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It subsequently stimulates the guanylate cyclase enzyme system in penile smooth muscle.

This results in increased levels of cyclic guanosine monophosphate (cGMP) and ultimately in smooth muscle relaxation, enhancement of arterial inflow, and veno-occlusion, producing adequate firmness for sexual activity. Recognized risk factors for ED include cardiovascular disease (CVD) (hypertension, atherosclerosis, and hyperlipidemia), diabetes, depression, alcohol use, smoking, pelvic/perineal surgery or trauma, neurologic disease, obesity, pelvic radiation, and Peyronie’s disease. One study suggested that the relationship between arterial disease and ED is very strong, with 49% (147 of 300) of patients with coronary artery disease noted on cardiac catheterization reporting significant erectile dysfunction. 6 Endothelial dysfunction has been indicated as the pathophysiologic mechanism responsible for both CVD and ED. 7 The Boston Area Community Health survey demonstrated a dose-response between smoking and incidence of erectile dysfunction. 8 Animal studies have demonstrated both smooth-muscle disruption and decreased production of neural nitric oxide synthase in cigarette-exposed animals. Some evidence exists to suggest that chronic inflammation associated with metabolic syndrome also plays a role in endothelial dysfunction and erectile function, possibly due to oxidative stress.

Examples of

common

Microvascular disease associated with diabetes is thought to compound the endothelial and neural injuries associated with this disease. Pelvic surgery may disrupt both neural and vascular pathways, resulting in ED. Hormone deficiency or hypogonadism, whether primary or secondary, has been thought to impact erectile function. Approximately a third of men in the European Male Aging Study demonstrated low testosterone, suggesting that hypogonadism is overrepresented among men with ED.

11 Hormone deficiency, however, is less frequently the cause of ED

than

Many

Understanding the relationship between testosterone and ED has been impaired by a lack of standardized measurement of this hormone and the cyclic nature of its release and consumption. Some self-administered measures may be useful in the primary care setting to screen for and evaluate the degree of ED. 12 The most commonly used instrument is the International Index of Erectile Function, a 15-item questionnaire that has been validated in many populations and is considered the gold standard to evaluate patients for ED. 13 The Sexual Health Inventory for Men is a short-form, 5-item questionnaire developed to monitor treatment progress.

12 It is important to recognize that short-form questionnaire does not evaluate specific areas of the sexual cycle, such as sexual desire, ejaculation, and orgasm; however, it may be useful in discussing ED with patients and evaluating treatment results over time.

If it is determined that ED is a problem, the patient evaluation should include a detailed sexual and medical history and a physical exam. In particular, it is important to evaluate the ED within the context of ejaculatory problems. There is a strong interplay between premature ejaculation (PE) and ED, with about a third of ED patients reporting PE.

The relationship between the PE and ED is bidirectional and successful treatment of one often requires treatment of the other.

A number of specific questions relating to sexual function can help the clinician evaluate the complaint of ED.

Questions should focus on the following: How long has ED been a problem, and did it start gradually or suddenly?

How frequently do you have intercourse currently, and how frequent was it in the past?

Do you have difficulty with penetration and/or loss of the erection during intercourse in the absence of premature ejaculation? How firm are your erections (use a scale of 1 to 10)?

Do your erections vary under different circumstances, such as with different partners, oral stimulation, or masturbation? Do you have morning or evening erections and, if so, what is the quality of these erections? Is there any new curve or bend to your penis to suggest Peyronie’s disease? What are the location and severity of the curvature? Are you having any difficulties with sexual desire, arousal, ejaculation, or orgasm? If so, did these difficulties occur with the onset of the

erectile

erectile

loss

Detailed neurologic examination to include gait and postural instability, with blood pressure changes, distal extremity and saddle sensation, and reflexes, including cremasterics and bulbocavernosus. Careful genital examination, noting testicular size (to screen sildenafil over the counter cvs for hypogonadism) and palpating the penis for Peyronie’s plaques.

Rectal examination to assess sphincter tone and evaluate the prostate. Careful abdominal examination looking for organomegaly masses or other signs of liver or kidney disease. Cardiopulmonary examination to help evaluate the patient's fitness for future treatment options. Once a complete sexual and medical history has been completed, appropriate laboratory studies should be conducted.

In the initial evaluation of ED, sophisticated laboratory testing is rarely necessary.

For example, serum testosterone (and sometimes prolactin) is typically only sildenafil 20 mg cost walgreens useful when the patient demonstrates hypogonadal features or testicular atrophy, or when clinical history is suggestive. Additional hormonal evaluation may include thyroid stimulating hormone in those with a clinical suspicion of hypothyroidism or appropriate diabetes screening in those presenting with a concern for impaired glucose metabolism. If the patient has not been evaluated with a lipid panel and hyperlipidemia is suspected, measurement and appropriate referral to internal medicine or cardiology is recommended.

In most cases, a tentative diagnosis can be established with a complete sexual and medical history, physical examination, and limited or no laboratory testing. The 2018 American Urological Association Guidelines for the treatment of Erectile Dysfunction recommend a complete history and physical and lifestyle modifications followed by a shared-decision-making approach for the existing medical treatments (Figure 1).

Erectile dysfunction is known to be associated with general sildenafil over the counter cvs health status, thus, lifestyle modification improves erectile function and decreases the rate of decline of function with aging.

One year after discontinuation of smoking, patients were found to have a 25% improvement in erectile quality. 16 In addition, multivariate analysis found obesity is associated with erectile dysfunction with an approximately 50% increase in ED in obese men as compared with normal weight men.

Over a 2-year period, a third of the men randomized to a weight loss program demonstrated resolution of erectile dysfunction. 10 A Mediterranean diet and nutritional counseling reported increased erectile quality.

18 Little evidence supports that increased physical activity alone improves erectile quality; however, the strong association between physical activity and lower BMI is well described, and therefore recommended for men with erectile dysfunction and without a contraindication to physical activity. The Massachusetts Male Aging Study demonstrated increased risk of ED among heavy alcohol users though the

impact

Although there are numerous options for nonsurgical treatment, oral phosphodiesterase-5 (PDE5) inhibitors should be offered as first-line treatment of patients with ED unless contraindicated. 19 Table 1 summaries the oral PDE5 drugs approved by the U.S.

Table 1: Phosphodiesterase-5 inhibitors for erectile dysfunction. These oral medications reversibly inhibit penile-specific PDE5 and enhance the nitric oxide–cGMP pathways of cavernous smooth muscle relaxation; that is, all prevent the breakdown of cGMP by PDE5. It is important to emphasize to patients that these drugs augment the body’s natural erectile mechanisms, therefore the neural and psychoemotional stimuli typically needed for arousal still need to be activated for the drugs to be efficacious.

According to a review of all randomized controlled trials evaluating sildenafil by the American Urological Association (AUA) Consensus Panel on Erectile Dysfunction, 36% to 76% of patients receiving the drug were "able to achieve intercourse" during treatment.

For tadalafil, four randomized controlled trials revealed that 11% to 47% of patients were "able to achieve intercourse." Similar efficacy has been observed with vardenafil, although studies are fewer. 19 A meta-analysis published in 2013 clearly sildenafil over the counter cvs demonstrated increased efficacy over placebo for all PDE5 inhibitors.

24 Head-to-head comparison suggested that tadalafil outperforms sildenafil on validated measures of erectile dysfunction, including the international index of erectile function and sexual encounter profile-2 and -3.

Typical side effects sildenafil generic over the counter include headache, flushing, dyspepsia, and nasal congestion. Visual abnormalities are encountered with sildenafil, but are unlikely with vardenafil and tadalafil. Back pain and myalgia can occur with tadalafil, but are unusual with sildenafil or vardenafil. Patients at high cardiovascular risk should not be treated for ED until their cardiac condition is stabilize. These conditions include unstable or refractory angina, myocardial infarction or cerebrovascular accident within the past 2 weeks, uncontrolled hypertension, New York Heart Association (NYHA) Functional Classification III-IV congestive heart failure, sildenafil over the counter cvs high-risk arrhythmias, hypertrophic obstructive cardiomyopathies, and moderate-to-severe valvular disease.

25 This class of drugs is also contraindicated in patients who use nitroglycerin or nitrate-containing compounds.

Although vardenafil does not seem to produce significant clinical QT prolongation, it has been suggested that it be avoided in patients who have congenital QT prolongation abnormalities and in patients using class I antiarrhythmic drugs, such as quinidine and procainamide. It is also best to avoid the use of vardenafil with class III antiarrhythmic drugs, such as amiodarone or sotalol.

Due to the risk of hypotension, caution should be used in patients using alpha blockers for prostate hyperplasia and patients using other antihypertensive medications and alpha blockers, which should not be co-administered with PDE5 inhibitors. In patients who take 50 mg of sildenafil or more and use alpha blockers, sildenafil dosing should be avoided for at least 4 hours after the dose of the alpha blocker.

In patients who take 25 mg of sildenafil, use of any alpha blockers is considered safe.

Dose-adjustment is recommended in patients with hepatic failure and with co-administration of drugs also metabolized by the cytochrome p450 enzymes.

There is a reported risk for

nonarteritic

Although the association is controversial, it is prudent to consider alternative treatments for ED in patients with NAION or at risk for it.

Withdrawal of Medications Causing or Contributing to ED. It is extremely important to take a complete drug history for patients reporting ED. Medications that may cause or contribute to ED include: Alcohol, nicotine, and illicit drugs Analgesics Anticonvulsants Antidepressants Antihistamines Antihypertensives sildenafil cvs over the counter Antiparkinson Antipsychotics Cardiovascular agents Cytotoxic agents Diuretics Hormones

and

The newer angiotensin II receptor antagonists may be less problematic with respect to ED, but long-term data is needed to evaluate this. Of the drugs used for depression, tricyclic antidepressants may be associated with erectile problems and other drugs may be substituted to prevent this complication.