Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and others not yet identified. Factors that mediate relaxation include acetylcholine, nitric oxide (NO), vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids.
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These are not currently approved by the FDA for ED management, but they may be offered through research studies (clinical trials). Patients who are interested should discuss the risks and benefits (informed consent) of each, as well as costs before starting any clinical trials. Most therapies not approved by the FDA are not covered by government or private insurance benefits.
The role of the endothelium in erectile function became clearer with the observation that the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, enhanced erectile function. Erection occurs with the release of nitric oxide (NO) from the vascular endothelial cells.17 The reduction in endothelial cell production of NO results in the negative impact on the smooth muscles in the corporal bodies and results in less relaxation of the smooth muscle cells with decrease in blood supply and resulting ED. A similar phenomenon is well known to impact the coronary arterial system resulting in CVD.

Alprostadil self-injection. With this method, you use a fine needle to inject alprostadil (Caverject Impulse, Edex) into the base or side of your penis. In some cases, medications generally used for other conditions are used for penile injections on their own or in combination. Examples include papaverine, alprostadil and phentolamine. Often these combination medications are known as bimix (if two medications are included) or trimix (if three are included).


In their extensive review, Bassil and coworkers summarise the benefits and risks, with benefits such as improvement of sexual function, bone density, muscle strength, cognition and overall improvement in quality of life. Among the risks that have been suggested include erythrocytosis, liver toxicity, worsening of sleep apnoea and cardiac function, possibly increasing symptoms of benign prostatic hyperplasia (BPH). They also note that although a possibility of stimulation of prostate cancer has been hypothesised, no scientific or clinical evidence exists to this possible risk.38
In some cases, ED can be a warning sign of more serious disease. One study suggests ED is a strong predictor of heart attack, stroke, and death from cardiovascular disease. The researchers say all men diagnosed with ED should be evaluated for cardiovascular disease. This does not mean every man with ED will develop heart disease, or that every man with heart disease has ED, but patients should be aware of the link.
Soler et al. 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 yet to be performed.
The liver is the largest gland and organ in the body. There are a variety of liver diseases caused by liver inflammation, scarring of the liver, infection of the liver, gallstones, cancer, toxins, genetic diseases, and blood flow problems. Symptoms of liver disease generally do not occur until the liver disease is advanced. Some symptoms of liver disease include jaundice, nausea and vomiting, easy bruising, bleeding excessively, fatigue, weakness, weight loss, shortness of breath, leg swelling, impotence, and confusion. Treatment of diseases of the liver depends on the cause.
Other hormone levels: Measurement of other hormones beside testosterone (luteinizing hormone [LH], prolactin level, and cortisol level) may provide clues to other underlying causes of testosterone deficiency and erectile problems, such as pituitary disease or adrenal gland abnormalities. Doctors may check thyroid levels in some individuals as both hypothyroidism (low thyroid function) and hyperthyroidism (overactive thyroid function) can contribute to erectile dysfunction.

Acupuncture may help treat psychological ED, though studies are limited and inconclusive. You’ll likely need several appointments before you begin to notice any improvements. When choosing an acupuncturist, look for a certified practitioner who uses disposable needles and follows U.S. Food and Drug Administration guidelines for needle disposal and sterilization.
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Approximately 95% of penile implant surgeries are successful in producing erections that enable men to have sexual intercourse. Moreover, patient satisfaction questionnaires show that up to 90% of men who have undergone penile implants say they would choose the surgery again, and overall satisfaction ratings are higher than those reported by men using oral medication or penile injection therapy.
Men can judge themselves pretty harshly when it comes to their performance in between the sheets. The unsettling fear of not being able to rise to the occasion becomes a reccurring nightmare for men that is often equated with failure, loss of dignity, and masculinity. If you suffer from erectile dysfunction (ED), don’t be so hard on yourself, since impotence can almost always be improved with treatment, without having to rely on Viagra or other medications. Whether you suffer from ED, or hope to prevent the condition, here are six tips to overcome impotence without the side effects of the little blue pill.
Other hormone levels: Measurement of other hormones beside testosterone (luteinizing hormone [LH], prolactin level, and cortisol level) may provide clues to other underlying causes of testosterone deficiency and erectile problems, such as pituitary disease or adrenal gland abnormalities. Doctors may check thyroid levels in some individuals as both hypothyroidism (low thyroid function) and hyperthyroidism (overactive thyroid function) can contribute to erectile dysfunction.
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.
A variety of personal habits and lifestyle choices have been linked to ED. In some ways, this is a good thing, since habits can be broken and choices reconsidered. What's more, many of the lifestyle factors that contribute to sexual problems are ones that affect overall health and well-being, both physical and mental. Addressing these factors, therefore, can have benefits beyond improving erectile dysfunction.
Of the drugs used for depression, tricyclic antidepressants may be associated with erectile problems and other drugs may be substituted to prevent this complication. Currently available substitutes include bupropion, nefazodone, and trazodone. The selective serotonin reuptake inhibitors (eg, fluoxetine, sertraline, paroxetine, citalopram) can also cause difficulties with ED, but they might also have other significant sexual side effects, including decreased libido and anorgasmia.
Tadalafil should not be used with alpha-blockers (except Flomax), medicines used to treat high blood pressure, and benign prostate hypertrophy (BPH) because the combination of tadalafil and an alpha-blocker may lower the blood pressure greatly and lead to dizziness and fainting. Examples of alpha-blockers include tamsulosin (Flomax), terazosin (Hytrin), doxazosin (Cardura), alfuzosin (Uroxatral), and prazosin (Minipress). Tamsulosin (Flomax) is the only alpha-blocker that patients can use safely with tadalafil. When tadalafil (20 mg) was given to healthy men taking 0.4 mg of Flomax daily, there was no significant decrease in blood pressure and so patients on this dose of tamsulosin (Flomax) can be prescribed tadalafil. The only alpha-blocker not tested with tadalafil is alfuzosin (Uroxatral), and no recommendations can be made regarding the interaction between the two.
In most healthy men, some of the drug will remain in the body for more than two days after a single dose of tadalafil. Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, doctors have to lower the dose and frequency of tadalafil in the following examples:
Men with medical conditions that may cause a sustained erection, such as sickle cell anemia, leukemia, or multiple myeloma, or a man who has an abnormally-shaped penis, may not benefit from these medications. Also, men with liver diseases or a disease of the retina, such as macular degeneration or retinitis pigmentosa, may not be able to take these medications, or may need to take the lowest dosage.

As blood flows into the penis, the corpora cavernosa swell, and this swelling compresses the veins (blood vessels that drain the blood out of the penis) against the tunica albuginea. Compression of the veins prevents blood from leaving the penis. This creates a hard erection. When the amount of cGMP decreases by the action of a chemical called phosphodiesterase type 5 (PDE5), the muscles in the penis tighten, and the blood flow into the penis decreases. With less blood coming into the penis, the veins are not compressed, allowing blood to drain out of the penis, and the erection goes down.
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.
It is important to understand that ED is frequently, if not usually, directly related to endothelial dysfunction, and that the release of NO by the vasculature of the penile arteries is directly related to the function of intact, healthy endothelium. In the face of endothelial dysfunction, the process of erection fails to occur in a normal fashion.16

"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.
Like all diabetic complications, ED can occur even when you have followed your doctor’s advice and carefully managed your diabetes. Also like all diabetes complications, ED is less likely to occur with good blood sugar control. Poorly controlled diabetes and high cholesterol increase the chances of vascular complications, which may lead to ED or other circulatory problems. In addition, regular smoking and alcohol use can contribute to ED.
Men who do not respond or tolerate oral medications are best treated with an internal penile pump (IPP) commonly known as an inflatable implant. The Internal Penile Pump is an inflatable, water-filled device. During the course of a 45-minute outpatient procedure, the pump is inserted through a one-inch opening in the scrotal sac. By squeezing the pump, (which is contained completely within the scrotum), for approximately a minute, fluid is pumped into the penis, resulting in a long lasting erection. To return the penis to its flaccid state, simply press and hold down the pump. Once inserted, there is no maintenance required for the pump, which can remain in place for a lifetime. Couples are once again able to have spontaneous sex. Normal sensation including orgasm and ejaculation are not affected.
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.
Having erection trouble from time to time isn't necessarily a cause for concern. If erectile dysfunction is an ongoing issue, however, it can cause stress, affect your self-confidence and contribute to relationship problems. Problems getting or keeping an erection can also be a sign of an underlying health condition that needs treatment and a risk factor for heart disease.
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