Erectile dysfunction - Emerging treatments

Restorative therapies for erectile dysfunction

Restorative therapies are novel treatments that aim to reverse disease pathology rather than just treat symptoms.[92] These treatments include low-intensity extracorporeal shock wave therapy (Li-ESWT), stem cell therapy (SCT), and platelet-rich plasma (PRP) therapy.[93] The theoretical mode of action of Li-ESWT is that the cellular microtrauma and cavitation produced in this type of therapy can stimulate the expression of angiogenesis-related factors, such as vascular endothelial growth factor (VEGF), so as to promote vascular regeneration.[94] Stem cells are unspecialised, undifferentiated cells found in both embryonic (i.e., placental/umbilical) and adult (i.e., mesenchymal: bone marrow, adipose) tissue. Studies show that these cells exhibit regenerative effects by releasing growth factors, cytokines, and chemokines; upregulating pathways to reduce inflammation, inhibit apoptosis, improve wound healing, and drive angiogenesis and neuritogenesis (i.e., axons, dendrites).[92] PRP is autologous blood plasma with supraphysiological concentrations of activated platelets. The mix of growth factors (platelet-derived growth factor, insulin-like growth factor, vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor) and activated platelets work together to facilitate mitogenesis and neo-angiogenesis, thereby reconstituting diseased tissues.[92] There is growing evidence that these therapies may be efficacious in treating erectile dysfunction, however, there is insufficient data to support the use of these therapies in clinical practice. Although promising, these therapies should be considered investigational until further research into long term safety and efficacy is available.[93]

Penile rehabilitation

Penile rehabilitation is an emerging topic in erectile restoration, as many physicians are proactively treating patients after prostate surgery or radiation as a pre-emptive measure to minimise ED later.[70] This may include the use of daily phosphodiesterase-5 (PDE5) inhibitors, vacuum devices, or the regular use of penile injections with vasoactive substances to enhance blood flow and minimise corporal atrophy during times of sexual inactivity.[95] However, there is a conflicting school of thought that penile rehabilitation is less effective than some advocates have argued.[96] [ ] Whether this increases or decreases the treatment arsenal for ED remains to be seen,[97] as studies have conflicting results. The REACTT trial demonstrated no long-term benefit for tadalafil for penile rehabilitation therapy.[95][98]

Bremelanotide

Central activation of melanocortin (MC) receptors may signal or modulate penile erection, and this strategy may prove to be an alternative to conventional therapy. Bremelanotide is a 'superpotent' MC agonist and has been tested in phase II human trials.[99] Statistically significant improvement in erectile function was observed, and the tolerability and adverse-effect profile was found to be acceptable. This agent may be useful for patients where PDE5 inhibitors have failed.[100] Intra-nasal bremelanotide may be an alternative in improving ED in men who do not respond to oral PDE5 inhibitors. Further studies are necessary to draw final conclusions on the efficacy of this drug in ED.[101][102] Co-administration of intra-nasal bremelanotide and sildenafil provided a significantly greater response than sildenafil alone.[103]

Gene therapy

Treatment of the underlying disease pathology has become the focus of emerging therapeutics for ED. Use of gene therapy is a potential candidate, though issues of safety and delivery remain hurdles. Gene therapy is attractive owing to the unique accessibility of the penis and the ability to deliver agents locally, exposing only the endothelial cells.[104] Further research is needed to determine the efficacy of these treatments.

Acupuncture

There is insufficient evidence to suggest that acupuncture is an effective intervention for treating ED.[105]