Inhibiteurs de la 5 phosphodiestérase

PDE 5 inhibitors and combination therapy

Studies have established a physiological link between erectile dysfunction and the urinary symptoms that accompany BPH (Benign Prostatic Hyperplasia).

Prescribed for erectile dysfunction, phosphodiesterase-5 (PDE 5) inhibitors -including sildenafil (Viagra) and vardenafil (Levitra) as well as tadalafil- augment cyclic GMP, a chemical that relaxes smooth muscle in the penis, improving blood flow during sexual stimulation. PDE 5 inhibitors also seem to relax smooth muscle in the bladder neck, urethra, and prostate. A handful of clinical trials have shown that these drugs improve both erectile function and urinary symptoms in men with both conditions.

Based on three studies that specifically evaluated the use of PDE 5 inhibitors for BPH, the FDA approved tadalafil as a stand-alone treatment for BPH-related urinary symptoms and as a dual treatment to address both BPH and erectile dysfunction. Participants took 5 mg of tadalafil a day—at the lower end of the dosing scale when this pill is prescribed for erectile dysfunction. In all three studies, daily tadalafil significantly improved BPH symptoms as assessed through patient questionnaires.

Although the fact that an erectile dysfunction drug can also perform double duty to relieve BPH may be welcome news to some men, it’s also important to appreciate the limitations. Most studies examining the use of PDE5 inhibitors have been relatively short—12 weeks—so researchers have little data on whether they affect the progression of BPH or instead only delay more aggressive treatments.

One of the studies involving tadalafil lasted a year, but there are no longer-term data on the safety of this or other PDE5 inhibitors.

May be these drugs lose their effectiveness over time, requiring higher doses.

The FDA advises men against taking tadalafil with nitrates (such as nitroglycerin), because combining these two types of drugs may cause a risky drop in blood pressure. Doctors have also advised their patients not to take tadalafil or the other PDE5 inhibitors with alpha blockers out of concern that the combination would make blood pressure levels crash. However, the drugs are often used together and in most cases do not cause problems. To be safe, the best practice is to start taking these medications at low doses and at different times of the day.


Combination therapy.

Because alpha blockers and 5-alpha-reductase inhibitors work differently, researchers have hypothesized that taking both types of medication in combination might be more effective for controlling symptoms than taking just one. When a doxazosin-finasteride combination was tested in a large trial, the combination was more effective than either drug alone at preventing a worsening of lower urinary tract symptoms.

However, the combination was also more likely to cause side effects (abnormal ejaculation, swollen ankles, shortness of breath), although only a few men were affected (less than 5 %). It was a similar story with tamsulosin-dutasteride, sold as Jalyn. Together the drugs were more effective than either drug alone, but there was a price to be paid: more problems afterward, including ejaculation disorders (retrograde ejaculation and others), decreased libido, and dizziness. A 2014 study confirmed that combination treatment with both an alpha blocker (tamsulosin or silodosin) and a 5-alpha-reductase inhibitor (finasteride or dutasteride) produced a threefold higher risk of ejaculatory problems than either drug alone.

One possible way to mitigate the erectile side effects of 5-alpha-reductase inhibitor treatment is to add the PDE5 inhibitor tadalafil. A 2014 study with nearly 700 men compared the effects of giving finasteride and tadalafil together to those of giving finasteride alone. Results showed that concurrent treatment was safe and effective at relieving lower urinary tract symptoms in men with BPH while also improving erectile function.


PDE5 inhibitors

  • Brock G, Broderick G, Roehrborn CG, et al. Tadalafil Once Daily in the Treatment
    of Lower Urinary Tract Symptoms (LUTS) Suggestive of Benign Prostatic Hyperplasia (BPH) in Men Without Erectile Dysfunction. BJU International 2013;112:990–97. PMID: 23937669.
  • Brock GB, McVary KT, Roehrborn CG, et al. Direct Effects of Tadalafil on Lower Urinary Tract Symptoms (LUTS) Versus Indirect Effects Mediated Through Erectile Dysfunction Symptom Improvement: Integrated Data Analyses from 4 Placebo-Controlled Clinical Studies. Journal of Urology 2014;191:405–11. PMID: 24096120.
  • Chapple CR, Roehrborn CG, McVary K, et al. 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. European Urology 2014; Electronic publication ahead of print. PMID: 25301757.
  • Egerdie RB, Auerbach S, Roehrborn CG, et al. Tadalafil 2,5 or 5 mg Administered Once Daily for 12 Weeks in Men with Both Erectile Dysfunction and Signs and Symptoms of Benign Prostatic Hyperplasia: Results of a Randomized, Placebo-Controlled, Double- Blind Study. Journal of Sexual Medicine 2012;9:271–81. PMID: 21981682.
  • Oelke M, Giuliano F, Mirone V, et al. Monotherapy with Tadalafil or Tamsulosin Similarly Improved Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in an International, Random- ized, Parallel, Placebo-Controlled Clinical Trial. European Urology 2012;61:917–25. PMID: 22297243.
  • Porst H, Kim ED, Casabe AR, et al. Efficacy and Safety of Tadalafil Once Daily in the Treatment of Men with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: Results of an Inter- national Randomized, Double-Blind, Placebo-Controlled Trial. European Urology 2011;60:1105–13. PMID: 21871706.


Combination therapy

  • Casabé A, Roehrborn CG, Da Pozzo LF, et al. Efficacy and Safety of the Coadministra- tion of Tadalafil Once Daily with Finasteride for 6 Months in Men with Lower Urinary Tract Symptoms and Prostatic Enlargement Secondary to Benign Prostatic Hyperplasia. Journal of Urology 2014;191(3):727–33. PMID: 24096118.
  • Gacci, M, Ficarra V, Sebastianelli A, et al. Impact of Medical Treatments for Male Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia on Ejacula- tory Function: A Systematic Review and Meta-Analysis. Journal of Sexual Medicine 2014;11(6):1154–66. PMID: 24708055.
  • McConnell JD, Roehrborn CG, Bautista OM, et al. The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia. New England Journal of Medi- cine 2003;349:2387–98. PMID: 14681504
  • Roehrborn CG, Siami P, Barkin J, et al.The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Out- comes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results
    from the Combat Study. European Urology 2010;57:123–31. PMID: 19825505