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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
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Abstract  

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
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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.
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http://www.aginganddisease.org/EN/10.14336/AD.2019.1028     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.
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