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Furthermore, treatment efficacy when compared to placebo occurs despite LOI or American Spinal Injury Association (ASIA) score characterizing impairment related to the injury (59,61).

compared the effectiveness and satisfaction associated with use of several ED therapies including sildenafil alone, intracavernosal injections (ICI) followed by sildenafil after ICI discontinuation and vacuum erections devices (VED) followed by sildenafil therapy after VED discontinuation (60).

Seventy percent of men receiving vasoactive medications preferred sildenafil to ICI, even though rigidity was superior in the ICI group. All men using VEDs were dissatisfied with that form of therapy. The duration of erections is also improved by sildenafil in men with SCI.

showed that sildenafil use increased the duration of erections from 8.4 to 10 minutes when compared to baseline.

Men using sildenafil were also more confident that they could maintain their erection compared to prior therapies such as VEDs (65). compared sildenafil to vardenafil and tadalafil (69). Sildenafil was effective in 85% of SCI patients, 74% of the patients on vardenafil and 72% of the patients on tadalafil. Sildenafil was associated with more rigid and longer lasting erections.

Additionally, 50 mg of sildenafil was effective in 55% of patients compared to more than 70% of the patients on vardenafil and tadalafil requiring 20 mg for a similar response. Men who used tadalafil were able to achieve erections 24 hours after administration, improving overall satisfaction related to the possible spontaneity of sexual encounters.

Del Popolo also evaluated the time/duration effectiveness of PDE5i sildenafil 50 mg versus tadalafil 10 mg (64). Tadalafil 10 mg significantly increased the percentage of successful intercourse attempts at 12–24 hours compared with sildenafil. One can suspect that vardenafil, which has a longer half-life than sildenafil, could offer a similar benefit but a study investigating this occurrence

has

Sildenafil use has led to increased patient satisfaction and partner satisfaction after initiating therapy (67).

showed that 88.2% of patients, and 85% of partners reported significantly improved sexual satisfaction and overall satisfaction regardless of pretreatment degree of ED or LOI.

Several pre-treatment factors have been described that may indicate success with PDE5i therapy. The presence of an upper motor neuron lesion up to T12 suggests a successful response, as well as requirement for a lower dosage of medication (62,68-71).

Additionally, the presence of residual erections after injury or an incomplete SCI (ASI-A vs.

ASIB-D) also improve the chance of PDE5i treatment success (59,67,68,71). Adverse effects related to PDE5i use with mild-moderate and transient (58). Furthermore, side effects viagra pills generic brand usually attenuate if use is not discontinued.

Autonomic dysreflexia, a life-threatening phenomenon characterized by bradycardia, hypertension, facial flushing and headaches associated with SCI lesions above T6, has not been reported with use.

However, hypotension leading to dizziness in individuals treated with sildenafil has been noted with high thoracic and cervical levels of injury (72).

No adverse events were noted within the study; however, the dizziness was reported by use of sildenafil 50 mg in the cervical LOI and 100 mg in the thoracic LOI patients.

Headache is the most reported side effect of all PDE5i, followed by dyspepsia and flushing.

Priapism, and death have not been reported after use of PDE5i by SCI patients.

Ultimately, PDE5i have had a significant impact on the treatment of ED in men with SCI.

The ease of use and tolerability of the medication has also led to improved satisfaction and quality of life that had been previously affected by SD. Head to head trials evaluating specific PDE5i within the SCI population are required to further elucidate drug preference. PDE5i should be considered first line therapy, however men with high thoracic and cervical lesions should be warned about an increased chance of dizziness with sildenafil and possibly other PDE5i use.

Parkinson’s disease (PD) PDE5i use in PD has not been well studied; however its benefits have been shown. Raffaele performed an open label, prospective study evaluating the efficacy of sildenafil 50 mg on demand and depressive symptoms experienced by the PD patient (73).

Erections were improved in approximately 85% of men and 75% noted improvements in their depressive symptoms as well. Sildenafil was well tolerated without significant side effects. , performed a shorter study showing improvements in erectile function but no change in depression and parkinsonisms after ED treatment (74).

Iatrogenic hypotension can occur in men in neurodegenerative disease using sildenafil (49).

placed men with PD and MSA on sildenafil and recorded blood pressure before and after.

Half of the 12 MSA patients developed postural hypotension, while none of the twelve PD patients did.

Since MSA can be difficult to distinguished diagnostically from PD, baseline blood pressure measurements prior to prescribing the medication and seeking medical assistance if symptomatic hypotension occurred was recommended for all patients with PD, and MSA.

Of note, none of the men with MSA who developed hypotension discontinued sildenafil use due to its effectiveness at improving their erections. Multiple sclerosis (MS) PDE5i for ED in patients with MS can be considered as reasonably effective and safe.

performed a randomized, multicenter, double-blind, flexible dose trial with open label extensions comparing sildenafil to placebo (75).

A nearly 4-fold increase in effective erections was noted in the treatment arm,

96%

Just less than half the men who responded to the tadalafil did so at the lower dosage of 10 generic viagra hims mg. Subjects in either studies did not have any significant adverse side effects beyond flushing, and headache with PDE5i use.

Spina bifida (SB) One study by Palmer and colleagues evaluated sildenafil use in SB males with thoracic lesions (76).

A prospective, blinded, randomized, placebo-controlled, dose-escalation, crossover study in 17 patients with SB and ED was performed.

All study participates took sets of tablet in groups, two sets of placebo, one of 25 mg, and the last 50 mg. Overall response to the tablet sets was measured by IIEF response and self-report of erectile rigidity.

Patients reported that taking 50 mg of sildenafil led to improved erections, duration of erections, frequency of erections and level of confidence compared to sildenafil 25 mg and more significantly compared to placebo. Of the five patients who reported side effects, two experienced mild hematological changes that reverted to baseline after study completion. Sildenafil has been previously suggested as a treatment option for ED in men with epilepsy (77,78). warned that PDE5i are potentially pro-convulsant and should be used with great caution in men with epilepsy (79).

Animal studies in rat and mice overwhelmingly suggest PDE5i can reduce seizure threshold.

PDE5i exerted their proconvulsive effect by lower seizure threshold possibly by worsening sleep or obstructive sleep apnea, causing cardiovascular changes, or leading to EEG changes specifically with tadalafil use.

Apomorphine is a non-selective D1/D2 receptor agonist with moderate efficacy and good tolerability in the treatment of mild ED (80).

Apomorphine can be administered via subcutaneous injection or sublingually. However, studies have shows a lower efficacy for apomorphine compared to oral sildenafil (81,82).

Apomorphine has a set role in the management of PD for non-motor symptoms, and has been reported to cause spontaneous erections and possible hypersexuality in PD men (83,84). Its role in the management of ED has been postulated for men with PD but should be considered as an alternative to sildenafil. Intracavernosal injections (ICI) Intracavenosal therapy involves injection of a vasoactive agent into the corpora cavernosa to effect smooth muscle relaxation and tumescence. In 1983, Brindley injected the corpora of several SCI men with phentolamine (85). Two out of the three men had a sufficient erection produced.

Since then multiple reports on the efficacy of intracavernosal therapy have been published using, phentolamine, papaverine, prostaglandin, vasoactive intestinal peptide (VIP), and these medications in combination (86-90). These medications have been found to be extremely effective for neurogenic ED due to their ability act locally and essentially bypassing neuronal pathways. Local therapies are usually considered second-line after PDE5i fail to elicit a desired response which can occur in about 25–30% of men with ED, in general (91).

Furthermore, the locally delivered medications can be quite dangerous if not used appropriately as priapism and significant pain with injections can occur.

These specific occurrences have been suggested as a reason for high discontinuation rates with intracavernosal therapy (92).

Papaverine is an opium alkaloid that acts as a non-specific PDEi that increases intracellular cAMP and cGMP leading corporal smooth muscle relaxation (93).

Intracavernosal papaverine injection was the first clinically effective pharmacological therapy for ED and led to a full erection in at least half of the patient in early studies (94,95). Alprostadil is a potent vasodilator and smooth muscle relaxant identical to the naturally occurring PGE1. PGE1 binds with specific receptors on smooth muscle

cells

PGE1 is the only FDA approved form of intracavernosal therapy and is available commercailly as EDEX, or Caverject.

Its efficacy was demonstrated in several clinical trials where the rate of responders

ranged

In men with prolonged use the pain is usually self-limited (99).

Vasoactive intestinal peptide (VIP) VIP is a neurotransmitter with regulatory actions on blood flow, secretion and muscle tone with intracorporal adenylate cyclase activation and smooth muscle relaxation.

VIP has been shown to elevate cAMP intracellular concentrations without affecting cGMP levels.

However, when VIP is given alone it may not induce erection and requires combination with phentolamine or papaverine for it to be effective (88). Common associated adverse effects were facial flushing and headache.

VIP in combination with phentolamine is currently being used in the UK and Europe and is seeking regulatory approval for use in the United States.

Phentolamine blocks post synaptic adrenergic ?1 receptors preventing smooth muscle contraction.

However, it also may interfere with prejunctional ?2 receptors, which may counteract the process (100). Consequently, this may be a reason phentolamine is not prescribed as monotherapy, and frequently is combined with papaverine, alprostadil or VIP. Multiple combinations of intracavernosal therapy exist and the effectiveness of them varies based on patient characteristics and varying dosing strength ( Table 1 ).

Combination therapy have been extremely effective in the SCI population, and have several advantages including a reduction in cost per dose and side effects base on the lowered dose of each component (101,102).

Effectiveness of combination therapy in the spinal cord population is well established, but no specific dose recommendations can be made based on the data (103-106). The use of combination therapy on other forms of neurogenic ED have not been well studied, but there use can be trialed as second-line therapy, or for populations were the side effects of PDE5i may preclude use such as in MSA due to hypotension.

Alprostadil may be delivered via the urethra in the form of a pellet (MUSE) (107). This form of therapy has been trialed in SCI men with intermediate success (108). Bodner trialed MUSE dose escalation in SCI men and found 1,000 ?g to be the most effective dose.

Several men had hypotension when a constriction ring was not used in conjunction with the MUSE therapy.

Vacuum erection devices (VED) VED involved placing the penis in a clear plastic tube where negative pressure created by the vacuum pump leads to penile engorgement and tumescence. Usually a constriction ring

can

Some men complain of bruising, a “cold” penis and pain associated with the constriction ring; however, in some men with NED sensation may not be intact mitigating the side effects of VEDs.

VEDs have reported effectiveness up to 90% in certain ED populations and it remains a non-invasive means to achieve and erection.

(109) compared VEDs with papaverine injections in 18 males with SCI.

The injections and pumps were equally effective in inducing erections and no adverse effects from the treatments were reported.

Treatment arms were crossed over, subsequently seven men chose the VED and seven men chose the papavarine highlighting equal efficacy in this population. In another treatment arm topical minoxidil was applied without any effective erections achieved by the study subjects.

VEDs in general have great success in the neurogenic population.

Limitations that may affect use are limited manual dexterity, cost due to non-insurance coverage, lack of spontaneity, artificiality of erection, obesity/buried penis, and anticoagulant use. Prior to the introduction of PDE5i in 1998, intracavernosal vasoactive medications and penile implant surgery were the mainstays of treatment. Penile implant surgery involves placement of inflatable or malleable rods within the corpora cavernosa to provide rigidity for intercourse.

Choice of which implant to place usually depends upon manual dexterity and function of the patient, patient anatomy, physician preference and surgical approach. performed penile implant surgery in 245 men with neurolgic impairment caused by spinal cord injury, CNS neoplasm, CNS infection, MS and SB (110).

Mean follow-up time of 7.2 years was achieved in 195 patients, 50 patients were excluded for lost to follow-up or death from nonurological causes.

Interestingly, 135 patients underwent penile implantation to assist with management of urinary incontinence and improve ability for condom/intermittent catheterization.

Ninety-two patients patient underwent implantation for ED. Eighty two percent of patients were satisfied with implantation for ED, and 67% of partners were satisfied. Complications included infection (5%), perforation (0–18%), and technical dysfunction (7–33%). Perforation rates were high with the malleable device when it was placed through a subcoronal incision.

After adopting an infrapubic approach the perforation rates dropped substantially.

Since the advent of PDE5i, many other selective and non-selective peripheral acting compounds have been developed or are in development.

Avanafil has shown promising results in treating ED in post-prostatectomy patients with suspected cavernous nerve injury (111). Other PDE5i marked in Asia such as udenafil, and mirodenafil also effective at treating ED may minimize side effects due to shorter half-lives (112-114).

Soluable guanylate-cyclase inhibitors and potassium channel activators are compounds that have induced erections in animal models but remain experimental requiring further investigation (115-117). Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118).

It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).

Melanocortin receptor agonists were found to induce erections serendipitously.

A study investigating the dermatologic use of Melanotan-II (MT-II) was found to generate erections unexpectedly leading to the development of MTII derivatives for ED treatment (120).

MT-II was initially used to induce pigment changes in the skin for artificial tanning but has been suspected to induce melanoma, however (121).

Finally, gene therapy and stem cell research has widened the frontier of ED treatment proposed as possibility to even reverse ED. Specifically, gene therapy pertains to repairing the cause of ED by restoring defective gene function and/or altering the expression of the mutant gene (32). Most of the available data on gene therapy are in the animal viagra pills shoppers model.

However, a phase I clinical trial in men with ED undergoing intracavernous injection with a DNA plasmid carrying the alpha-subunit of the corporal smooth muscle Maxi-K channel showed promise in increased erectile function based on IIEF assessment sustained throughout the 3-month study period (122).

Recently, several advances in the uses of stem cells have bet met with great anticipation. Stem cells have the ability to differentiate into different cell lines based on the cellular signaling they receive. Bone marrow mononuclear cells in particular have been used for the treatment of ED in animal models. recently delivered bone marrow-mononuclear cells (BM-MNC) into the intracavernous smooth muscle of post radical prostatectomy men (123). The open label, dose escalation phase I/II trial showed improvements in IIEF-15 assessment as well as increased vascularization of the corpora based on penile Doppler arterial velocity measurements. Although promising, further investigation in humans is required to substantiate BM-MNCs impact on erections, and erectile function recovery going forward. Clearly, PDE5i have revolutionized the treatment of ED in general and the neurogenic ED population is no exception.

They remain safe and effective in most men with neurogenic ED; however, care must be taken in prescribing PDE5i to men high spinal cord lesions, MSA or possibly PD.

VEDs are minimally-invasive and can be as effective as other modalities at leading to erection. However, high discontinuation rates are associated with VED use related to pain, difficulty using the device or cold penis.

Intracavernosal therapy has been a mainstay of treatment for neurogenic ED and remains extremely successful in the SCI population.

Trial of intracavernosal therapy for other causes of neurogenic ED can be considered second-line therapy, but there is a relative paucity of data for clinical outcomes related to its use outside of SCI men.

Surgical therapy via penile implantation remains another second line approach and may also be utilized to assist men with bladder management.

Higher complication rates of infections, and perforation have been reported compared to neurologically intact men. Many other compounds are currently being evaluated for the treatment of neurogenic ED as well as gene and stem cell therapy, but still should be considered investigational until substantiated by randomized controlled trials. Neurogenic ED remains difficult to diagnose and treat effectively. It is important to realize that many men with neurologic disorders may have ED related to disease related factors separate from the insult to the neuro-erectile pathway. These disease related factors must be addressed prior or simultaneously with pharmacologic and/or surgical therapy to effectively treat their SD. As awareness of the complexities of normal sexual function increase so will the recognition of SD in this population. This movement will lead to improved quality of life in men with neurologic disorders, as proven by the strong link between sexual function and quality of life. Conflicts of Interest: The authors have no conflicts of interest to declare. AXOL THERAPY FOR ERECTILE DYSFUNCTION, ENHANCED SEXUAL PERFORMANCE NOW AVAILABLE AT COLORADO UROLOGY. BREAKTHROUGH, NON-INVASIVE TREATMENT CALLED AXOL THERAPY FOR ERECTILE DYSFUNCTION AND ENHANCED SEXUAL PERFORMANCE NOW AVAILABLE AT COLORADO UROLOGY. Axol Softwave Therapy is a new treatment for erectile dysfunction (ED) and for men who want enhanced sexual performance. The in-office treatment is non-invasive, safe, and effective with virtually no side effects.

Axol Therapy is an alternative to ED medications, surgical implants, penile pumps, and injections.

Denver, CO (February 24, 2020) – The men’s sexual health specialists at Colorado Urology now offer an exciting new treatment option for men living with erectile dysfunction (ED) called Axol Softwave Therapy. This safe and non-invasive treatment option is helping many men with ED achieve spontaneous and natural erections without the help of medications. The therapy can also be used to enhance a man’s sexual performance. About 5 in 10 men experience erectile dysfunction (ED) at some point in their lives. First-line therapies often include oral medication to help men achieve an erection. Now, Axol Therapy is providing a safe and effective alternative. This non-invasive procedure uses gentle full-spectrum, low-intensity sound waves that stimulate revascularization, a process in which new blood vessels form. Axol Therapy promotes improved blood flow to the penis, reduces inflammation, and stimulates the migration of the body’s stem cells for long-term healing.

The new treatment is helping men to achieve natural erections without ED medications, pumps, injections, or penile implants.

Learn about Axol Softwave Therapy at Colorado Urology: https://www.coloradouro.com/specialties/axol-softwave-therapy/.

Axol Therapy is a modern approach to healing the body by using four types of energy: Heat,

Electrohydraulic

Unfocused acoustic waves are delivered to the shaft of the penis using a treatment wand that features a patented unfocused electrohydraulic acoustic wave. The pulsed acoustic waves are delivered through generic viagra hims the skin into the tissue to open and repair aging blood vessels, stimulate new blood vessel growth, restore blood flow, and improve erectile quality.

Axol Therapy typically takes only 20 minutes, once a week, for a total of six sessions in the physician’s office.

For men who are the right candidates, Axol Therapy is a safe and effective option without the side effects often experienced with oral medications.

Most patients can get the quality, rigid erections they once had with Axol Therapy’s gentle acoustic pulse treatment within just six office visits.

Incremental improvement in erectile function may be seen after just a few sessions.

There are a number of significant benefits to Axol Therapy. For men who are candidates for this treatment option, a future without erectile dysfunction is perhaps the biggest one.

The restoration of a man’s vitality and spontaneous active sex life are also major benefits of this exciting new treatment. Erectile dysfunction (ED) is defined as difficulty in getting and maintaining an erection that is firm enough for sex. This condition is very common, and is actually the most frequent sexual health complaint from men of all ages. At Las Vegas Urology, our team of urologists is able to offer the complete spectrum of treatment for ED that you wont find anywhere else.

Generally all symptoms of erectile dysfunction will contribute to an inability to develop or sustain an erection.

If you experience erectile dysfunction in rare instances, and you have no other related health conditions, you should be able to manage your ED without much trouble. Such situations are completely normal, and should not warrant a significant amount of worry. However, if you begin to become concerned about erectile dysfunction and how much it is impacting your daily life, we encourage you to see a specialist. ED normally stems from two separate categories of physical and mental health issues. Most often, erectile dysfunction is the result of a physical problem. These can include a variety of different situations, but they typically relate to: Not having enough blood flow to the penis – Conditions like heart disease, diabetes, and hardened arteries can all restrict the functions of an individual’s circulatory system, which can prevent proper amounts of blood flow to certain areas of the body.

It may also be difficult for an individual to keep blood in the penis long enough to sustain an erection. Problems with the nerve endings – Damage to the pelvic region can often lead to damage of the nerves.

Injury, cancer treatments, or even a disrupted signal from the brain can all cause these nerves to malfunction and diminish a person’s senses.

Side effects of medication – There is always a risk to taking a medication, but some risks can impact sexual function both temporarily and long-term.

Make sure to discuss all possible side effects to a new medication with your healthcare provider. Other cases of erectile dysfunction may be caused by emotional or psychological issues, such as: Stress Depression Anxiety Relationship problems Worry about poor sexual performance.