Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Mirabegron improves erectile function in men with overactive bladder and erectile dysfunction: a 12-week pilot study

Abstract

Phosphodiesterase type 5 inhibitors (PDE5i) is the only approved oral treatment for erectile dysfunction (ED) in the US, and alternative management remains necessary when this treatment fails or is contraindicated. Targeting other pathways than the NO-cGMP pathway and/or combining this approach with PDE5i may introduce new treatments for men who are unresponsive to PDE5i. This study aims to evaluate whether Mirabegron improves erectile function in men with concurrent overactive bladder and mild to moderate ED. Twenty subjects, 40–70 years old, registering International Index of Erectile Function (IIEF) score 11–25 and International Prostate Symptom Score 8–20, were treated with Mirabegron therapy for 12 weeks. Study participants were re-administered IIEF and OAB-q questionnaires on weeks 2, 4, 8, and 12 and assessed for adverse events. The primary and secondary endpoints were an increase in the IIEF-5 score of 4 units and a decrease in the Overactive Bladder questionnaire (OAB-q) symptom severity score of 10 units between study time points. Thirteen men completed the 12-week study. Mirabegron treatment improved the IIEF-5 scores in five patients (38.4%) by 4 points or more, whereas IIEF-5 scores were not affected by Mirabegron treatment in eight patients (61.5%). There were no clinically relevant decreases in the IIEF-5 score. Significant improvements were observed in intercourse satisfaction at week eight compared to baseline (p = 0.01). Orgasmic function and sexual desire were not affected by Mirabegron treatment. As expected, Mirabegron treatment reduced OAB symptoms based on OAB-q short form (p = 0.006) and OAB-q total health-related quality of life (HRQL) scores compared to baseline (p = 0.03). Residual bladder volumes were not affected by treatment. No serious side effects were reported during the study period. This study suggests that Mirabegron may improve both EF and OAB-related symptoms in some individuals without causing serious adverse events.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: CONSORT diagram of the clinical trial.
Fig. 2: Changes in IIEF-5 scores.
Fig. 3: Changes in OAB-q short form and OAB-q Total HRQL scores.

References

  1. 1.

    NIH Consensus Conference. Impotence: NIH consensus development panel on impotence. JAMA. 1993;270:83–90.

  2. 2.

    Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol. 2000;163:460–3.

    CAS  Article  Google Scholar 

  3. 3.

    Rosen RC, Fisher WA, Eardley I, Niederberger C, Nadel A, Sand M. The multinational Men’s Attitudes to Life Events and Sexuality (MALES) study: I. prevalence of erectile dysfunction and related health concerns in the general population. Curr Med Res Opin. 2004;20:607–17.

    Article  Google Scholar 

  4. 4.

    Braun MH, Sommer F, Haupt G, Mathers MJ, Reifenrath B, Engelmann UH. Lower urinary tract symptoms and erectile dysfunction: comorbidity or typical “aging male” symptoms? Results of the “Cologne Male Survey”. Eur Urol. 2003;44:588–94.

    CAS  Article  Google Scholar 

  5. 5.

    Hatzimouratidis K, Hatzichristou DG. A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs. 2005;65:1621–50.

    CAS  Article  Google Scholar 

  6. 6.

    Limoncin E, Gravina GL, Corona G, Maggi M, Ciocca G, Lenzi A, et al. 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. 2017;5:863–72.

    CAS  Article  Google Scholar 

  7. 7.

    Liao X, Qiu S, Bao Y, Wang W, Yang L, Wei Q. 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. 2019;37:1061–74.

    CAS  Article  Google Scholar 

  8. 8.

    Cirino G, Sorrentino R, di Villa Bianca RD, Popolo A, Palmieri A, Imbimbo C, et al. Involvement of beta 3-adrenergic receptor activation via cyclic GMP- but not NO-dependent mechanisms in human corpus cavernosum function. Proc Natl Acad Sci U S A. 2003;100:5531–6.

    CAS  Article  Google Scholar 

  9. 9.

    Uchida H, Shishido K, Nomiya M, Yahamaguchi O. Involvement of cyclic AMP-dependent and –independent mechanisms in the relaxation of rat detrusor muscle via β–adrenoceptors. Eur J Pharmacol. 2005;518:195–202.

    CAS  Article  Google Scholar 

  10. 10.

    Hristov KL, Cui X, Brown SM, Liu L, Kellet WF, Petkov GV. Stimulation of beta-3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca2+-activated K+ channels. Am J Physiol Cell Physiol. 2008;295:1344–53.

    Article  Google Scholar 

  11. 11.

    Mitidieri E, Tramontano T, Gurgone D, Imbimbo C, Mirone V, Fusco F, et al. β(3) adrenergic receptor activation relaxes human corpus cavernosum and penile artery through a hydrogen sulfide/cGMP-dependent mechanism. Pharmacol Res. 2017;124:100–4.

    CAS  Article  Google Scholar 

  12. 12.

    Maggiore ULR, Cardozo L, Ferrero S, Sileo F, Cola A, Del Deo F, et al. Mirabegron in the treatment of overactive bladder. Expert Opin Pharmacother. 2014;15:873–87.

    CAS  Article  Google Scholar 

  13. 13.

    Rosen R, Altwein J, Boyle P, Kirby RS, Lukacs B, Meuleman E, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol. 2003;44:637–49.

    Article  Google Scholar 

  14. 14.

    Gur S, Peak T, Yafi FA, Kadowitz PJ, Sikka SC, Hellstrom WJ. Mirabegron causes relaxation of human and rat corpus cavernosum: could it be a potential therapy for erectile dysfunction? BJU Int. 2016;118:464–74.

    CAS  Article  Google Scholar 

  15. 15.

    Alexandre EC, Kiguti LR, Calmasini FB, Silva FH, da Silva KP, Ferreira R, et al. Mirabegron relaxes urethral smooth muscle by a dual mechanism involving beta3-adrenoceptor activation and alpha1-adrenoceptor blockade. Br J Pharm. 2016;173:415–28.

    CAS  Article  Google Scholar 

  16. 16.

    Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49:822–30.

    CAS  Article  Google Scholar 

  17. 17.

    Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999;11:319–26.

    CAS  Article  Google Scholar 

  18. 18.

    Coyne KS, Thompson CL, Lai J-S, Sexton CC. An overactive bladder symptom and health-related quality of life short-form: validation of the OAB-q SF. Neurourol Urodyn. 2015;34:255–63.

    Article  Google Scholar 

  19. 19.

    Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the erectile function domain of the International Index of Erectile Function scale. Eur Urol. 2011;60:1010.

    Article  Google Scholar 

  20. 20.

    Carlson KV, Rovner ES, Nair KV, Deal AS, Kristy RM, Schermer CR. Factors associated with improvements in patient-reported outcomes during mirabegron or antimuscarinic treatment of overactive bladder syndrome: A Registry Study (PERSPECTIVE). Adv Ther. 2019;36:1906–21.

    Article  Google Scholar 

  21. 21.

    Herschorn S, Staskin D, Tu LM, Fialkov J, Walsh T, Gooch K, et al. Patient-reported outcomes in patients with overactive bladder treated with mirabegron and tolterodine in a prospective, double-blind, randomized, two-period crossover, multicenter study (PREFER). Health Qual Life Outcomes. 2018;16:69.

    Article  Google Scholar 

  22. 22.

    Ko KJ, Choo MS, Chang YS, Kim JC, Lee KS. A multicenter prospective study for overactive bladder patient treatment satisfaction with mirabegron after being unsatisfied with antimuscarinic therapy (FAVOR study). Neurourol Urodyn. 2020;39:2417–24.

    CAS  Article  Google Scholar 

  23. 23.

    Wagg A, Staskin D, Engel E, Herschorn S, Kristy RM, Schermer CR. Efficacy, safety, and tolerability of mirabegron in patients aged ≥65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR). Eur Urol. 2020;77:211–20.

    CAS  Article  Google Scholar 

  24. 24.

    Chapple CR, Cruz F, Cardozo L, Staskin D, Herschhorn S, Choudhury N, et al. Safety and efficacy of mirabegron: analysis of a large integrated clinical trial database of patients with overactive bladder receiving mirabegron, antimuscarinics, or placebo. Eur Urol. 2020;77:119–28.

    CAS  Article  Google Scholar 

  25. 25.

    Lessing C, Schmitz A, Albers B, Schrappe M. Impact of sample size on variation of adverse events and preventable adverse events: systematic review on epidemiology and contributing factors. Qual Saf Health Care. 2010;19:1–5.

    Article  Google Scholar 

  26. 26.

    de Oliveira MG, Rojas-Moscoso JA, Bertollotto GM, Candido TZ, de A Kiguti LR, et al. Mirabegron elicits rat corpus cavernosum relaxation and increases in vivo erectile response. Eur J Pharmacol. 2019;858:172447.

    Article  Google Scholar 

  27. 27.

    Iitsuka H, Tokuno T, Amada Y, Matsushima H, Katashima M, Sawamoto T, et al. Pharmacokinetics of mirabegron, a β3-adrenoceptor agonist for treatment of overactive bladder, in healthy Japanese male subjects: results from single- and multiple-dose studies. Clin Drug Investig. 2014;34:27–35.

    CAS  Article  Google Scholar 

  28. 28.

    Krauwinkel W, van Dijk J, Schaddelee M, Eltink C, Meijer J, Strabach G, et al. Pharmacokinetic properties of mirabegron, a β3-adrenoceptor agonist: results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women. Clin Ther. 2012;34:2144–60.

    CAS  Article  Google Scholar 

  29. 29.

    Chapple CR, Dvorak V, Radziszewski P, Van Kerrebroeck P, Wyndaele JJ, Bosman B, et al. A phase II dose-ranging study of mirabegron in patients with overactive bladder. Int Urogynecol J. 2013;24:1447–58.

    Article  Google Scholar 

  30. 30.

    Frazier EP, Peters SL, Braverman AS, Ruggieri MR Sr., Michel MC. Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and beta-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 2008;377:449–62.

    CAS  Article  Google Scholar 

  31. 31.

    McCambridge J, Witton J, Elbourne DR. Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects. J Clin Epidemiol. 2014;67:267–77.

    Article  Google Scholar 

Download references

Funding

This investigator-sponsored research study was provided funding and drug support by Astellas Pharma Global Development Inc.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Arthur L. Burnett.

Ethics declarations

Competing interests

ALB served as principal investigator on this clinical trial and he is a consultant/advisor for Astellas Pharmaceuticals.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Karakus, S., Musicki, B. & Burnett, A.L. Mirabegron improves erectile function in men with overactive bladder and erectile dysfunction: a 12-week pilot study. Int J Impot Res (2021). https://doi.org/10.1038/s41443-021-00455-2

Download citation

Search

Quick links