Abstract
Purpose
Men affected by multiple sclerosis often experience neurogenic overactive bladder (OAB), lower urinary tract symptoms and erectile dysfunction (ED). The aim of the study was to investigate modifications of urinary and sexual functions after administration of daily tadalafil (TAD) 5 mg.
Methods
Twenty men were enrolled in a single-blind, 4-week prospective study while 10 men without treatment served as controls. Primary outcomes were changes from baseline of International Prostate Symptom (IPSS), OAB questionnaire (OAB-q-short form) and International Index of Erectile Function (IIEF-5) scores. To evaluate the influence of bladder filling on somatic reflexes, we studied variations of the H-reflex evoked by electrical stimuli applied to the tibial nerve at the popliteal fossa and recorded from the soleus muscle. Also testosterone/estradiol (T/E) ratio was measured before and after treatment.
Results
In TAD group, an improvement in IPSS (p < 0.001), OAB-q (p < 0.001) and IIEF-5 (p < 0.001) scores was found. Also, an increase in Q max (p < 0.01) and T/E ratio (p < 0.01) was found with a concomitant reduction in post-void residual volume (p < 0.001) without any changes in the H-reflex.
Conclusions
The study demonstrates for the first time that daily TAD in patients with multiple sclerosis improves storage symptoms, post-void residual volume, steroid hormone pattern and ED without urodynamic changes.
Similar content being viewed by others
References
Leboeuf L, Cohen B, Gousse AE (2008) Multiple sclerosis. In: Corcos J, Schick E (eds) Textbook of the neurogenic bladder. CRC Press, Boca Raton, pp 294–311
Oppenheimer DR (1978) The cervical cord in multiple sclerosis. Neuropathol Appl Neurobiol 4:151–162
Fernandez O (2002) Mechanisms and current treatments of urogenital dysfunction in multiple sclerosis. J Neurol 249:1–8
Quarto G, Autorino R, Gallo A et al (2007) Quality of life in women with multiple sclerosis and overactive bladder syndrome. Int Urogynecol J Pelvic Floor Dysfunct 18:189–194
Ebers GC, Sadovnick AD, Risch NJ (1995) A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 377:150–151
Poser CM (1994) The epidemiology of multiple sclerosis: a general overview. Ann Neurol 36:S180–S193
Kanai A, Andersson KE (2010) Bladder afferent signaling: recent findings. J Urol 183:1288–1295
Andersson KE (2011) Antimuscarinic mechanisms and the overactive detrusor: an update. Eur Urol 59:377–386
Chapple CR, Roehrborn CG, McVary K et al (2015) Effect of tadalafil on male lower urinary tract symptoms: an integrated analysis of storage and voiding international prostate symptom subscores from four randomised controlled trials. Eur Urol 67:114–122
Pofi R, Gianfrilli D, Badagliacca R et al (2016) Everything you ever wanted to know about phosphodiesterase 5 inhibitors and the heart (but never dared ask): How do they work? J Endocrinol Invest 39:131–142
Burks J, Chancellor M, Bates D et al (2013) Development and validation of the actionable bladder symptom screening tool for multiple sclerosis patients. Int J MS Care Winter 15:182–192
Radicioni A, Lenzi A, Spaziani M et al (2013) A multicenter evaluation of immunoassays for follicle-stimulating hormone, luteinizing hormone and testosterone: concordance, imprecision and reference values. J Endocrinol Invest 36:739–744
Conte A, Bettolo CM, Onesti E et al (2009) Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis. Eur J Pain 13:472–477
Lombardi G, Macchiarella A, Del Popolo G (2010) Efficacy and safety of tadalafil for erectile dysfunction in patients with multiple sclerosis. J Sex Med 7:2192–2200
Bruzziches R, Francomano D, Gareri P et al (2013) An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors. Expert Opin Pharmacother 14:1333–1344
Uckert S, Stief CG (2011) Treatment of erectile dysfunction and lower urinary tract symptoms by phosphodiesterase inhibitors. Handb Exp Pharmacol 204:307–322
Andersson KE, Uckert S, Stief C et al (2007) Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS. Neurourol Urodyn 26:928–933
Yoshimura N, Skei S, de Groat WC (2001) Nitric oxide modulates Ca(2+) channels in dorsal root ganglion neurons innervating rat urinary bladder. J Neurophysiol 86:304–311
Caremel R, Oger-Roussel S, Behr-Roussel D et al (2010) Nitric oxide/cyclic guanosine monophosphate signaling mediates an inhibitory action on sensory pathways of the micturition reflex in the rat. Eur Urol 58:616–625
Persson K, Igawa Y, Mattiasson A et al (1992) Effects of inhibition of the l-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro. Br J Pharmacol 107:178–184
Sesatomi K, Hiragata S, Miyazato M et al (2008) Nitric oxide-mediated suppression of detrusor overactivity by arginase inhibitor in rats with chronic spinal cord injury. Urology 72:696–700
Artim DE, Kullman FA, Daughtery SL et al (2009) Activation of the nitric oxide-cGMP pathway reduces phasic contractions in neonatal rat bladder strips via protein kinase G. Am J Physiol Renal Physiol 297:F333–F340
Kanai A, Zabbarova I, Oefelein M et al (2012) Mechanisms of action of botulinum neurotoxins, b3-adrenergic receptor agonists, and PDE5 inhibitors in modulating detrusor function in overactive bladders: ICI-RS 2011. Neurourol Urodyn 31:300–308
Sculptoreanu A, Artim DE, de Groat WC (2009) Neurokinins inhibit low threshold inactivating K+ currents in capsaicin responsive DRG neurons. Exp Neurol 219:562–573
Minegawa T, Aizawa N, Igawa Y et al (2012) Inhibitory effects of phosphodiesterase 5 inhibitor, tadalafil, on mechanosensitive bladder afferent nerve activities of the rat and on acrolien-induced hyperactivity of these nerves. BJU Int 110:E259–E266
Aizawa N, Igawa Y, Nishizawa O et al (2011) Effects of nitric oxide on the primary bladder afferent activities of the rat with and without intravesical acrolein treatment. Eur Urol 59:264–271
Vignozzi L, Filippi S, Morelli A et al (2012) Testosterone/estradiol ratio regulates NO-induced bladder relaxation and responsiveness to PDE5 inhibitors. J Sex Med 9:3028–3040
Greco EA, Pili M, Bruzziches R et al (2006) Testosterone:estradiol ratio changes associated with long-term tadalafil administration: a pilot study. J Sex Med 3:716–722
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All the authors have no conflict of interest.
Ethical approval
The research involves human participants.
Informed consent
Each subject signed a detailed informed consent before entering the study.
Additional information
D. Francomano and A. Ilacqua have contributed equally to this article.
Rights and permissions
About this article
Cite this article
Francomano, D., Ilacqua, A., Cortese, A. et al. Effects of daily tadalafil on lower urinary tract symptoms in young men with multiple sclerosis and erectile dysfunction: a pilot study. J Endocrinol Invest 40, 275–279 (2017). https://doi.org/10.1007/s40618-016-0557-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-016-0557-y