Sexual stimulation causes the release of neurotransmitters from cavernosal nerve endings and relaxation factors from endothelial cells lining the sinusoids. NOS produces NO from L-arginine, and this, in turn, produces other muscle-relaxing chemicals, such as cGMP and cyclic adenosine monophosphate (cAMP), which work via calcium channel and protein kinase mechanisms (see the image below). This results in the relaxation of smooth muscle in the arteries and arterioles that supply the erectile tissue, producing a dramatic increase in penile blood flow.
Causes of impotence are many and include heart disease, high cholesterol, high blood pressure, obesity, metabolic syndrome, Parkinson's disease, Peyronie's disease, substance abuse, sleep disorders, BPH treatments, relationship problems, blood vessel diseases (such as peripheral vascular disease and others), systemic disease, hormonal imbalance, and medications (such as blood pressure and heart medications).

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).
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The medications are extremely effective, which is very good. And the medications are, for the most part, extremely well-tolerated. But there are, like with any medications, a potential downside. The one absolute downside to the use of any of these erection what we call PDE5 medications is if a patient is using a nitroglycerin medication. And nitroglycerins are used for heart disease and for angina, for the most part, although there are some recreational uses of nitrites. And that’s important because your blood vessels will dilate and your blood pressure will drop. And that is an absolute contraindication.


"Sexual relations are not only an important part of people's wellbeing. From a clinical point of view, the inability of some men to perform sexually can also be linked to a range of other health problems, many of which can be debilitating or potentially fatal," says Professor Gary Wittert, Head of the Discipline of Medicine at the University of Adelaide and Director of the University's Freemasons Foundation Centre for Men's Health.
Men with a rare heart condition known as long QT syndrome should not take vardenafil since this may lead to abnormal heart rhythms. The QT interval is the time it takes for the heart's muscle to recover after it has contracted and is measured on an electrocardiogram (EKG). In addition, vardenafil is not recommended for men taking medications that can affect the QT interval such as quinidine, procainamide, amiodarone, and sotalol.
When other treatments haven’t helped, a penile implant may be the right solution. A penile implant is a medical device that is surgically placed into a penis to mimic the look and performance of a natural erection9. Implants are custom-fitted to your anatomy. Sensitivity and the ability to ejaculate aren’t typically affected either, so you’ll be able to have an orgasm normally (unless you have a medical condition that prevents this)7.
Stress is your body responding to your environment. And it’s a good thing—in limited doses. When you get stressed out your body makes chemicals like adrenaline that make you stronger, faster, fitter, and even able to think more clearly. Most people call this reaction the “fight-or-flight” response, and it’s a life-saver in dangerous situations. In a very real sense, adrenaline makes you a part-time superhero. The problems happen when your body deals with constant stress.
Unfortunately, some patients may have an overly simplified understanding of the role of PDE5 inhibitors in ED management. Such patients may not expect or be willing to undergo a long evaluation and testing process to obtain a better understanding of their sexual problem, and they may be less likely to involve their partner in discussing their sexual relationship with the physician. They may expect to obtain medications through a phone call to their doctor or even over the Internet, with minimal or no physician contact at all.
Your Ro physician may recommend trying the medication under different circumstances. Using the medication the first time can be anxiety provoking so they may suggest using it alone until you are familiar with its effect or side effects. If you’ve been prescribed ED medication on the Ro platform, please contact a physician if you have any questions. You are not alone. Use every tool you can and asking questions when you need answers is one of them.
A cold slice of watermelon can do more than just satisfy thirst and hunger during the warm summer months; it can help with bedroom satisfaction. Citrulline, the amino acid found in high concentrations of watermelon, is found to improve blood flow to the penis. A 2011 study revealed men who suffered from mild to moderate ED and took L-citrulline supplementation showed an improvement with their erectile function and were very satisfied. Natural watermelon juice, or “nature’s Viagra,” can also be easier on the stomach, since taking pills like Viagra can cause nausea and diarrhea.
The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present. The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16
And surgery comes with its own serious risks, such as developing incontinence or impotence, while radiation can result in urinary problems. — Peter Loftus, WSJ, "Surgery Adds Three Years to Lives of Prostate-Cancer Patients, Study Finds," 12 Dec. 2018 Male-impotence pill Viagra began facing generic competition late last year, while the Lyrica pain treatment is expected to confront generics at the end of this year. — Jonathan D. Rockoff, WSJ, "Pfizer Narrows Guidance on Tougher Pricing, Generic Competition," 30 Oct. 2018 Arkham Horror Third Edition is a classic struggle of agency versus impotence, set in the uncanny world of H.P. Lovecraft’s Cthulhu mythos. — Charlie Theel, Ars Technica, "Arkham Horror Third Edition: The classic Lovecraft adventure returns," 24 Nov. 2018 There’s obviously a lot of anger and frustration here toward the US government at the moment—along with side effects like bottled rage and sometimes a creeping sense of ineptitude or impotence about our ability to do anything about it. — Corey Seymour, Vogue, "Pussy Riot's Nadya Tolokonnikova On Her New Guide To Activism, Raising The Next President Of Russia, And Her "Holy War" On Fairy Tales," 12 Oct. 2018 In exchange for political impotence, they would be mostly left alone and allowed to get rich. — Paul Mozur, New York Times, "Inside China’s Dystopian Dreams: A.I., Shame and Lots of Cameras," 8 July 2018 Their suspicion is compounded by rumors that the polio vaccine causes impotence, death and, ironically, paralysis. — Meher Ahmad, New York Times, "Pakistan Has Just One New Polio Case, but Isn’t Declaring Victory Yet," 20 May 2018 Fighting back, even as an exercise in impotence, did a lot for McCain. — Alex Horton, Washington Post, "John McCain rebelled at the Naval Academy — and as a POW — long before he was a Senate maverick," 3 May 2018 Feelings of desperation and impotence are being felt throughout Central America, where the lawlessness, endemic poverty and levels of gang violence akin to war zones that have driven so many families from their homes show little signs of abating. — Washington Post, "Violence keeps Central Americans coming to US despite Trump," 21 June 2018
Tests such as the bulbocavernosus reflex test are used to determine if there is sufficient nerve sensation in the penis. The physician squeezes the glans (head) of the penis, which immediately causes the anus to contract if nerve function is normal. A physician measures the latency between squeeze and contraction by observing the anal sphincter or by feeling it with a gloved finger inserted past the anus.
Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED. [14] These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
Adverse effects related to PDE5i use with mild-moderate and transient (58). Furthermore, side effects 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.
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
An analysis of 14 studies involving more than 90,000 patients with ED confirmed the relation between ED and an increased risk of cardiovascular events and mortality. [56] Compared with patients without ED, those with ED had a 44% increased risk of cardiovascular events, a 25% increased risk of all-cause mortality, a 62% increased risk of MI, and a 39% increased risk of cerebrovascular events. Treatment of ED, either through lifestyle interventions or by pharmacologic means, may improve prognosis and reduce risk.
Diabetes mellitus: Erectile dysfunction tends to develop 10 to 15 years earlier in diabetic men than among nondiabetic men. The increased risk of erectile dysfunction among men with diabetes mellitus may be due to the earlier onset and greater severity of atherosclerosis (hardening of the arteries) that narrows the arteries and thereby reduces the delivery of blood to the penis. Atherosclerosis can affect the arteries in the penis, as well as the arteries in the pelvis that supply the penile arteries. Diabetes mellitus also causes erectile dysfunction by damaging nerves that go to the penis, much like the effect of diabetes on nerves in other areas of the body (diabetic neuropathy). Diabetes can also affect the muscles in the penis, leading to troubles with erections. Smoking cigarettes, obesity, poor control of blood glucose levels, and having diabetes mellitus for a long time further increase the risk of erectile dysfunction in people with diabetes.
Other form of sexual dysfunction, such as premature ejaculation and loss of libido (decreased sexual desire), are also very common. The NHSLS found that 28.5% of men 18-59 years of age reported premature ejaculation, and 15.8% lacked interest during the past year. An additional 17% reported anxiety about sexual performance, and 8.1% indicated a lack of pleasure from sexual activity.
Treatment. prostatitis or another acute infection affecting the genitalia can cause temporary impotence that clears up in response to antibiotics. The smooth muscle relaxant sildenafil (viagra) was introduced in 1998 as a treatment for organic impotence. Administration of testosterone may be indicated if low levels of this hormone are found in a blood sample. If impotence is organic and does not respond to other therapies, a penile prosthesis can be implanted; this is usually done surgically by a urologist. Other therapies include the use of vacuum tumescence devices and penile injection of pharmacologic agents that cause dilation.
Besides PDE5 inhibitors and among second-line therapies are VCDs which are clear plastic chambers placed over the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis. An erection beyond 30 min is not recommended. These devices can be a bit cumbersome, but are very safe.40
Inside the cell, NOS catalyzes the oxidation of L-arginine to NO and L-citrulline. Endogenous blockers of this pathway have been identified. The gaseous NO that is produced acts as a neurotransmitter or paracrine messenger. Its biologic half-life is only 5 seconds. NO may act within the cell or diffuse and interact with nearby target cells. In the corpora cavernosa, NO activates guanylate cyclase, which in turn increases cyclic guanosine monophosphate (cGMP). Relaxation of vascular smooth muscles by cGMP leads to vasodilation and increased blood flow.
ICI therapy often produces a reliable erection, which comes down after 20-30 minutes or with climax. Since the ICI erection is not regulated by your penile nerves, you should not be surprised if the erection lasts after orgasm. The most common side effect of ICI therapy is a prolonged erection. Prolonged erections (>1 hour) can be reversed by a second injection (antidote) in the office.
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