Endothelial Dysfunction in Patients With Erectile Dysfunction: A Double-Blind, Randomized-Control Trial Using Tadalafil

Overview

Journal Sex Med

Publisher Oxford University Press

Date 2019 Jan 15

PMID 30638829

Citations 4

Authors

Smita Pattanaik

Pawan Kaundal

Ravimohan S Mavuduru

Shrawan K Singh

Arup K Mandal

Affiliations

Soon will be listed here.

Abstract

Objective: To assess whether tadalafil improves endothelial dysfunction(EnD) in a placebo-controlled randomized-control trial.

Methods: Erectile dysfunction and EnD were assessed by the International Index of Erectile Function (IIEF-5) and flow-mediated dilation (FMD) of the brachial artery respectively, at baseline and 4 weeks by blinded observer. Patients with FMD of < 15% were randomized in 1:1 ratio to receive either placebo or tadalafil. Both placebo and tadalafil in similar-appearing capsules but coded separately, were dispensed by a blinded co-investigator. Compliance and drug-related events were recorded. The randomization codes were then decoded and appropriate statistical tests applied.

Results: 89 patients were randomized and 82 completed the study. Both groups were comparable. Posttreatment, there were significant improvements in IIEF-5 score (pre- vs posttreatment; tadalafil: 11.432 vs 15.937, P < .001 and placebo 11.232 vs 14.935, P < .00) and FMD% pre- vs posttreatment; tadalafil: 11.222 vs 13.827, P < .001 and placebo: 11.617 vs 14.027, P < .001). Intergroup comparison did not show any significant difference in IIEF scores (mean change in tadalafil vs placebo group: 3.719 vs 4.433, P = .223) and FMD% (mean change tadalafil vs placebo group: 2.426 and 2.829, P = .528). The adverse events were significantly more in the tadalafil group (tadalafil vs placebo 14 adverse reactions [ADR] vs 5 ADR, P < .001).

Conclusion: The response of low-dose tadalafil on IIEF and FMD is largely similar to placebo; however, the utility of FMD% in young patients and placebo effect needs to be studied further. Pattanaik S, Kaundal P, Mavuduru RS, et al. Endothelial Dysfunction in Patients With Erectile Dysfunction: A Double-Blind, Randomized-Control Trial Using Tadalafil. Sex Med 2019;7:41-47.

Citing Articles

Phosphodiesterase type 5 inhibitors as treatment for erectile dysfunction: a webinar-based poll unveiling perceptions of healthcare professionals.

Moazin M, Baazeem A, Al-Bakri A, Al Dayel A, Amir A, Al Sifri S J Comp Eff Res. 2024; 13(7):e230155.

PMID: 38775343 PMC: 11225304. DOI: 10.57264/cer-2023-0155.

The Effect of Phosphodiesterase-type 5 Inhibitors on Erectile Function: An Overview of Systematic Reviews.

Pyrgidis N, Mykoniatis I, Haidich A, Tirta M, Talimtzi P, Kalyvianakis D Front Pharmacol. 2021; 12:735708.

PMID: 34557099 PMC: 8452927. DOI: 10.3389/fphar.2021.735708.

Placebo Responses Among Men With Erectile Dysfunction Enrolled in Phosphodiesterase 5 Inhibitor Trials: A Systematic Review and Meta-analysis.

Stridh A, Ponten M, Arver S, Kirsch I, Abe C, Jensen K JAMA Netw Open. 2020; 3(3):e201423.

PMID: 32196105 PMC: 7084170. DOI: 10.1001/jamanetworkopen.2020.1423.

Effect of Icariside II and Metformin on Penile Erectile Function, Histological Structure, Mitochondrial Autophagy, Glucose-Lipid Metabolism, Angiotensin II and Sex Hormone in Type 2 Diabetic Rats With Erectile Dysfunction.

Zhang J, Li S, Zhang S, Wang Y, Jin S, Zhao C Sex Med. 2020; 8(2):168-177.

PMID: 32147433 PMC: 7261708. DOI: 10.1016/j.esxm.2020.01.006.

References

Sullivan M, Thompson C, Dashwood M, Khan M, Jeremy J, Morgan R . Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease?. Cardiovasc Res. 2000; 43(3):658-65. DOI: 10.1016/s0008-6363(99)00135-2. View

Dalli E, Segarra L, Ruvira J, Esteban E, Cabrera A, Lliso R . [Brachial artery flow-mediated dilation in healthy men, men with risk factors, and men with acute myocardial infarction. Importance of occlusion-cuff position]. Rev Esp Cardiol. 2002; 55(9):928-35. DOI: 10.1016/s0300-8932(02)76731-6. View

Faulx M, Wright A, Hoit B . Detection of endothelial dysfunction with brachial artery ultrasound scanning. Am Heart J. 2003; 145(6):943-51. DOI: 10.1016/S0002-8703(03)00097-8. View

Kaiser D, Billups K, Mason C, Wetterling R, Lundberg J, Bank A . Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease. J Am Coll Cardiol. 2004; 43(2):179-84. DOI: 10.1016/j.jacc.2003.07.042. View

Rosano G, Aversa A, Vitale C, Fabbri A, Fini M, Spera G . Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol. 2005; 47(2):214-20. DOI: 10.1016/j.eururo.2004.10.002. View

Witte D, Westerink J, de Koning E, van der Graaf Y, Grobbee D, Bots M . Is the association between flow-mediated dilation and cardiovascular risk limited to low-risk populations?. J Am Coll Cardiol. 2005; 45(12):1987-93. DOI: 10.1016/j.jacc.2005.02.073. View

Aversa A, Greco E, Bruzziches R, Pili M, Rosano G, Spera G . Relationship between chronic tadalafil administration and improvement of endothelial function in men with erectile dysfunction: a pilot study. Int J Impot Res. 2006; 19(2):200-7. DOI: 10.1038/sj.ijir.3901513. View

Guay A . ED2: erectile dysfunction = endothelial dysfunction. Endocrinol Metab Clin North Am. 2007; 36(2):453-63. DOI: 10.1016/j.ecl.2007.03.007. View

Shechter M, Issachar A, Marai I, Koren-Morag N, Freinark D, Shahar Y . Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Int J Cardiol. 2008; 134(1):52-8. DOI: 10.1016/j.ijcard.2008.01.021. View

10.

de Araujo A, da Silva F, Salvi F, Awad M, da Silva E, Damiao R . The management of erectile dysfunction with placebo only: does it work?. J Sex Med. 2009; 6(12):3440-8. DOI: 10.1111/j.1743-6109.2009.01496.x. View

11.

Charakida M, Masi S, Luscher T, Kastelein J, Deanfield J . Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J. 2010; 31(23):2854-61. DOI: 10.1093/eurheartj/ehq340. View

12.

Huang Y, Zheng F, Yao F, Liu G, Bian J, Gao Y . [Daily medication of low-dose tadalafil improves endothelial function and erectile hardness of ED patients]. Zhonghua Nan Ke Xue. 2011; 16(11):1052-5. View

13.

La Vignera S, Condorelli R, DAgata R, Vicari E, Calogero A . Dysfunction of the endothelial-platelet pathway in patients with erectile dysfunction before and after daily treatment with tadalafil. Andrologia. 2011; 44(3):152-6. DOI: 10.1111/j.1439-0272.2010.01124.x. View

14.

Rosen R, Allen K, Ni X, Araujo A . Minimal clinically important differences in the erectile function domain of the International Index of Erectile Function scale. Eur Urol. 2011; 60(5):1010-6. DOI: 10.1016/j.eururo.2011.07.053. View

15.

Yao F, Huang Y, Zhang Y, Dong Y, Ma H, Deng C . Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young men with low risk of coronary heart disease. Int J Androl. 2012; 35(5):653-9. DOI: 10.1111/j.1365-2605.2012.01273.x. View

16.

Porst H, Brock G, Kula K, Moncada I, Montorsi F, Basson B . Effects of once-daily tadalafil on treatment satisfaction, psychosocial outcomes, spontaneous erections, and measures of endothelial function in men with erectile dysfunction but naive to phosphodiesterase type 5 inhibitors. J Androl. 2012; 33(6):1305-22. DOI: 10.2164/jandrol.111.015289. View

17.

Pelliccione F, DAngeli A, DAndrea S, Barbonetti A, Pezzella A, Necozione S . Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk. Asian J Androl. 2014; 16(2):290-4. PMC: 3955343. DOI: 10.4103/1008-682X.122347. View

18.

Seftel A . Re: tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk. J Urol. 2015; 192(1):179-80. DOI: 10.1016/j.juro.2014.04.073. View

19.

Rodriguez-Miguelez P, Seigler N, Harris R . Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test. J Vis Exp. 2016; (110). PMC: 4942014. DOI: 10.3791/54011. View

20.

Aversa A, Fittipaldi S, Francomano D, Bimonte V, Greco E, Crescioli C . Tadalafil improves lean mass and endothelial function in nonobese men with mild ED/LUTS: in vivo and in vitro characterization. Endocrine. 2017; 56(3):639-648. DOI: 10.1007/s12020-016-1208-y. View