sacral Pathway but Limited to Conus Terminalis While these injuries will interrupt the reflexive pathway, most will spare the TLP and therefore preserve psychogenic erections. Injuries to sacral nerves interrupt response to genital stimulation. These SCI injury patients may have loss of reflexes involving S2–S5, including bulbocavernosus and bulboanal reflexes. Studies have

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shown that ∼80 % of patients with these injuries will maintain sexual function via psychogenic stimulation [3••]. D. Lesions Involving Sacral Pathway but Extending to Cauda Equina Lesions involving the cauda equina are highly variable. Injuries in this anatomical segment (caudal to L1– L2) will almost always result in interruption of the sacralreflexive pathway. However, higher lesions involving the cauda equina may also disrupt TLP-CNS connections and lead to complete loss of sexual function through loss of psychogenic and reflexive erections. Spinal cord injuries caudal to L2 often have the worst outcome in regard to sexual function following SCI and are often refractory to treatment [6].

Ejaculation Ejaculation is a more complex neurologic process when compared to achieving erections. Ejaculation requires the coordinated innervation of both sympathetic and parasympathetic nerves as well as somatic innervation [7]. Because of this complex innervation, a high percentage of SCI patients will suffer difficulties with ejaculation, most commonly retrograde ejaculation, despite the ability to achieve an erection. Men with incomplete SCI lesions have better ejaculation rates than those with complete injuries across all spinal levels. Studies have shown that patients with lower motor neuron (LMN) injuries above L2 have the highest likelihood of retaining the ability to achieve natural ejaculation (without use of stimulation techniques) [8]. This is thought to be due to the ability to retain psychogenic erections. Unfortunately, 18 % of patients with complete LMN injury report the ability to ejaculate, while only 4 % on patients with complete upper motor neuron (UMN) retain the ability. Patients with incomplete injuries, whether UMN or LMN, report rates between 35 and 70 % [9•]. Similarly, the ability to achieve orgasm is affected by level and completeness of lesion. Studies show that 38 % of men with complete and 47 % of men with incomplete lesions report the ability to achieve orgasm [10]. Sexuality After the initial period of spinal shock following SCI, most men will resume sexual activity within 12 months [10]. JH Ku et al. demonstrated “time since injury” to be an independent predictor of sexual activity. In this study, patients who were >24 months out from SCI were more likely to engage in sexual intercourse than those patients whose SCI was within the previous 24 months (45.8 v. 17.1 %) [4]. Further, studies have shown that following SCI, men remain interested in sex and however, the level of desire and frequency of intimacy

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decrease [11]. One particular study demonstrated that pre-SCI, 48 % of men had intercourse less than or equal to one time per week versus 70 % following SCI [9]. Conversely, the percentage of men engaging in intercourse greater than or equal to two times per week decreased from 52 to 30 % following SCI [12]. While SCI alters frequency of intercourse, it has also been shown to affect the type of sexual activity. Studies demonstrate that 99 % of men reported their favorite sexual activity to be penile-vaginal intercourse pre-SCI, while only 16 % preferred this method post-SCI, most preferring oral intercourse. Sexual satisfaction has also been shown to decrease following SCI. This data was found to be consistent regardless of the level or severity (partial v. complete) SCI [10]. Finally, men who are able to perform self-catheterization had significantly higher sexual activity rates than those patients who depended on a caregiver for catheterization or chronic urinary catheter (40.4 v. 18.8 %) [4]. Semen Parameters In addition to the high incidence of ejaculatory dysfunction in SCI patients, there is also a reported decrease in semen parameters [13]. The most commonly documented abnormalities are poor motility and viability. These semen changes are seen as early as 2 weeks following injury [14]. Many hypotheses have been studied, including scrotal temperature, time since injury, bladder management, and ejaculatory method with mixed results. Multiple studies have been done on testicular function in SCI patients. Studies have demonstrated that ∼65 % of men with SCI demonstrated abnormal spermatogenesis on testicular biopsy [15]. This is thought to be due in part to high incidence of hypothalamic-pituitary axis abnormalities in this patient population, including high incidence of hyperprolactinemia. While results of studies on scrotal temperature have been mixed, some have demonstrated that increased scrotal temperatures due to thigh adduction and prolonged sitting in wheel chair to be correlated with decreased sperm motility [16–18]. Further, it is hypothesized that decreased sympathetic innervation may lead to decreased sperm epididymal peristalsis and therefore decreased sperm transmission. This stagnation may lead to decreased sperm motility and abnormal morphology [13, 19]. These studies correlate with decreased semen parameters in men with sperm stagnation due to obstructive azospermia without SCI [13]. Furthermore, seminal fluid has demonstrated an increase in reactive-oxidated species (ROS) in men with SCIs. Increased ROS leads to a rapid decrease in intracellular ATP and increase oxidative stress with resulting decrease in motility [20]. Previous studies performed on men without SCI have shown decreased sperm motility and a sevenfold decrease in fertility in men with high ROS levels. Finally, studies have shown that sperm collected from men without SCI show decreased motility when exposed to seminal plasma from SCI patients [21].

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The constituents of seminal plasma remain the most promising hypothesis in the evaluation of decreased fertility in SCI patients [13].

Clinic Evaluation of SCI Patients Physical Exam Along with a full physical examination, evaluating ability to maintain sexual function in SCI patients requires a full neurological evaluation of pelvic sensation and perineal reflexes. Cutaneous sensation of the genital area is mediated through T10–S5 sensory nerves. There are four main pelvic reflexes that are described. The reflexes are evaluated by visualization, palpation, or EMG recordings. The ability to elicit these reflexes demonstrates continuity of sacral pathway and therefore ability to achieve reflexive erections [3••]. In addition to evaluation of pelvic reflexes, it is important to perform a thorough evaluation of dermal sensation involving the genital and perineum that is innervated by nerve roots T10–S5. A. Bulbocavernosus Reflex (S2, S3) The bulbocavernosus reflex is triggered via stimulation of the glans penis and demonstrates contraction of bulbocavernosus muscle. This reflex is noted with contraction of muscle between the scrotum and anus and is indicative of S2, S3 function. B. Bulboanal reflex (S3, S4) This reflex is triggered again, via pressure applied to glans and an intact reflex demonstrates contraction of the anal sphincter. C. External Anal sphincter (S3, S4) This reflex is investigated by applying light tactile sensation to area surrounding anus and leads to contraction of anal sphincter. D. Cutaneous-anal reflex (S4, S5) Nociceptors are activated via needle stimulation near the anus and results in increased anal sphincter tone.

Clinical Testing Nocturnal Penile Tumescence Nocturnal erections occur during REM sleep [22]. Nocturnal penile tumescence (NPT) can be used as a tool to differentiate psychogenic versus organic erections. Nocturnal erections that occur during REM sleep are mediated by reflexive pathway and not directly related to psychogenic (dream content) pathway [3••]. Therefore, patients with NPT will have an intact reflexive pathway, with or without an intact TLP. SCI patients without NPT likely have disruption of reflexive pathway, but

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may maintain in intact TLP. Therefore, while NPT evaluation is a resource to evaluate for sacral pathway, it offers little information on the health of TLP [23]. Skin Potentials Skin potentials specifically designed for evaluation of sexual function in SCI patients involves stimulation of sympathetic penile nerves and recordings of penile tumescence. Stimulation of these nerves communicates impulses to higher CNS structures via brainstem and then caudal transmission via sympathetic nerves. Positive results from skin potential leads to penile tumescence and indicates continuity of thoracolumbar pathway and ability to achieve psychogenic erections. Skin potentials provide no information on health or continuity of reflexive pathway, but when used in conjunction with NPT, the two studies can interpret the remaining health of both erectile pathways [3••].

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example, patients who report continuous leakage of urine as a result of poor sphincter activity likely have impaired sacral pathway innervation and will have impaired reflexive erections. Patients who demonstrate urinary control via relaxation of the urinary sphincter demonstrate continuity between thoraco-lumbar nerves and higher CNS structures. Further, sensation of bladder filling and perceived urge to urinate can be used to better delineate the extent of SCI. The sensation of bladder filling and first sensation to urinate is mediated by sacral nerves (reflexive erections), whereas the imminent need to urinate is the result of bladder distention and is reliant of T10–L2 spinal pathways (psychogenic erections). Finally, rectal sensation is mediated by sacral pathway. Patients who need for digital disimpaction likely have discontinuity of sacral pathway (poor reflexive erections). Adjusting common questionnaires to include specific articles regarding visceral and somatic sensation or function can help physicians better define the level and extent of injury [3••, 24].

Urodynamic Testing Urodynamic testing is a tool well known to urologists to evaluate bladder-sphincter-CNS communication. Knowledge of neurological pathways involved in UDS testing can be used to extrapolate functional status of sexual pathways. This is true due to the fact that sexual function is reliant on the same neurological innervation as bladder and sphincter function [3••]. During urodynamic testing, detrusor contractions are an indication of parasympathetic function involving the pelvic nerve (S2, S3, and S4). Patients who demonstrate detrusor activity should therefore have reflexive erectile function [23]. Further, contraction of internal urethral sphincter and bladder neck is indicative of sympathetic efferent activity involving the hypogastric nerve (T11, T12, L1, and L2). Therefore, patients with preservation of sphincter activity via sympathetics likely have preservation of psychogenic sexual function. Finally, those patients who demonstrate hypotonia of the bladder and sphincter likely have disruption of both pathways due to a lower lesion involving cauda equina and will have loss of both erectile pathways and poor sexual function outcomes [3••]. Sexual Interview Despite the fact that there have been advances in treatment of sexual dysfunction, many physicians are reluctant to discuss this topic with SCI patients. Additionally, most spinal cord patients lack cutaneous sensation inferior to the level of the lesion and many underestimate their residual ability to achieve erections [23]. These two facts combined have led to under investigation and failure of treatment in SCI patients. In this patient population, typical questionnaires must be amended to evaluate somatic and visceral function. For

Therapies Available in the Treatment of Sexual Dysfunction in SCI Patients While multiple studies have evaluated the ability of male SCI patients to achieve erections as well as ways to improve these rates, there is a paucity of studies focusing on other aspects of sexual dysfunction in SCI patients [9•]. Erectile Dysfunction Although the majority of SCI patients will retain some ability to achieve an erection, most of these patients will report some decrease in erectile ability when compared to pre-SCI. Patients report erections that are not predictable, insufficiently rigid, or short lasting to enable intercourse. In a study by Lombardi et al., only 25 % of SCI patients reported erections that were suitable for intercourse without intervention [25]. A. Intracavernosal Injections Intracavernosal injections were once the main treatment for sexual dysfunction in this patient population. Injected medications include papaverine, phentolamine, prostaglandin E1, or a combination of these medications. Studies have shown these medications to be equally effective across all levels of SCI. Often these medications are effective at lower dosages than those in the general population, due to the patient’s residual sexual function [3••]. Similar to patients without SCI, it is important to initiate therapy at the lowest dose and titrating to effect. Although these medications are effective at low doses in this patient population, there is also a higher reported incidence of priapism following injection compared to

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the general population [6]. The overall satisfactory erection response rate varies between 90 and 95 % [26] B. PDE5-Is As the use of phosphodiesterase 5-inhibitors (PDE5Is) increased in the general population, so has the use in SCI patients [6]. Schmid et al. demonstrated sildenafil to be an effective treatment for ED in this patient population. The study found that 93 % patients with preservation of a least one pathway (sacral or thoracolumbar) have erections suitable for intercourse following use of sildenafil. Conversely, patients with lower injuries causing discontinuity of both pathways showed no benefit despite higher doses of the medication. Independent predictors of PDE5i success were lesions above T12, higher residual reflexive erections, and incomplete lesions [27]. Without question, the most reported favorable parameter for therapy success is the presence of an upper motor neuron lesion above the sacral pathway [28, 29]. While some studies report a higher incidence of side effects (headaches, flushing, dyspepsia, and dizziness) when compared to general population [30], this is not consistent. In fact, most studies have found that the adverse effects of PDE5is in this population were mild to moderate and of short duration. The most frequently reported side effect was headache with 41.7 % of men reporting in the first 4 weeks of treatment and only 10 % thereafter [31]. Patients with complete lesions above T6, who are physiologically prone to autonomic dysreflexia, were able to safely use sildenafil without any reports of autonomic dysreflexia [6, 27]. A meta-analysis performed by DeForge et al. demonstrated that sildenafil use in the SCI patients resulted in 79 % successful erectile function [26]. These results are comparable to statistics reports in general population (72–79 % improvement) and higher than reported improvement in diabetic patients (48–72 %) [32]. Not only have PDE5is been shown to improve erectile rates, but also studies have shown their role in improving sexual satisfaction (both patient and partner) as well as quality of life [27]. Recently, studies have been performed demonstrating the effectiveness of new PDE5is including tadalafil and vardenafil [33, 34]. When comparing intracavernosal injection with PDE5is, although the side-effect profiles are different, there is a similar incidence and severity of reported side effects between the two interventions. As PDE5is become more popular, the use on intracavernosal injection has largely decreased. C. Vacuum-Assisted Device Similar to their use in non-SCI patients, SCI patients who utilize a vacuum-assisted device often report erections that are not firm enough for erection, “cold-blue” penis, or a non-rigid base that makes vaginal penetration difficult. Regardless, patients report satisfaction rates between 85 and 90 %. Complications include higher

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reported necrosis rates in this population due to decreased genital sensation. Moreover, these devices require manual dexterity, which is often compromised in this patient population. Overall, patients report equal response rates and satisfaction scores when comparing intracavernosal injections and vacuumassisted devices with similar complication rates. In fact, in those patients who used both medications, 50 % chose to remain with each intervention [26]. D. Penile Prosthesis The first report of penile prosthesis dates back to the 1930s. Fortunately, many advances have been made in the modern-day prosthesis. Penile prosthesis come in two forms, inflatable or malleable. While these devices are used frequently in non-SCI patients, they have somewhat limited role in SCI patients; in fact, their use is decreasing in frequency. Studies have shown the device explantation rate to be higher in the SCI population [35]. This is due in part to increased erosion rates thought to be secondary to decreased sensation. The rate of infection is also reported higher in this population. Studies have shown an explantation rate of 10–25 % in SCI patients [9•, 26]. Penile prosthesis is also limited in SCI patients due to need for manual dexterity to operate any of the devices. E. Sacral Nerve Modulation Sacral nerve modulation is often utilized for patients with refractory lower-urinary-tract symptoms, but a recent studied performed by Lombardi et al. investigated its utilization in sexual dysfunction patients. Of the patients with significant LUTS, 42.3 % also had concomitant erectile dysfunction. Following device implantation, 36 % of patients with ED secondary to known neurological injury demonstrated significant improvement in IIEF5 scores [36]. While this study was not conducted solely on SCI patient, it reports encouraging results and further investigation with larger sample size is necessary. Van Der Aa et al. implanted sacral nerve stimulators in patients with complete spinal cord lesions. Results demonstrated that 91 % of patients who underwent device implantation achieved full sustainable erections that were suitable for intercourse [37].

Ejaculatory Techniques Besides erectile function, the cause of decreased fertility in SCI patients is often due to an increase in retrograde ejaculation and decrease in semen parameters. In men who lack the ability to ejaculate, penile vibratory stimulation or rectalprobe electroejaculation may be used [38]. With penile vibratory stimulation, a probe is placed against the penis and provides mechanical stimulation to achieve ejaculation. This method requires preservation of reflexive pathway. This is the

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most commonly utilized method due to its ability to be used in home or clinic setting. Patients also prefer this method as it is less invasive than other techniques. Further, studies have shown that sperm retrieval rates and fertilization rates via this method were superior to electro-ejaculation technique. Alternatively, rectal probe electroejaculation is used in those patients who are unable to ejaculate using vibratory stimulation. This method is used only in the clinic setting and is more invasive than vibratory stimulation. The cumulative success in sperm retrieval is reported at 86 % via these two methods [13]. Once the semen specimen is collected, insemination may occur via multiple reproductive techniques. Improving Semen Parameters Data on improving semen parameters in SCI patients is sparse. Some researchers have demonstrated an improvement in morphology and motility with frequent vibratory stimulation to ejaculation when continued over 12 weeks. Conversely, other studies have demonstrated improvement in total number of motile spermatozoa with prolonged abstinence from ejaculation. Studies have also found a correlation between improved spermatogenesis and improved bladder management. These reports have demonstrated an improvement in sperm quality in those patients who performed intermittent self-catheterization versus those patients with chronic indwelling urethral or suprapubic catheters [39]. This may be due in part by decreased rates of urinary tract infections in patients with better bladder management. Supplements including highdose vitamin C/E and zinc were of no benefit.

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Conclusion SCI patients present an interesting and complex group of symptoms including: neurogenic bowel, bladder, and sexual dysfunction. While neurogenic bowel and bladder has been intensely studied, sexual dysfunction due to SCI remains a smaller breadth of research. Without intervention, a majority of these patients will be infertile due to the following: erectile dysfunction, ejaculatory dysfunction, changes in sexuality, and decreased semen parameters. The pathophysiology behind neurogenic sexual dysfunction is quite similar to that of neurogenic bowel and bladder, and data from these can be extrapolated to investigate sexual dysfunction. The clinical evaluation of SCI patients involves a thorough neurological exam as well as a patient interview that is tailored to include residual erectile, visceral, and somatic function. Goals of sexual therapy in SCI patients include the following: treatment of erectile dysfunction, providing modified ejaculatory techniques, improving semen parameters, and tailoring cognitive-behavioral therapy based on patient’s level and completeness of spinal cord lesion. Many of the therapies that are utilized in the general population may also be used in SCI patients, but it is important to be aware of the specific dosages, side effects, and limitations of each therapy. Compliance with Ethics Guidelines Conflict of Interest Eric M. DeRoo and Matthew J. Mellon declare that they have no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

Cognitive-Behavioral Modification While medications and vacuum-assisted devices have proven to be effective in this patient population, many physicians prescribe these without considering the individual patient’s residual sexual function. The use of cognitive-behavior treatment may improve sexual function regardless of the level of lesion. For example, patients with higher lesions involving the TLP should be instructed to explore and practice the use of perineal/ genital stimulation in order to achieve maximal sexual function (i.e., pressure applied to glans). Patients are also instructed to avoid stimulation that leads to an inhibiting response that decreases sexual function (i.e., bending of the erect penis) [23]. Alternatively, patients with lower SCIs are instructed to utilize arousing visual, olfactory, and auditory stimuli in order to achieve erection. Regardless of cognitive-behavioral treatment modality, both patient and partner should be aware and practice different modalities of stimulation tailored to the patient [3••].

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