Erectile Dysfunction (ED)

Conditions that may be associated with ED include diabetes, [27, 28, 29] hypertension, [30] , atrial fibrillation, [31] and CAD, as well as neurologic disorders, endocrinopathies, benign prostatic hyperplasia, [32] , sleep apnea [33] , chronic obstructive pulmonary disease (COPD), [34] and depression (see Table 1 below).

How do health care professionals treat ED?

The parasympathetic nervous system is primarily involved in sustaining and maintaining an erection, which is derived from S2-S4 nerve roots. 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. Relaxation of the sinusoidal smooth muscle increases its compliance, facilitating rapid filling and expansion.

What to expect from your doctor

The venules beneath the rigid tunica albuginea are compressed, resulting in near-total occlusion of venous outflow. These events produce an erection with an intracavernosal pressure of 100 mm Hg. Additional sexual stimulation initiates the bulbocavernous reflex. The ischiocavernous muscles forcefully compress the base of the blood-filled corpora cavernosa, and the penis reaches full erection and hardness when intracavernosal pressure reaches 200 mm Hg or more. At this pressure, both inflow and outflow of blood temporarily cease.

Extracorporeal Shockwave Therapy (ESWT)

Detumescence results from cessation of neurotransmitter release, breakdown of second messengers by phosphodiesterase, and sympathetic nerve excitation during ejaculation. Contraction of the trabecular smooth muscle reopens the venous channels, allowing the blood to be expelled and thereby resulting in flaccidity. Both ED and low testosterone (hypogonadism) increase with age. The incidence of the latter is 40% in men aged 45 years and older. [17] Testosterone is known to be important in mood, cognition, vitality, bone health, and muscle and fat composition. [35, 36, 37, 38] 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. Diseases and Conditions Associated With Erectile Dysfunction (Open Table in a new window) Conditions associated with reduced nerve and endothelium function (eg, aging, hypertension, smoking, hypercholesterolemia, and diabetes) alter the balance between contraction and relaxation factors (see Pathophysiology).

These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation.

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It also plays a key role in sexual dysfunction (eg, low libido, poor erection quality, ejaculatory or orgasmic dysfunction, reduced spontaneous erections, or reduced sexual activity). The association between low testosterone and ED is not entirely clear. Although these 2 processes certainly overlap in some instances, they are distinct entities. Some 2-21% of men have both hypogonadism and ED; however, it is unclear to what degree treating the former will improve erectile function. [19] About 35-40% of men with low testosterone see an improvement in their erections with testosterone replacement; however, almost 65% of these men see no improvement.

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One study examined the role of testosterone supplementation in hypogonadal men with ED. These men were considered nonresponders to sildenafil, and their erections were monitored by assessing nocturnal penile tumescence (NPT). After these men were given testosterone transdermally for 6 months, the number of NPTs increased, as did the maximum rigidity with sildenafil. [20] This study suggests that a certain level of testosterone may be necessary for PDE5 inhibitors to function properly. In a randomized double-blind, parallel, placebo-controlled trial, sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with ED and low testosterone levels.

Horny goat weed

[21] The objective of the study was to determine whether the addition of testosterone to sildenafil therapy improves erectile response in men with ED and low testosterone levels. However, in contrast, a recent systematic review of published studies, the authors concluded that overall, the addition of testosterone to PDE-5 inhibitors might benefit patients with ED associated with testosterone levels of less than 300 ng/dL (10.4 nmol/L) who failed monotherapy. [22] A limitation of existing studies are their heterogeneous nature and methodological drawbacks. The mechanisms by which testosterone plays a role in erectile function are not completely understood. A study evaluating the effect of testosterone on erections in surgically castrated rabbits and control animals, in which the rabbits’ intracavernosal pressures were compared after cavernosal nerve stimulation, determined that castrated rabbits had much lower pressures after stimulation than control rabbits did. In some patients, sexual dysfunction may be the presenting symptom of these disorders. Given the multiplicity of possible etiologic factors, it may be difficult to determine how much any given factor is contributing to the problem. A thorough evaluation is necessary for correct identification of the specific cause or causes in any given individual. Vascular diseases account for nearly 50% of all cases of ED in men older than 50 years.

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These diseases include atherosclerosis, peripheral vascular disease, myocardial infarction (MI), and arterial hypertension. Vascular damage may result from radiation therapy to the pelvis and prostate in the treatment of prostate cancer. [39] Both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are highly susceptible to radiation damage, can induce ED. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy; fortunately, some respond to one of the PDE5 inhibitors. Trauma to the pelvic blood vessels or nerves can also lead result in ED.

Bicycle riding for long periods has been implicated as an etiologic factor; direct compression of the perineum by the bicycle seat may cause vascular and nerve injury.

Erectile Dysfunction Injections

[23] Notably, the pressures increased when castrated rabbits received exogenous testosterone replacement. Another study compared the response of surgically and medically castrated rabbits to vardenafil with that of control rabbits. [24] Castrated rabbits did not respond to vardenafil, whereas noncastrated rabbits did respond appropriately. This result suggests that a minimum amount of testosterone is necessary for PDE5 inhibitors to produce an erection. Another study found that castrated rats had erections if given testosterone alone or dihydrotestosterone (DHT) and 5-alpha reductase inhibitors but not if given testosterone and 5-alpha reductase inhibitors.

Shockwave Therapy

[25] This finding suggests that DHT is the active component and is necessary at a certain level for rats to have an erection. This study also measured intracavernosal pressure to monitor erections and NOS activity in the penile cytosol. [25] NO levels correlated with intracavernosal pressure, which suggests that testosterone and DHT act through NOS. Testosterone and DHT may act at the genomic level to stimulate production of NOS. It appears that testosterone has NOS-independent pathways as well. [40] On the other hand, bicycling for less than 3 hours per week may be somewhat protective against ED. [40] Some of the newer bicycle seats have been designed to diminish pressure on the perineum.

• Some men find relief through natural remedies, but evidence may be limited.
• Erectile dysfunction can be an early warning sign of cardiovascular disease.
• Lifestyle counseling is often part of comprehensive ED management.
• Regular exercise improves overall endothelial function.
• Medications like PDE5 inhibitors are most effective when taken properly.
• Psychological therapies are effective for ED with psychological causes.
• Surgery is considered when pharmacological and non-invasive options are ineffective.

Diabetes is a well-recognized risk factor for ED. A systematic review and meta-analysis found that the prevalence of ED was 37.5% in type 1 diabetes, 66.3% in type 2 diabetes, and 52.5% in diabetes overall—a rate approximately 3.5 times higher than that in controls. [42] The etiology of ED in diabetic men probably involves both vascular and neurogenic mechanisms.

• Oral medications like sildenafil, tadalafil, and vardenafil are common treatments for erectile dysfunction.
• Lifestyle changes such as exercise, weight loss, and quitting smoking can improve erectile function.
• Psychotherapy may help address psychological causes like anxiety, depression, or relationship issues.
• Vacuum erection devices use suction to draw blood into the penis, helping achieve an erection.
• Penile injections involve injecting vasodilators directly into the penis for an immediate effect.
• Hormone therapy may be prescribed if low testosterone levels are contributing to ED.
• Surgical options include penile implants or vascular surgery to restore blood flow.

Evidence indicates that establishing good glycemic control can minimize this risk.

The Massachusetts Male Aging Study (MMAS) documented an inverse correlation between ED risk and high-density lipoprotein (HDL) cholesterol levels but did not identify any effect from elevated total cholesterol levels.

Treatments and Therapies

In cost of vardenafil one study, castrated rats were implanted with testosterone pellets and then divided into a group that received an NOS inhibitor (L-nitro-L-arginine methyl ester [L-NAME]) and a control group that received no enzyme. [26] The castrated rats that were given testosterone pellets and L-NAME still had partial erections, a result suggesting the presence of a pathway independent of NOS activity. Organic, physiologic, endocrine, and psychogenic factors are involved in the ability to obtain and maintain erections. In general, ED is divided into 2 broad categories, organic and psychogenic. Although most ED was once attributed to psychological factors, pure psychogenic ED is in fact uncommon; however, many men with organic etiologies may also have an associated psychogenic component. [17] Another study involving male subjects aged 45-54 years found a correlation with abnormal HDL cholesterol levels but also found a correlation with elevated total cholesterol levels. The MMAS included a preponderance of older men.

• PDE5 inhibitors are effective but may cause side effects like headaches and flushing.
• Smoking cessation improves blood vessel health, enhancing erectile function.
• Weight management helps reduce the risk factors associated with ED.
• Pelvic floor exercises can strengthen muscles involved in erection and urination.
• Counseling may help men with ED related to psychological or emotional issues.
• Hormonal treatments are suitable for those with hormonal imbalances.
• Surgical interventions are typically reserved for cases unresponsive to other treatments.

Men with sleep disorders commonly experience ED. [43] Heruti et al recommended that in adult male patients, ED should be considered when a sleep disorder—especially sleep apnea syndrome—is suspected, and vice versa. Hypogonadism that results in low testosterone levels adversely affects libido and erectile function. Hypothyroidism is a very rare cause of ED.