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This review examines the underlying causes associated with ED and PE addyi tablet buy online and evaluates currently available treatment options and those under investigation.

2010;45:17-27.) Erectile dysfunction (ED) and ejaculatory disorders such as premature ejaculation (PE) are considered the most common types of sexual dysfunction in men. "The inability to achieve or maintain an erection sufficient for satisfactory sexual performance," is a commonly accepted definition of impotence by the National Institutes of Health; however it is now recognized by the

American

1 ED reportedly affects up to 40% of men between the ages of 40 and 70 and is more likely to develop with aging. 2-4 Despite broad consensus on a single definition, PE is commonly characterized by the inability to delay ejaculation, which occurs before or soon after the initiation of intercourse and is subsequently associated with feelings of distress or frustration.

5,6 Unlike ED which is more prevalent in older men, PE is considered one of the most common male sexual disorders and occurs with similar frequency in men, independent of age. The penis is comprised of several key structures: the corpus cavernosum encased within the tunica albuginea, the corpus spongiosum containing the urethra, and the extensive vascular system of arteries and veins. 8 In the flaccid state, penile smooth muscle tissue is contracted and arterial blood flow which supplies the sinusoidal cavities within the pair of corpora cavernosa is equal to venous drainage from them.

With the exception of nocturnal penile tumescence, a sensory stimulus initiates the erectile process via two coordinated pathways involving vasoactive substances, prostaglandins, and circulating catecholamines. 9,10 Nitric oxide, which is synthesized and released from endothelial cells, crosses into smooth muscle cells and enhances the activity of guanylate cyclase, which catalyzes the formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP).

The second pathway involves prostaglandin E 1 -mediated activation of G proteins within smooth muscle cells, followed by stimulation of adenylate cyclase and increased production of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). 9 By decreasing intracellular calcium concentrations, both cGMP and cAMP cause smooth muscle relaxation, which leads to increased cavernosal arterial blood flow and decreased venous drainage resulting in an erection.

Neurogenic disorders involving the central nervous system (CNS) or peripheral nervous system such as stroke, spinal cord injury, Parkinson's disease, and multiple sclerosis have also been associated with ED.

Furthermore, patients with a history of benign prostatic hyperplasia (BPH), Peyronie's disease, hypogonadism, or those who have had a radical prostatectomy secondary to prostate cancer are at greater risk of addyi tablet buy online developing ED.

Drug induced causes of erectile dysfunction are common and can complicate the medical management of underlying conditions associated with ED such as hypertension, depression, and BPH (Table 1).

Beta blockers, selective serotonin reuptake inhibitors (SSRIs), and the uroselective alpha adrenergic receptor antagonists have been associated with the loss of libido or ejaculatory disorders, which can result in drug discontinuation by patients and suboptimal treatment of these conditions.

Researchers examining the role of drug exposures in the prevalence of erectile dysfunction found that hypertensive patients taking selected antihypertensive therapy increased the odds of ED prevalence, compared with patients not taking selected antihypertensive therapy (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.6-5.9).

Despite the high prevalence of erectile disorders, identifying the presence of this condition remains flibanserin online order challenging for the physician as patients are often reluctant to discuss this sensitive problem. Although patients may be more inclined to share these issues when the discussion is initiated by their healthcare provider, physicians' themselves may also have some uneasiness with this conversation. A recent review of several studies found that the prompt recognition and addyi tablet buy online treatment of ED symptoms associated with underlying endothelial cell dysfunction may improve ED related outcomes by decreasing the development or progression of vascular comorbidities. Approximately 80% of men diagnosed with ED will have organic disease; thus the AUA diagnosis and treatment guidelines recommend a thorough medical history

and

Several tools have been developed to assess treatment outcomes such as the International Index of Erectile Function (IIEF), the Erectile Dysfunction of Inventory of Treatment Satisfaction (EDITS), and the Premature Ejaculation Tool. The IIEF is a self-administered questionnaire that contains 15 questions which assess several domains, such as: erectile function, orgasm, sexual desire, and satisfaction.

1 The IIEF-5 is an abbreviated version of the IIEF which serves as a useful measure of treatment response and is generally more applicable to a clinical practice setting. Patient diaries, such as the Sexual Encounter Profile (SEP), are also commonly utilized to document improvement in clinical outcomes. Questions 2 and 3 from the SEP address a patient's ability to attain an erection sufficient for intercourse (SEP2) and the maintenance of the erection through completion of intercourse (SEP3).

Currently available agents for the management of ED include: the oral phosphodiesterase type 5 (PDE 5) inhibitors, intraurethral and intracavernous prostaglandin E 1 formulations, injectable phentolamine and papaverine, and testosterone preparations.

Trazodone, yohimbine, and herbal products have been utilized in the treatment of ED but are not recommended for use by the AUA.

The arrival of sildenafil (Viagra) to the US market in 1998 was the first FDA approved oral PDE 5 inhibitor.

It was followed shortly by vardenafil (Levitra) and tadalafil (Cialis) in 2003, marking a shift in the management of ED as more patients began to seek treatment with the availability of these more convenient pharmacologic options.

All 3 agents exert their effect by selectively blocking PDE 5 in cavernosal smooth muscle cells, which leads to a greater concentration of cGMP, thereby enhancing the effects of smooth muscle relaxation and cavernosal blood flow resulting in prolonged erectile function.

The efficacy of the PDE 5 inhibitors has been demonstrated in several patient populations with ED due to organic and psychogenic causes.

In a pooled analysis of several sildenafil studies, 63%, 74%, and 82% of sildenafil-treated patients who received 25 mg, 50 mg, and 100 mg, respectively, reported improvement in their erections, compared to only 24% of placebo-treated patients.

15 Similar results were observed in vardenafil-treated patients in whom escalating doses were also associated with better outcomes, between 58% and 66% of patients on vardenafil buy generic viagra without a prescription reported success with intercourse regardless of the drug dose.

18 Two studies in tadalafil-treated patients showed that 62% and 77% of patients were successful with SEP2, compared to 39% and 43% of placebo-treated patients, respectively ( P 17 Despite a lack of trials that compare these agents, all are considered equally effective for the treatment of ED by the AUA. As a result of their mild vasodilatory effects, caution should be exercised when the PDE 5 inhibitors are coadministered with other antihypertensive agents.

The administration of nitrate-containing preparations are contraindicated with sildenafil, vardenafil, and tadalafil due to the profound hypotensive effects of this drug combination.

Furthermore, because of the underlying association of ED with cardiovascular disease, clinicians should carefully assess whether these agents are indicated in a particular patient.