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Efficacy of Neuromodulation Interventions for the Treatment of Sexual Dysfunction: A Systematic Review (2022)
Max Y. Jin; Ryan S. D’Souza, MD; Alaa A. Abd-Elsayed, MD
Objectives: The primary aim of this review was to analyze the literature on the efficacy of neuromodulation interventions in treating both male and female sexual dysfunction.
Materials and Methods: Studies were identified from PubMed, Scopus, PsychINFO, CINAHL, and Cochrane. Results were synthesized qualitatively without pooling owing to the heterogeneous nature of outcome assessments.
Results: Overall findings from studies generally supported that neuromodulation interventions were associated with improvement in sexual function. Specific domains that improved in male patients included erectile function, desire, and satisfaction, whereas desire, arousal, orgasm, lubrication, quality of “sex life,” intercourse capability, and dyspareunia improved in female patients. Male ejaculation, orgasm, and intercourse capability were the only domains that continued to decline after the use of neuromodulation interventions, although this was only reported in one study.
Conclusion: Our review suggests that there may be a promise and potential utility of neuromodulation in improving sexual dysfunction; however, further research is needed.
INTRODUCTION
Sexual dysfunction is defined as significant distress that is caused by repeated problems related to the experience, response, and pleasure from performing sex.1 The types of sexual dysfunction can be separated into sexual desire disorders, sexual arousal disorders, orgasmic disorders, and genital pain disorders.2 Sexual desire disorder consists of hypoactive sexual desire disorder.2,3 Sexual arousal disorders include erectile dysfunction (ED) and persistent genital arousal.2,4 Orgasmic disorders include premature ejaculation, anejaculation, and female orgasmic disorder.2,4 Genital pain disorders include dyspareunia and vaginismus.2
Sexual dysfunction can negatively impact patient quality of life and emotional functioning. Primarily, sex life is negatively impacted owing to both emotional and physical discomfort, in addition to a lack of functionality.5 Decreased sexual function is related to poor marital satisfaction.6 In addition, a couple’s capability of having children is threatened because of reduced sexual intercourse. Sexual dysfunction not only impacts a person’s sex life but also places people at a higher risk for depression and other mood disorders.7
An important distinction to make is that sexual dysfunction from neurological conditions is pathologically different from those associated with nonneurological conditions. This is important because patients with neurological conditions including traumatic brain injury, Parkinson's disease, multiple sclerosis, spinal cord injury, and diabetic neuropathy experience an increased prevalence of sexual dysfunction.8 Neurological disorders can alter the processing of sexual stimuli through the disruption of long spinal tracts between the cortex and the sacral nerve roots or the pelvic autonomic nerves.9 Although etiologies may be distinct, we query whether neuromodulation may potentially benefit sexual dysfunction regardless of the etiology.
Many treatments for sexual dysfunction, including neuromodulation, do not differentiate between neurologic and non-neurologic causes. The typical management of sexual dysfunction involves psychosexual counseling therapy consisting of general sex therapy, systematic desensitization, and directed masturbation.2,3,10–14 Psychosexual counseling is the only treatment option available for many disorder types. For other disorders, treatment options may vary. ED is the most prevalent sexual disorder and has several approved treatments.2 Pharmaceutical treatment includes phosphodiesterase-5 inhibitor medications (sildenafil, tadalafil, or vardenafil). Alternatively, patients may receive penile injections (alprostadil).12 Other treatments include vacuum constriction devices, intraurethral prostaglandin suppositories, and penile prostheses.12 For orgasmic disorders such as premature ejaculation, pharmaceutical options include serotonin reuptake inhibitors, tricyclic antidepressants, or topical lidocaine.10 Anejaculation can be managed by stopping any intake of alpha-blockers and antidepressants.11 The use of penile vibratory stimulation is another treatment option.11 If retrieval of semen is desired in patients who experience anejaculation, treatment modalities include artificial insemination, electroejaculation, and other surgical methods.11 Genital pain disorders are treated with physiotherapy that includes pelvic floor exercises.14 Vaginismus also can be treated with pelvic floor botulinum toxin injections, although physiotherapy may be more effective.15 Alternatively, pelvic pain can be managed with the application of lidocaine or the administration of tricyclic antidepressants or gabapentinoids.14 Hormone replacement therapy (HRT) is a common treatment method for female sexual dysfunction (FSD). Estrogen replacement therapy is a specific type of HRT used that improves pain, lubrication, arousal, and orgasm symptoms.16,17 In addition to systemic therapies, estrogen can be applied locally in the form of creams (eg, topical vaginal estrogen) to reduce vaginal atrophy.16 Vaginal dilator therapy is an alternative treatment option for managing vaginal atrophy.18 Testosterone supplementation through patches or gels also has been used for the treatment of FSDs. Testosterone supplementation may improve the frequency of sexual activity, pleasure, and fantasy.16,18 Recently, advances have been made in vaginal laser treatment that allows for increased vascularity and the production of collagen, although this treatment is not approved by the Food and Drug Administration.18 Patients with sexual dysfunction and underlying gynecological conditions (eg, pelvic organ prolapse) may require a multidisciplinary approach that involves treating the gynecological conditions first.19
Neuromodulation interventions including spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are emerging therapies that can be used in lieu of opioids, other pharmacologic agents, and other interventional options. Currently, SCS is indicated for failed back surgery syndrome, refractory angina pectoris, peripheral arterial disease, complex regional pain syndrome, painful diabetic neuropathy, and nonsurgical low back pain.20 For urinary and bowel dysfunction, sacral nerve stimulation is a common neuromodulation intervention. Sacral nerve stimulation is currently indicated for urinary retention, urinary frequency, urge incontinence, and fecal incontinence.21 Although neuromodulation interventions are an uncommon indication, patients also may experience a positive improvement in sexual function with the use of SCS and other neuromodulation interventions.22
There are significant knowledge gaps regarding the efficacy of neuromodulation interventions for sexual dysfunction. In the neuromodulation literature, a major knowledge gap exists on the regain or recovery of neurological function after the application of SCS or PNS. It is common for disorders of sexual dysfunction also to comprise neurological deficits within the genitourinary system, and we query whether neuromodulation interventions may be associated with improvements in neurological function. The purpose of this systematic review is to analyze all available literature that reports the use of SCS, PNS, or other neuromodulation interventions in the treatment of sexual dysfunction. The target population is anyone experiencing sexual dysfunction, regardless of etiology. The primary outcome of this review is to determine the efficacy of neuromodulation interventions in treating sexual dysfunction, as indicated on specific objective sexual function questionnaires.
Future Directions
Additional research is warranted in neuromodulation for sexual dysfunction. A major area that needs additional research is the effectiveness in patients with no urinary symptoms or spinal cord injury. Currently, it remains unknown if the improvements in sexual function are due to the treatment of other painful symptoms or to direct improvement of neurological deficits from neuromodulation. In addition, further research is needed to determine the extent to which sexual function improves. It would be interesting to determine whether outcomes of sexual dysfunction from neuromodulation differ based on stimulation parameters that include waveform, amplitude, frequency, and location.83,84 Research on neuromodulation for sexual dysfunction would benefit from researchers being more transparent about their stimulation protocols. Adverse-event data also need to be highlighted as more evidence accumulates for neuromodulation interventions in this patient population with sexual dysfunction.85 As the application of neuromodulation therapy becomes more prominent and common for a variety of disorders, dissemination of accurate information and education for physicians and patients will be paramount.86 A final important area for further research is on patients with certain risk factors. It is not known whether patients with risk factors such as high preoperative opioid requirements87,88 or a history of genitourinary surgery experience inadequate results.
CONCLUSIONS
Our review synthesized the current literature on neuromodulation interventions for the treatment of sexual dysfunction. Our study suggests that there may be the promise and potential utility of neuromodulation in improving sexual function. However, the certainty of study findings is limited because of the considerable clinical and methodologic heterogeneity present among included studies. Further, powered, comparative, and randomized trials are still warranted to establish definitive evidence.
Max Y. Jin; Ryan S. D’Souza, MD; Alaa A. Abd-Elsayed, MD
Objectives: The primary aim of this review was to analyze the literature on the efficacy of neuromodulation interventions in treating both male and female sexual dysfunction.
Materials and Methods: Studies were identified from PubMed, Scopus, PsychINFO, CINAHL, and Cochrane. Results were synthesized qualitatively without pooling owing to the heterogeneous nature of outcome assessments.
Results: Overall findings from studies generally supported that neuromodulation interventions were associated with improvement in sexual function. Specific domains that improved in male patients included erectile function, desire, and satisfaction, whereas desire, arousal, orgasm, lubrication, quality of “sex life,” intercourse capability, and dyspareunia improved in female patients. Male ejaculation, orgasm, and intercourse capability were the only domains that continued to decline after the use of neuromodulation interventions, although this was only reported in one study.
Conclusion: Our review suggests that there may be a promise and potential utility of neuromodulation in improving sexual dysfunction; however, further research is needed.
INTRODUCTION
Sexual dysfunction is defined as significant distress that is caused by repeated problems related to the experience, response, and pleasure from performing sex.1 The types of sexual dysfunction can be separated into sexual desire disorders, sexual arousal disorders, orgasmic disorders, and genital pain disorders.2 Sexual desire disorder consists of hypoactive sexual desire disorder.2,3 Sexual arousal disorders include erectile dysfunction (ED) and persistent genital arousal.2,4 Orgasmic disorders include premature ejaculation, anejaculation, and female orgasmic disorder.2,4 Genital pain disorders include dyspareunia and vaginismus.2
Sexual dysfunction can negatively impact patient quality of life and emotional functioning. Primarily, sex life is negatively impacted owing to both emotional and physical discomfort, in addition to a lack of functionality.5 Decreased sexual function is related to poor marital satisfaction.6 In addition, a couple’s capability of having children is threatened because of reduced sexual intercourse. Sexual dysfunction not only impacts a person’s sex life but also places people at a higher risk for depression and other mood disorders.7
An important distinction to make is that sexual dysfunction from neurological conditions is pathologically different from those associated with nonneurological conditions. This is important because patients with neurological conditions including traumatic brain injury, Parkinson's disease, multiple sclerosis, spinal cord injury, and diabetic neuropathy experience an increased prevalence of sexual dysfunction.8 Neurological disorders can alter the processing of sexual stimuli through the disruption of long spinal tracts between the cortex and the sacral nerve roots or the pelvic autonomic nerves.9 Although etiologies may be distinct, we query whether neuromodulation may potentially benefit sexual dysfunction regardless of the etiology.
Many treatments for sexual dysfunction, including neuromodulation, do not differentiate between neurologic and non-neurologic causes. The typical management of sexual dysfunction involves psychosexual counseling therapy consisting of general sex therapy, systematic desensitization, and directed masturbation.2,3,10–14 Psychosexual counseling is the only treatment option available for many disorder types. For other disorders, treatment options may vary. ED is the most prevalent sexual disorder and has several approved treatments.2 Pharmaceutical treatment includes phosphodiesterase-5 inhibitor medications (sildenafil, tadalafil, or vardenafil). Alternatively, patients may receive penile injections (alprostadil).12 Other treatments include vacuum constriction devices, intraurethral prostaglandin suppositories, and penile prostheses.12 For orgasmic disorders such as premature ejaculation, pharmaceutical options include serotonin reuptake inhibitors, tricyclic antidepressants, or topical lidocaine.10 Anejaculation can be managed by stopping any intake of alpha-blockers and antidepressants.11 The use of penile vibratory stimulation is another treatment option.11 If retrieval of semen is desired in patients who experience anejaculation, treatment modalities include artificial insemination, electroejaculation, and other surgical methods.11 Genital pain disorders are treated with physiotherapy that includes pelvic floor exercises.14 Vaginismus also can be treated with pelvic floor botulinum toxin injections, although physiotherapy may be more effective.15 Alternatively, pelvic pain can be managed with the application of lidocaine or the administration of tricyclic antidepressants or gabapentinoids.14 Hormone replacement therapy (HRT) is a common treatment method for female sexual dysfunction (FSD). Estrogen replacement therapy is a specific type of HRT used that improves pain, lubrication, arousal, and orgasm symptoms.16,17 In addition to systemic therapies, estrogen can be applied locally in the form of creams (eg, topical vaginal estrogen) to reduce vaginal atrophy.16 Vaginal dilator therapy is an alternative treatment option for managing vaginal atrophy.18 Testosterone supplementation through patches or gels also has been used for the treatment of FSDs. Testosterone supplementation may improve the frequency of sexual activity, pleasure, and fantasy.16,18 Recently, advances have been made in vaginal laser treatment that allows for increased vascularity and the production of collagen, although this treatment is not approved by the Food and Drug Administration.18 Patients with sexual dysfunction and underlying gynecological conditions (eg, pelvic organ prolapse) may require a multidisciplinary approach that involves treating the gynecological conditions first.19
Neuromodulation interventions including spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are emerging therapies that can be used in lieu of opioids, other pharmacologic agents, and other interventional options. Currently, SCS is indicated for failed back surgery syndrome, refractory angina pectoris, peripheral arterial disease, complex regional pain syndrome, painful diabetic neuropathy, and nonsurgical low back pain.20 For urinary and bowel dysfunction, sacral nerve stimulation is a common neuromodulation intervention. Sacral nerve stimulation is currently indicated for urinary retention, urinary frequency, urge incontinence, and fecal incontinence.21 Although neuromodulation interventions are an uncommon indication, patients also may experience a positive improvement in sexual function with the use of SCS and other neuromodulation interventions.22
There are significant knowledge gaps regarding the efficacy of neuromodulation interventions for sexual dysfunction. In the neuromodulation literature, a major knowledge gap exists on the regain or recovery of neurological function after the application of SCS or PNS. It is common for disorders of sexual dysfunction also to comprise neurological deficits within the genitourinary system, and we query whether neuromodulation interventions may be associated with improvements in neurological function. The purpose of this systematic review is to analyze all available literature that reports the use of SCS, PNS, or other neuromodulation interventions in the treatment of sexual dysfunction. The target population is anyone experiencing sexual dysfunction, regardless of etiology. The primary outcome of this review is to determine the efficacy of neuromodulation interventions in treating sexual dysfunction, as indicated on specific objective sexual function questionnaires.
Future Directions
Additional research is warranted in neuromodulation for sexual dysfunction. A major area that needs additional research is the effectiveness in patients with no urinary symptoms or spinal cord injury. Currently, it remains unknown if the improvements in sexual function are due to the treatment of other painful symptoms or to direct improvement of neurological deficits from neuromodulation. In addition, further research is needed to determine the extent to which sexual function improves. It would be interesting to determine whether outcomes of sexual dysfunction from neuromodulation differ based on stimulation parameters that include waveform, amplitude, frequency, and location.83,84 Research on neuromodulation for sexual dysfunction would benefit from researchers being more transparent about their stimulation protocols. Adverse-event data also need to be highlighted as more evidence accumulates for neuromodulation interventions in this patient population with sexual dysfunction.85 As the application of neuromodulation therapy becomes more prominent and common for a variety of disorders, dissemination of accurate information and education for physicians and patients will be paramount.86 A final important area for further research is on patients with certain risk factors. It is not known whether patients with risk factors such as high preoperative opioid requirements87,88 or a history of genitourinary surgery experience inadequate results.
CONCLUSIONS
Our review synthesized the current literature on neuromodulation interventions for the treatment of sexual dysfunction. Our study suggests that there may be the promise and potential utility of neuromodulation in improving sexual function. However, the certainty of study findings is limited because of the considerable clinical and methodologic heterogeneity present among included studies. Further, powered, comparative, and randomized trials are still warranted to establish definitive evidence.
