Erectile dysfunction or ED is defined as the consistent inability to attain or maintain a penile erection sufficient for adequate sexual relations ie penetration. The prevalence of ED reported in the United States is 52% of men age. 40 to 70 years and 70% of men older than 70.
Although once thought to be a psychogenic disorder, the current evidence has proven up to 80% of all ED cases have an organic pathology.
ED is associated with many comorbidities including age, obesity, smoking, alcohol abuse, cardiovascular disease, diabetes, depression, prior pelvic surgery, spinal cord disease and many others.
The first symptom in many cardiovascular conditions is ED.
The American Urological Association has outlined many therapies for ED. These include,
- Phosphodiesterase type 5 inhibitors
- Intracavernosal injection with vasoactive substances
- Intraurethral suppositories of prostaglandin E1
- Vacuum assisted devices.
- Penile prosthesis
There is a high prevalence of non-responders to the above, therefore novel therapies have emerged to treat ED. These include platelet rich plasma and regenerative treatments such as exosomes.
Phosphodiesterase 5 Inhibitors- This class of drugs has become the first line treatment for ED. Up to 60% who take PDE5-I, show a moderate to good response. For these drugs to work, patients must have intact molecular and nervous system pathways and sexual stimulation. Therefore, in cases where the nitric oxide pathway is diseased, they have shown a lack of efficacy. Examples of these conditions are diabetes with peripheral neuropathy, post radical prostatectomy for cancer, vaso-occlusive disease and hypogonadal diseases. There are four oral PDE-5I available in the US,
Sildenafil (Viagra), Vardenafil (Levitra), Tadalafil (Cialis), Avanafil (Stendra)
Side effects are common including headaches, muscle aches, flushing, nasal congestion and vision related problems.
Intracavernosal Injection- This class involved the injection of vaso- active drugs into the corpus cavernosa. These vaso- active drugs include alprostadil, papaverine and phentolamine. These drugs can be used as monotherapy, bi-mix or tri-mix.
Patients usually have failed PDE-5I or have damaged nerves for erection. Dropout rates are high in this class due to cost or desire for other options.
Intraurethral prostaglandin E1 Suppository- this class uses a PGE1 suppository placed into the urethra. Current statistics show a efficacy rate of 45% to 65% of success when using this treatment. Most common side effect was urethral pain and other adverse effects are dizziness, hypotension and profuse sweating.
Vacuum erectile devices- The device is placed over the penis and a vacuum is created drawing blood into the penis. Then an occlusive ring is placed at the base as a constrictive band. Discontinuation is 30% or more due to decreased sensation, bruising and difficulty of use. Patients on anti-coagulant therapy have a greater risk of bruising. Patients with a large fat apron or a buried penis have difficulty using the method.
Surgery- Surgery is commonly offered for refractory cases. The implanted device is a three-piece inflatable penile prosthesis. This surgery is a high cost, invasive procedure. Complications related to this surgery are infections and bleeding. These devices are not long lasting, and the 10-year survival rate is 86%. This is caused by cylinder erosion, migration and reservoir displacement. They can also be plagued by auto inflation.
Centrally acting treatments for ED
Melanocortin is a potent cyclic alpha melanocortin stimulating hormone analog. The initiation of erections without sexual stimulation is the difference between melanocortin and PDE5-1 (Viagra). This is an injectable drug that was found in studies to be effective in psychogenic cases of ED. This drug has a long latency time with a common side effect of severe nausea. Studies have been stopped due to this side effect.
Bremelanotide is a metabolite of melanocortin. This drug can be given nasally. Most common side effect was nausea and flushing. Also reported to cause headache, sweating and low back pain in some studies. Vyleesi has been approved in the US for women with generalized hypoactive sexual desire. More male studies are currently underway.
Peripherally acting treatments for ED
New phosphodiesterase type 5 inhibitors, both topically and sublingual administration are in development. These agents are similar to existing PDE5-1 drugs, however the duration of action is much longer.
Potassium channel activators are located on the arterial and corporal smooth muscle and are sites for drug interaction. Formulations to activate these channels are potential options for the treatment of ED. Increasing potassium currents in the vascular smooth muscle reduces vascular tension in the penile arteries and the corpus, this has led to erections in animal models so far and is in human trials presently.
Nitric oxide is a key modulator of erection from cavernosal nerve endings and penile artery endothelial cells. L-arginine induces endothelial nitric oxide. L-arginine administration resulted in noted improvements in ED.
Glyceryl trinitrate is a well-known vasodilatory agent with a well-tolerated safety profile. This agent causes vasodilation by releasing NO in vascular smooth muscle resulting in erection. Clinical trials have shown a 70% efficacy rate in 10 minutes after administration with minimal side effects.
Platelet Rich Plasma in the Treatment of ED
Platelet Rich Plasma has been shown to stimulate and accelerate tissue healing. PRP acts on cells to increase their numbers (mitogenesis) and stimulate vascular growth (angiogenesis) and thus promote healing. Platelets contain a multitude of growth factors and cytokines that are paramount in the regenerative cascade. Many studies have shown PRP injections modify key pathophysiologic mechanisms leading to ED through anti-inflammatory, reparative, neuroprotective and neurotrophic effects.
There are many studies proving the efficacy of PRP in the treatment of ED. However, only one randomized placebo-controlled trial has been published regarding the use of PRP intracavernosal injections as monotherapy for erectile dysfunction. This study has shown an impressive response in erections in a group of patients and proves that PRP can reverse this dysfunction in certain disease states. PMID 33906807
Exosomes in the Treatment of ED
Exosomes are nanosized particles secreted by cells under certain physiological conditions. Exosomes have a structure that is made by the plasma membrane through encapsulating extracellular components and membrane proteins. Exosomes contain many constituents such as metabolites, proteins, lipids and nucleic acids. Exosomes are involved in intracellular communication. Studies have shown exosomes improved the tissue structure of the corpus cavernosum in animal models. This was accomplished by the downregulation and expression of TGF-B1. This is a profibrotic cytokine recognized as a key factor in the development of fibrosis. Exosomes blocked the effects of TGF-B1. Also, exosomes significantly increased nitric oxide pathways which are key in the production of an erection.
Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA cleared and designed for safety, sterility and effectiveness. Our kits have been scientifically manufactured to provide a platelet concentrate, devoid of red blood cells with a minimum number of leukocytes, critical to the regenerative process.
Juventix Regenerative Medical offers a patent pending LED Activator to activate the platelets and begin the regenerative process. The activation is a critical step in the release of cytokines, growth factors and bioactive proteins and is accomplished with LED light. This negates the use of chemical additives such as Calcium Chloride, Thrombin or Collagen. This LED activation provides sustained growth factor release versus older methods of activation.
Juventix Regenerative Medical supplies a Bio-incubator that transforms the Platelet Rich Plasma into and Injectable Platelet Rich Fibrin. The Platelet Rich Fibrin, commonly called “the second generation of platelet products” has different cytokines and growth factors than the original PRP. These different cytokines provide an anti-inflammatory environment and can be used confidently in inflammatory conditions.
Juventix Regenerative Medical is collaborating with Evolutionary Biologics to offer a complete line of regenerative products such as exosomes. These regenerative products can be stand alone therapies or used in conjunction with other therapies such as PRP or PRF.
RESTORE, REVIVE, REGENERATE- JUVENTIX REGENERATIVE MEDICAL
Dr. Robert McGrath
- Platelet Rich Plasma Improves Erectile Function: A Double Blind, Randomized, Placebo Controlled Clinical Trial
J Sex Med 2021 May;18(5):926-935. PMID 33906807
- Erectile Dysfunction: Is Platelet Rich Plasma the New Frontier for Treatment in Patients with Erectile Dysfunction? A Review of Existing Evidence
Front Reprod Health 2022 Aug 16;4:944765 PMID 36303622
- Effects of Stem Cell Derived Exosome Therapy on Erectile Dysfunction: A Systematic Review and Meta Analysis of Preclinical Studies
Sex Med 2023 Apr;11(2): qfac019. PMID 36910707
Front Endocrinol 2023 Mar 9;14:1123383. PMID 36967787
World J Mens Health 2021 Jan;39(1): 48-64. PMID 32202086