Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2020, Vol. 11 Issue (5) : 1202-1218     DOI: 10.14336/AD.2019.1028
Review Article |
Practical Approaches to Treat ED in PDE5i Nonresponders
Zhonglin Cai1, Xiaoqing Song2, Jianzhong Zhang1, Bin Yang3, Hongjun Li1,*
1Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
2Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
3Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China
Download: PDF(637 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

Erectile dysfunction (ED) is a common sexual disorder in adult males and one of the most important factors affecting their quality of life and that of their partners. Although PDE5 inhibitors (PDE5is) are the first choice for improving erectile function, there is a substantial proportion of ED patients, termed PDE5i nonresponders, who do not respond to PDE5is. Because of the lack of effective therapies, these patients always have serious social and psychological problems due to ED, which should be addressed. Here, we review the available literature about ED and PDE5is and propose several strategies for mitigating ED in PDE5i nonresponders.

Keywords erectile dysfunction      phosphodiesterase type 5 inhibitors      rescue strategy      nonresponders     
Corresponding Authors: Li Hongjun   
About author:

These authors contributed equally to this work.

Just Accepted Date: 29 October 2019   Issue Date: 21 September 2020
E-mail this article
E-mail Alert
Articles by authors
Cai Zhonglin
Song Xiaoqing
Zhang Jianzhong
Yang Bin
Li Hongjun
Cite this article:   
Cai Zhonglin,Song Xiaoqing,Zhang Jianzhong, et al. Practical Approaches to Treat ED in PDE5i Nonresponders[J]. Aging and disease, 2020, 11(5): 1202-1218.
URL:     OR
Approaches for rescue treatment in PDE5i nonrespondersPDE5i nonresponseRescue therapy with/without PDE5isRef.
PDE5iDosageDosing regimenPDE5iDosageDosing regimenOther therapeutic approachesSalvage success rate
Increased PDE5i dosesSildenafil100 mgOn demandSildenafil150 or 200 mgOn demandNA24.1%38
Different dosing regimensTadalafil20 mgOn demandTadalafilFlexible doses of 10 and 20 mgOnce dailyNA58.0%46
Different dosing regimensVardenafil20 mgOn demandVardenafil10 mgOnce dailyNA38.8%47
Different PDE5isSildenafil100 mgOn demandVardenafilFlexible doses of 10 and 20 mgOn demandNA12.0%48
Different PDE5isSildenafil≤100 mgOn demandVardenafilFlexible doses of 5, 10 and 20 mgOn demandNA53.0%49
Non-drug therapeutic approaches with or without PDE5isAt least one PDE5i (20 mg for tadalafil or vardenafil hydrochloride, 100 mg for sildenafil)Taking the same PDE5i as PDE5i nonresponseVED70.0%59
Non-drug therapeutic approaches with or without PDE5isTadalafil5?mgOnce dailyNANANALiSWT41.7%62
Non-drug therapeutic approaches with or without PDE5isPDE5is (unclear in detail)NANANALiSWT60.0%63
Non-drug therapeutic approaches with or without PDE5isSildenafil (100 mg), tadalafil (20 mg), and vardenafil (20 mg) as needed or tadalafil (5 mg) dailyTaking the same PDE5i as PDE5i nonresponseLiSWT67.3%64
Attention to psychological factorsSildenafil100 mgOn demandSildenafil100 mgOn demandTrazodone (50 or 100 mg, once daily)66.7%68
PDE5is combined with other non-PDE5i drugsHighest available dosage of sildenafil, tadalafil, or vardenafil therapyTadalafil10 mgOnce dailyTestogel (5 g up to 10 g, once daily)33.1%110
PDE5is combined with other non-PDE5i drugsSildenafil100 mgOn demandSildenafil100 mgOn demandOral testosterone undecanoate (Restandol, 80 mg, bid or tid)34.3% after testosterone replacement only, 37.5% more after combined therapy111
PDE5is combined with other non-PDE5i drugsTadalafil20 mgOn demandTadalafil20 mgTwice a weekTestogel (5 g, once daily)NA (improvement in IIEF-EF)113
PDE5is combined with other non-PDE5i drugsSildenafil100 mgOn demandSildenafil100 mgOn demandAtorvastatin (40 mg, once daily)NA (significant improvements in all IIEF-5 questions and GEQ)117
Table 1  Direct evidence of rescue treatment in PDE5i nonresponders.
Figure 1.  Management of patients with ED and hypogonadism. In patients with ED, more attention should be paid to testosterone supplementation after hypogonadism is confirmed by the detection of testosterone. In patients with ED and hypogonadism, some will recover from ED after treatment with PDE5is, but others will show nonresponsiveness to PDE5is; in these cases, ED can be treated by adding testosterone to the PDE5i treatment. The reason for this lack of a response is that PDE5 is under the control of testosterone, and a normal testosterone level is the basis for the full effect of PDE5is. Therefore, in ED patients with hypogonadism, we recommend giving priority to testosterone supplementation to treat a portion of them and using a combination of testosterone supplementation and PDE5is for the remaining patients.
Figure 2.  Management of strategies to treat ED in PDE5i nonresponders. In the management of PDE5i nonresponders, the first-line strategies consist of lifestyle adjustments and improved pharmacotherapy with PDE5is, including sufficient medication attempts, increased PDE5i doses, different dosing regimens, different PDE5is and the combined use of long-acting and short-acting PDE5is. If the patient has an obvious mental disorder, we should focus on the patient’s psychology and give corresponding treatment, such as attaching importance to the partner’s role and providing psychological intervention, including drugs, sexual counseling and cognitive behavioral therapy. In addition, strategies of improved pharmacotherapy with PDE5is and lifestyle adjustments should be added. If ED patients have comorbidities, comorbidity-related strategies, such as the selection of PDE5is with greater effects on ED and the management of medications for comorbidities of ED, including associated medication modifications, and combining PDE5is with other non-PDE5i drugs, should be fully considered on the basis of the strategies of improved pharmacotherapy with PDE5is and lifestyle adjustments. If necessary, non-drug therapeutic approaches with or without PDE5is can be selected according to the actual treatment profile of each PDE5i nonresponder. It is worth noting that in process of treating every PDE5i nonresponder, patient management should be of great concern. Periodic follow-up visits should be carried out to find any deficiencies in the ED treatment process. Good communication should also be established through patient counseling to resolve patients' concerns and ensure the smooth implementation of treatment.
[1] Allen MS, Walter EE (2019). Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. J Sex Med, pii: S1743-6095(19)30354-6.
[2] Lin H, Wang T, Ruan Y, Liu K, Li H, Wang S, et al.(2018). Rapamycin Supplementation May Ameliorate Erectile Function in Rats With Streptozotocin-Induced Type 1 Diabetes by Inducing Autophagy and Inhibiting Apoptosis, Endothelial Dysfunction, and Corporal Fibrosis. J Sex Med, 15(9):1246-1259.
[3] Li H, Gao T, Wang R (2016). The role of the sexual partner in managing erectile dysfunction. Nat Rev Urol, 13:168-77.
[4] Geerkens MJM, Al-Itejawi HHM, Nieuwenhuijzen JA, Meuleman EJM, Lissenberg-Witte BI, van Moorselaar RJA, et al. (2019). Sexual Dysfunction and Bother Due to Erectile Dysfunction in the Healthy Elderly Male Population: Prevalence from a Systematic Review. Eur Urol Focus. pii: S2405-4569(19)30079-3.
[5] Moncada I, Martinez-Salamanca J, Ruiz-Castañe E, Romero J (2018). Combination therapy for erectile dysfunction involving a PDE5 inhibitor and alprostadil. Int J Impot Res, 30(5):203-208.
[6] Hawksworth DJ, Burnett AL (2015). Pharmacotherapeutic management of erectile dysfunction. Clin Pharmacol Ther, 98(6):602-10.
[7] McMahon CN, Smith CJ, Shabsigh R (2006). Treating erectile dysfunction when PDE5 inhibitors fail. BMJ, 332: 589-92
[8] Moon KH, Park SY, Kim YW (2019). Obesity and Erectile Dysfunction: From Bench to Clinical Implication. World J Mens Health, 37(2):138-147.
[9] Albersen M, Mwamukonda KB, Shindel AW, Lue TF (2011). Evaluation and treatment of erectile dysfunction. Med Clin North Am, 95(1):201-12.
[10] Milenkovic U, Campbell J, Roussel E, Albersen M (2018). An update on emerging drugs for the treatment of erectile dysfunction. Expert Opin Emerg Drugs, 23(4):319-330.
[11] Echeverri Tirado LC, Ferrer JE, Herrera AM (2016). Aging and Erectile Dysfunction. Sex Med Rev, 4(1):63-73.
[12] Mulhall JP, Giraldi A, Hackett G, Hellstrom WJG, Jannini EA, Rubio-Aurioles E, et al. (2018). The 2018 Revision to the Process of Care Model for Management of Erectile Dysfunction. J Sex Med, 15(10):1434-1445.
[13] McCabe MP, Sharlip ID, Lewis R, Atalla E, Balon R, Fisher AD, et al. (2016). Incidence and prevalence of sexual dysfunction in women and men: a consensus statement from the Fourth International Consultation on Sexual Medicine 2015. J Sex Med, 13:144-152.
[14] Ayta IA, McKinlay JB, Krane RJ (1999). The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int, 84:50.
[15] Goldstein I, Chambers R, Tang W, Stecher V, Hassan T (2018). Real-world observational results from a database of 48 million men in the United States: Relationship of cardiovascular disease, diabetes mellitus and depression with age and erectile dysfunction. Int J Clin Pract, 72(4):e13078.
[16] Schulster ML, Liang SE, Najari BB (2017). Metabolic syndrome and sexual dysfunction. Curr Opin Urol, 27(5):435-440.
[17] Bilgutay AN, Pastuszak AW (2015). PEYRONIE'S DISEASE: A REVIEW OF ETIOLOGY, DIAGNOSIS, AND MANAGEMENT. Curr Sex Health Rep, 7(2):117-131.
[18] Pavone C, D'Amato F, Dispensa N, Torretta F, Magno C (2015). Smoking, diabetes, blood hypertension: possible etiologic role for Peyronie’s disease? Analysis in 279 patients with a control group in Sicily. Arch Ital Urol Androl, 87(1):20-4.
[19] Herrero A, Marcos MGalindo P (2018). Clinical and biochemical correlates of male hypogonadism in type 2 diabetes. Andrology, 6(1):58-63.
[20] Zhang J, Li X, Cai Z, Li H, Yang B (2019). Association between testosterone with type 2 diabetes in adult males, a meta-analysis and trial sequential analysis. Aging Male, 16:1-12.
[21] Anderson R, Moses R, Lenherr S, Hotaling JM, Myers J (2018). Spinal cord injury and male infertility-a review of current literature, knowledge gaps, and future research. Transl Androl Urol, 7(Suppl 3):S373-S382.
[22] Atiemo HO, Szostak MJ, Sklar GN (2003). Salvage of sildenafil failures referred from primary care physicians. J Urol, 170(6 Pt 1):2356-8.
[23] Korakas E, Dimitriadis G, Raptis A, Lambadiari V (2018). Dietary Composition and Cardiovascular Risk: A Mediator or a Bystander? Nutrients, 10(12). pii: E1912.
[24] Poudel A, Zhou JY, Story D, Li L (2018). Diabetes and Associated Cardiovascular Complications in American Indians/Alaskan Natives: A Review of Risks and Prevention Strategies. J Diabetes Res, 2018:2742565.
[25] Szafran-Dobrowolska J, Renke M, Jeżewska M (2019). Is it worth to continue to analyse the factors of cardiovascular risk among the sailors? Review of literature. Int Marit Health, 70(1):17-21.
[26] Chiang PK, Yang FY (2019). A potential treatment of low intensity pulsed ultrasound on cavernous nerve injury for erectile dysfunction. Med Hypotheses, 122:19-21.
[27] Barazani Y, Stahl PJ, Nagler HM, Stember DS (2015). Is there a rationale for penile rehabilitation following radical prostatectomy? Am J Mens Health, 9(1):35-43.
[28] Fenstermaker M, Dupree JM, Hadj-Moussa M, Ohl DA (2018). Management of Erectile Dysfunction and Infertility in the Male Spinal Cord Injury Patient. Curr Urol Rep, 19(7):47.
[29] Jiann BP, Yu CC, Su CC, Huang JK (2004). Rechallenge prior sildenafil nonresponders. Int J Impot Res, 16(1):64-8.
[30] Jackson SE, Firth J, Veronese N, Stubbs B, Koyanagi A, Yang L, et al. (2019). Decline in sexuality and wellbeing in older adults: A population-based study. J Affect Disord, 245:912-917.
[31] Khan S, Amjad A, Rowland D (2019). Potential for Long-Term Benefit of Cognitive Behavioral Therapy as an Adjunct Treatment for Men with Erectile Dysfunction. J Sex Med, 16(2):300-306.
[32] Shallcross AJ, Willroth EC, Fisher A, Dimidjian S, Gross JJ, Visvanathan PD, et al. (2018). Relapse/Recurrence Prevention in Major Depressive Disorder: 26-Month Follow-Up of Mindfulness-Based Cognitive Therapy Versus an Active Control. Behav Ther, 49(5):836-849.
[33] McCullough AR, Barada JH, Fawzy A, Guay AT, Hatzichristou D (2002). Achieving treatment optimization with sildenafil citrate (Viagra) in patients with erectile dysfunction. Urology, 60(2 Suppl 2): 28-38.
[34] Hellstrom WJ, Elhilali M, Homering M, Taylor T, Gittleman M (2005). Vardenafil in patients with erectile dysfunction: achieving treatment optimization. J Androl, 26(5):604-9.
[35] Sontag A, Rosen RC, Litman HJ, Ni X, Araujo AB (2013). The role of initial success rates and other factors in determining reliability of outcomes of phosphodiesterase inhibitor therapy for erectile dysfunction: a pooled analysis of 17 placebo-controlled trials of tadalafil for use as needed. J Sex Med, 10(2):541-50.
[36] Steidle CP, McCullough AR, Kaminetsky JC, Crowley AR, Siegel RL, Deriesthal H, et al. (2007). Early sildenafil dose optimization and personalized instruction improves the frequency, flexibility, and success of sexual intercourse in men with erectile dysfunction. Int J Impot Res, 19(2):154-60.
[37] Montorsi F, McCullough A (2005). Efficacy of sildenafil citrate in men with erectile dysfunction following radical prostatectomy: a systematic review of clinical data. J Sex Med, 2(5):658-67.
[38] McMahon CG (2002). High dose sildenafil citrate as a salvage therapy for severe erectile dysfunction. Int J Impot Res, 14(6):533-8.
[39] Shin YS, Lee SW, Park K, Chung WS, Kim SW, Hyun JS, et al. (2015). Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction. Int J Impot Res, 27(3):95-102.
[40] McMahon C, Lording D, Stuckey B, Tan V, Gillman M, White W, et al. (2006). Vardenafil improved erectile function in a "real-life" broad population study of men with moderate to severe erectile dysfunction in Australia and New Zealand. J Sex Med, 3(5):892-900.
[41] Porst H, Gacci M, Büttner H, Henneges C, Boess F (2014). Tadalafil once daily in men with erectile dysfunction: an integrated analysis of data obtained from 1913 patients from six randomized, double-blind, placebo-controlled, clinical studies. Eur Urol, 65(2):455-64.
[42] Lee JG, Kim BD, Han CH, Lee KK, Yum KS (2018). Evaluation of the effectiveness and safety of a daily dose of 5?mg of tadalafil, over an 8-week period, for improving quality of life among Korean men with andropause symptoms, including erectile dysfunction: A pilot study. Medicine (Baltimore), 97(51):e13827.
[43] Jiang H, Zhao LM, Lin HC, Yan S, Liu JH, Zhu ZH, et al. (2018). Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: interim results of a multicenter, randomized, open-label trial. Asian J Androl, 20(6):587-592.
[44] Carrier S, Brock GB, Pommerville PJ, Shin J, Anglin G, Whitaker S, Beasley CM Jr (2005). Efficacy and safety of oral tadalafil in the treatment of men in Canada with erectile dysfunction: a randomized, double-blind, parallel, placebo-controlled clinical trial. J Sex Med, 2(5):685-98.
[45] Romero Otero J, García Gómez B, Medina Polo J, Jiménez Alcaide E, García Cruz E, Sallent Font A, et al. (2014) Evaluation of current errors within the administration of phosphodiesterase-5 inhibitors after more than 10 years of use. Urology, 83:1334-1338.
[46] McMahon C (2004). Efficacy and safety of daily tadalafil in men with erectile dysfunction previously unresponsive to on-demand tadalafil. J Sex Med, 1(3):292-300.
[47] Javaroni V, Queiroz Miguez M, Burla A, Oigman W, Neves MF (2012). Response to on-demand vardenafil was improved by its daily usage in hypertensive men. Urology, 80(4):858-64.
[48] Brisson TE, Broderick GA, Thiel DD, Heckman MG, Pinkstaff DM (2006). Vardenafil rescue rates of sildenafil nonresponders: objective assessment of 327 patients with erectile dysfunction. Urology, 68(2):397-401.
[49] Hatzichristou DG, Aliotta P, Auerbach S, Barkin J, Lording D, Murdock M, et al. (2005). Erectile response to vardenafil in men with a history of nonresponse to sildenafil: a time-from-dosing descriptive analysis. Clin Ther, 27(9):1452-61.
[50] Rubio-Aurioles E, Glina S, Abdo CH, Hernandez-Serrano R, Rampazzo C, Sotomayor M, et al. (2009) Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: a geographical comparison from a single arm, open-label study. J Sex Med, 6(10):2836-50.
[51] Li HJ, Bai WJ, Dai YT, Xu WP, Wang CN, Li HZ (2016). An analysis of treatment preferences and sexual quality of life outcomes in female partners of Chinese men with erectile dysfunction. Asian J Androl, 18(5):773-9.
[52] Ahn TY, Lee SW, Kim SW, Yang DY, Park NC, Min KS, et al. (2007). Treatment preferences in men with erectile dysfunction: an open label study in Korean men switching from sildenafil citrate to tadalafil. Asian J Androl, 9(6):760-70.
[53] Ozgur BC, Gonenc F, Yazicioglu AH (2009). Sildenafil or vardenafil nonresponders' erectile response to tadalafil. Urol J, 6(4):267-71.
[54] Corona G, Rastrelli G, Burri A, Jannini EA, Maggi M (2016). The safety and efficacy of Avanafil, a new 2(nd) generation PDE5i: comprehensive review and meta-analysis. Expert Opin Drug Saf, 15(2):237-47.
[55] Caretta N, Palego P, Ferlin A, Garolla A, Bettella A, Selice R, et al. (2005). Resumption of spontaneous erections in selected patients affected by erectile dysfunction and various degrees of carotid wall alteration: role of tadalafil. Eur Urol, 48(2):326-31.
[56] Cui H, Liu B, Song Z, Fang J, Deng Y, Zhang S, et al. (2015). Efficacy and safety of long-term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction. Andrologia, 47(1):20-4.
[57] Sun L, Peng FL, Yu ZL, Liu CL, Chen J (2014). Combined sildenafil with vacuum erection device therapy in the management of diabetic men with erectile dysfunction after failure of first-line sildenafil monotherapy. Int J Urol, 21(12):1263-7.
[58] Chen J, Sofer M, Kaver I, Matzkin H, Greenstein A (2004). Concomitant use of sildenafil and a vacuum entrapment device for the treatment of erectile dysfunction. J Urol, 171(1):292-5.
[59] Canguven O, Bailen J, Fredriksson W, Bock D, Burnett AL (2009). Combination of vacuum erection device and PDE5 inhibitors as salvage therapy in PDE5 inhibitor nonresponders with erectile dysfunction. J Sex Med, 6(9):2561-7.
[60] Srini VS, Reddy RK, Shultz T, Denes B (2015). Low intensity extracorporeal shockwave therapy for erectile dysfunction: a study in an Indian population. Can J Urol, 22(1):7614-22.
[61] Brunckhorst O, Wells L, Teeling F, Muir G, Muneer A, Ahmed K (2019). A systematic review of the long-term efficacy of low-intensity shockwave therapy for vasculogenic erectile dysfunction. Int Urol Nephrol, 51(5):773-781.
[62] Wang CJ, Lu YM, Li CC, Wu WJ, Chien TM (2019). Low-intensity shock wave therapy ameliorates erectile dysfunction in men with pelvic fractures associated with urethral injury. Int J Impot Res, 31(3):218-222.
[63] Bechara A, Casabé A, De Bonis W, Ciciclia PG (2016). Twelve-Month Efficacy and Safety of Low-Intensity Shockwave Therapy for Erectile Dysfunction in Patients Who Do Not Respond to Phosphodiesterase Type 5 Inhibitors. Sex Med, 4(4):e225-e232.
[64] Tsai CC, Wang CJ, Lee YC, Kuo YT, Lin HH, Li CC, et al. (2017). Low-intensity extracorporeal shockwave therapy can improve erectile function in patients who failed to respond to phosphodiesterase type 5 inhibitors. Am J Mens Health, 11(6):1781-90.
[65] Chen S, Peng D, Xu X, Gao J, Dai F, Zuo C, et al. (2017). Assessment of erectile dysfunction and associated psychological distress in Chinese men with type 2 diabetes mellitus. Int J Impot Res, 29(5):210-214.
[66] Cheng CM, Lin YC, Chang KC (2017). Psychological Distress is Correlated with Erectile Dysfunction Among Patients Receiving Methadone Maintenance in Taiwan. J Dual Diagn, 13(4):312-316.
[67] Hehemann MC, Kashanian JA (2016). Can lifestyle modification affect men’s erectile function? Transl Androl Urol, 5(2):187-94.
[68] Taneja R (2007). A rational combination pharmacotherapy in men with erectile dysfunction who initially failed to oral sildenafil citrate alone: a pilot study. J Sex Med, 4(4 Pt 2):1136-41.
[69] Chambers SK, Occhipinti S, Schover L, Nielsen L, Zajdlewicz L, Clutton S, et al. (2015). A randomised controlled trial of a couples-based sexuality intervention for men with localised prostate cancer and their female partners. Psychooncology, 24(7):748-56.
[70] Pisano F, Falcone M, Abbona A, Oderda M, Soria F, Peraldo F, et al. (2015). The importance of psychosexual counselling in the re-establishment of organic and erotic functions after penile prosthesis implantation. Int J Impot Res, 27(5):197-200.
[71] Nowroozi MR, Amini E, Ayati M, Jamshidian H, Radkhah K, Amini S (2015). Applying extender devices in patients with penile dysmorphophobia: assessment of tolerability, efficacy, and impact on erectile function. J Sex Med, 12(5):1242-7.
[72] Chertin B, Natsheh A, Ben-Zion I, Prat D, Kocherov S, Farkas A, et al. (2013). Objective and subjective sexual outcomes in adult patients after hypospadias repair performed in childhood. J Urol, 190(4 Suppl):1556-60.
[73] Chambers SK, Occhipinti S, Stiller A, Zajdlewicz L, Nielsen L, Wittman D, et al. (2019). Five-year outcomes from a randomised controlled trial of a couples-based intervention for men with localised prostate cancer. Psychooncology, 28(4):775-783.
[74] White ID, Wilson J, Aslet P, Baxter AB, Birtle A, Challacombe B, et al. (2015). Development of UK guidance on the management of erectile dysfunction resulting from radical radiotherapy and androgen deprivation therapy for prostate cancer. Int J Clin Pract, 69(1):106-23.
[75] Banner LL, Anderson RU (2007). Integrated sildenafil and cognitive-behavior sex therapy for psychogenic erectile dysfunction: a pilot study. J Sex Med, 4(4 Pt 2):1117-25.
[76] Giuri S, Caselli G, Manfredi C, Rebecchi D, Granata A, Ruggiero GM, et al. (2017). Cognitive Attentional Syndrome and Metacognitive Beliefs in Male Sexual Dysfunction: An Exploratory Study. Am J Mens Health, 11(3):592-599.
[77] Wittmann D, Carolan M, Given B, Skolarus TA, An L, Palapattu G, et al. (2014). Exploring the role of the partner in couples' sexual recovery after surgery for prostate cancer. Support Care Cancer, 22:2509-15.
[78] Bai WJ, Li HJ, Dai YT, He XY, Huang YR, Liu JH, et al. (2015). An open-label, multicenter, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men naive to phosphodiesterase 5 inhibitor therapy. Asian J Androl, 17:61-7.
[79] Chen L, Shi GR, Huang DD, Li Y, Ma CC, Shi M, et al. (2019). Male sexual dysfunction: A review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention. Biomed Pharmacother, 112:108585.
[80] Jannini EA, Lombardo F, Lenzi A (2005). Correlation between ejaculatory and erectile dysfunction. Int J Androl, 28(2 suppl):40-5.
[81] el-Sakka AI (2008). Severity of erectile dysfunction at presentation: effect of premature ejaculation and low desire. Urology, 71: 94-98.
[82] Jannini EA, McMahon C, Chen J, Aversa A, Perelman M (2011). The controversial role of phosphodiesterase type 5 inhibitors in the treatment of premature ejaculation. J Sex Med, 8(8):2135-43.
[83] Jannini EA, Lenzi A, Isidori A, Fabbri A (2006). Subclinical erectile dysfunction: Proposal for a novel taxonomic category in sexual medicine. J Sex Med, 3(5):787-794.
[84] Mamas MA, Reynard JM, Brading AF (2003). Nitric oxide and the lower urinary tract: Current concepts, future prospects. Urology, 61:1079-85.
[85] Abdel-Hamid IA, El Naggar EA, El Gilany AH (2001). Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation. Int J Impot Res, 13:41-5.
[86] Chen J, Mabjeesh NJ, Matzkin H, Greenstein A (2003). Efficacy of sildenafil as adjuvant therapy to selective serotonin reuptake inhibitor in alleviating premature ejaculation. Urology, 61:197-200.
[87] Salonia A, Maga T, Colombo R, Scattoni V, Briganti A, Cestari A, et al. (2002). A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. J Urol, 168:2486-9.
[88] Aversa A, Pili M, Francomano D, Bruzziches R, Spera E, La Pera G, et al. (2009). Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation. Int J Impot Res, 21:221-7.
[89] Mattos RM, Marmo Lucon A, Srougi M (2008). Tadalafil and fluoxetine in premature ejaculation: Prospective, randomized, double-blind, placebo-controlled study. Urol Int, 80: 162-5.
[90] McMahon CG, Stuckey BG, Andersen M, Purvis K, Koppiker N, Haughie S, et al. (2005). Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation. J Sex Med, 2:368-75.
[91] Althof SE, Rowland DL (2008). Identifying constructs and criteria for the diagnosis of premature ejaculation: Implication for making errors of classification. BJU Int, 102:708-12.
[92] Sáenz de Tejada I, Anglin G, Knight JR, Emmick JT (2002). Effects of tadalafil on erectile dysfunction in men with diabetes. Diabetes Care, 25(12):2159-64.
[93] Liao X, Qiu S, Bao Y, Wang W, Yang L, Wei Q (2019). Comparative efficacy and safety of phosphodiesterase type 5 inhibitors for erectile dysfunction in diabetic men: a Bayesian network meta-analysis of randomized controlled trials. World J Urol, 37(6):1061-1074.
[94] Buvat J, van Ahlen H, Schmitt H, Chan M, Kuepfer C, Varanese L (2006). Efficacy and safety of two dosing regimens of tadalafil and patterns of sexual activity in men with diabetes mellitus and erectile dysfunction: Scheduled use vs. on-demand regimen evaluation (SURE) study in 14 European countries. J Sex Med, 3(3):512-20.
[95] Ziegler D, Merfort F, Van Ahlen H, Yassin A, Reblin T, Neureither M (2006). Efficacy and safety of flexible-dose vardenafil in men with type 1 diabetes and erectile dysfunction. J Sex Med, 3(5):883-891.
[96] García-Perdomo HA, Echeverría-García F, Tobías A (2017). Effectiveness of Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction in Patients with Spinal Cord Trauma: Systematic Review and Meta-Analysis. Urol Int, 98(2):198-204.
[97] Soler JM, Previnaire JG, Denys P, Chartier-Kastler E (2007). Phosphodiesterase inhibitors in the treatment of erectile dysfunction in spinal cord-injured men. Spinal Cord, 45(2):169-73.
[98] Khorrami MH, Javid A, Moshtaghi D, Nourimahdavi K, Mortazavi A, Zia HR (2010). Sildenafil efficacy in erectile dysfunction secondary to spinal cord injury depends on the level of cord injuries. Int J Androl, 33(6):861-4.
[99] Del Popolo G, Li Marzi V, Mondaini N, Lombardi G (2004). Time/duration effectiveness of sildenafil versus tadalafil in the treatment of erectile dysfunction in male spinal cord-injured patients. Spinal Cord, 42(11):643-8.
[100] Nehra A, Grantmyre J, Nadel A, Thibonnier M, Brock G (2005). Vardenafil improved patient satisfaction with erectile hardness, orgasmic function and sexual experience in men with erectile dysfunction following nerve sparing radical prostatectomy. J Urol, 173(6):2067-71.
[101] Limoncin E, Gravina GL, Corona G, Maggi M, Ciocca G, Lenzi A, et al. (2017). Erectile function recovery in men treated with phosphodiesterase type 5 inhibitor administration after bilateral nerve-sparing radical prostatectomy: a systematic review of placebo-controlled randomized trials with trial sequential analysis. Andrology, 5(5):863-872.
[102] Raina R, Lakin MM, Agarwal A, Mascha E, Montague DK, Klein E, et al. (2004). Efficacy and factors associated with successful outcome of sildenafil citrate use for erectile dysfunction after radical prostatectomy. Urology, 63(5):960-6.
[103] Fode M, Østergren PB, Jensen CFS, Jakobsen H, Sønksen J (2018). Treatment effects of phosphodiesterase-5 inhibitors may improve with time following nerve-sparing radical prostatectomy. Scand J Urol, 52(2):108-110.
[104] Miner MM, Barnes A, Janning S (2010). Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: a post hoc analysis of the vardenafil statin study. J Sex Med, 7(5):1937-47.
[105] Warde N (2011). Therapy: Two birds, one stone: Tadalafil is an effective treatment for men with both BPH-LUTS and ED. Nat Rev Urol, 8:643.
[106] Shamloul R, Ghanem H (2013). Erectile dysfunction. Lancet, 381(9861):153-65.
[107] Baumhäkel M, Schlimmer N, Kratz M, Hackett G, Jackson G, Böhm M (2011). Cardiovascular risk, drugs and erectile function--a systematic analysis. Int J Clin Pract, 65(3):289-98.
[108] Aversa A, Francomano D, Lenzi A (2015). Does testosterone supplementation increase PDE5-inhibitor responses in difficult-to-treat erectile dysfunction patients. Expert Opin Pharmacother, 16(5): 625-8.
[109] Jannini EA, Isidori AM, Aversa A, Lenzi A, Althof SE (2013). Which is first? The controversial issue of precedence in the treatment of male sexual dysfunctions. J Sex Med, 10(10):2359-69.
[110] B uvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, et al. (2011). Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). J Sex Med, 8(1):284-93.
[111] Hwang TI, Chen HE, Tsai TF, Lin YC (2006). Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil alone. Int J Impot Res, 18(4):400-4.
[112] Yassin DJ, Yassin AA, Hammerer PG (2014). Combined testosterone and vardenafil treatment for restoring erectile function in hypogonadal patients who failed to respond to testosterone therapy alone. J Sex Med 11(2):543-52.
[113] Yassin AA, Saad F, Diede HE (2006). Testosterone and erectile function in hypogonadal men unresponsive to tadalafil: results from an open-label uncontrolled study. Andrologia, 38(2):61-8.
[114] Porst H, Burnett A, Brock G, Ghanem H, Giuliano F, Glina S, et al. (2013). SOP conservative (medical and mechanical) treatment of erectile dysfunction. J Sex Med, 10(1):130-71.
[115] Yan H, Zong H, Cui Y, Li N, Zhang Y (2014). The efficacy of PDE5 inhibitors alone or in combination with alpha-blockers for the treatment of erectile dysfunction and lower urinary tract symptoms due to benign prostatic hyperplasia: a systematic review and meta-analysis. J Sex Med, 11(6):1539-45.
[116] El-Sisi AA, Hegazy SK, Salem KA, AbdElkawy KS (2013). Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase. Int J Impot Res, 25(4):143-8.
[117] Dadkhah F, Safarinejad MR, Asgari MA, Hosseini SY, Lashay A, Amini E (2010). Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil. Int J Impot Res, 22(1):51-60.
[118] Herrmann HC, Levine LA, Macaluso J Jr, Walsh M, Bradbury D, Schwartz S, et al. (2006). Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil? Hypothesis and pilot trial results. J Sex Med, 3(2):303-8.
[119] Jaffe JS, Antell MR, Greenstein M, Ginsberg PC, Mydlo JH, Harkaway RC (2004). Use of intraurethral alprostadil in patients not responding to sildenafil citrate. Urology, 63(5):951-4.
[120] Safarinejad MR (2006). Salvage of sildenafil failures with cabergoline: a randomized, double-blind, placebo-controlled study. Int J Impot Res, 18(6):550-8.
[121] Gutierrez P, Hernandez P, Mas M (2005). Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders. Int J Impot Res, 17(4):354-8.
[122] Verze P, Margreiter M, Esposito K, Montorsi P, Mulhall J (2015). The Link Between Cigarette Smoking and Erectile Dysfunction: A Systematic Review. Eur Urol Focus, 1(1):39-46.
[123] Harte CB, Meston CM (2012). Association between smoking cessation and sexual health in men. BJU Int, 109:888-96.
[124] Grover S, Mattoo SK, Pendharkar S, Kandappan V (2014). Sexual dysfunction in patients with alcohol and opioid dependence. Indian J Psychol Med, 36:355-65.
[125] Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB (2003). Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med, 139:161-8.
[126] Kalter-Leibovici O, Wainstein J, Ziv A, Harman-Bohem I, Murad H, Raz I (2005). Clinical, socioeconomic, and lifestyle parameters associated with erectile dysfunction among diabetic men. Diabetes Care, 28:1739-44.
[127] Larsen SH, Wagner G, Heitmann BL (2007). Sexual function and obesity. Int J Obes (Lond), 31:1189-98.
[128] Kolotkin RL, Head S, Hamilton M, Tse CK (1995). Assessing Impact of Weight on Quality of Life. Obes Res, 3:49-56.
[129] Esposito K, Giugliano F, Maiorino MI, Giugliano D (2010). Dietary factors, Mediterranean diet and erectile dysfunction. J Sex Med, 7:2338-45.
[130] Nicolosi A, Moreira ED Jr, Shirai M, Bin Mohd Tambi MI, Glasser DB (2003). Epidemiology of erectile dysfunction in four countries: cross-national study of the prevalence and correlates of erectile dysfunction. Urology, 61:201-6.
[131] Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB, McKinlay JB (2000). Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk? Urology, 56:302-6.
[132] Cialis® (tadalafil) (2018). Full Prescribing Information. Indianapolis, IN: Eli Lilly and Company.
No related articles found!
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd