Treatment response to sildenafil in men with erectile dysfunction relative to concomitant comorbidities and age

Goldstein, Irwin; Stecher, Vera J.; Carlsson, Martin

doi:10.1111/ijcp.12939

Cited by 7 publications

(8 citation statements)

References 12 publications

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“…Azab et al 31 demonstrated that PDE5is were less effective in men with hypertension and ED than in ED patients without hypertension. In addition, Goldstein et al 32 also showed similar results as well as treatment response rates of sildenafil for hypertensive ED patients decreasing with increasing age. As PDE5 was mostly localized in SM, the CCSM loss observed in our present study could also be attributed to the PDE5 reduction.…”

Section: Discussionmentioning

confidence: 70%

“…Although PDE5is are the first‐line treatment for ED patients, almost 35% of patients show low or no response to PDE5is, 30 which has perplexed clinicians and patients alike. Recent studies also revealed that PDE5is have less of an effect in hypertensive patients, especially in patients older than 65 years old 31,32 . Actually, responsiveness to PDE5is is dependent on NO/cGMP pathway integrity and PDE5 enzyme expression.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in the phosphodiesterase type 5 pathway and oxidative stress correlate with erectile function in spontaneously hypertensive rats

Liu

et al. 2020

J Cellular Molecular Medi

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Alterations in the phosphodiesterase type 5 pathway and oxidative stress correlate with erectile function in spontaneously hypertensive rats

Liu

et al. 2020

J Cellular Molecular Medi

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“…In fact, Mendelian randomization of genome-wide association studies suggested that type 2 diabetes has a direct causal effect on ED [ 25 , 26 ]. However, from a clinical viewpoint, the main challenge is that diabetic men represent a difficult-to-treat population of ED patients, since their therapeutic response to conventional treatment with PDE5 inhibitors is reduced [ 27 , 28 ]. This is probably related to a highly defective NO/cGMP pathway in penile vascular tissue in diabetic men with ED [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase

El Assar,

La Fuente,

Sosa

et al. 2024

IJMS

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Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCβ2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.

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“…Among them, a total of 55 patients were treated with PDE5 inhibitors (sildenafil) for 4 weeks, after which their IIEF scores, EHSs and SEPs were also collected (Figure 1). As in most trials, the sildenafil dose was 50 mg, taken about one hour before sexual activity in this study 31 . Approval of this study was obtained from the local medical ethics committee.…”

Section: Methodsmentioning

confidence: 99%

“…As in most trials, the sildenafil dose was 50 mg, taken about one hour before sexual activity in this study. 31 Approval of this study was obtained from the local medical ethics committee. This study was approved by the Medical Ethics Committee of Nanfang Hospital and registered in the Chinese Clinical Trial Registry (NO.…”

Section: Data Collection and Protocolmentioning

confidence: 99%

Effects of “metabolic memory” on erectile function in diabetic men: A retrospective case‐control study

et al. 2020

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Objective This study was performed to explore the effects of metabolic memory on diabetic erectile dysfunction (ED), especially the severity and response to treatment. Methods Through medical records and follow‐up by telephone, 67 patients meeting the criteria with a clinical diagnosis of ED and a diabetic history of more than 5 years were enrolled for erectile function analysis. They were divided into a glycemic control group, a glycemic non‐control group and a metabolic memory group according to glycemic levels and treatments for diabetes in the past 5 years, and they were treated with phosphodiesterase type 5 (PDE5) inhibitors for 4 weeks. Erectile function and efficacy were assessed by the International Index for Erectile Function (IIEF), the Erection Hardness Score (EHS), and the Sexual Encounter Profile (SEP). Results The patients in the glycemic control group performed better in erectile function than those in the other groups. The patients in the glycemic control group received a significantly greater score on both the EHS and the five domains of the IIEF than did the patients in the glycemic non‐control group and the metabolic memory group (all P < .001). There were also statistically significant differences favoring the glycemic control group (P < .05) in SEP2 and SEP3 success rates. However, there were no significant differences between the metabolic memory group and the glycemic non‐control group in these erectile function assessments (P > .05). Significant negative correlations were seen between HbA1c levels at the time of consultation and the scores on the IIEF‐EF and the EHS (Pearson r‐values of −0.338 with P = .005 and −0.273 with P = .025, respectively). HbA1c levels at the first diagnosis of diabetes mellitus (DM) were also significantly negatively correlated with scores on the IIEF‐EF and the EHS with greater Pearson correlation coefficients (Pearson r‐values of −0.478 with P < .001 and −0.392 with P = .001, respectively). Significant improvements on each of the erectile function assessments were observed among diabetic patients with ED, but no significant difference in efficacy was observed between each group. Conclusions The phenomenon of metabolic memory did have a significant influence on ED in men with diabetes, associated with the severity of ED but not the response to medical treatment. Early hyperglycemia exposure would have long‐term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. Patients summary In this report, we looked at the erectile functions of 67 patients with a clinical diagnosis of ED and a diabetic history of more than 5 years. We found that early hyperglycemia exposure would have long‐term disadvantageous effects on erectile function in diabetic patients with ED, which would be sustained even after the patients achieve better glycemic control. We further found that the effects were associated with the severity of ED but not the response to medical treatment ...

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Treatment response to sildenafil in men with erectile dysfunction relative to concomitant comorbidities and age

Abstract: The treatment response was significantly greater with sildenafil vs placebo in men with ED and each comorbidity regardless of age.

Cited by 7 publications

References 12 publications

Alterations in the phosphodiesterase type 5 pathway and oxidative stress correlate with erectile function in spontaneously hypertensive rats

Alterations in the phosphodiesterase type 5 pathway and oxidative stress correlate with erectile function in spontaneously hypertensive rats

PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase

Effects of “metabolic memory” on erectile function in diabetic men: A retrospective case‐control study

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