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Erectile dysfunction ED is one of the most common chronic diseases affecting men and its prevalence increases with aging. It is also the most frequently diagnosed sexual dysfunction in the older male population. A of different diseases potentially worsening sexual function may occur in elderly people, together with polypharmacy. Related causes of ED are variable and can include arterial, neurogenic, hormonal, cavernosal, iatrogenic, and psychogenic causes. The aim of the present review was to examine the main aspects of erectile dysfunction going through epidemiology and pathophysiology and revise most of ED in elderly disabled men and in those affected with psychiatric disorders.

Lastly we tried to focus on the main aspects of nonpharmacological and pharmacological treatments of ED and the recreational use in the elderly. It is widely known that PDE5-I have lower response rates in older men than in younger patients, but they have the advantages of ease of use and excellent safety profile, also in the elderly. It is also the most frequently diagnosed sexual dysfunction in the older male population [ 1 ].

ED is defined as the inability of a man to attain and maintain an adequate erection for satisfactory sexual intercourse. It has become an issue only in the late years, because before the 20th century individuals often did not live beyond the reproductive years. Furthermore, elderly men are often affected with several diseases, leading to polypharmacy; many drugs potentially worsen sexual function [ 2 ]. This also means that a careful assessment of potential drug-drug interactions is requested [ 2 ].

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Related causes of ED are variable and can include arterial, neurogenic, hormonal, cavernosal, iatrogenic, and psychogenic causes [ 3 ]. It is now widely accepted that ED is predominantly due to underlying vascular causes, particularly atherosclerosis [ 4 ].

Lastly we tried to focus the main aspects of treatment of ED and the recreational use in the elderly. In fact an active sexual life is perfectly in agreement with the geriatrics motto that doctors should help patients to add the life in their years and not the years in their life. An extensive Medline search was made using the keywords: elderly, comorbidities, erectile dysfunction, epidemiology, pathophysiology, endothelial dysfunction, phosphodiesterase-5 inhibitors, and polypharmacy. Due to the great amount of studies on this field, we chose only the most recent articles. In a large US study, the proportion of sexually active males declined from All epidemiologic studies clearly show an increasing age-related prevalence and severity of ED.

Some studies have pointed out that normal erectile function is not a prerequisite to remain sexually active [ 7 — 9 ]. Notwithstanding sexual problems are frequent among older adults, they are infrequently discussed with physicians [ 9 ]. Asking about sexual health remains difficult or embarrassing for many primary care physicians and at the same time many patients find that raising sexual issues with their doctor is difficult.

However, after the age of 60 years, the ED rate increases independently of comorbidities such as coronary artery disease, diabetes, and hypertension [ 10 ]. Furthermore, elderly men are often affected with several diseases and take a lot of drugs, many of which are potentially worsening sexual function.

On the other hand, preserving a good sexuality in both old men and women is remarkable for trying to improve their quality of life. ED is frequently found in the elderly because it is associated with the same underlying risk factors as vascular disease and includes hypertension, diabetes mellitus DMhyperlipidemia, smoking, and obesity which are common during aging.

Some evidence shows that ED can be greatly improved not only by some drugs such as phosphodiesterase-inhibitors PDE5-Ibut also by treating the risk factors directly [ 11 ]. These include cessation of smoking, correction of hyperlipidemia, and amelioration of obesity through weight loss. In fact, all of them result in amelioration of endothelial health [ 11 ]. There is a close relationship between ED, aging, and endothelial dysfunction EDys.

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Minor risk factors such as inflammation, hypoxia, oxidative stress, and hyperhomocysteinemia are also related to ED and EDys. Data suggest that ED may be an early manifestation of endothelial dysfunction EDys in the presence or absence of cardiovascular risk factors CRF [ 13 ]. Therefore, men with ED may be at increased risk for cardiovascular adverse events and ED may be considered as a sentinel symptom in patients with occult cardiovascular disease CVD [ 14 ].

ED in aging males is the result of various factors which exert negative effects on multiple levels in erectile biology [ 15 ]. First, in the aging male, the vascular supply to the penis is compromised. In humans, postmortem studies have revealed that aging is often associated with increasing degrees of atherosclerotic vascular alterations in the arterial bed of the penis [ 16 ]. Second, the relative proportion of -adrenergic receptor subtypes is modulated by aging in arteries.

This means that a lot of age-related changes are found in the human prostatic, bladder, and erectile tissue [ 17 ]. Another remarkable factor closely contributing to impaired vasodilation in the corpus cavernosum and the penile arterial supply of the older man is endothelial dysfunction.

In fact, erectile function is dependent on nitric oxide NO production by penile endothelium and thus ED is associated with reduced plasma NO levels [ 11 ]. Deficiency of endothelial-derived NO is also believed to be the primary defect that links insulin resistance and EDys [ 11 ]. Clinical and biochemical markers of EDys include 1 reduced expression and activity of endothelial nitric oxide synthase eNOSreduced synthesis of NO, and increased production of the asymmetric dimethylarginine ADMAa competitive, endogenous inhibitor of eNOS; 2 increased production of free radicals of inflammatory cytokines such as interleukin-6 IL-6C-reactive protein CRPand tumor necrosis factor- TNF- and increased endothelial apoptosis [ 1119 ].

In fact, endothelial dysfunction in aging has been attributed to the presence of NO scavengers in the corpus cavernosum, the most obvious candidates being superoxide anions, whose production is augmented in aging endothelial cells [ 20 ]. This causative link is further strengthened by the fact that use of inhibitors of cyclooxygenase and vitamin C, which are both powerful antioxidants, can prevent age-related endothelium-dependent vasodilation decrease in humans [ 20 ].

Furthermore, the presence of reactive oxygen species ROS is able to cause an inflammatory state of the endothelium resulting in predisposition to atherosclerosis, thereby further reducing blood flow to the erectile tissue. In the aged endothelium, this further in the inactivation of endothelium NO synthase eNOS through a decrease in phosphorylation of its positive regulatory site and an increase in phosphorylation of its negative regulatory site [ 21 ].

Animal models represented by aged rats have clearly shown that a decreased activity of eNOs is also responsible for the increase in apoptosis of the endothelium. Third, the percentage of smooth muscle steadily decreases with aging [ 1122 ]. In fact, corpora cavernosa of aged men present excessive deposition of collagen fibers which in corporal fibrosis. These changes are similar to those ones observed in the media of the penile arteries [ 23 ]. These alterations result in an impaired expandability of the erectile tissue, and therefore the mechanism by which the expanding sinusoids compress the emissary veins against the tunica albuginea becomes defective.

This le to corporeal venous leakage which typically presents as the inability to maintain an erection as it is frequently seen in the aged male. Finally, another factor contributing to the above described changes in smooth muscle and collagen content of the corpus cavernosum is androgen deficiency.

In fact, this can lead to a marked increase in connective tissue deposition. Moreover, venoocclusive dysfunction might be due to an increase in fat containing cells in the subtunical region of penile tissue sections, as shown from orchiectomized animals [ 24 ]. Overall, the presence of androgens regulates the normal morphology and function of the cavernous nerves and keeps the endothelium in a healthy condition. A low testosterone T level is positively associated with the presence and severity of atherosclerosis and a reduction in plasma T might contribute to increased arterial stiffness, which in turn has been associated with increased cardiovascular risk and mortality [ 25 ].

The Rotterdam study, a population-based cohort study, showed that low levels of endogenous androgens are associated with increased likelihood of atherosclerosis in elderly men [ 26 ]. Low T was linked to cardiovascular mortality, morbidity in men of varying age, and cardiovascular risk factors CRF [ 27 ]. Men have a higher rate of CVD than women [ 11 ]. The role of androgens in determining vasodilation has been recently investigated.

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However, the final role of T has still to be recognized, since three different meta-analyses have documented an association between low T and CV mortality but not with CV events [ 30 — 32 ]. In particular, low T has been linked to increased blood pressure, dyslipidemia, atherosclerosis, arrhythmias, thrombosis, endothelial dysfunction, and impaired left ventricular function. Recently, Isidori et al. The development of a pathophysiology-oriented algorithm deed to avoid inappropriate treatments and support whether to start with TRT, PDE5-I only, or both is requested, in order to improve diagnosis and individualize a correct management [ 33 ].

On the same line, it has been shown that, in late-onset hypogonadism LOHTRT is able to improve central obesity in patients affected with metabolic syndrome MetS and glycometabolic control in patients with MetS and type-2 diabetes mellitus as well as to increase lean body mass, along with insulin resistance and peripheral oxygenation [ 3435 ].

Importantly, the increased waist circumference is the major determinant of MetS-associated hypogonadism, whereas androgen deprivation increases abdominal adiposity. Moreover, in cross-sectional studies longitudinal evidence has shown that low T is associated with a higher risk of subsequent development of MetS, although the reverse condition is also possible [ 3435 ]. It has not yet been clarified which are the possible factors in MetS responsible for the low T [ 34 ]. However, it should be recognized that the of studies on benefits of T supplementation is too limited to draw final conclusions [ 35 ].

The aim was to assess the association between testosterone therapy and all-cause mortality, myocardial infarction, or stroke. The absolute rate of events was Therefore, the use of testosterone therapy was associated with increased risk of adverse outcomes. No ificant difference in the effect size of testosterone therapy among those with and without coronary artery disease test for interaction, was reported [ 36 ].

A of related heart conditions are common causes of ED, including hypertension, dyslipidemia, atherosclerosis, heart disease and, among metabolic diseases, diabetes.

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Some types of physical trauma and injuries, especially those affecting the pelvic area or spinal cord, may cause nerve damage leading to erectile dysfunction. Orthopedic surgery, fistula surgery, and surgeries on prostate, colon, or rectal cancer can also ificantly contribute to the decrease of sexual function. All of these conditions are very frequent in elderly patients; comorbidities and polytreatment are a hard challenge in elderly people health management.

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In fact, sexual function requires abilities in movements which can be hampered. In the following section we will try to examine in detail some different diseases potentially able to interfere with sexual function in the elderly. Data collected from 1, randomly selected, community-dwelling men as part of the Florey Adelaide Male Ageing Study showed that with increasing age diabetes appears to be independently associated with moderate-to-severe ED [ 37 ]. In particular, several studies have shown that lower levels of glycated hemoglobin and therefore a good glycemic control are able to reduce the prevalence of ED and its severity [ 38 — 40 ].

Importantly, pulse pressure, that is, the difference between systolic and diastolic blood pressure, an index of arterial stiffness, was suggested to predict incident major cardiovascular events in patients affected with ED [ 4344 ]. In a consecutive series of 1, mean age ED may predict the onset of cardiovascular events from 2 to 5 years earlier; both conditions share the same pathogenetic mechanism, which is endothelial dysfunction [ 43 ].

Congestive heart failure CHF is another frequent disease in elderly patients potentially leading to ED. A sufficient control of symptoms is able to improve sexual dysfunction; if this approach does not work, PDE5-I are the first-line therapy [ 45 ]. Spinal cord injuries can be present in elderly men as a result of juvenile or recent trauma; PDE5-I are also safe and effective options for these men. The sexual desire, erectile, and ejaculatory functions are impaired after stroke. A lack of sexual desire is the major cause of an absence of sexual intercourse.

The specific locations of the stroke lesions, such as the left basal ganglia and right cerebellum, might be associated with sexual desire and ejaculation disorder, respectively [ 47 ]. In a survey on stroke patients mean age Of course, the complete or partial inabilities in moving are a further obstacle other than sexual dysfunction per sewhen elderly patients are affected with spinal cord injuries or stroke. This on turn can lead to depression, feelings of inutility, and impairment of the ability to recover.

Sexual dysfunction SD is also a frequent problem for multiple sclerosis patients and appears to be associated with gender. In fact women report more SD than men. Overall, this is another disease where the emotional dimension of SD is related to disability in the aged men [ 48 ]. Loss of desire and dissatisfaction with their sexual life are encountered in both genders and worsen concomitantly to the progression of Parkinsonian symptoms. Hypersexuality, erectile dysfunction, and problems with ejaculation are found in male patients.

Hypothalamic dysfunction is mostly responsible for the sexual dysfunction decrease in libido and erection in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy [ 49 ].

Optimal dopaminergic treatment should facilitate sexual encounters of the couple and appropriate counselling diminishes some of the problems i. At present ED is often underrecognized and undertreated in dementia and few data are available. Loss of desire can be present in different forms of dementia, whereas hypersexuality can be found in the early-to-moderate stages of frontal dementia.

In particular, hypersexual behavior may be a particular feature of behavioral variant frontotemporal dementia bvFTDwhich affects ventromedial frontal and adjacent anterior temporal regions specialized in interpersonal behavior. One patient, with early and predominant right anterior temporal involvement, was easily aroused by slight stimuli, such as touching her palms [ 52 ]. ED is often the cause of depressive disorders in elderly people [ 28 ]. Andropause, ED, and psychiatric disorders often share specific physical and psychological symptoms which complicate the clinical management of elderly men.

In particular, anxiety disorders and depression are more frequently linked to sexual dysfunction. Mood disorders may enhance the risk of ED in elderly people. Depressive symptoms are related to sexual dysfunction more frequently than anxiety symptoms.

However, according to some authors, ED in elderly psychiatric patients seems to be the expression of androgenic deficit rather than psychiatric symptoms per se [ 53 ]. Moreover, in elderly psychiatric patients, symptoms related to hypogonadism have a relationship with ED and both of them can influence sexual performance [ 54 ]. Recently some biopsychosocial risk factors have been considered to be responsible for ED. Erectile function worsens with increasing age and fat abdominal mass. Furthermore, the lack of a regular partner, alcohol abuse, and last but not least the presence of depressive and anxiety symptoms worsens its severity [ 37 ].

ED was shown to be closely linked to depressive symptoms, together with some factors such as life style, smoking, and alcohol [ 55 ]. Hypogonadism, ED, and premature ejaculation show ificant correlations with physical and mental health in men and in particular with quality of life, metabolic syndrome, cardiovascular diseases, and depressive symptoms [ 56 ]. Definitely concomitant ED and depression are really very high; the temporal relationship between these disorders may also be inverted. In other words, ED may be the cause or the consequence of depressive disorder.

Men with severe depression have a twofold probability for ED compared to nondepressed subjects [ 57 ]. Depression as the consequence of ED was assessed in a recent Canadian study together with the effect of sildenafil citrate, PDE5-I, in patients with untreated depressive symptoms [ 58 ]. ED in elderly psychiatric patients is not only found in depressive and anxiety disorders, but also can represent the complication of antipsychotic treatment in long lasting treatment of bipolar disorder. First generation of antipsychotics is more frequently involved in sexual performance worsening, compared to second-generation drugs [ 60 ].

Lastly, ED may represent a frequent symptom in somatization disorders, especially in men of over 45 years old [ 61 ]. Treatment strategies include nonpharmacological and pharmacological procedures. Nonpharmacological treatment includes counseling, life style changes, and medication changes, because a lot of drugs taken by old people can result in negative interference on sexual function.

An open communication with the patient and his partner is the first step to set realistic outcome goals.

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