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Keywords:

  • Sexual Dysfunction;
  • Sexual Function;
  • Chronic Illness;
  • Neurologic Disease;
  • Renal Disease;
  • Psychiatric Disease

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

Introduction.  Direct and indirect effects of chronic disease on sexual health are frequent and complex, but guidelines for their optimal management are lacking. With improved surgical and medical treatment of the underlying disease, the numbers of men and women needing assessment and management of associated sexual dysfunction are increasing.

Aim.  To provide recommendations/guidelines for the clinical management of sexual dysfunction within the context of chronic illness.

Methods.  An international consultation in collaboration with the major sexual medicine associations assembled 186 multidisciplinary experts from 33 countries into 25 committees. Nine experts from four countries compiled the recommendations of sexual dysfunction in chronic illness and cancer with four focusing on neurological, renal, and psychiatric disease and lower urinary tract symptoms (LUTS). Searches were conducted using Medline, Embase, Lilacs, and Pubmed databases.

Main Outcome Measures.  Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate.

Results.  Some conclusions concerning prevalence and pathophysiology of sexual dysfunction in the context of neurological disorders, end-stage renal failure, LUTS, and psychiatric disease were made. Optimal assessment of the multiple factors affecting sexuality when one or both partners are chronically ill is outlined. Evidence-based recommendations for management are presented. Comorbid depression is frequent and independently determines prevalence of sexual dysfunction in many conditions.

Conclusions.  There is need for more research and scientific reporting on prevalence, pathophysiology, and optimal treatment of sexual dysfunction associated with chronic illness. Screening for and managing comorbid depression is strongly recommended. Basson R, Rees P, Wang R, Montejo AL, and Incrocci L. Sexual function in chronic illness. J Sex Med 2010;7:374–388.


Introduction

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

Advances in surgical and medical treatment have greatly improved survival for patients with chronic illness such that their quality of life including their sexual life is important. Many factors contribute directly or indirectly to sexual dysfunction related to chronic illness as shown in Table 1.

Table 1.  Factors involved in sexual dysfunction associated with chronic disease and cancer
TypeMechanismsExamples
  1. ED = erectile dysfunction.

DirectChange in sexual desire from diseaseTypically reduced, e.g., from high prolactin and anemia of chronic renal failure [1]. May be increased, e.g., from some brain disorders [2].
Disruption of genital response from diseaseED from multiple sclerosis [3], hypertension [4], orgasmic disorder from multiple sclerosis [5].
Disruption of genital response from surgeryRadical prostatectomy and ED [6], radical hysterectomy and reduced genital congestion/reduced lubrication [7], orgasmic disorder after radical vulvectomy [8]
Disruption of genital response from radiationED from vascular (and also likely nerve) damage after radiotherapy for prostate cancer [9]; vaginal stenosis and friability from radiation for pelvic cancer [10]
Dyspareunia and disruption of sexual desire and response from chemotherapySudden ovarian failure after chemotherapy for breast cancer [11]; testicular failure after intensive chemotherapy for hematopoietic transplantation [12]
Disruption of sexual desire and response from antiandrogen treatmentGnRH therapy for prostate cancer [13]
Disruption of genital response from aromatase inhibitorsLoss of sexual genital sensitivity, and exacerbation of vaginal atrophy from aromatase inhibition post breast cancer [14]
Disruption of sexual desire and response from painPain from any chronic condition is a potent sexual distraction
Disruption of sexual desire and response from nonhormonal medicationsNarcotics can depress desire through gonadotropin suppression [15]; selective serotonin reuptake inhibitors reduce desire and response [16]
IndirectReduction of self-imageReduced by disfiguring surgeries, stomas, incontinence, altered appearance (e.g., drooling and altered faces of Parkinson's, altered skin color and muscle wasting of renal failure)
Depressed moodDepression and mood lability commonly accompany chronic illness; depression major determinant of sexual function in women with renal failure [17] or multiple sclerosis [18]; strong link between ED and subsequent depression [19]
Impaired mobilityReduced ability to caress, hug, and hold a partner; to sexually self-stimulate, to stimulate a partner, to move into positions for intercourse, to pelvically thrust in spinal cord injury, Parkinson's, brain injury, postamputation
Reduced energyFatigue may take its toll on sexuality especially desire, e.g., from renal failure or chemotherapy
Partnership difficultiesDifficulties finding a partner, dysfunction in the partner who assumes a care giver role, institutionalization, fear of becoming a burden to a partner, lack of independence. Relationship discord from stressors of living with medicalized lives (e.g., three times weekly hemodialysis)
Sense of loss of sexuality from imposed infertilityFrom surgery removing gonads or uterus, from chemotherapy or radiotherapy causing gonadal failure
Fear of sex worsening medical conditionAvoiding sex fearing a further stroke

Our objectives are to identify the prevalence and pathophysiology of sexual dysfunction associated with chronic illness and its treatment and to identify accepted and emerging treatments of dysfunction. Any means of potential prevention of dysfunction will be noted. This manuscript will address sexuality in the context of neurological, renal, and psychiatric disease and a separate manuscript will address the context of cancer.

Assessment

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

We recommend assessment and treatment from a multidisciplinary perspective given that sexual problems relating to chronic illness are multifactorial. The structured interview remains the most important assessment tool and it is optimal for patients in committed relationships to include both partners, seeing them together and individually. Table 2 outlines items requiring assessment when chronic illness is present in one or both partners.

Table 2.  Assessment of sexual dysfunction associated with chronic illness
  1. ED = erectile dysfunction.

• Review past medical and psychiatric history
• Review current medical status: consider respiratory, cardiac, mobility, and continence requirements for sexual activity including intercourse, self stimulation, and orgasm
• Review current medications
• List the sexual dysfunctions, their duration, and whether the dysfunction is also present with self-stimulation or with other partners
• Clarify relationship status and quality
• Review the environment for sex: home/institution/“medicalization,” e.g., hemodialysis machines, respirators, lack of independence in daily living
• Review any chronic pain
• Assess consequences of illness on sexual self image (concerns with regard to attractiveness, physical appearance)
• Review dysfunctions in detail:
○ Clarify motivations for sex including “desire/drive” and desire to satisfy partner; identify reasons for avoiding sex
○ For ED check erections on waking from sleep
○ Clarify subjective arousal/excitement, pleasure
○ Review variety and usefulness of sexual stimuli
○ Assess couple's sexual communication
○ Consider the importance of distracting thoughts or negative emotions during sex
○ Determine if wanted orgasms are possible, very delayed, nonintense, painful
○ Identify ejaculation difficulties—delayed, too early, painful, absent
○ Review if intercourse is possible
○ Assess female dyspareunia: introital, deeper, how constant, exacerbation from partner's ejaculation fluid, postcoital burning, postcoital dysuria
○ Asses male dyspareunia: immediate, delayed, any physical changes
• Clarify sexual response pre illness: any dysfunction, how rewarding, how important was sex, any desire discrepancy, paraphilia
• Review impact of medications on desire and response
• Review treatment of sexual dysfunction to date
• Complete a full physical exam including genital exam: usually necessary because of the medical condition, particularly important for neurological illness and when there is ED, dyspareunia, or pain with arousal
• Complete psychological exam exploring mood, anxiety, insomnia, and life stressors
• Laboratory investigations—as necessary especially when needed to monitor anemia, high prolactin, hypogonadism, thyroid disorders. Estrogen levels usually assessed by the history and the genital/pelvic examination
• Specialized testing of genital blood flow, e.g., Doppler studies of cavernosal flow for ED—rarely indicated as results do not alter treatment options

Sexual Dysfunction Associated with Neurological Disease

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

Direct effects of brain trauma and stroke mostly result from neuronal damage to the frontal and temporal lobes of the brain including the more deeply located limbic structures. Epilepsy arising in the hippocampal/amygdaloid circuitry of the temporal lobes has greatest potential to affect sexuality which can be further compromised by side effects from antiepileptic drugs. Sexual dysfunction in Parkinson's disease is linked both to depletion of central dopamine and peripheral autonomic neuropathy. Spinal autonomic pathways and ascending sensory pathways from the genitalia are selectively implicated in multiple sclerosis (MS) as well as spinal cord injury (SCI). Peripheral neuropathies (somatic and autonomic), cauda equina injury, and iatrogenic pelvic nerve plexus injury from surgery or radiation of the genital autonomic nerve supply disrupt the peripheral aspect of the genital and sexual response. Importantly, in most of these neurological disorders, comorbid depression is a major contribution to sexual dysfunction.

Table 3 outlines the epidemiology and treatment of sexual dysfunction in brain injury, stroke, MS, SCI, epilepsy, and Parkinson's disease.

Table 3.  Epidemiology of sexual dysfunctions in neurological disorders with comments re treatment
 Prevalence of sexual difficultyComments with regard to etiologyComments with regard to treatmentLOE
  1. AED = antiepileptic drug; CBT = cognitive behavioral therapy; ED = erectile dysfunction; EJD = ejaculatory disorder; FSFI = Female Sexual Function Index; LOE = level of evidence; PD = Parkinson's disease; PGE = prostaglandin E1; PVS = penile vibrostimulation; SHBG = sex hormone binding globulin; SSRI = selective serotonin reuptake inhibitor; t = testosterone; TBI = traumatic brain injury; TES = The Endocrine Society (American); TLE = temporal lobe epilepsy.

Head injury36–54% for severer levels of TBI compared with 15% of healthy controls [20]. Mostly erectile/ejaculatory dysfunction in men, reduced lubrication/dyspareunia in women. Pituitary injury prevalence unclear.Depression more important than severity of TBI in both sexes [21]. Medications (especially mood altering) account for up to one-quarter of cases of ejaculatory failure [22]. Screen for pituitary damage at 3 and 12 months.Treat spasticity with baclofen, tizanidine, botox, sclerosing agents4
Treat hypersexuality with CBT, SSRIs, clobazam, antiandrogens, dopamine antagonists, and some atypical antipsychotics [3]4
Replace testosterone according to TES [23]4
Spinal cord injuryOrgasm is achieved by less than half of subjects of either gender. About 50% of men are able to ejaculate when incomplete cord lesions are included. As few as 4% of men with complete, high lesions achieve ejaculation even though reflex erections remain intact [24]Chronic pain in relation to cord injury occurs in as many as one-third of cases, at least in men, to potentially interact with depression and the autonomic aspects of sexual dysfunction [24]Sildenafil for ED [25]2
PGE1 for ED [3]4
Tadalafil for EjD [26]1
Vardenafil for EjD [27]1
Midodrine to supplement PVS for EjD [28]4
Sildenafil for reduced lubrication [29]2
Treat spasticity with baclofen, etc.4
Multiple sclerosis (MS)Of men who are still ambulant, 60% have ED and 40–50% have ejaculatory/orgasmic dysfunction with reduced desire [30]. In ambulant, newly diagnosed women (mean time since first symptom of MS, 2.7 years), sexual dysfunctions according to FSFI scores were present in 34.9% of sample compared with 21.3% healthy controls [5]Eventually well over half of either sex are affected, predominantly by ED in 75% of men and by loss of genital sensation in up to 62% of women [3]Sildenafil for ED [31]1
PGE1 for ED [32]3
Sildenafil for reduced vaginal lubrication [33]2
Treat spasticity with Baclofen, etc.4
StrokeAn internally controlled study of 75 men and 25 women showed a dissatisfaction rate of 58.6% of men compared with 21.3% before the stroke and in 44% of the women compared with 20% prior to the stroke [34]With depression as one of the exclusion criteria, sexual desire poststroke in patients aged 40–80 years was still decreased or absent compared with prestroke in 61.9% of men (n = 63) and 52.5% of women (n = 40) having mild or no neurological disability after 6 months [35] ED has better prognosis in men <65 years [36]Sildenafil for ED [3]4
Treat spasticity with Baclofen, etc.4
Treat hypersexuality as for head injury4
ParkinsonismBoth men and women [37,38] with PD report sexual dissatisfaction more commonly than controls—the major determinants being age, severity of disease, and depressionCaregiver partners (especially women partners) show an important degree of sexual dysfunction in several studies [39]Sildenafil [40] or apomorphine [41] for ED2
PGE1 for ED [3]4
Deep brain stimulation to subthalamic nucleus for ED [42]4
Treat hypersexuality by d/c dopamine agonists, add quetiapine if necessary [3,43]3/4
EpilepsyHyposexuality follows but does not predate the onset of epilepsy [3] and is more common in TLE. Men with localization-related epilepsy taking no AEDs have abnormally low sexual function [44]. Women with epilepsy have higher rates of disinterest and orgasmic dysfunction compared with controls [45]Epilepsy has biological as well as psychological effects upon sexual well-being. AEDs may increase SHBG and lower t-levels (phenobarbitone, phenytoin, and carbamazepine) or reduce SHBG (valproic acid). Lamotrigine seems sexually neutral.Choose AEDs that are neutral to P450 enzyme system and therefore do not alter SHBG [46]4
In men, replace t [47]3

Recommendations

Our graded recommendations regarding treating sexual dysfunction in neurological disorders include:

  • • 
    For any neurological disorder, Grade C recommendation to treat commonly comorbid depression by psychological and medication means; caution is needed with bupropion due to its propensity to worsen seizures.
  • • 
    For any neurological disorder, Grade C recommendation for intracavernosal prostaglandin E-1 injections if phosphodiesterase type 5 (PDE5) inhibitor is contraindicated [3].
  • • 
    In head injury, Grade C recommendation for treatment of pituitary growth hormone deficiency and gonadotropin deficiency as defined by U.S. Endocrine Society criteria[23,48,49].
  • • 
    In head injury and stroke, Grade C recommendation for treating hypersexuality in brain trauma and stroke as in the table [33].
  • • 
    In Parkinson's disease, Grade C recommendations for treatment of hypersexuality: (i) Step 1, stop dopamine agonist and continue levodopa [43]; (ii) Step 2, if necessary, add quetiapine (no dopamine antagonist)[3]; (iii) Subsidiary recommendations in Table 3. Grade B recommendation for apomorphine[41] and Grade A for sildenafil in the treatment of erectile dysfunction (ED)[40]. Deep brain stimulation can improve sexuality in men but not in women[42] (Grade C).
  • • 
    In stroke/SCI/MS, Grade C recommendation for baclofen, tizanidine, botox, and sclerosing agents to reduce limb spasticity inhibiting sexual movements.
  • • 
    In SCI, Grade A recommendation for ED using tadalafil [26], vardenafil [27], sildenafil [29], and PGE1[3]. Also, Grade A for tadalafil [26], vardenafil [27] to increase likelihood of orgasm/ejaculation.
  • • 
    For ED in MS, Grade A for sildenafil [31], Grade B for PGE1 [32].
  • • 
    Grade C recommendation for sildenafil to induce (minor) increase in vaginal lubrication in SCI [29] and MS [33].
  • • 
    Grade C recommendation for alpha-adrenergic agonist midodrine as an adjunct to penile vibratory stimulation to enhance ejaculation in SCI at T10 and above [28].
  • • 
    In epilepsy, Grade C recommendation in men to switch to a P450 enzyme-inhibiting or an enzyme-neutral antiseizure drug if there is hypogonadism from barbiturate or phenytoin or carbamazepine [46]. Grade B recommendation for testosterone replacement according to U.S. Endocrine Society criteria in hypogonadal men unable to discontinue barbiturate, phenytoin, or carbamazepine [47]. Grade C recommendation for an enzyme-neutral antiseizure drug to replace valproic acid causing weight gain or symptoms of polycystic ovary syndrome[50]. Grade D reflects uncertainty with regard to sexual advantages of lamotrigine. Grade C for anterior temporal lobectomy to eliminate epileptic sexual automatisms causing distress [51].

Sexual Dysfunction Associated with End-Stage Renal Disease

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

Prevalence of dysfunction is high and etiology is complex due to commonly comorbid diabetes, hypertension, coronary artery disease, and depression. Moreover, the symptom burden from bone and joint pain from osteodystrophy, fatigue, anorexia, nausea, stomatitis, unpleasant taste, prurititis, and malnutrition is extensive. The prevalence, pathophysiology, and treatment of sexual dysfunction within end-stage renal disease are shown in Tables 4 and 5.

Table 4.  Pathophysiological mechanisms involved in dysfunction associated with end-stage renal disease in men and therapy options
DysfunctionPathophysiological mechanismComments with regard to therapy and level of evidence
  1. ANS = autonomic nervous system; ED = erectile dysfunction; ESRD = end-stage renal disease; DM = diabetes mellitus; FSH = follicle stimulating hormone; GnRH = gonadotropin-releasing hormone; HT = hypertension; HD = hemodialysis; LOE = level of evidence; LH = luteinizing hormone; NO = nitric oxide; NOS = nitric oxide synthase; PD = peritoneal dialysis; PDE5i = phosphodiesterase type 5 inhibitors; PGE1 = prostaglandin E1.

Erectile dysfunction: Prevalence 55–85% in men with uremia or on peritoneal and/or HD with possible further increase after transplantation [52–54]Anemia-associated decreased NO productionRecombinant human erythropoietin (CEPO) in some but not all patients with ESRD [55]. May be useful in 80% of men with ESRD on dialysis compared with only 20% of uremic men (i.e., not receiving dialysis) [56] LOE 3
Endothelial dysfunction from associated HT, DM; Reduced NO production associated with increased production of dimethylarginine [57]; uremia-associated reduced bioavailability of arginase, reduced NOS expression, quenching of NO by increased reactive oxygen species, and inhibition of NOS [58]; veno-occlusive dysfunction [59]; ANS dysfunction associated with uremia [60]Use PDE5is to magnify action of remaining NO assuming no nitrate therapy [61] LOE 2; Reduce dose in uremia but not when dialyzed; Transplantation may improve ED [62] LOE 2; PGE1 benefits those nonresponsive to or unable to take PDE5is [63] LOE 2
Iatrogenic: transplantation may worsen or induce ED [53]Sildenafil effective and safe post–transplant [62]
Associated depressionEffectively treating ED can encourage remission of depression in men without ESRD [64]
Low sexual desire: Low desire present in 45–100% uremic patients and those undergoing HD [65] and 41% in one study of 201 post-transplant patients [52]Low testosterone: Leydig cell dysfunction but rise in LH blunted. LH pulse amplitude [DOWNWARDS ARROW], GnRH pulsatility [DOWNWARDS ARROW]Testosterone therapy of limited benefit due in part to anemia and high prolactin. EPO partially corrects low testosterone [66]
High prolactin secretion “autonomous” possibly stimulated by 2° hyperparathyroidismIn older studies, bromocriptine effectively reduced prolactin but with minimal sexual benefit. Prolactin reduced by dihydroxy vitamin D with possible sexual benefit. No recent studies
Anemia of renal failure and associated fatigueErythropoietin, despite only partial correction of low T, Hct, and high LH/FSH and prolactin, shows some sexual benefit in male hemodialyzed (but not uremic) patients [66]; Debility, fatigue, anemia may also improve with nandrolone concomitant with erythropoietin [67]
Depression is independently associated with sexual dysfunction [68]Treating depression improves sexual function [1].
Chronic pain reported by 85% [69]No studies of sexual benefit of adequate analgesia
Psychosexual: altered self-image medicalization of bedroom for HDHolistic approach to therapy recommended
Orgasmic disorder: 21% with HD, 17% with PD and 14% post-transplant in one large study [52]Low testosteroneSee above with regard to testosterone
Neuropathy: uremic, diabetic: autonomic and somaticVibrostimulation as in other situations of nerve damage but no studies
Table 5.  Pathophysiological mechanisms involved in dysfunction associated with end-stage renal disease in women and therapy options
DysfunctionPathophysiological mechanismComments with regard to therapy and level of evidence
  1. EJD = ejaculatory dysfunction; ESRD = end-stage renal disease; HD = hemodialysis; NO = nitric oxide; LH = luteinizing hormone; PDEi = phosphodiesterase inhibitors; SSRIs = selective serotonin reuptake inhibitors; RCT = randomized controlled trial.

Low sexual desire: Low desire prevalent in 45–100% uremic patients and those undergoing HD [65] and 30–80% post transplant [52,70]Anovulation: no or decreased LH surge (the associated testosterone decrease not studied), but levels of LH are abnormally high in the follicular phase. LH levels fail to rise after administration of estrogen, strongly suggesting a defect in the positive hypothalamic feedback mechanism [1]. Forty percent of women with ESRD are totally amenorrheic and less than 10% have regular menses. Premature menopause commonNo studies of investigational testosterone therapy in women; One small open controlled study showed transdermal estrogen plus progestin supplementation improved desire in dialyzed women [71]
Sexual motivation reduced from anemia due to uremic menorrhagia (although amenorrhea is more common)Progesterone cyclically or daily but sexual function not studied
No desire triggered during women's sexual experience as painful outcome expected from chronic estrogen deficiency-associated dyspareuniaLocal vulvar vaginal estrogen therapy not contraindicated but minimally studied
High prolactin secretion “autonomous” possibly stimulated by 2° hyperparathyroidismIn older studies, bromocriptine effectively reduced prolactin but with minimal sexual benefit. Prolactin reduced by dihydroxy vitamin D with possible sexual benefit. No recent studies
Anemia of renal failure and associated fatigueErythropoietin and women's sexuality minimally studied: general benefit to well-being expected to improve sexual motivation
Depression is independently associated with sexual dysfunction [17]. Sad experiences without clinical depression are a risk factor for low desire [72]Treating depression improves sexual function [1]. SSRI-associated low desire not helped by PDEi in women without ESRD [73]
Chronic pain including bone pain, headaches, painful neuropathy reported by 85% [69]No studies of sexual benefit of adequate analgesia
Psychosexual and interpersonal issues. Altered self-image, medicalization of bedroom for HDHolistic approach to therapy recommended
Orgasmic disorder: Prevalence: significantly more frequent than in controls [17,72] with HD, and post-transplant [52]Anovulation associated low testosteroneNo studies of investigational testosterone therapy in women
Neuropathy: uremic, diabetic: somatic and autonomicVibrostimulation: no studies
Depression and SSRIs related dysfunctionOne RCT showing benefit from sildenafil, but women did not have ESRD [73]
Genital arousal disorder: Prevalence: significantly greater than in controls [17,72]Impaired genital congestion—likely from uremia and diabetes reducing bioavailable NO as in menPotential enhancement of genital congestion from PDEi not studied in ESRD, but one small RCT showed evidence of benefit in diabetes[74] Subjective arousal improves after transplant, but genital congestion does not [75]
Subjective arousal disorder: Prevalence unknownMultiple stressors and symptomsSubjective arousal improves after transplant [75]; One small open controlled study showed transdermal estrogen plus progestin supplementation improved “sexual satisfaction” in dialyzed women [71]
Dyspareunia: Prevalence 25% with HD and 20% post-transplant in one large study [52]Vulvovaginal atrophy from estrogen deficiency pre- and post- (often premature) menopauseLocal estrogen therapy not contraindicated but minimally studied
Recurrent candidiasis when diabetes underlies the ESRDNo studies of prophylaxis with acidifying agents or antifungals in women with ESRD

Recommendations

Our recommendations for the management of sexual dysfunction in end-stage renal failure are as follows:

  • • 
    Given the complex etiologies, holistic assessment and treatment of sexual dysfunction are recommended (Grade C).
  • • 
    Recombinant EPO therapy is guided by hemoglobin level. However, its use is recommended for ED (Grade C) and for low desire in men and women (Grade C) [66].
  • • 
    Sildenafil is recommended for ED during hemodialysis and peritoneal dialysis (Grade B) [61].
  • • 
    Although improvements cannot be guaranteed, transplant may improve ED (Grade C) [62].
  • • 
    Sildenafil is recommended for ED post-transplant (Grade B ) [62].
  • • 
    Transplantation may improve sexual desire in men and women (Grade C) [76].

Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

Male LUTS and Sexual Dysfunction

Male LUTS and sexual dysfunction are conditions encountered on a daily basis in urology practice. A great deal of epidemiologic and clinical research has shown that LUTS and sexual dysfunction are strongly linked (Grade B) [77–86]. Multidisciplinary human study is warranted on the basis of the possible common pathogenesis for LUTS and sexual dysfunction (Grade C) [87]. Current clinical research focuses on the overlap and interactions of therapies for these conditions. It is clear that α-adrenergic receptor antagonists do not have a negative effect on erectile function, but tamsulosin does cause significant ejaculatory dysfunction (Grade B) [88–90]. 5-α-Reductase inhibitors for LUTS are associated with adverse effects on sexual function in the first 2 years of the treatment (Table 6) (Grade A) [91–94]. There is also a cumulative risk of sexual side effects with combination therapy of α-adrenergic receptor antagonists and 5-α-reductase inhibitors (Grade A) [95,96]. Recently, studies demonstrated that PDE5 inhibitors have significant and clinically relevant effect to improve LUTS (Table 7) (Grade A) [97–99]. Future studies need to target the pathogenesis of LUTS-associated ED to identify novel pharmacotherapy.

Table 6.  Effect of medications for LUTS on sexual function
MedicationED (%)EjD (%)CommentsEvidence level
  1. N/A = no information; Do = doxazosin; F = finasteride; Du = dutasteride; T = tamsulosin; LUTS = lower urinary tract symptoms; ED = erectile dysfunction.

α-receptor antagonist    
 Tamsulosin/placebo4/49/1(1) None of the four agents has a negative effect on erectile function when compared with placebo; (2) Tamsulosin has obvious side effect on ejaculatory function.1–3
 Doxazosin/placebo4/40.4/1
 Terazosin/placebo5/51/1
 Alfuzosin/placebo3/40.3/(N/A)
5-α-Reductase inhibitors    
 Finasteride/placebo16/68/2(1) Both finasteride and dutasteride are associated with comparable adverse effects on sexual function; (2) The rates of these adverse effects become comparable to placebo after the treatment was continued more than 2 years.I
 Dutasteride/placebo4.7/1.71.4/0.5I
Combination therapy   I
 Placebo3.320.83There is a cumulative risk of sexual side effects with combination therapy when compared to monotherapy or placebo. 
 Doxazosin3.561.10
 Finasteride4.531.78
 Combination (Do + F)5.113.05
 Tamsulosin3.81.9
 Dutasteride6.01.1
 Combination (Du + T)7.46.6
AntimuscarinicsN/AN/A N/A
 Oxybutynin  There is no well-designed study regarding this class of medications on male sexual function. 
 Tolterodine
 Trospium chloride
 Solifenacin
 Darifenacin
Table 7.  Effect of PDE5 inhibitors on LUTS
AuthorPDE5iPopulationStudy durationΔIPSSΔEFPLOE
CTCTCT
  1. Δ = change of scores; C = placebo group; T = treatment group; LOE = level of evidence; LUTS = lower urinary tract symptoms; PDE5i = phosphodiesterase type 5 inhibitors.

McVary et al. 2007 [97]Sildenafil18018912 weeks1.936.321.869.17<0.00011
McVary et al. 2007 [98]Tadalafil14313812 weeks1.73.81.47.7<0.0011
Stief et al. 2008 [99]Vardenafil1131098 weeks3.65.91.57.5<0.0011

Sexual Dysfunction Associated with LUTS in Women

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

Epidemiology studies suggest an association of LUTS with female sexual dysfunction (FSD) (Table 8) [100–105]. However, well-designed population studies with validated questionnaires to look at this association are needed given the complexity of FSD and the wide spectrum of LUTS (Grade C). The pathophysiology of LUTS-associated FSD is poorly understood; however, both the anatomical proximity of the bladder and urethra to the vaginal canal and the shared spinal reflexes that are under descending control from higher centers may be relevant [106] and research is greatly needed (Grade C). Limited publications suggest that nonsurgical treatment for LUTS appears to benefit sexual function (Grade C) [107–111]. However, current urogynecologic pelvic surgeries for LUTS can improve, worsen, or have no effect on female sexual function (Grade C) [112–120]. All patients should be well informed regarding this conflicting information before their surgical procedures. Currently, there is no publication available to recommend any prevention strategy for LUTS-associated FSD. Through better understanding of their pathophysiology, prevention of both conditions may be possible (Grade C).

Table 8.  Association of LUTS and FSD
AuthorStudy designPopulationFSDEvidence level
(%)ORFSFI
  1. N/A = no information for control; * = OR (odds ratio) varies by the type of LUTS; FSFI = Female Sexual Function Index (data with significant difference are included); LUTS = lower urinary tract symptoms; FSD = female sexual dysfunction.

Salonia et al. 2004 [100]Cross-sectional (with age-matched control)216 (102)46 (N/A) Desire2.0 vs. 3.23
Lubrication3.2 vs. 4.4
Satisfaction2.7 vs. 4.0
Pain1.8 vs. 4.0
Aslan et al. 2005 [101]Cross-sectional (with age-unmatched control)21 (18)  Desire2.8 vs. 4.03
Lubrication3.9 vs. 4.9
Orgasm3.8 vs. 4.6
Satisfaction4.1 vs. 4.6
Møller et al. 2005 [102]Prospective nonrandomized2,284 2.9–5.7*  3
Kim et al. 2005 [103]Cross-sectional3,3725.24.16–5.08*3
Özel et al. 2006 [104]Retrospective (LUTS with/without prolapse)20153 (30) no libido; 49 (30) no orgasm   4
Sen et al. 2006 [105]Cross-sectional (with age-matched control)153 (89)  Desire2.87 vs. 3.353
Lubrication3.44 vs. 3.75
Satisfaction3.39 vs. 3.83
Pain3.96 vs. 4.28

Sexual Dysfunction in Psychiatric Disease

  1. Top of page
  2. ABSTRACT
  3. Introduction
  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References

Psychiatric disorders and drugs used in their treatment are frequently associated with sexual dysfunction. Loss of sexual desire can be the presenting symptom of depression, and sexual problems remaining despite antidepressant medication may challenge patient compliance. However, more commonly, compliance is hampered by the onset of new sexual dysfunction associated with antidepressant or antipsychotic medication. Inquiry about sexual function should be made in the first assessment interview prior to any treatment and periodically through treatment.

Depression

The various aspects of depression including low interest, low energy, low self-esteem, and anhedonia can all impact on sexual function. Also, the associated deterioration of communication skills can impair personal relationships, and social isolation and irritability can similarly interfere. Sexual desire is decreased in the majority of depressive patients, with studies suggesting some doubling of its prevalence compared with controls [121]. All aspects of sexual response may be affected.

Antidepressants and Sexual Dysfunction

Selective serotonin reuptake inhibitors, venlafaxine, duloxetine, tricyclic agents show a higher incidence of sexual dysfunction than other antidepressants that are less serotonergic including bupropion, mirtazapine, moclobemide, tianeptine, and agomelatine. Of note, sexual dysfunction is the most frequent adverse effect of these serotonergic drugs with an incidence of up to 50% [122]—not only affecting the patient's quality of life but leading to therapeutic noncompliance with long-term treatment, possibly causing some 50% of patients to drop out [123]. All aspects of sexual function can deteriorate from antidepressant drugs, mainly loss of libido and delay of orgasm.

The mechanisms involved in antidepressant-related sexual dysfunction include an increase of serotonin activity, anticholinergic effect, dopamine (D2) blockade, nitric oxide inhibition, α-1 blockade (priapism), and increased prolactin.

Management of Antidepressant-Associated Sexual Dysfunction

Drug substitution is an option in cases of drug-induced sexual dysfunction. Although mirtazapine can improve sexual difficulties, other adverse effects can appear such as weight increase and somnolence [124]. Bupropion has shown little dysfunction [125], perhaps due to its dopaminergic mechanism of action. Also as there is no serotonergic activity; weight gain and sedation are also generally absent. Agomelatine, a new antidepressant, is an agonist of melatonin receptors (MT1 and MT2), and antagonists at 5HT2C, and shows a very low degree of sexual dysfunction [126–128].

Sometimes, gradual reduction of dose of medication is helpful for sexual function and may maintain mood control. Drug holidays, although possibly affective, can undermine treatment compliance and cause drug discontinuation or return of depressive symptoms. “Antidotes” that have been evaluated include the benefit from sildenafil [129] or tadalafil [130] for drug-induced ED. One recent trial suggests that antidepressant-induced orgasmic dysfunction in women might be improved by sildenafil [73]. When medication switches or additions do not relieve a sexual dysfunction, it is important to validate and explain to patients the etiology of their sexual difficulties and consider psychological treatments including CBT, sex therapy, and mindfulness.

Psychosis: Schizophrenia and Sexual Dysfunction

Dependent on the course of the psychosis, patients suffering from schizophrenia have a variety of sexual difficulties. Those with persistent illness tend to have deteriorated sexual function. However, patients with good evolution of their disease maintain sexual interest but, yet, might have emotional difficulties in expressing their sexual needs. Up to 90% of chronically psychotic patients can have sexual dysfunction of complex etiology including the illness itself-reduced motivation, difficult relationships with others, affective deficit, difficulties finding or keeping a partner, or from antipsychotic therapy [131].

Sexual Dysfunction from Antipsychotic Medication

In general, antipsychotics that increase prolactin (haloperidol and typicals, risperidone, amisulpride, and paliperidone) are associated with more sexual problems than those which do not (quetiapine, aripiprazole, ziprasidone, and olanzapine). Interestingly, although clozapine hardly raises prolactin, sexual dysfunction is common. Also, prolactin levels per se may not correlate with sexual dysfunction or with psychosis control. Rather, the increased ability for emotional regulation from effective antipsychotic drugs benefits sexual function [132]. Other mechanisms involved in antipsychotic-induced dysfunction include sedation from histamine blockade, cholinergic blockade, and adrenergic blockade. Conventional antipsychotics block D2 receptors on pituitary lactotrophes and so prevent inhibition of prolactin secretion by dopamine.

When semistructured sexual function interviews are used, sexual dysfunction rates of between 50% and 63% are detected in treated schizophrenic outpatients [133]. Lower frequency rates are found using the same methods in nonmedicated psychotic patients [134]. Highest rates of dysfunction have been associated with thioridazine where the most common complaints are ED and retrograde ejaculation [135–137].

Management of Antipsychotic-Induced Sexual Dysfunction

There is minimal study to guide management. Drug holidays undermine treatment compliance. There is a lack of control data to support the use of any antidotes such as amantadine. However, the use of sildenafil may allow improvement in ED [138]. Substitution may be helpful for instance switching to olanzapine, quetiapine, aripiprazole, or ziprasidone [139,140].

Recommendations

Our recommendations regarding sexual function in psychiatric disease include:

  • • 
    Psychotropic drug-related sexual dysfunction should be addressed given the real risk of noncompliance as well as impaired quality of life [123] (Grade C)
  • • 
    Sexual history including specific scales prior to initiating drugs and a follow-up are strongly recommended (Grade C)
  • • 
    Sexual side effects should be important when initially selecting long-term psychotropic drugs: select drugs with low risk of dysfunction (Grade C)
  • • 
    To lessen drug-induced dysfunction, choose quetiapine, aripiprazole, ziprasidone, and olanzapine rather than risperidone, amisulpride, and paliperidone [139,141] (Grade B)
  • • 
    Avoid serotonergic antidepressants [122,125,127] (Grade A)
  • • 
    Choose agomelatine [126,127] or bupropion [125] (Grade B)
  • • 
    PDE inhibitors may benefit antidepressant-induced male sexual dysfunction [129,130] (Grade B)
  • • 
    Sildenafil may improve antipsychotic drug-associated ED [138] (Grade B)
  • • 
    Sildenafil may improve antidepressant-induced female orgasmic disorder [73] (Grade B)

Conflict of Interest: No conflict of interest to declare for Drs. Basson, Incrocci, Rees, and Wang.

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  2. ABSTRACT
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  4. Assessment
  5. Sexual Dysfunction Associated with Neurological Disease
  6. Sexual Dysfunction Associated with End-Stage Renal Disease
  7. Sexual Dysfunction Associated with Lower Urinary Tract Symptoms (LUTS)
  8. Sexual Dysfunction Associated with LUTS in Women
  9. Sexual Dysfunction in Psychiatric Disease
  10. Acknowledgment
  11. References
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