sign in sign up
<<
Home , Erectile dysfunction, Sexual medicine, Urology

Sexual Function/

Erectile Dysfunction: AUA Guideline

Arthur L. Burnett, Ajay Nehra, Rodney H. Breau, Daniel J. Culkin, Martha M. Faraday, Lawrence S. Hakim, Joel Heidelbaugh, Mohit Khera, Kevin T. McVary, Martin M. Miner, Christian J. Nelson, Hossein Sadeghi-Nejad, Allen D. Seftel and Alan W. Shindel

From the American Urological Association Education and Research, Inc., Linthicum, Maryland

Purpose: The purpose of this guideline is to provide a clinical strategy for the Abbreviations and diagnosis and treatment of . Acronyms Materials and Methods: A systematic review of the literature using the Pubmed, AEs ¼ adverse events Embase, and Cochrane databases (search dates 1/1/1965 to 7/29/17) was con- ¼ ducted to identify peer-reviewed publications relevant to the diagnosis and AUA American Urological Association treatment of erectile dysfunction. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, ED ¼ erectile dysfunction and Conditional Recommendations with additional statements presented in the EF ¼ erectile function form of Clinical Principles or Expert Opinions. ICI ¼ Results: The American Urological Association has developed an evidence-based IU ¼ intraurethral guideline on the management of erectile dysfunction. This document is PDE5i ¼ type designed to be used in conjunction with the associated treatment algorithm. 5 inhibitors Conclusions: Using the shared decision-making process as a cornerstone for TD ¼ deficiency care, all should be informed of all treatment modalities that are not VED ¼ vacuum device contraindicated, regardless of invasiveness or irreversibility, as potential first- line treatments. For each treatment, the clinician should ensure that the man Accepted for publication May 3, 2018. and his partner have a full understanding of the benefits and risk/burdens The complete unabridged version of the associated with that choice. guideline is available at http://jurology.com/. This document is being printed as submitted independent of editorial or peer review by the Key Words: physiological , men’s health, cardiovascular editors of The Journal of UrologyÒ. diseases, clinical decision/making, psychological sexual dysfunction

BACKGROUND The Panel believes that shared The sexual response cycle is decision-making is the cornerstone of conceptualized as a sequential series the treatment and management of of psychophysiological states that ED, a model that relies on the con- usually occur in an orderly progres- cepts of autonomy and respect for sion. These phases were character- persons in the clinical encounter. It is ized by as also a process in which the desire, arousal, , and resolu- and the clinician together determine tion. Erectile dysfunction (ED) can the best course of based on be conceptualized as an impairment a discussion of the risks, benefits in the arousal phase of sexual and desired outcome. Using this response and is defined as the approach, all men should be informed consistent or recurrent inability to of all treatment options that are not attain and/or maintain penile erec- medically contraindicated to deter- tion sufficient for sexual satisfaction, mine the appropriate treatment. including satisfactory sexual Although many men may choose to performance.1,2 begin with the least invasive option,

0022-5347/18/2003-0633/0 https://doi.org/10.1016/j.juro.2018.05.004 ® THE JOURNAL OF Vol. 200, 633-641, September 2018 www.jurology.com j 633 Ó 2018 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. Printed in U.S.A. 634 AUA GUIDELINE ON ERECTILE DYSFUNCTION

the Panel notes that it is valid for men to begin with family history of , and substance any type of treatment, regardless of invasiveness use. Key questions regarding ED include identifying or reversibility. Men also may choose to forego the onset of symptoms, symptom severity, degree of treatment. In each scenario, the clinician’s role is bother, specification of whether the problem involves to ensure that the man and his partner have a attaining and/or maintaining an erection, situational full understanding of the benefits and risks/burdens factors (e.g., occurring only in specific contexts, only of the various management strategies (see when with a partner, only with specific partners), the supplementary figure, http://jurology.com/). presence of nocturnal and/or morning , the presence of masturbatory erections, and prior use of erectogenic therapy.6 The presence of nocturnal and/ GUIDELINE STATEMENTS or morning erections suggests (but does not confirm) For more information on the American Urological a psychogenic component to ED symptoms that Association (AUA) nomenclature system that was would benefit from further investigation. used to arrive at statement type and body of evi- Vital signs including pulse and resting blood dence strength see table 1 in the supplementary pressure should be assessed. Genital examination unbridged guideline (http://jurology.com/). should include assessment of penile skin lesions and 1. Men presenting with symptoms of ED placement/configuration of the urethral meatus. should undergo a thorough medical, sexual Examination of the for occult deformities or and psychosocial history, a physical exami- plaque lesions should occur with the penis held nation, and selective laboratory testing. stretched and palpated from the pubic bone to the (Clinical Principle) coronal sulcus.7 The presence/absence of a palpable 2. For the man with ED, validated ques- plaque should not be taken as definitive evidence for tionnaires are recommended to assess the clinically relevant penile deformity such as Peyro- severity of ED, to measure treatment effec- nie’s Disease. If Peyronie’s Disease is suspected, tiveness, and to guide future management. then additional diagnostic procedures should be (Expert Opinion) undertaken. Digital is not 3. Men should be counseled that ED is a risk required for evaluation of ED; however, benign marker for underlying hyperplasia is a common comorbid condi- (CVD) and other health conditions that may tion in men with ED and may merit evaluation and warrant evaluation and treatment. (Clinical treatment. Principle) With the possible exception of glucose/hemoglo- 4. In men with ED, morning serum total bin A1c and serum lipids, no routine serum study is testosterone levels should be measured. likely to alter ED management. Serum total (Moderate Recommendation; Evidence Level: testosterone should be measured in all men with ED Grade C) to determine if testosterone deficiency (TD), defined 5. For some men with ED, specialized as total testosterone <300 ng/dL with the presence testing and evaluation may be necessary to of symptoms and signs, is present. For complete guide treatment. (Expert Opinion) information on TD, please see the AUA guideline on 6. For men being treated for ED, referral to the evaluation and management of testosterone a professional should be deficiency.8 considered to promote treatment adherence, Psychological factors (e.g., , , reduce performance anxiety, and integrate relationship conflict) and psychosexual issues may treatments into a sexual relationship. (Mod- be primary or secondary contributors to ED.9,10 erate Recommendation; Evidence Level: Thoughtful discussion of these issues with men Grade C) and their partners is a key component of patient When the man’s presenting concern is ED, a education and can promote acceptance of incorpo- comprehensive evaluation and targeted physical rating a mental health/sexuality expert into the exam should be performed. Given that many men are treatment plan. Psychotherapy and psychosexual uncomfortable broaching sexual concerns with a counseling focus on helping patients and their , it is critical that the physician initiate the partners improve communication about sexual inquiry.3 Validated questionnaires may provide an concerns, reducing anxiety related to entering and opportunity to initiate a conversation about ED; during a sexual situation, and introducing strate- examples include the Erection Hardness Score4 and gies for integrating ED treatments into their sexual the Sexual Health Inventory for Men.5 General relationship. For men with predominantly psycho- factors to consider when a man pre- genic ED, providers should offer a referral to a sents with ED are age, comorbid medical and psy- psychotherapist as either an alternative or adjunct chological conditions, prior , medications, to medical treatment to ED. AUA GUIDELINE ON ERECTILE DYSFUNCTION 635

Risk markers are attributes that predict 8. Men with ED should be informed increased probability of a disease state but are not regarding the treatment option of an FDA- part of the causal pathway; ED is a risk marker for approved oral phosphodiesterase type 5 systemic cardiovascular disease. The Princeton inhibitor (PDE5i), including discussion of Consensus Conference, an inter-specialty meeting benefits and risks/burdens, unless contra- centered on preserving cardiac function and opti- indicated. (Strong Recommendation; Evi- mizing sexual health, has identified ED as a sub- dence Level: Grade B) stantial independent risk marker for cardiovascular 9. When men are prescribed an oral PDE5i disease. Findings from the Pre- for the treatment of ED, instructions should vention Trial indicated that the presence of ED was be provided to maximize benefit/efficacy. as strong a predictor of future cardiac events as (Strong Recommendation; Evidence Level: cigarette or a family history of myocardial Grade C) infarction.11 The diagnosis of ED provides a pivotal 10. For men who are prescribed PDE5i, the opportunity to discuss cardiovascular risk. The dose should be titrated to provide optimal ef- clinician should communicate this increased risk to ficacy. (Strong Recommendation; Evidence the man with ED, to his partner, and to other Level: Grade B) relevant clinicians (i.e. the provider) The FDA-approved oral phosphodiesterase type 5 so that appropriate referrals and interventions can inhibitors (PDE5i) available for management of ED be discussed and implemented. in the U.S. include sildenafil, tadalafil, vardenafil, For some men with ED, generally those who and avanafil. Several other PDE5i have been present with complex histories, specialized testing approved for use in other countries. PDE5i medi- and evaluation may be necessary. These tests cations have been extensively studied, with nearly a include nocturnal penile tumescence and rigidity quarter of a million men evaluated from the general testing; intracavernosal injection (ICI); penile ED population and approximately 25,000 men duplex ultrasound (which may be combined with evaluated from various special populations ICI to produce a more detailed and quantitative including those with specific underlying conditions assessment of penile vascular response);12 cav- (e.g., , benign prostate hyperplasia/lower ernosometry; and selective internal pudendal urinary tract symptoms, post radical prostatec- angiography. tomy). Data from individual studies and trials, 7. Clinicians should counsel men with ED including analyses that pooled data across multiple who have comorbidities known to negatively trials14-17 and reports of published systematic affect erectile function that lifestyle modifi- reviews18 suggest that sildenafil, tadalafil, and cations, including changes in diet and vardenafil, and avanafil have similar efficacy in the increased physical activity, improve overall general ED population, dose-response effects across health and may improve erectile function. PDE5i medications are small and non-linear, and on (Moderate Recommendation; Evidence Level: demand dosing versus daily dosing for tadalafil Grade C) appears to produce the same level of efficacy. Fewer The presence of ED indicates the likely presence studies focused on special populations, but in gen- of other comorbid conditions and risk factors, eral findings are similar to those reported in the particularly cardiovascular risk factors and general ED population.19-26 The data suggest, how- .13 Diverse literature that focused on lifestyle ever, that men with diabetes and men who are post- changes, primarily healthier diets and increased have more severe ED at baseline and , indicate that these interventions may have respond less robustly to PDE5i. small positive effects on erectile function (EF) and The most frequently reported adverse events broader, positive effects on overall health. The (AEs) in men using PDE5i are dyspepsia, headache, diagnosis of ED, and the associated interference flushing, back pain, nasal congestion, myalgia, vi- with sexual life, may motivate re-evaluation of sual disturbance, and dizziness (table 2 in supple- lifestyle choices and create the motivation for mentary unbridged guideline, http://jurology.com/). behavioral changes that ultimately may reduce Average rates are similar across medications with future vascular risks and improve erectile function. the exception of dyspepsia (lowest rates reported The man’s presentation for evaluation of ED there- with avanafil), flushing (lowest rates reported with fore creates an opportunity for the clinician to tadalafil), and myalgia (lowest rates reported with emphasize to him and his partner the importance of vardenafil and avanafil). Most AEs followed a dose- a healthy lifestyle to general health and quality of response pattern such that men who were random- life, but also to support optimal erectile function and ized to active treatment reported statistically increase the probability that ED treatments will be significantly higher rates of AEs than did men who effective. were randomized to ; the percentage of men 636 AUA GUIDELINE ON ERECTILE DYSFUNCTION

reporting a particular AE increased as dose induced by prostate cancer treatments. PDE5i have increased. been investigated most extensively for the purpose The use of nitrate-containing medications in of penile rehabilitation because of their non- combination with a PDE5i can cause a precipitous invasiveness and ease of administration. Trials drop in blood pressure. As such, men taking nitrates have not demonstrated that early PDE5i use (i.e., regularly should not use PDE5i medications. within 45 days of prostate cancer therapy) improves In men with mild to moderate hepatic or renal unassisted EF, although most studies reported that impairment or men with spinal cord , PDE5i PDE5i are effective in assisting erections on-demand should be used with caution at least initially at during the course of the trial. lower doses given the potential for delayed meta- Psychosocial support is also an integral compo- bolism. In men with severe renal or , nent of the penile rehabilitation strategy. Given the use of PDE5i is generally not recommended. impact of ED after prostate cancer treatment, Given that incorrect use of PDE5i (e.g., lack of particularly its suddenness and severity for many , medication taken with a large men undergoing radical prostatectomy, it is not meal) accounts for a large percentage of treatment surprising that men in this setting commonly failures, men who are prescribed a PDE5i should be experience depression, anxiety and relationship carefully instructed in the appropriate use of the .31 Clinicians should educate men regarding medication. In particular, it should be explained the sexual effects of prostate cancer treatments and that sexual stimulation is necessary and that more set realistic expectations regarding functional than one trial with the medication may be required recovery, including the possibility that recovery to establish efficacy. may be more challenging for men who have multiple When prescribing a PDE5i, the clinician must ED risk factors. balance the goals of the man and his partner for 12. Men with ED and testosterone deficiency successful sexual activity, the need to prescribe an (TD) who are considering ED treatment with a effective PDE5i dose, and the need to minimize AEs. PDE5i should be informed that PDE5i may be The clinician should work with the man and his more effective if combined with testosterone partner to find the dose that meets treatment ex- therapy. (Moderate Recommendation; Evi- pectations without resulting in unacceptable levels dence Level: Grade C) of AEs. This process may require that initial doses If a man with ED is also diagnosed with TD, then be titrated up or down until the optimal dose is he should be counseled that testosterone therapy in identified. combination with a PDE5i is more likely to be 11. Men who desire preservation of erectile effective than the PDE5i alone. Testosterone ther- function after treatment for prostate cancer apy is not an effective monotherapy for ED;32 if the by radical prostatectomy (RP) or radio- man’s goal is amelioration of ED symptoms, then he therapy (RT) should be informed that early should be counseled regarding the need for ED use of PDE5i post-treatment may not improve in addition to testosterone therapy. spontaneous, unassisted erectile function. However, testosterone therapy may provide some (Moderate Recommendation; Evidence Level: global health benefits (e.g., improved bone density). Grade C) For detailed information on possible health benefits The development of cavernous nerve-sparing of testosterone therapy, AEs associated with surgical procedures (i.e., the application of tech- testosterone therapy, and recommended monitoring niques that preserve the peri-prostatic penile nerve protocols for men prescribed testosterone, refer to supply required for penile erection) has led to the AUA guideline on the evaluation and manage- improved rates of erectile function recovery after ment of testosterone deficiency.8 radical pelvic .27 Even with nerve-sparing 13. Men with ED should be informed techniques many men will experience ED after regarding the treatment option of a vacuum pelvic operations.28 Similarly, modifications in erection device (VED), including discussion of the delivery of radiation for pelvic malignancies benefits and risks/burdens. (Moderate Recom- have resulted in better erection preservation after mendation; Evidence Level: Grade C) treatment.29 However, ED remains common after Vacuum erection devices (VED) are associated pelvic radiation, with approximately 36% of patients with high rates of patient and partner satisfaction reporting new-onset ED at 2 years post-treatment.30 (mean 77% for both patients and partners) and are Strategies for penile rehabilitation aim to prevent an effective and low-cost treatment option for select or reduce the extent of long-term erectile impair- men with ED. They are effective in the general ED ment and/or latency of erectile function recovery. population as well as in men with diabetes, spinal The objective of these strategies is to counteract cord injury, post-prostatectomy, and other condi- pathophysiologic mechanisms of erectile dysfunction tions.33,34 Only VEDs containing a vacuum limiter AUA GUIDELINE ON ERECTILE DYSFUNCTION 637

should be used. VED may be purchased over-the- Men who have contraindications to the use of counter or procured via prescription. Clinicians PDE5i, prefer not to take an oral medication, or find should counsel men with ED prior to beginning that PDE5i are inadequate or ineffective, may choose VED treatment about the potential occurrence of the ICI approach to treating ED. ICI medications are AEs. Most AEs are minor and resolved without effective in diverse groups of men, including men intervention, and include: transient penile pete- from the general ED population as well as among men chiae or bruising; discomfort or pain; difficulty with with other conditions such as diabetes, cardiovascu- ; and difficulty with the device. Men who lar risk factors, men who are post-prostatectomy, and are receiving anti-coagulant therapy and/or who men with spinal cord .38-42 have bleeding disorders or have a history of pria- The most commonly used outcome measure in ICI pism should use VEDs with caution. studies is the percentage of men who reported 14. Men with ED should be informed achieving an erection sufficient for successful in- regarding the treatment option of intra- tercourse. These percentages ranged from 53.7% to urethral (IU) alprostadil, including discussion 100% without marked differences across medica- of benefits and risks/burdens. (Conditional tions or medication combinations. The second most Recommendation; Evidence Level: Grade C) commonly used outcome measure was the percent of 15. For men with ED who are considering men who reported being satisfied with the treat- the use of IU alprostadil, an in-office test ment. These percentages ranged from 46.3% to should be performed. (Clinical Principle) 98.8% with the lowest satisfaction rates associated Intraurethral (IU) medication involves the with use (mean 53.4%). insertion of a delivery catheter into the meatus and Men should be thoroughly counseled regarding depositing an alprostadil ( E1) pellet the potential differential risk profiles of the various in the to induce an erection sufficient for ICI substances. The most serious AE associated intercourse. IU alprostadil is a treatment option for with ICI medications is with lowest rates men for whom PDE5i are contraindicated, for men of priapism (mean 1.8%) reported in studies using or partners who prefer to avoid oral medication, alprostadil. The Panel notes that identifying the and/or for men or partners who prefer not to use the appropriate dose of medication and instructing the needles required for ICI medications.35,36 The man in dose titration is critical to minimize the risk largest study to assess the efficacy of IU alprostadil of priapism. Pain is also a common consequence of reported that of the 461 men assigned to the ICI injections; the literature suggests that pain alprostadil condition, 299 (64.9%) achieved at least rates are highest when papaverine or alprostadil one episode of intercourse at home,37 while other are used as single agents, and when papaverine is studies reported successful intercourse rates from used in combination with . Penile 29.5% to 78.1%. fibrosis or plaque and penile deformities have been IU alprostadil should not be prescribed until a reported with use of ICI with considerable range man has undergone instruction in the technique, an across medications (4.5% - 13%). initial dose-titration in the office, and detailed Men considering ICI therapy should first have an counseling regarding possible AEs. in-office injection test,42 and should be informed 16. Men with ED should be informed that although injectable non-prostaglandin agents regarding the treatment option of intra- have been used to successfully manage ED for de- cavernosal injections (ICI), including discus- cades, none are formally FDA-approved for this sion of benefits and risks/burdens. (Moderate indication. Recommendation, Evidence Level: Grade C) 18. Men with ED should be informed 17. For men with ED who are considering regarding the treatment option of penile ICI therapy, an in-office injection test should implantation, including discussion be performed. (Clinical Principle) of benefits and risks/burdens. (Strong Recom- ICI medications are administered by injecting mendation, Evidence Level: Grade C) alprostadil, papaverine, phentolamine, and/or atro- 19. Men with ED who have decided on penile pine into the corpus cavernosum of the penis to implantation surgery should be counseled produce an erection. Only alprostadil is FDA- regarding post-operative expectations. (Clin- approved in the U.S. for ICI injection, and it is the ical Principle) only medication typically used as a single agent. 20. Penile prosthetic surgery should not be The three other medications with established effi- performed in the presence of systemic, cuta- cacy for ED are typically used in combination with neous, or urinary tract . (Clinical one another (e.g., papaverine þ phentolamine, Principle) alprostadil þ papaverine þ phentolamine; alpros- Prosthesis implantation has been performed tadil þ papaverine þ phentolamine þ atropine). successfully in men from the general ED population 638 AUA GUIDELINE ON ERECTILE DYSFUNCTION

as well as in men from a variety of special pop- underwent various versions of penile venous liga- ulations.43 Men and their partners should be thor- tion surgery indicate that penile venous ligation oughly counseled regarding the benefits and surgery is unlikely to result in long-term successful potential risks of this treatment to ensure appro- management of ED for the overwhelming majority priate choice of device, realistic post-operative ex- of men and delays treatment with other more reli- pectations, and potential for high satisfaction.44 able options such as penile prosthesis surgery.48 Men and their partners should be counseled 23. For men with ED, low-intensity extra- regarding AEs in the peri- and post-operative corporeal shock wave therapy should be period, including penile edema or hematoma, considered investigational. (Conditional corporeal injury, urethral injury, and acute urinary Recommendation; Evidence Level: Grade C) retention. These AEs are rarely serious and gener- 24. For men with ED, intracavernosal stem ally resolve with supportive care or minimal inter- cell therapy should be considered investiga- vention. Infection is a serious AE that typically tional. (Conditional Recommendation; Evi- occurs within the first three months after surgery dence Level: Grade C) and usually requires removal of the prosthesis. 25. For men with ED, platelet-rich plasma Although no randomized studies have compared therapy should be considered experimental. outcomes between prosthesis models with and (Expert Opinion) without infection-inhibiting coatings, observational Findings from randomized sham-controlled trials studies indicate that coated models have greatly that have evaluated low-intensity extracorporeal reduced infection rates with most series reporting shock wave therapy and ICI stem cell therapy do rates of 1-2% when these models are implanted.45,46 not clearly indicate that benefits reliably outweigh Given the invasive and essentially irreversible risks/burdens for men with ED, and these treat- nature of penile prosthesis implantation surgery, ments should only be considered investiga- counseling regarding short- and long-term post- tional.49,50 Platelet-rich plasma therapy should not operative expectations is essential. The Panel notes be offered to men with ED unless it is administered that penile prosthesis surgery should not be un- in the context of an institutional review board dertaken if the man has evidence of systemic or approved experimental clinical research protocol. At cutaneous or if he has a urinary tract this time, no full-text peer-reviewed publications infection. are available to constitute an evidence base. 21. For young men with ED and focal pelvic/ penile arterial occlusion and without docu- mented generalized vascular disease or FUTURE DIRECTIONS veno-occlusive dysfunction, penile arterial Advancements in ED management can be expected reconstruction may be considered. (Conditional to continue into the future in parallel with ongoing Recommendation, Evidence Level: Grade C) progress in the field of sexual more Penile arterial reconstruction surgery may be broadly. Developments in delivery, di- considered for the man with ED who is young and agnostics, and therapeutics will be the un- who does not have veno-occlusive dysfunction or any derpinnings of improved, evidence-based clinical evidence of generalized vascular disease or other practice in this field. Scientific discovery in the comorbidities that could compromise vascular vascular biology and neurophysiology of penile integrity. erection will continue to take center stage with Overall, data indicate that predicting whether particular focus on molecular and cellular signaling arterial will result in long- pathways and growth factor mechanisms that may term success for a given man is extremely difficult, be exploited to produce the next generation of even in men without comorbidities and with good pharmacotherapeutics as well as gene, stem cell, vascular health. In addition, proper diagnosis and regenerative therapies. Technologic advance- requires a thorough investigation. A recent study ments can also be expected to impact surgical pro- reported that nearly 50% of men initially identified cedures ranging from penile reconstructive to as good candidates for arterial reconstruction were prosthetic to tissue replacement surgeries (e.g., not properly diagnosed.47 penile transplantation). 22. For men with ED, penile venous surgery is not recommended. (Moderate Recommen- dation, Evidence Level: Grade C) DISCLAIMER Penile venous surgery is not recommended This document was written by the Erectile because of the lack of compelling evidence that Dysfunction Guideline Panel of the American Uro- it constitutes an effective ED management strategy logical Association Education and Research, Inc. in most men. Randomized trials of men who The Practice Guidelines Committee (PGC) of the AUA GUIDELINE ON ERECTILE DYSFUNCTION 639

AUA selected the committee chair. Panel members literature review, they are necessarily time-limited. were selected by the chair. Membership of the Panel Guidelines cannot include evaluation of all data on included specialists in urology, , and emerging technologies or management, including with specific expertise on this disorder. those that are FDA-approved, which may immedi- The mission of the Panel was to develop recom- ately come to represent accepted clinical practices. mendations that are analysis-based or consensus- For this reason, the AUA does not regard tech- based, depending on Panel processes and available nologies or management which are too new to be data, for optimal clinical practices in the treatment addressed by this guideline as necessarily experi- of muscle-invasive . mental or investigational. Funding of the Panel was provided by the AUA. Panel members received no remuneration for their work. Each member of the Panel provides an CONFLICT OF INTEREST (COI) DISCLOSURES ongoing conflict of interest disclosure to the AUA. Consultant/Advisor: Arthur Burnett: Auxilium, While these guidelines do not necessarily estab- American Medical Systems, Coloplast, Pfizer, lish the standard of care, AUA seeks to recommend Astellas, Lilly, Genomic Health; Mohit Khera: and to encourage compliance by practitioners with Abbvie, Boston Scientific, ATYU Pharmaceuticals, current best practices related to the condition being Coloplast, Endo Pharmaceuticals, VIVUS; Kevin treated. As medical knowledge expands and tech- McVary: NeoTract, NxThera, Boston Scientific; nology advances, the guidelines will change. Today Health Publishing: Arthur Burnett: Practical Re- these evidence-based guidelines statements repre- views in Urology, European Urology, Urology sent not absolute mandates but provisional pro- Times, Journal of , , posals for treatment under the specific conditions International Urology and ; Mohit described in each document. For all these reasons, Khera: Journal of Sexual Medicine; Hossein the guidelines do not pre-empt physician judgment Sadeghi-Nejad: Journal of Sexual Medicine; Alan in individual cases. Shindel: Endotext.com; Investment Interest: Alan Treating must take into account var- Shindel: Genomic Health; Leadership Position: iations in resources, and patient tolerances, needs, Arthur Burnett: Reflexonic, The Center for In- and preferences. Conformance with any clinical timacy After Cancer Therapy; Mohit Khera: Sexual guideline does not guarantee a successful outcome. Medicine Society of North America; Martin Miner: The guideline text may include information or rec- American Society of Men’s Health; Christian ommendations about certain drug uses (‘off label’) Nelson: Association of Peyronie’s Disease Advo- that are not approved by the Food and Drug cates; Hossein Sadeghi-Nejad: Sexual Medicine Administration (FDA), or about medications or Society of North America; Allen Seftel: The Jour- substances not subject to the FDA approval process. nal of UrologyÒ, American Society, Mid- AUA urges strict compliance with all government Atlantic Section of AUA, International Journal of regulations and protocols for prescription and use of Impotence Research; Ajay Nehra: International these substances. The physician is encouraged to Society of Men’s Health; Meeting Participant/ carefully follow all available prescribing informa- Lecturer: Lawrence Hakim: ENDO Urology, Slate/ tion about indications, contraindications, pre- Auxilium; Owner, Product Development: Allen cautions and warnings. These guidelines and best Seftel: Patient Pocket, LLC; Scientific Study/Trial: practice statements are not intended to provide Arthur Burnett: Medispec, Endo Pharmaceuticals, legal advice about use and misuse of these Acorda Therapeutics, National Institutes of substances. Health; Kevin McVary: Astellas, NIDDK, Sophris; Although guidelines are intended to encourage Martin Miner: Ichelxix; Christian Nelson: National best practices and potentially encompass available Institutes of Health; Allen Seftel: Ixchelsis, technologies with sufficient data as of close of the Progenics.

REFERENCES

1. Impotence. NIH Consensus Statement 1992; 3. Marwick C: Survey says patients expect little 5-item version of the international index of 10: 1. physician help on sex. JAMA 1999; 281: 217. erectile function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 1999; 4. Mulhall JP, Goldstein I, Bushmakin AG et al: 2. McCabe MP, Sharlip ID, Atalla E et al: Defini- 11: 319. Validation of the erection hardness score. J Sex tions of sexual dysfunctions in women and men: Med 2007; 4: 1626. a consensus statement from the Fourth inter- 6. Althof SE, Rosen RC, Perelman MA et al: Stan- national consultation on sexual medicine 2015. 5. Rosen RC, Cappelleri JC, Smith MD et al: dard operating procedures for taking a sexual J Sex Med 2016; 13: 135. Development and evaluation of an abridged, history. J Sex Med 2013; 10: 26. 640 AUA GUIDELINE ON ERECTILE DYSFUNCTION

7. Ghanem HM, Salonia A and Martin-Morales A: from placebo-controlled trials. Curr Med Res a systematic review and meta-analysis of ran- SOP: physical examination and laboratory testing Opin 2006; 22: 2111. domized placebo-controlled trials. Mayo Clin for men with erectile dysfunction. J Sex Med Proc 2007; 82: 20. 2013; 10: 108. 20. Kloner RA, Brown M, Prisant LM et al: Effect of in patients with erectile dysfunction 33. Baltaci S, Aydos K, Kosar A et al: Treating 8. Mulhall JP, Trost LW, Brannigan RE et al: Eval- taking antihypertensive therapy. Sildenafil study erectile dysfunction with a vacuum tumescence uation and management of testosterone defi- group. Am J Hypertens 2001; 14: 70. device: a retrospective analysis of acceptance ciency: AUA guideline. J Urol 2018; 200: 423. and satisfaction. Br J Urol 1995; 76: 757. 21. Giuliano F, Oelke M, Jungwirth A et al: 9. McCabe MP and Althof SE: A systematic once daily improves ejaculatory function, erectile 34. Dutta TC and Eid JF: Vacuum constriction de- review of the psychosocial outcomes associ- function, and sexual satisfaction in men with vices for erectile dysfunction: a long-term, ated with erectile dysfunction: does the lower urinary tract symptoms suggestive of prospective study of patients with mild, mod- impact of erectile dysfunction extend beyond benign prostatic hyperplasia and erectile erate, and severe dysfunction. Urology 1999; aman’s inability to have sex? J Sex Med dysfunction: results from a randomized, placebo- 54: 891. 2014; 11: 347. and tamsulosin-controlled, 12-week double-blind study. J Sex Med 2013; 10: 857. 35. Padma-Nathan H, Hellstrom WJ, Kaiser FE et al: 10. Corona G, Petrone L, Mannucci E et al: Treatment of men with erectile dysfunction with Assessment of the relational factor in male 22. Rosas SE, Wasserstein A, Kobrin S et al: Pre- transurethral alprostadil. Medicated urethral patients consulting for sexual dysfunction: the liminary observations of sildenafil treatment for system for erection (MUSE) study group. N Engl concept of couple sexual dysfunction. J Androl erectile dysfunction in dialysis patients. Am J J Med 1997; 336: 1. 2006; 27: 795. Dis 2001; 37: 134. 36. Williams G, Abbou CC, Amar ET et al: Efficacy 11. Thompson IM, Tangen CM, Goodman PJ et al: 23. Soler JM, Previnaire JG, Denys P et al: Phos- and safety of transurethral alprostadil therapy in Erectile dysfunction and subsequent cardiovas- phodiesterase inhibitors in the treatment of men with erectile dysfunction. MUSE study cular disease. JAMA 2005; 294: 2996. erectile dysfunction in spinal cord-injured men. group. Br J Urol 1998; 81: 889. Spinal Cord 2007; 45: 169. 12. Sikka SC, Hellstrom WJ, Brock G et al: Stan- 37. Ekman P, Sj€ogren L, Englund G et al: Optimizing 24. Nurnberg HG, Hensley PL, Gelenberg AJ et al: dardization of vascular assessment of erectile the therapeutic approach of transurethral Treatment of -associated sexual dysfunction: standard operating procedures for alprostadil. BJU Int 2000; 86: 68. duplex ultrasound. J Sex Med 2013; 10: 120. dysfunction with sildenafil: a randomized controlled trial. JAMA 2003; 289: 56. 38. Coombs PG, Heck M, Guhring P et al: A review of 13. Lee JH, Ngengwe R, Jones P et al: Erectile 25. Zelefsky MJ, Shasha D, Branco RD et al: Pro- outcomes of an intracavernosal injection therapy dysfunction as a risk programme. BJU Int 2012; 110: 1787. equivalent. J Nucl Cardiol 2008; 15: 800. phylactic sildenafil citrate improves select as- pects of sexual function in men treated with 39. Lakin MM, Montague DK, VanderBrug 14. Brock GB, McMahon CG, Chen KK et al: Efficacy radiotherapy for prostate cancer. J Urol 2014; Medendorp S et al: Intracavernous injection 192: and safety of tadalafil for the treatment of 868. therapy: analysis of results and complications. J erectile dysfunction: results of integrated ana- Urol 1990; 143: 1138. lyses. J Urol 2002; 168: 1332. 26. Mulhall JP, Burnett AL, Wang R et al: A phase 3, placebo controlled study of the safety and effi- 40. Linet OI and Ogrinc FG: Efficacy and safety of 15. Buvat J, Hatzichristou D, Maggi M et al: Efficacy, cacy of for the treatment of erectile intracavernosal alprostadil in men with erectile and satisfaction with sildenafil citrate dysfunction after nerve sparing radical prosta- dysfunction. The Alprostadil Study Group. N Engl 189: 100-mg titration compared with continued 50-mg tectomy. J Urol 2013; 2229. J Med 1996; 334: 873. dose treatment in men with erectile dysfunction. 27. Walz J, Epstein JI, Ganzer R et al: A critical BJU Int 2008; 102: 1645. 41. Lloyd LK and Richards JS: Intracavernous phar- analysis of the current knowledge of surgical macotherapy for management of erectile 16. Buvat J, Buttner H, Hatzimouratidis K et al: anatomy of the prostate related to optimisation dysfunction in . Paraplegia Adherence to initial PDE-5 inhibitor treatment: of cancer control and preservation of continence 1989; 27: 457. randomized open-label study comparing tadalafil and erection in candidates for radical prosta- once a day, tadalafil on demand, and sildenafil tectomy: an update. Eur Urol 2016; 70: 301. 42. El-Sakka AI: Intracavernosal on demand in patients with erectile dysfunction. 28. Schover LR, Fouladi RT, Warneke CL et al: The self vs office injection therapy in patients J Sex Med 2013; 10: 1592. with erectile dysfunction. Int J Impot Res use of treatments for erectile dysfunction among 2006; 18: 180. 17. Edwards D, Hackett G, Collins O et al: Varde- survivors of prostate carcinoma. Cancer 2002; 95: nafil improves sexual function and treatment 2397. 43. Akdemir F, Okulu E and Kayigil O: Long-term satisfaction in couples affected by erectile Ò 29. al-Abany M, Steineck G, Agren Cronqvist AK outcomes of AMS Spectra penile prosthesis dysfunction (ED): a randomized, double-blind, et al: Improving the preservation of erectile implantation and satisfaction rates. Int J Impot placebo-controlled trial in PDE5 inhibitor-naive 5: function after external beam radiation ther- Res 2017; 184. men with ED and their partners. J Sex Med apy for prostate cancer. Radiother Oncol 3: 44. Kramer AC and Schweber A: Patient expecta- 2006; 1028. 57: 2000; 201. tions prior to Coloplast Titan penile prosthesis 18. Berner MM, Kriston L and Harms A: Efficacy of 30. van der Wielen GJ, van Putten WL and predicts postoperative satisfaction. PDE5-inhibitors for erectile dysfunction. A Incrocci L: Sexual function after three- J Sex Med 2010; 7: 226. comparative meta-analysis of fixed-dose dimensional conformal radiotherapy for prostate regimen randomized controlled trials adminis- 45. Serefoglu EC, Mandava SH, Gokce A et al: Long- cancer: results from a dose-escalation trial. Int tering the international index of erectile function term revision rate due to infection in hydrophilic- J Radiat Oncol Biol Phys 2007; 68: 479. in broad-spectrum populations. Int J Impot Res coated inflatable penile prostheses: 11-year 2006; 18: 229. 31. Sadovsky R, Basson R, Krychman M et al: Cancer follow-up. J Sex Med 2012; 9: 2182. and sexual problems. J Sex Med 2010; 7: 349. 19. Blonde L: Sildenafil citrate for erectile dysfunc- 46. Carson CC 3rd, Mulcahy JJ and Harsch MR: tion in men with diabetes and cardiovascular risk 32. Bolona ER, Uraga MV, Haddad RM et al: Long-term infection outcomes after original factors: a retrospective analysis of pooled data Testosterone use in men with sexual dysfunction: antibiotic impregnated inflatable penile AUA GUIDELINE ON ERECTILE DYSFUNCTION 641

prosthesis implants: up to 7.7 years of followup. venous surgery for venogenic erectile dysfunc- blind, sham controlled study. J Urol 2012; J Urol 2011; 185: 614. tion. J Urol 1994; 151: 880. 187: 1769. 47. Dabaja AA, Teloken P and Mulhall JP: A critical analysis of candidacy for penile revasculariza- 50. Yiou R, Hamidou L, Birebent B et al: Safety of 49. Vardi Y, Appel B, Kilchevsky A et al: Does low intracavernous bone marrow-mononuclear cells tion. J Sex Med 2014; 11: 2327. intensity extracorporeal shock wave therapy for postradical prostatectomy erectile dysfunc- 48. Stief CG, Djamilian M, Truss MC et al: Prognostic have a physiological effect on erectile function? tion: an open dose-escalation pilot study. Eur factors for the postoperative outcome of penile Short-term results of a randomized, double- Urol 2016; 69: 988.