Useful Implications of Low-dose Long-term Use of PDE-5 Inhibitors

Sex Med Rev. 2016 Jul;4(3):270-284. doi: 10.1016/j.sxmr.2015.12.005. Epub 2016 Mar 19.


Introduction: Phosphodiesterase type 5 (PDE-5) hydrolyzes cyclic guanylate monophosphate (cGMP) specifically to 5' GMP, promoting successful corporeal vascular relaxation and penile erection during sexual stimulation. Oral PDE-5 inhibitors such as sildenafil, vardenafil, tadalafil, and avanafil have provided noninvasive, effective, well-tolerated treatment for erectile dysfunction (ED) patients and, at the same time, stimulated both academic and clinical interests. Lately, some oral PDE-5 inhibitors were released as low-dose preparations with the concept of potential daily administration and long-term use.

Aim: To highlight the possible potential implications of low-dose long-term use of PDE-5 inhibitors.

Method: A systematic review was carried out until December 2015 based on a search of all concerned articles in MEDLINE, medical subjects heading (MeSH) databases, Scopus, The Cochrane Library, EMBASE, and CINAHL databases without language restriction. Key words used to assess the outcome and estimates for concerned associations were: PDE-5 inhibitors; erectile dysfunction; low-dose; long-term; sildenafil; tadalafil; vardenafil; avanafil.

Main outcome measures: Demonstrating different implications for low-dose long-term use of PDE-5 inhibitors.

Results: Low-dose and/or long-term use of PDE-5 inhibitors was shown to put forth beneficial sound effects in different medical implications with potentials that could be extended for different utilities. These implications included sexual, urogenital, cardiovascular, pulmonary, cutaneous, gastrointestinal, and reproductive, as well as neurological disorders. However, it is evident that most potential appliances were carried out experimentally on preclinical studies with off-label indications.

Conclusion: Making use of and exploring low-dose and/or long-term use of several PDE-5 inhibitors for their possible implications seem to be valuable in different medical disorders. Increased knowledge of the drug characteristics, comparative treatment regimens, optimal prescribing patterns, and well-designed clinical trials are needed before these agents can be recommended for use.

Keywords: Avanafil; Chronic Use; Erectile Dysfunction; Low-Dose; PDE-5 Inhibitors; Sildenafil; Tadalafil; Vardenafil.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Dose-Response Relationship, Drug
  • Erectile Dysfunction / drug therapy*
  • Humans
  • Male
  • Phosphodiesterase 5 Inhibitors / adverse effects
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Sildenafil Citrate / therapeutic use
  • Tadalafil / therapeutic use
  • Treatment Outcome
  • Vardenafil Dihydrochloride / therapeutic use


  • Phosphodiesterase 5 Inhibitors
  • Vardenafil Dihydrochloride
  • Tadalafil
  • Sildenafil Citrate