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Erectile Dysfunction in Young Men—A Review of the Prevalence and Risk
Factors
Hoang Minh Tue Nguyen, BA, Andrew T. Gabrielson, BA, and Wayne J. G. Hellstrom, MD, FACS
ABSTRACT
Introduction: Erectile dysfunction (ED) is an important health concern that can significantly affect a man’s
psychosocial well-being. ED has traditionally been considered a disease of old age; however, contemporary
evidence suggests a growing incidence of ED in men younger than 40 years. The process of achieving an erection
is multifaceted; there are many potential mechanisms that can be disrupted. It is critical to identify the specific
causes of ED before proceeding with potentially costly and invasive therapeutic options. Advances in diagnostic
and treatment modalities offer opportunities to identify and manage young men with ED.
Aim: To provide an update on the prevalence and risk factors of ED in young men and to provide a framework
to guide clinicians in identifying and managing the affected young man.
Methods: Comprehensive review of the literature pertaining to ED in young men.
Main Outcome Measures: ED in young men was assessed by outlining the prevalence according to recent
epidemiologic studies. The pathophysiology, diagnostic considerations, risk factors, and etiologies were reviewed.
Results: Large multinational studies have estimated the prevalence of ED in young men to be as high as 30%.
Several studies have stratified the etiologies of ED into psychogenic and organic causes. Psychogenic etiologies of
ED include depression, anxiety, and partner-related difficulties. These patients tend to experience sudden onset
of symptoms, with decreased libido and good quality of spontaneous or self-stimulated erections. Organic eti-
ologies include vasculogenic, endocrinologic, neurogenic, iatrogenic, and structural components. These patients
usually experience gradual onset of symptoms and a low to normal libido. Conservative treatments such as
phosphodiesterase type 5 inhibitors continue to be the mainstay treatment.
Conclusions: ED in young men is an increasingly common condition. A careful diagnostic evaluation should
focus on the identification of any underlying etiology to ensure appropriate management of patients. Nguyen
HMT, Gabrielson AT, Hellstrom WJG. Erectile Dysfunction in Young Men—A Review of the Prevalence
and Risk Factors. Sex Med Rev 2017;X:XXXeXXX.
Copyright 2017, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
Key Words: Erectile Dysfunction; Young Men; Risk Factors; Prevalence; Treatment
INTRODUCTION
Erectile dysfunction (ED), as defined by the International
Consultation on Sexual Medicine, is the consistent and recurrent
inability to acquire or sustain an erection of sufficient rigidity and
duration to engage in satisfactory sexual intercourse.
1
Despite the
relatively high prevalence of ED, our knowledge of this condition
had remained limited until the 1970s. Since that time, advances
in molecular biology techniques have drastically improved our
understanding of penile physiology and the pathophysiology
underlying ED.
2e4
The process of achieving an erection involves
coordination among psychological, neurological, and vascular
pathways, which combine to facilitate a physiologic response in
the penile vasculature. In response to parasympathetic signaling
received from the pudendal and pelvic splanchnic nerve plexuses,
the penile cavernosal tissue releases nitric oxide (NO). NO in-
duces relaxation of cavernosal smooth muscle through a cyclic
guanosine monophosphateemediated decrease in intracellular
calcium. Filling of the cavernosal sinusoids obstructs venous
outflow from the penis by compression of the veins against the
tunica albuginea, allowing for maintenance of an erection. The
transient increase in cyclic guanosine monophosphate is termi-
nated by phosphodiesterase type 5 (PDE5). Detumescence is
achieved by adrenergic receptor activation, which leads to
rhythmic contraction of the cavernosal smooth muscle, pro-
moting a decrease in arterial diameter and thereby inducing
Received April 27, 2017. Accepted May 27, 2017.
Department of Urology,Tulane University School of Medicine, New Orleans,
LA, USA
Copyright ª2017, International Society for Sexual Medicine. Published by
Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.sxmr.2017.05.004
Sex Med Rev 2017;-:1e13 1
venous outflow.
2e4
Given the complexity with which the psy-
chological and physiologic pathways intersect, there are myriad
ways in which they can become disrupted and cause ED in
young men.
Historically, ED has been considered an age-dependent
disease, with most men developing signs and symptoms of ED
after 65 years of age. However, recent studies have demonstrated
an increasing incidence of ED in men younger than 40 years, and
this trend is likely underestimated because of under-reporting by
younger patients.
5
Until the 1970s, ED in men younger than 40
years was believed to be primarily of psychogenic origin. As such,
diagnostic evaluation of young men with ED before the 1970s
consisted almost exclusively of obtaining a psychosexual history
and offering treatments limited to behavioral therapy and
herbal supplementation.
6
Recent studies, which will be outlined
further in the following sections of this review, have reported
that as many as 87% of young men with ED also have an
organic (vascular, neurologic, hormonal, fibroproliferative, or
medication-induced) component to their condition.
7
ED is an important health concern that significantly affects
quality of life and can have a detrimental effect on a man’s
psychosocial well-being. ED is one of the few disorders that will
motivate young men to see an urologist; as such, there is a need
for increased awareness among practitioners. Although advances
in screening (ie, penile duplex ultrasound, endocrine evaluation,
etc) and treatment (ie, oral pharmacotherapy, intracavernosal
injection [ICI] therapy, and penile prosthesis) have improved ED
detection and management, it is not uncommon for young men
with sexual dysfunction to be dismissed without a proper workup
for non-psychogenic etiologies.
The goal of this review is to provide an update on available
data regarding psychogenic and organic disorders associated with
ED in young men. The authors also aim to provide a framework
to guide clinicians in identifying young men with ED and
improving the management of this growing patient population.
EPIDEMIOLOGY
The reported prevalence of ED in the general population has
been highly variable because of differences in ED criteria,
population selection, and modalities used to measure erectile
function. It has been well described in the literature that the
prevalence of ED is positively correlated with age, with 52% of
men 40 to 70 years old with some degree of ED.
8
One American
cross-sectional study found a fourfold increase in the prevalence
of ED in men in their 70s compared with men in their 20s.
8
These findings are consistent with another multinational study
involving 27,839 men in eight countries that demonstrated the
prevalence of ED in men in their 70s to be 37% compared with
11% in men in their 30s and 8% in men in their 20s.
9
One
age-stratified study conducted on 948 Turkish men with an five-
item International Index of Erectile Function score lower than 21
used psychiatric evaluation, nocturnal penile tumescence with
the RigiScan, and penile Doppler ultrasound to determine the
etiology of ED. The investigators stratified patients based on
whether they were older or younger than 40 years. It found that
85.2% of the 526 men younger than 40 years had psychogenic
ED as the primary etiology compared with 14.8% exhibiting an
organic cause of their ED (arteriogenic, venogenic, neurogenic,
endocrinologic, drug-induced, or mixed). This is in stark contrast
to the group of patients older than 40 years, which presented a
40.7% prevalence of psychogenic ED and a 59.3% prevalence of
organic ED.
10
Interestingly, another retrospective study conducted at the
University of CaliforniaeSan Francisco found that only 13% of
men younger than 40 years (N ¼100) had exclusively psycho-
genic ED.
7
The seemingly contradictory findings from these
studies might be reconciled by differences in the classification of
pure vs mixed etiologies of ED. Researchers in Florence reported
that the percentage of men younger than 40 years consulting for
ED in their clinic had increased from 5% in 2010 to more than
15% in 2015.
11
Another population-based study was conducted
in Switzerland with more than 2,500 young men 18 to 25 years
old. Participants completed a sexual function survey while
undergoing medical screening for the military. This study found
that as many as 30% of participants had varying degrees of ED.
12
When taken together, studies support the notion that ED is
increasingly becoming a common concern in young men, and as
such, it is important to improve awareness and appropriate
screening by clinicians.
PATHOPHYSIOLOGY AND DIAGNOSIS
The pathogenesis of ED is often multifactorial, involving
interplay between physiologic and psychological stimuli. The
International Society for Sexual Medicine (ISSM) stratifies the
mechanisms underlying ED into two major components: organic
and psychogenic. Patients with psychogenic ED tend to experi-
ence sudden onset of symptoms, with decreased libido and good
quality spontaneous or self-stimulated erections. In contrast,
organic ED is often associated with a gradual onset of symptoms
and a normal libido.
13
However, it is important to note that
organic and psychogenic subdivisions merely represent a spectrum
of disease. The etiology of ED in young men is often multifac-
torial, involving psychogenic and organic components (Table 1).
The organic component can be further subdivided into
vasculogenic, endocrinologic, neurogenic, and structural etiol-
ogies. Patients most often develop vasculogenic ED as a conse-
quence of generalized atherosclerosis.
14
Advanced atherosclerotic
disease can occlude the arterial vasculature supplying the corpora
cavernosa, thereby decreasing perfusion pressure and ultimately
decreasing erectile rigidity. Likewise, inadequate venous occlu-
sion from trauma, aging, anxiety, or fibroelastic changes in the
penis can contribute to poor erectile function.
15,16
A patient with
suspected vasculogenic ED can be evaluated for arterial inflow,
blood retention, and venous outflow using ICI and stimulation,
penile duplex Doppler ultrasonography, or penile angiography.
Sex Med Rev 2017;-:1e13
2Nguyen et al
Clinicians also can selectively use penile magnetic resonance
imaging; however, the former modalities have been demonstrated
to better detect vasculogenic abnormalities.
17
Different endocrine disorders also have been implicated in the
development of ED, including alterations in the hypothalamic-
pituitary axis, adrenal insufficiency, diabetes, hyperprolactinemia,
and hyper- and hypothyroidism.
18
These disorders have demon-
strated an association with loss of libido and erectile response to
sexual stimuli. Patients with a suspected endocrinologic etiology of
ED need to be evaluated for hypogonadism and thyroid
dysfunction.
Given the tight link between neuronal stimulation and
vascular response in the penis, there are myriad neurogenic
causes of ED, including traumatic spinal cord injury (SCI) and
cavernous or pudendal nerve injury after surgery or pelvic frac-
ture.
19
One of the most common iatrogenic causes of neurogenic
Peyronie’s disease (PD) is damage to the cavernous or pudendal
nerves during radical prostatectomy. The advent of nerve-sparing
radical prostatectomy has since lowered the incidence of ED
from almost 100% to 30% to 50%.
20
Diagnosis of neurogenic
ED can be difficult, because few sensitive, specific, and reliable
tests exist. Penile glans biothesiometry involves placement of an
electromagnetic device onto the penile shaft and glans and then
measuring sensory perception in response to vibratory stimuli of
changing intensity.
21
Unfortunately, this procedure does not
adequately simulate physiologic changes that occur in the penis
during erection, and high intraindividual variability limits its use
in clinical practice.
17
The bulbocavernosus reflex test measures
bulbocavernosus muscle response to electrode stimulation.
Unfortunately, the utility of this test is confined to the pudendal
nerve, and studies have found that most patients with neurogenic
ED exhibit damage to the dorsal penile nerve.
6
Structural causes
of ED are less common; however, there is a documented
association between PD and impotence.
22
Similar to the organic causes of ED, the psychogenic
component can be multifaceted and difficult for clinicians to
treat. The ISSM subdivides psychogenic ED into generalized and
situational etiologies. Generalized causes of psychogenic ED can
include age-related decreases in libido and chronic disorders of
sexual intimacy. Situational causes of psychogenic ED can
involve psychological distress (ie, depression, job instability, post-
traumatic stress disorder), performance anxiety, and partner-
related difficulties (ie, unstable interpersonal relationship).
Obtaining a thorough psychosocial history is critical to identi-
fying risk factors for patients with suspected psychogenic ED.
17
Because many ED cases involve psychogenic and organic
components, many young men might experience a vicious cycle
of emotional and physical stress associated with their ED.
Because life stressors and pre-existing comorbidities can
contribute to the development of ED, erectile problems can
generate anxiety that exacerbates the situation. Furthermore, a
patient’s concerns over his erectile capacity and durability could
potentiate a previously innocuous organic cause of ED. The
patient’s self-esteem undoubtedly becomes negatively affected for
himself and his partner. As a result, patients might modify their
behavior to avoid settings of intimacy or abstain from sexual
encounters altogether. The astute clinician can interrupt this
cycle through effective counseling of patients. This can be
accomplished by reassuring the patient that ED is very common
in the male population and emphasizing that there are many
effective treatments available with minimal side effects. There
also should be a discussion of the interconnectedness of life
events, pre-existing health conditions, and the development of
ED. By addressing the combined role of ED therapy and psy-
chosexual counseling in the management of ED, the physician
can help assuage the patient’s concerns.
23
These etiologies and risk factors underlying ED, particularly in
young men, are elaborated further in the following sections.
ETIOLOGIES AND RISK FACTORS
Vasculogenic and Structural Conditions
Vascular and structural risk factors for young men with ED
include focal arterial occlusive disease, subclinical endothelial
dysfunction, and PD. There has been much speculation as to
Table 1. Etiology and risk factors of erectile dysfunction in young
men
Vasculogenic and structural conditions
Focal arterial occlusive disease
Subclinical endothelial dysfunction
Peyronie’s disease
Endocrine disorders
Thyroid dysfunction
Diabetes
Klinefelter syndrome
Cryptorchidism
Congenital hypogonadotropic hypogonadism
Acquired hypogonadotropic hypogonadism
High soy diets
Neurogenic conditions
Multiple sclerosis
Epilepsy
Intramedullary nailing of femoral fractures
Lumbar spine procedures
Spinal cord injury
Medication side effects
Antidepressants
Non-steroidal anti-inflammatory drugs
Neuroleptics
Antiepileptics
Finasteride
Intrapsychic disorders
Depression
Anxiety
Relational components
Conflicts
Sex Med Rev 2017;-:1e13
Erectile Dysfunction in Young Men 3
whether young men develop vascular ED because of subclinical
perineal trauma. A study by Lehmann et al
24
supported these
speculations by looking at 91 men with ED, and without a history
of perineal trauma, who underwent penile angiography. In that
study, young men were more likely to have focal arterial occlusive
disease and exposure to subclinical trauma. This concept has been
demonstrated in the bicycling community. Cross-sectional studies
have noted that young men who ride bicycles more than 3 hours
per week have an increased risk of developing ED. This phe-
nomenon is believed to be secondary to perineal pressure from
bicycle seats that lower peak cavernosal artery systolic pressure to
zero and temporarily occlude penile vessels. This leads to focal
arterial occlusive disease by causing arterial insufficiency, resulting
in an upregulation of connective tissue synthesis and inhibition of
vascular smooth muscle growth. Ultimately, this disrupts func-
tional penile compliance, culminating in ED.
25
In addition, subclinical endothelial dysfunction, determined
by blood pressure, C-reactive protein level, total cholesterol and
triglyceride levels, and carotid intima-media thickness, can be a
risk factor for ED. In a study by Yao et al,
26
young men with
ED—but a low risk for cardiovascular (CV) disease—were
compared with young men without ED. Men with ED were
found to have increased systolic blood pressure, C-reactive
protein level, total cholesterol and triglyceride levels, carotid
intima-media thickness, Framingham risk scores, and lower flow-
mediated brachial vasodilation, although all these values were
within normal limits. This study suggests that many young men
with ED might not have overt clinical CV disease but still have
subclinical CV factors that predispose them to ED.
Another risk factor for ED in young men is PD, which is
believed to develop from repeated (micro)trauma to the tunica
albuginea with the formation of a plaque that results in penile
curvature when erect. Although PD is associated with aging, it
has been estimated that as many as 8.2% of patients with PD are
younger than 40 years, and 21% of these young men have ED.
27
The onset of PD in young men is often acute.
28
Although rare,
PD also can occur in teenagers. In a study of 32 teenagers with
PD, 37% had ED. Furthermore, this group was more likely than
older men with PD to present with multiple Peyronie plaques.
29
PD can contribute to ED by causing veno-occlusive dysfunction
and impaired cavernosal arterial flow.
30
Moreover, PD is asso-
ciated with a significant physical and psychological burden,
which contributes to the multifactorial etiology for ED.
31
Rosen
et al
32
conducted a qualitative study on men with PD and
observed that four core domains had an impact on sexual and
psychosocial health in these patients: namely, sexual function,
pain and discomfort, self-image, and social isolation. These
studies suggested that PD can contribute to mixed risk factors of
psychogenic and organic etiologies for the development of ED.
Endocrine Disorders
Endocrinopathies can affect erectile function; however, they
are an uncommon source of ED in young men. For example,
testosterone deficiency is a more common cause of ED in older
men. Only 4% of men younger than 50 years with ED were
found to have low testosterone; however, it is unclear whether
this was contributing to ED in this population.
27
In certain
populations of young men, such as those with HIV, there is a
premature decrease in serum testosterone levels. In one study,
16% of young men with HIV were observed to have significant
testosterone deficiency.
33
When present, hormonal causes of ED in young men can
include hyperthyroidism, diabetes, Klinefelter syndrome (KS),
cryptorchidism, congenital hypogonadotropic hypogonadism
(CHH), and acquired hypogonadotropic hypogonadism (AHH).
First, men with thyroid dysfunction usually have ED and, in
general, have poorer erectile function than disease-free men.
34
Krassas et al
35
found that among Greek men with thyroid
dysfunction, 63% of men with hypothyroidism and 70% with
hyperthyroidism had some element of ED compared with 34%
in the control group. The mechanism relating thyroid dysfunc-
tions to ED remains unknown.
17
In animal models of hyper-
thyroidism, it was found that hyperthyroidism impaired
NO-dependent relaxation of the corpora cavernosa.
36,37
Thus,
hyperthyroidism could cause ED based on a direct effect of
thyroid hormone on penile function. Hypothyroidism might be
associated with lower levels of serum testosterone, dehydroepi-
androsterone sulfate, and dehydroepiandrosterone, thus contrib-
uting to ED through decreased bioavailability of testosterone.
38
Second, diabetes has a well-established and strong association
with ED. In some populations, the prevalence has been reported
in up to 75% of men with diabetes.
17
Bortolotti et al
39
observed
in their prospective study that the incidence of ED in patients
with diabetes was 68 cases per 1,000 patients per year compared
with 25.9 cases per 1,000 patients per year in the general pop-
ulation. As the prevalence of early-onset diabetes increases, this
major risk factor will likely contribute more to the prevalence of
ED in young men. Interestingly, although metabolic syndrome is
associated with ED in older men, no association has been found
for men younger than 50 years.
40
KS is another risk factor for ED. The prevalence of KS is 1 in
500 to 1,000.
26
Many men with KS do not have the classic
appearance of eunuchoid body habitus, micro-orchidism, and
micropenis. There is a broad phenotypic spectrum with many
men appearing essentially normal. Individuals with KS often
present to urology clinics with infertility, poor libido, or ED.
Men with KS have low testosterone and increased follicle-
stimulating hormone, luteinizing hormone, and estradiol.
41
Corona et al
42
examined 1,386 consecutive patients presenting
with sexual dysfunction and observed that 23 (1.7%; average
age ¼40 years) had KS. Of those men, 22.7% with KS had
severe ED.
38
In an earlier study using a non-validated ques-
tionnaire on sexual function in 40 men with KS (average age ¼
32.2 years), 2.5% of them had severe ED.
43
When patients with
KS were compared with testosterone-matched control subjects,
ED was not found to be associated with the syndrome.
42
This
Sex Med Rev 2017;-:1e13
4Nguyen et al
suggests that ED in KS is more likely to be associated with
hypogonadism than specifically with the syndrome.
41
Cryptorchidism also can lead to low testosterone levels,
thereby contributing to ED. A study of 49 patients with crypt-
orchidism who had orchiopexy for 10 months to 13 years found
that these young men were less sexually active than matched
controls.
44
Another disease that can cause ED is CHH, including
Kallmann syndrome, a rare disease with a prevalence of 1 in
4,000 to 10,000.
27
Patients usually present with pubertal fail-
ure.
45
In a study by Aydogan et al
46
of 39 men with CHH (mean
age ¼21.9 years), before treatment with testosterone replace-
ment therapy, 100% experienced sexual dysfunction (erectile
function was not specifically mentioned but was addressed as part
of the Arizona Sexual Experiences Scale). Testosterone replace-
ment therapy improved sexual functions in these patients.
However, micropenis is usually a primary sexual hindrance in
these patients.
47
Similar to CHH, AHH is frequently associated with ED and
loss of libido. AHH can have various causes including prolacti-
noma, head trauma, pituitary surgery, infundibular or sellar cysts,
drug and alcohol abuse, hemochromatosis, and sarcoidosis.
48
A diagnosis of AHH can be made by measuring serum testos-
terone, follicle-stimulating hormone, and luteinizing hormone
levels and by magnetic resonance imaging of the sella in cases
with high clinical suspicion.
49
Among the endocrinopathies, high soy diets have been con-
jectured to be linked to ED. Daidzein is a soy isoflavone and a
phytoestrogen that has been studied in animal models. Large
amounts of daidzein cause histologic changes in the penile
structure of rats, including a decrease in smooth muscle and
elastic fiber content and an increase in collagen.
50
When juvenile
rats were exposed to daidzein in relatively large amounts, they
were found to have impaired erectile function in a dose-related
manner in adulthood.
51
Apart from the animal models, there
has been one case report of a 19-year-old man who developed
sudden onset of loss of libido and ED after ingestion of large
quantities of soy-based products; he eventually regained full
sexual function 1 year after cessation of soy consumption.
52
Neurogenic Conditions
Normal erectile function is largely dependent on the neuro-
logic system. Erectile physiology is deeply involved with spinal,
supraspinal, peripheral, somatic, and autonomic pathways.
In men younger than 40 years, common neurologic causes of ED
include multiple sclerosis (MS), epilepsy, intramedullary nailing
of femoral fractures, lumbar spine procedures, and SCI.
27
In a
large population-based study of men with MS using a national
database, of whom 28.4% were younger than 40, men with MS
were 2.2 times more likely to have ED.
53
The etiology of ED in
patients with MS is complicated and likely involves a mix of
cognitive decline, nerve dysfunction, illness-related stress, and
possible inflammation-dependent endothelial dysfunction.
17
Epilepsy is another risk factor for ED. In a large population-
based study, men in their 30s with ED were 3.04 times more
likely to have been diagnosed with epilepsy.
54
The etiology of
ED in patients with epilepsy also is complicated and not well
elucidated. In most studies involving epilepsy and sexual
dysfunction, endocrine abnormalities were found in men with
epilepsy, especially in men treated with liver enzyme-inducing
epileptics. However, in most of these studies, concurrent
assessment of functioning and desire was not performed. As such,
the effect of the hormonal abnormalities on sexual functions
remains unclear.
55
In some of these studies, the endocrine
abnormalities and/or hyposexuality occurred before the start of
antiepileptic drugs. Moreover, in certain cases, treatment of
seizures with surgery improved sexual functioning of patients.
55
The etiology of ED in patients with epilepsy is likely to
involve a mix of neurologic, psychiatric, cognitive, endocrine,
iatrogenic, and psychosocial factors.
55
Repair of femoral fractures also has been associated with ED.
A study of young men (average age ¼27.1 years at time of
trauma) found that men with intramedullary nailing of femoral
heads had a higher likelihood of ED compared with those with
tibial fractures—up to 40.5%.
56
The postulated mechanism is
due to countertraction on the fracture table that leads to
pudendal neurapraxia.
27
In addition, neurologic damage can occur during lumbar spine
surgeries and contribute to ED. In a prospective study of patients
younger than 50 years who underwent lumbar spine decom-
pression, 34.3% of them developed ED after surgery. Moreover,
those who had greater neurologic symptom etiology were at
higher risk for persistent sexual dysfunction, suggesting likely
irreversible nerve damage from lumbar spine pathology.
57
Men
who have such lesions and undergo corrective surgical procedures
need to be advised about the significant higher probability of ED
associated with such interventions.
Similarly, SCI is a risk factor for ED in young men. A study of
two randomized clinical trials of oral PDE5 inhibitors involving
248 men with SCI and ED found that the average age of patients
with SCI and ED was 37.7 years.
58
Another recent systematic
review and meta-analysis on treatment with ICIs in 392 men
with SCI and ED found that the median age was 35.1 years,
highlighting that SCI can be a significant contributor to the
incidence of ED in younger men.
59
The pathophysiology of
impairment of erectile function by SCI depends on the type of
SCI in location within the spinal cord and completeness of the
injury.
59
These impairments can involve psychogenic erections
and/or reflexive erections.
59
Medication Side Effects
Many medications used by young men are associated with
ED, including antidepressants, non-steroidal anti-inflammatory
drugs, neuroleptics, antiepileptics, and finasteride.
Sex Med Rev 2017;-:1e13
Erectile Dysfunction in Young Men 5
Selective serotonin reuptake inhibitors are well recognized to
cause sexual dysfunction but are not known to induce ED
specifically. In a randomized, placebo-controlled, double-blinded
study of men with an average age of 29.5 years using citalopram
or fluoxetine, the medications did not directly affect penile
erection as objectively assessed by RigiScan Plus (GOTOP
Medical, St Paul, MN, USA). However, impairment in the
subjective assessment of erectile function was observed with
citalopram.
60
Selective serotonin reuptake inhibitors, in partic-
ular paroxetine, also can inhibit cholinergic receptors and NO
synthase, contributing to ED.
61
In addition, selective serotonin
reuptake inhibitors have been observed to downregulate the
hypothalamic-pituitary-testis axis in men with depression.
62
Serotonin levels can be predictive of other sexual dysfunctions
in young men (eg, premature ejaculation).
63
Moreover, ED has
been reported in patients using other psychotropic drugs, such as
lithium and benzodiazepines.
64
Furthermore, regular non-steroidal anti-inflammatory drug
usage is associated with ED, more than what is expected for age
and comorbidities (adjusted odds ratio ¼1.38).
65
McKanna
et al
66
suggested that prostaglandins made by cyclooxygenase-2
in the vas deferens could be essential for penile erection. Inhi-
bition of this process by the use of non-steroidal anti-inflam-
matory drugs could contribute to ED.
65
In addition, all
neuroleptics are notorious for causing ED, in part because of
increased prolactin levels.
67
Antiepileptic drugs such as top-
iramate and pregabalin also are associated with ED, likely from a
vasculogenic mechanism.
68
Another medication frequently used by young men is finas-
teride (Propecia, Merck, Kenilworth, NJ, USA), which is indi-
cated for the prevention and reversal of male pattern baldness. In
a study of 1,553 young men (18e41 years of age), 1.4% of those
using finasteride had ED, whereas only 0.9% of men exposed to
placebo had ED.
69
A study of men 21 to 46 years old who used
finasteride for male pattern baldness and developed new-onset
sexual dysfunction exhibited persistent sexual side effects, with
92% of patients reporting ED.
70
Dutasteride (Avodart, Glax-
oSmithKline, Philadelphia, PA, USA) is another 5a-reductase
inhibitor that works similarly to finasteride and is commonly
prescribed off-label for androgenetic alopecia. A recent meta-
analysis involving 17 randomized clinical trials and 46,733
patients found that there were no differences between finasteride
and dutasteride in risk for ED.
71
As such, dutasteride is another
risk factor for ED.
Intrapsychic Disorders
There is a well-known association between sexual dysfunctions
and psychiatric conditions. Depression and anxiety are the main
intrapsychic risk factors for ED in young men.
Population-based studies have found a cross-sectional associ-
ation between ED and depressive symptoms.
72e75
In addition,
among men seeking help for ED, depression has been associated
with a greater severity of ED.
76,77
The relation between ED and
depression also seems to be a two-way street. Although ED is
associated with occurrence of depression, treatment of ED with
PDE5 inhibitors has been associated with improvement in
depressive symptoms.
78
Although most of these studies were not
designed to assess the relationship between ED and depression
specifically in young men, the few studies available in younger
populations have confirmed these results. In a population-based
study in Switzerland of more than 2,500 men 18 to 25 years old
who participated in a sexual function survey while undergoing
medical screening for the military, the prevalence of ED was
30%. Among the correlated conditions with ED, mental health
demonstrated an independent association, apart from a shorter
sexual lifespan, impaired physical health, and the use of medi-
cations without a medical prescription.
12
The results from this
study were prospectively extended to 3,700 men assessed at
baseline and 15.5 months later. Among the predictors, including
drug abuse, lifestyle, body mass index, and perceived physical
fitness, only depression and perceived impairment in mental
health were associated with the development and persistence of
ED.
79
In an internet-based study of a sample of 844 North
American medical students with an average age of 25.7 years, ED
was reported by 13%; ED also had a significant association with
depressive symptoms, whose frequency increased as ED severity
increased.
80
In a retrospective population-based study of
approximately 3,500 Finnish men 18 to 48 years old, depression
was found to be a significant predictor of ED. Moreover, this
study demonstrated that anxiety played a significant part and that
men with more sexual experiences had ED less frequently,
suggesting the positive influence of sexual experience and self-
confidence.
81
As mentioned earlier, anxiety can be involved in the patho-
genesis of ED, often at the initiation of sexual life.
11
Anxiety can
lead to a disproportionate focus on the quality of erection,
creating a cognitive distraction that adversely affects arousal and
subsequently the erection itself.
82e84
In addition, at least one
sexual failure can result in anxiety, with loss of sexual confidence,
increasing fear, and contributing to the avoidance of sexual
experiences that ultimately increase the probability of future
failures, creating a vicious cycle.
82
Excessive concerns for phys-
ical, particularly genital, self-image also can create a cognitive
distraction that diverts psychological resources from sex, leading
to impaired functioning.
85,86
A recent study of 367 military
personnel younger than 40 years supported this cognitive
explanation by associating a diminished male genital self-image
with sexual anxiety and a higher probability of ED.
87
Relational Components
The association between ED and deterioration of a couple
relationship is well documented. In a study of 1,873 men 18 to
44 years old consulting for sexual dysfunction, men reporting
conflicts within the couple were characterized by a broad spec-
trum of sexual symptoms, including a severe degree of ED.
88
There seems to be a bidirectional relation between ED and
distress in couple relationship. In the Female Experience of
Sex Med Rev 2017;-:1e13
6Nguyen et al
Men’s Attitudes to Life Events and Sexuality (FEMALES) study,
293 female partners of men complaining of ED were surveyed on
the quality of their sexual experience. Women in this study
reported a significant decrease in satisfaction of sexual intercourse
after the onset of ED in their partners. Sexual desire, arousal,
satisfaction, and orgasm were improved in the women whose
partners used PDE5 inhibitors.
89
In a different study of 632
sexually active couples in which the male partner was 18 to 80
years old, ED was confirmed as a risk factor for female sexual
dysfunction, including deterioration in arousal, sexual satisfac-
tion, and orgasm and an increase in sexual pain.
90
PDE5 inhibitor effectiveness in improving male and female
sexual function has been confirmed by a number of randomized
clinical trials that compared the efficacy of PDE5 inhibitor vs
placebo in enhancing couples’sexual function.
91e95
Recently, a
study compared the use of vardenafil 10 mg oral tablets with the
use of this drug in combination with cognitive-behavioral sexual
therapy in 30 couples with male partners having ED. The study
showed that there was improvement of male sexual function in
the two study arms, but this improvement was sustained only in
the couples receiving vardenafiland sex therapy.
96
Moreover,
female sexual satisfaction and function were improved only in the
arm with drug and sex therapy, suggesting that additional rela-
tionship therapy works better and lasts longer than only the use
of an ED medication.
11
Although these studies included men younger than 40 years, it
should be noted that the mean age of enrolled men is often
shifted toward middle age. It is conceivable that the effect of
couple relationship on ED is different in younger men because of
the lack of experience of both parties, fear of emotional
involvement, limited privacy, and/or concern for undesired
pregnancy.
11
ED AS A SURROGATE MARKER FOR OTHER
UNDERLYING DISEASE PROCESSES
Recent evidence has suggested a strong association between
ED and other conditions such as CV disease, diabetes, hyper-
tension, and metabolic syndrome.
97
Several studies have
demonstrated an association between ED and CV disease, the
most notable of which was the Olmsted County Study of
Urinary Symptoms and Health Status Among Men. This study
involving 1,402 men found that ED in young men was a
statistically significant predictor of future CV events compared
with men without ED. It was suggested that ED and coronary
artery disease might be different manifestations of the same
vascular disease process.
98
Another study involving 300 patients
with documented coronary artery disease found that as many as
70% of patients reported ED before symptoms of coronary artery
disease.
99
This finding is consistent with another study con-
ducted by Huang et al,
100
which evaluated the prevalence of CV
risk factors in a young population of men 18 to 40 years old
reporting weak masturbatory erection. Their study found that
those men with weak masturbatory erection had a higher
prevalence of CV risk factors such as endothelial dysfunction and
insulin resistance compared with their non-ED counterparts.
This suggests that weak masturbatory erections also might be a
sign of early CV risk in young men.
ED also has been tightly correlated with the presence and
severity of metabolic diseases such as diabetes. ED and diabetes
share many pathophysiologic similarities such as microvascular
damage, neuropathy, and endothelial dysfunction. Dysregulation
of NO production in the presence of chronic hyperglycemia seen
in diabetes can mirror the pathophysiologic mechanisms that
underlie ED.
101
Several studies have supported the association
between diabetes and ED. One study screened 1,417 men for
ED and assessed their glycemic control with fasting glucose
measurement. Interestingly, this study found a prevalence of
11.5% of undiagnosed diabetes in men with ED compared with
only 2.8% in men without ED.
102
In addition, another popu-
lation study found a threefold increase in the probability of
developing ED in patients with diabetes.
8
These data support the
notion that ED could represent a sentinel marker of metabolic
dysfunction. Regardless of the etiology of ED, all patients should
receive screening and follow-up for CV and endocrinologic dis-
eases, especially if the ED presents at a young age.
MANAGEMENT
After diagnosing a young man with ED, physicians have
multiple options for treatment, including behavioral therapy, oral
medical therapy, ICI therapy, intraurethral suppository, penile
revascularization, inflatable penile prosthesis, hormone supple-
mentation therapy, and stem cell (SC) therapy
103
(Table 2).
Oral therapy with PDE5 inhibitors is the most popularly used
treatment with a high success rate because of its effectiveness and
ease of use. PDE5 inhibitors remain first-line drug therapies for
ED.
104
The four main PDE5 inhibitors that are currently
marketed include sildenafil (Viagra, Pfizer, New York, NY,
USA), tadalafil (Cialis, Lilly, Indianapolis, IN, USA), vardenafil
(Levitra, GlaxoSmithKline), and avanafil (Stendra, Vivus,
Mountain View, CA, USA). Oral PDE5 inhibitors can be used
in men with psychogenic ED, SCI, mild venous leak, or mild
arterial insufficiency to overcome these deficits.
58,103
It is
important to recognize the side effect and safety profiles of PDE5
inhibitors to maintain patient compliance and safety. PDE5
inhibitors have additive effects on the NO pathway, resulting in
their contraindication in patients taking any form of nitrates,
Table 2. Management of young men with erectile dysfunction
Oral therapy with phosphodiesterase type 5 inhibitors
Intracavernosal injection therapy
Intraurethral suppository
Penile revascularization
Inflatable penile implant
Hormone supplementation therapy
Stem cell therapy
Sex Med Rev 2017;-:1e13
Erectile Dysfunction in Young Men 7
because they can cause life-threatening hypotension. Although
this is less of a worry for young patients with ED, it is recom-
mended by the American Heart Association consensus panel that
nitrates not be administered within 24 hours of sildenafil use.
105
Common side effects include variable effects on olfaction, insulin
action, platelet aggregation, color changes in vision, and vascular
tone due to cross-reactivity of PDE5 inhibitors and other PDE
receptors.
106
Although it is widely accepted that there are no
significant differences in efficacy and safety profiles among the
four PDE5 inhibitors, avanafil has shown potential in decreasing
typical side effects in younger men.
107
Other forms of therapy include ICI therapy and intraurethral
suppository. The only injectable medication for ED approved by
the Food and Drug Administration (FDA) is alprostadil
(Caverject Impulse, Pfizer), a synthetic form of prostaglandin E1.
Alprostadil (MUSE, Meda, Somerset, NJ, USA) also is available
in suppository form for intraurethral administration and as an
intraurethral cream. These are effective alternative methods to
deliver erectogenic drugs locally to the penis. Alprostadil works
by binding to specific receptors on smooth muscle cells, activates
intracellular adenylate cyclase to produce cyclic adenosine 30,50-
cyclic monophosphate, and induces cavernosal smooth muscle
relaxation, resulting in tumescence of the penis.
108
The efficacy
of alprostadil has been demonstrated in phase 2 and 3 clinical
trials.
109,110
One multicenter study demonstrated significant
long-term efficacy and durability of alprostadil in the treatment
of ED. Of the 1,161 men treated in the study, 74% reported
overall improvement in erectile function on most clinical end
points even after adjusting dose strength to their individual
responsiveness. Alprostadil can be used alone or in combination
with papaverine and phentolamine. Once monotherapy with
alprostadil fails, combination therapy exhibits a synergistic
mechanism that can elicit maximal erectile responses.
111e113
Combination therapy also can help avoid side effects of mono-
therapy, such as penile pain with alprostadil or scar formation
with papaverine. For efficacy, phentolamine plus papaverine
(bi-mix) is found to be more effective than intracavernosal
papaverine, whereas bi-mix might be as effective as intra-
cavernosal alprostadil.
114
Adding alprostadil to the bi-
mix (tri-mix) might be more effective than the bi-mix.
114
Patients are usually administered a small dose of alprostadil to
inject, particularly in patients with non-vasculogenic ED. Side
effects of ICI include pain at the injection site, hematoma or
ecchymosis, prolonged erection or priapism, and penile fibrotic
lesions.
115
Disadvantages of ICI include lack of spontaneity with
the partner and shortened half-life of medication if not
refrigerated.
106
In addition to pharmacologic therapies, penile revasculariza-
tion is a highly specific surgical procedure. Microvascular arterial
bypass penile revascularization is usually offered to men 20 to 40
years old with pure arterial flow insufficiency. The procedure
uses a donor artery (the inferior epigastric artery) to anastomose
it to a recipient artery (eg, the dorsal penile artery), bypassing the
penile arterial blockage.
116e120
The best candidates for this
procedure are younger patients with a history of blunt trauma to
the penis, perineum, or pelvis with a defined arterial lesion by
imaging studies, and intact neurologic, psychologic, and hor-
monal workup.
116e120
Complications of the surgery include
traumatic disruption of the anastomosis from blunt pelvic
trauma, decreased penile sensation, pain secondary to injury to
the dorsal nerves, and, rarely, glans hyperemia.
116
As techniques
of dissecting the dorsal artery from the dorsal penile neuro-
vascular bundle improved, the risks of these complications have
decreased.
106
In addition, inflatable penile prostheses are a tertiary option to
treat ED. Although traditionally viewed as a last-resort treatment
for men whose previous treatments have failed, penile prostheses
can provide substantial benefit to young men who have various
conditions such as post-priapism, fractured penis, or pelvic floor
trauma. The ideal penile prosthesis replicates the penis in normal
flaccidity and tumescence. The device that closely matches this
ideal is a three-piece inflatable device.
106
The shortcoming of
penile prostheses includes the lack of tumescence of the glans and
possible penile length loss, particularly after a prior implant was
removed for infection.
For young men with signs and symptoms of hypogonadism
and subnormal serum testosterone levels, testosterone supple-
mentation can be offered after a discussion of the risks and
benefits of testosterone in young fertile men. Testosterone has its
major effect on libido rather than ED.
121e123
Currently, there
are three FDA-approved methods of testosterone supplementa-
tion: transdermal, intramuscular depot injection, and injectable
pellets into the upper buttocks. The most common side effect of
topical testosterone preparations is local skin irritation. Other
side effects include emotional lability, breast tenderness, infer-
tility, polycythemia, and potential CV risks.
124,125
An alternative
for testosterone supplementation for men with secondary
hypogonadism is clomiphene (Clomid, Sanofi-Aventis, Bridge-
water, NJ, USA). Although clomiphene is not approved by the
FDA for the treatment of secondary hypogonadism, it has been
making its way into the mainstream for men with these diseases.
Clomiphene works by antagonizing the hypothalamus and the
pituitary gland, resulting in an increase of gonadotropin-releasing
hormones, luteinizing hormone, and follicle-stimulating
hormone. In consequence, clomiphene stimulates testosterone
production and maintains spermatogenesis and testicular volume
in men with secondary hypogonadism. Compared with pure
testosterone therapy, clomiphene has the advantage of not
unfavorably affecting seminal parameters in symptomatic hypo-
gonadal men seeking to maintain fertility.
126
This makes
clomiphene an ideal choice for treatment of ED in young men
with secondary hypogonadism.
SC therapy is starting to generate interest to treat ED in young
men whose previous treatments have failed. A rat model indi-
cated that injecting embryonic SCs into rats with neurogenic ED
improved their erectile function.
127
In a human study, ICI of
Sex Med Rev 2017;-:1e13
8Nguyen et al
umbilical cord SCs in seven men with diabetes mellitus improved
their erectile function.
128
Of importance, there still needs to be
randomized clinical trials on a large scale to validate these early
results and determine their overall effects in men. Hence, at this
time SC therapy should not be offered to the general population,
unless it is a registered government trial with placebo and
treatment arms and under experimental oversight. Patients
should not be charged money for such studies. Nevertheless, SC
therapy is an exciting new possibility for young men who do not
respond to current treatments.
CONCLUSION
ED has historically been referred to as a condition of older
men; however, recent epidemiologic studies have shown that ED
prevalence is significant in younger men, too. Recent studies
have demonstrated that the prevalence of ED in this population
might be underestimated due to under-reporting and could be as
high as 30%. This suggests that ED is becoming increasingly
more common in younger men and that clinicians need to
expand their awareness and screening for ED in this specific
population.
Although previously hypothesized to be almost exclusively
psychogenic in nature, ED in young men is currently recognized
to have a number of organic risk factors. Vasculogenic and
structural changes such as focal arterial occlusive disease, sub-
clinical endothelial dysfunction, and PD can contribute to ED by
impeding arterial flow or causing veno-occlusive dysfunction.
The complexity of this disorder also calls for vigilant screening
and counseling for men engaging in at-risk activities for ED, such
as prolonged cycling. When screening for ED, physicians need to
consider endocrinologic risk factors such as diabetes, thyroid
disease, excessive soy consumption, and KS. This is especially
important with the increasing incidence of obesity and diabetes
within the younger population. Further investigation on the role
of soy products and ED in younger men is warranted. In addi-
tion, neurogenic risk factors such as MS, epilepsy, intramedullary
nailing of femoral fractures, and lumbar spine procedures should
be taken into consideration in screening and counseling patients
with ED. Young men should be made aware of these contribu-
tors to ED before undergoing such procedures. Moreover,
physicians should warn young men that ED might be precipi-
tated as an adverse effect of taking certain medications. It is
important to note that the most prevalent risk factors for ED
among young men are psychogenic in nature. It is essential to
address the intrapsychic and relational risk factors in screening
and treating young men with ED. The bidirectional relation
between ED and psychogenic risk factors also is noteworthy, and
suggests more involvement of PDE5 inhibitors and cognitive-
behavioral therapy in treating ED and psychogenic risk factors
such as depression and relational conflicts.
For treatment of ED in young men, oral PDE5 inhibitors such
as sildenafil, tadalafil, vardenafil, and avanafil remain first-line
used oral agents and have very good success rates due to
proven efficacy, good tolerability, and ease of administration.
However, there is a growing interest in developing therapies to
cure ED in young men, because oral PDE5 inhibitors provide
only short-term symptomatic relief. Therapies such as ICI, penile
revascularization, inflatable penile prosthesis, hormonal supple-
mentation, and SC therapies are being more widely investigated
and used in the treatment of ED in young men.
This article summarizes the prevalence and risk factors of ED
in young men and highlights psychogenic and organic risk factors
that must be taken into consideration by physicians when
working up or screening for ED in this specific population.
Corresponding Author: Wayne J.G. Hellstrom, MD, FACS,
Department of Urology, Tulane University School of Medicine,
1430 Tulane Avenue, 86-42, New Orleans, LA 70112-2632,
USA. Tel: 504-988-3361; Fax: 504-988-5059; E-mail: whellst@
tulane.edu
Conflicts of Interest: Mr Nguyen and Mr Gabrielson claim no
conflicts of interests. Dr Hellstrom is a consultant for Pfizer.
Funding: None.
STATEMENT OF AUTHORSHIP
Category 1
(a) Conception and Design
Hoang Minh Tue Nguyen; Andrew T. Gabrielson; Wayne J.G.
Hellstrom
(b) Acquisition of Data
Hoang Minh Tue Nguyen; Andrew T. Gabrielson
(c) Analysis and Interpretation of Data
Hoang Minh Tue Nguyen; Andrew T. Gabrielson
Category 2
(a) Drafting the Article
Hoang Minh Tue Nguyen; Andrew T. Gabrielson
(b) Revising It for Intellectual Content
Wayne J.G. Hellstrom
Category 3
(a) Final Approval of the Completed Article
Hoang Minh Tue Nguyen; Andrew T. Gabrielson; Wayne J.G.
Hellstrom
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