The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) study, designed to determine whether an individual man’s sexual outcomes after most common treatments for early-stage prostate cancer could be accurately predicted on the basis of baseline characteristics and treatment plans, found that 2 years after treatment, 177 (35%) of 511 men who underwent prostatectomy reported the ability to attain functional erections suitable for intercourse. [45]
The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles. Although the membrane receptors play an important role, downstream signaling pathways are also important. The RhoA–Rho kinase pathway is involved in the regulation of cavernosal smooth muscle contraction. [12]
The common PDE5 inhibitor drugs approved in the United States are sildenafil (Viagra), vardenafil (Levitra and Staxyn, the generic form), tadalafil (Cialis), or avanafil (Stendra). All of the currently approved PDE5 inhibitors work in the same way. They differ in the number of available doses, how quickly they work and last in your system, the dosing, and to some extent in the side effects. However, they generally share the same indications and contraindications. Currently, tadalafil is the only medication that patients can take on a daily basis and is approved for the treatment of both ED and BPH (benign enlargement of the prostate).
Some men should not take PDE5 inhibitors. They can cause hypotension (abnormally low blood pressure that can lead to fainting and even shock) when given to patients who are taking nitrates (medications taken for heart disease). Therefore, patients taking nitrates daily should not take any of the PDE5 inhibitors. Nitrates relieve angina (chest pain due to insufficient blood supply to the heart muscle because of narrowing of the coronary arteries); these include nitroglycerine tablets, patches, ointments, sprays, and pastes, as well as isosorbide dinitrate and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate also are in some recreational drugs called "poppers."
ED usually has something physical behind it, particularly in older men. But psychological factors can be a factor in many cases of ED. Experts say stress, depression, poor self-esteem, and performance anxiety can short-circuit the process that leads to an erection. These factors can also make the problem worse in men whose ED stems from something physical.
Conditions that may be associated with ED include diabetes, [25, 26, 27] hypertension, [28] , and CAD, as well as neurologic disorders, endocrinopathies, benign prostatic hyperplasia, [29] , sleep apnea [30] , COPD, [31] and depression (see Table 1 below). [32, 33, 34, 35] In fact, almost any disease may affect erectile function by altering the nervous, vascular, or hormonal systems. Various diseases may produce changes in the smooth muscle tissue of the corpora cavernosa or influence the patient’s psychological mood and behavior.
This procedure is usually performed before and after injection of a smooth-muscle-relaxing medication into the penis, which normally should significantly increase the diameter of the penile arteries. The procedure itself is painless. Duplex ultrasonography is most useful in evaluating possible penile arterial disorders, but in those individuals considering surgery for problems with the arteries to the penis, a more invasive study, angiogram, is needed to identify the location of the damaged artery.
Because the burning side effect is triggered by alprostadil, the formulations with the least alprostadil — tri-mix and certain versions of bi-mix — could work for men who experience burning with the single-drug formula. But some men might choose alprostadil alone because the multi-drug cocktails can cost more and must be dispensed by a compounding pharmacy — one that is authorized to mix medications on site — which could mean the added hassle of a long drive to pick up the drug.
ED may occur with or without other sexual dysfunction, including decreased libido (decreased interest in sexual activity), orgasmic dysfunction (troubles achieving an orgasm/climax), and ejaculatory dysfunction (problems with the fluid released during sex, including lack of ejaculation [anejaculation], small volume ejaculate, ejaculation that occurs too quickly [premature ejaculation], ejaculate that goes backward into the bladder [retrograde ejaculation] and pain with ejaculation).

When a man becomes sexually excited, muscles in their penis relax. This relaxation allows for increased blood flow through the penile arteries. This blood fills two chambers inside the penis called the corpora cavernosa. As the chambers fill with blood, the penis grows rigid. Erection ends when the muscles contract and the accumulated blood can flow out through the penile veins.
Iatrogenic hypotension can occur in men in neurodegenerative disease using sildenafil (49). Hussain et al. 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.
SD in MS can be classified into three categories. Primary SD is due directly due to MS-related neurological deficits, secondary SD is related to physical impairments and symptoms or drugs used for MS treatment, and tertiary SD is due to the psychological, social and cultural problems attributed to MS (38). These classifications are important, and underscore the importance of addressing all the issues leading to SD not just the neurologic impairment.
If you can't take one of these oral medications, your physician may have you try Caverject (alprostadil for injection), a hormone that you inject into your penis using a fine needle, or Muse (alprostadil urogenital), a tiny suppository that you insert into the tip of the penis. Both of these will bring on an erection within five to 15 minutes without sexual stimulation.
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.
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).
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:
The severity of ED has been correlated with the extent of CVD. Banks et al reported that the risk of future CV events increased progressively according to ED severity.28 This was shown in both men with and without known CVD at baseline and after controlling for confounders. Solomon and colleagues found an inverse correlation between international index of erectile function (IIEF) scores and plaque burden seen on coronary angiography.29 In addition, Yaman et al demonstrated a significant correlation between ED severity on IIEF questionnaires and coronary artery calcification.30
Several medications can interfere with the chemical processing of PDE5i medications by the liver. These can include ketoconazole (an antifungal medication known by the brand name Nizoral), erythromycin (an antibiotic), and cimetidine (also known as Tagamet, for reducing stomach acid). A lower dose of PDE5i medications should be used if one is taking any of these medications.
As is true in so many medical conditions, lifestyle modifications, considered first-line therapy, can have a salutary effect in ED management, and men should be encouraged to make the necessary changes to the benefit of their sexual function and to their overall health as well. Despite the benefits of behaviour modification, men presenting with ED want the physician to help with measures that can have an immediate impact.
A physical exam checks your total health. Examination focusing on your genitals (penis and testicles) is often done to check for ED. Based on your age and risk factors, the exam may also focus on your heart and blood system: heart, peripheral pulses and blood pressure. Based on your age and family history your doctor may do a rectal exam to check the prostate. These tests are not painful. Most patients do not need a lot of testing before starting treatment.
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