FIRST CONSULT

Erectile dysfunction
Revised: February 10, 2012
Copyright Elsevier BV. All rights reserved.

Key points

Erectile dysfunction (ED, or impotence) is the inability to achieve or

maintain penile erection sufficient for sexual penetration or the rapid
detumescence of erection prior to completion of intercourse
Identifiable reversible causes, such as medications or stress, should
be sought assiduously
Patients with ED should also be evaluated for cardiovascular disease
and classified appropriately to their level of tolerance for both
therapy and sexual activity
Immediate action is required when ED occurs as the presenting
feature of a more serious disorder (eg, diabetes mellitus or a spinal
lesion)
Treatment
options
include
anti-depression
medication,
psychotherapy,
ED-specific
medications,
vacuum-constriction
devices, injections, surgery, and lifestyle modification
Prognosis is variable and depends on the etiology, severity, and
chronicity of the underlying disease

Background
Description

ED is the inability to attain an erection rigid enough to permit sexual

penetration
Penile detumescence (failure to maintain an erection sufficient to
complete intercourse) is a complimentary aspect of ED that is often
unrecognized by clinicians
Etiologies include endocrine, vascular, and neurologic disease;
traumatic injury; psychogenic factors; and iatrogenic causes (eg,
radical pelvic surgery or irradiation)
Treatment is aimed at the cause, such as ED secondary to
depression
If a psychogenic cause of ED cannot be identified, the clinician
should systematically eliminate organic causes
ED can cause marked distress and interpersonal difficulty

Epidemiology

Incidence:

The incidence of ED is estimated to be one in every five men

Frequency:

The overall annualized risk of ED in men is about 26 cases per 1,000

ED is a vastly under-reported problem
Greater than 70% of ED is thought to remain undiagnosed in the
U.S.

Demographics:

o
o
o

Age: Age-stratified occurrence of ED is estimated at the following:

2% of men in their 40s
25% of men in their 60s
89% of men in their 80s
Gender: occurs only in men
Socioeconomic status: The risk for ED increases with lower
educational and socioeconomic status

Causes and risk factors

Causes
Common causes:

Psychogenic: primary or secondary

Endocrine: diabetes mellitus , hypogonadism
Vascular: arterial insufficiency, veno-occlusive dysfunction
Medications: antihypertensives, antidepressants, antipsychotics,
antihistamines, nicotine, alcohol, and others
Neurogenic: stroke , multiple sclerosis , temporal lobe epilepsy , peripheral
neuropathy, autonomic or sensory neuropathy
Surgical: radical prostatectomy or cystectomy, abdominoperineal
resection
Radiation: external beam radiation, implantation of radioactive
seeds
Pelvic trauma

Rare causes:

Endocrine:
hypothalamic-pituitary-testicular
axis
dysfunction, hyperthyroidism , hypothyroidism ,
hyperprolactinemia, Cushing
syndrome

Vascular: venous leakage, arteriovenous malformation

Spinal cord trauma or tumor
Neurotransmitter deficiency

Systemic illness: renal failure , chronic obstructive pulmonary disease , cirrhosis

Myotonic dystrophy
Peyronie disease

Idiopathic reaction to a medication

Serious causes:

Diabetes mellitus
Hypothalamic-pituitary-testicular axis dysfunction
Hyperthyroidism or hypothyroidism
Hyperprolactinemia
Cushing syndrome
Peripheral neuropathy or autonomic or sensory neuropathy
Spinal cord trauma or tumor
Central nervous system disorders including stroke, multiple
sclerosis, or temporal lobe epilepsy
Neurotransmitter deficiency
Renal failure
Chronic obstructive pulmonary disease
Cirrhosis
Myotonic dystrophy

Contributory or predisposing factors

Alcohol
Drugs, both legal and illicit (eg, anabolic steroids, heroin, and
marijuana)
Smoking

Screening
Although the importance of taking a sexual history in all patients is always advised, there is
no clear-cut evidence in the literature to support systematic screening of healthy
asymptomatic men for ED.

Primary prevention
There is no firm evidence regarding the effectiveness of measures to prevent ED. Treatment
of diseases that can underlie ED may, however, be indicated.

Diagnosis
Summary approach

o
o

ED is a clinical syndrome or symptom, and the diagnosis is based on

the patients history. Standardized questionnaires are helpful, and a
frank interview of the sexual partner contributes greatly to an
understanding in many cases
The International Index of Erectile Function-5 (IIEF-5) may confirm
and categorize the severity of erection dysfunction. The 5-question
survey assesses recent (6-month) quantitative and qualitative
aspects of erectile function and arrives at a sum of ordinal responses
as a symptom score. A total score of 5 to 7 indicates severe ED; 8 to
11 indicates moderate dysfunction, 12 to 16 mild-to-moderate
dysfunction, 17 to 21 mild dysfunction, and lower than 22 indicates
no ED
The American Psychiatric Association has also produced diagnostic
criteria for male erectile disorder (impotence):
Diagnostic and statistical manual of mental disorders. 4th ed.
Washington, DC: American Psychiatric Association; 2000:545-7
These criteria state that ED (as a psychogenic disorder) can
be diagnosed if
There is persistent or recurrent inability to attain an
adequate erection or to maintain it until completion of the sexual
activity
The problem causes marked distress or interpersonal
difficulty
The problem is not better accounted for by another Axis
I psychiatric disorder (other than a sexual dysfunction), and it is not
due exclusively to the effects of a substance or to a general medical
condition
In taking a history, it is important for the dialogue to be conducted
in a non-threatening, comfortable manner. Some physicians like to
introduce the patient to the subject by prior reassuring mail contact,
if possible, and some may include a questionnaire to be filled in
before the first personal interview. Standardized questionnaires are
available. Interview of the partner contributes greatly

Clinical presentation
Symptoms

Erections absent, poor quality, and/or not sustained

Symptoms of underlying neurologic, psychogenic, endocrine, or
vascular disease

Symptoms resulting from past urologic surgery, radiation, or use of

certain offending medications

Signs

There may be no abnormalities on physical examination

Anatomic abnormalities including micropenis, chordee or penile
plaques (suggestive of Peyronie disease ), and small or malpositioned
testes
Signs of hypogonadism, including small or atrophic testes and
decreased body hair
Signs of other endocrine disease, including diabetes mellitus,
pituitary disorders, and endocrine end-organ dysfunction
Signs of vascular disease, including hypertension, ischemic ulcers,
and diminished peripheral pulses
Signs of neurologic disease, as demonstrated by focal neurologic
abnormalities. Look specifically for absence of the bulbocavernosus
reflex and abnormal perineal sensation
Tumors involving the phallus or testicles (rare) or the prostate
(common), as suggested by nodules, induration, or enlargement

Examination

Look for signs of anemia and renal or liver disease (eg, pallor,
sallowness, tremor, telangiectasia)
Examine for hypertension, ischemic ulcers, absent peripheral pulses
Neurologic examination to check for problems such as hemiparesis
following stroke and impaired gait of multiple sclerosis
Look for signs of major hormonal dysfunction (eg, hypothyroid
facies, hyperthyroid eye signs, lack of facial hair and gynecomastia in
hypopituitarism)
During the abdominal examination, look for surgical scars and renal,
hepatic, or other masses
Digital rectal examination and prostatic evaluation are essential;
hypertrophy and postprostatectomy states are significant
Presence of penile plaques is suggestive of Peyronie disease
Absence of bulbocavernosus and cremasteric reflexes suggests
neurologic impairment (bulbocavernosus reflex is elicited by
squeezing the glans penis and noting anal sphincter constriction)
Check size, position, and consistency of testes, and check for
tenderness, masses, and nodularity
Test of penile vibratory sensation may be conducted in the office if
there is access to biothesiometry

Questions to ask
Presenting condition:

What does the problem mean for you?Is it failure to achieve or to

maintain an erection?
For how long have you had the problem?Long-standing problems
may prove more intractable
Did the problem come on suddenly?Slow onset occurs with age and
causes that have a gradual effect, while rapid onset may indicate a
specific event, psychologic or physical
Has the problem occurred before?Recurrence is a feature of
psychogenic ED
Do you wake up in the morning with an erection?The sudden onset
of ED, with normal morning erections, points toward psychogenic ED
Do you still feel the desire for sexual intercourse?A poor relationship
points toward psychogenic ED
When you get an erection, is it normal? Is it rigid enough for
penetration, and can you sustain it long enough for coitus?Full,
normal erection that is not sustained points toward psychogenic ED
Do you have normal erections with masturbation and other
partners?If the answer is positive, the cause is almost certainly
psychogenic
Have you noticed any change in your sexual organs?Secondary
sexual characteristics decrease in hypogonadism (hypopituitarism),
and the penis curves in Peyronie disease
Are there any emotional problems at present, or problems with your
partner?Emotion plays an important part in the sexual drive, and the
problem is likely to be psychogenic in origin
Are you generally well?Any concurrent disease can decrease libido
Do you have heart or circulation problems, diabetes, or liver or
kidney problems?All can contribute to ED, as can some medications
used to treat them
Have you had any abdominal or pelvic surgery?Could point to an
underlying disease or postoperative vascular or neurologic
complications. There could be a functional problem, such as
retrograde ejaculation after prostatectomy
Is your weight steady and your appetite normal?Changes can
suggest the presence of unsuspected diabetes or thyroid disease
Do you suffer with excessive fatigue?Hormone imbalances and
chronic disease could be the cause of this symptom
Do you suffer from excessive thirst?This occurs in diabetes mellitus
and also diabetes insipidus, which can occur with pituitary adenomas
Do you still shave as regularly as before?Absent or retarded growth
of facial hair may suggest hypopituitarism or hyperprolactinemia
Has there been any change in sensation or strength in your limbs?
Could point to a neurologic disorder or be a manifestation of
hypogonadism

Have you had any headaches, breast enlargement, visual

disturbances, or discharge from your nipples (galactorrhea)?These
symptoms may point to hyperprolactinemia
Are you experiencing any mood disturbances?Depression and other
mental illness can dispose to psychogenic ED. Some of the drugs
used in treatment may also be implicated. ED can be an underlying
symptom of depression but does not, by itself, cause depression
What medication are you taking (including over the counter)?Many
classes of medication directly cause ED

Contributory or predisposing factors:

Are you a smoker?Smoking impairs circulation and creates other,

secondary problems such as chronic obstructive pulmonary disease,
which may contribute to ED
How much alcohol do you consume?Excessive consumption points
to alcohol as a source of ED
What recreational drugs do you take?Opioids, amphetamines,
anabolic steroids, testosterone, and marijuana use can cause ED

Family history:

Does anyone in your family suffer from diabetes/thyroid

disease/circulatory disease? Is there a family history of malignancies,
specifically prostate cancer or colorectal cancer?Although there are
no significant common familial conditions/malignancies contributing
to ED, they can have an impact in some cases

Diagnostic testing
Extensive testing is usually not necessary in evaluation of erectile dysfunction. When
appropriate clinical clues are apparent from history and physical, the following may be
of value in determining an organic etiology for the condition:

Random or fasting blood glucose to look for diabetes mellitus, which

predisposes patients to ED

Serum chemistry, liver function, and lipid studies and complete blood count may be

useful in confirming clinical suspicion of underlying chronic diseases

such as diabetes, cardiovascular disease, renal insufficiency, or liver
disease
Total and free testosterone : serum assay of fasting, morning total
testosterone level to evaluate hypothalamic-pituitary-testis axis
dysfunction. Free (bioavailable) testosterone should be checked if
total testosterone is low

Prolactin levels

(if
testosterone
is
low)
to
assess
for
hyperprolactinemia as a cause of ED
Plasma follicle-stimulating hormone (FSH) and serum luteinizing hormone
(LH) levels (if testosterone is low) to differentiate primary versus
secondary hypogonadism
Thyroid function tests, including thyroid-stimulating hormone (TSH) , to look for
hyper- or hypothyroidism
Nocturnal penile tumescence and rigidity testing establishes presence or
absence of penile rigidity during sleep. Normal erections during sleep
imply a psychologic etiology of ED
Combined intracavernosal injection of alprostadil into the penile corpora followed by
patient stimulation may differentiate vascular causes of ED (no erectile

response) from psychosocial causes (presence of erectile response)

Penile duplex Doppler sonography measures penile arterial and venous
blood
Cavernosometry and cavernosography measure intracavernosal pressure and
permit imaging of the penile corpora
Bilateral internal pudendal and inferior epigastric arteriography may be useful in
evaluating arterial insufficiency

Random or fasting blood glucose

Description

Pinprick finger test or venous blood sample

Normal ranges

Random glucose: <200 mg/dL

Fasting glucose: <135 mg/dL

Comments

Inexpensive, widely available, and easy to perform

Serum chemistry, liver function, and lipid studies

Description

Serum chemistry: venous blood sample for chemistry assays

Liver function: venous blood sample for liver function studies
Lipid panel: venous blood sample to assay blood lipids

Normal ranges
Serum chemistry:

Blood urea nitrogen: 7 to 21 mg/dL

Creatinine: 0.5 to 1.4 mg/dL
Sodium: 137 to 145 mEq/L
Chloride: 98 to 110 mEq/L
Bicarbonate: 22 to 26 mEq/L
Potassium: 3.6 to 5.0 mEq/L
Calcium: 9 to 10.5 mg/dL

Liver function:

Alanine aminotransferase: 0 to 35 IU/L

Aspartate aminotransferase: 0 to 35 IU/L
Alkaline phosphatase: 30 to 120 IU/L
Gamma-glutamyl transpeptidase: 11 to 51 IU/L
Albumin: 4 to 6 g/dL
Bilirubin (direct): 0 to 0.2 mg/dL
Bilirubin (indirect): 0.1 to 1.0 mg/dL
Prothrombin time: 10 to 12 seconds

Lipid panel:

Total cholesterol: 120 to 200 mg/dL

Triglycerides: 50 to 250 mg/dL
HDL cholesterol: >45 mg/dL
LDL cholesterol: <130 mg/dL
VLDL cholesterol: 7 to 32 mg/dL

Comments
Serum chemistry:

May be helpful in confirming diagnosis of underlying chronic

diseases, such as renal insufficiency

Liver function:

May help diagnose underlying chronic conditions causing hepatic

dysfunction

Lipid panel:

May serve as indirect evidence for underlying vascular disease

Sample should usually be drawn after a 12-hour fast

Complete blood count

Description

Venous blood sample

Normal ranges

Leukocyte count: 4,500 to 11,000/L

Differential count:
Neutrophilssegmented: 1,800 to 7,800/L
Neutrophilsbands: 0 to 700/L
Lymphocytes: 1,000 to 4,800/L
Monocytes: 0 to 800/L
Eosinophils: 0 to 450/L
Basophils: 0 to 200/L
Erythrocyte count: 3.9 to 5.5 106/L
Hemoglobin: 14.0 to 17.5 g/dL
Hematocrit: 41% to 50%
Platelet count: 150 to 350 103/L

Comments

May be helpful in confirming diagnosis of a number of underlying

chronic conditions

Total and free testosterone

Description

Venous blood sample for hormonal assay of male biomarkers

Normal ranges

Total testosterone: 280 to 1100 ng/dL

Free testosterone: 0.3 to 2 pg/mL

Comments

Indicated in patients with suspected hypogonadism (decreased

libido, bilateral testicular atrophy, reduced amount of body hair). In
the absence of these symptoms, the cost utility of ordering these
tests is questionable
Should be done fasting in the early morning and may need to be
repeated 1 to 3 times in order to confirm abnormally low levels
Testosterone levels are decreased in patients with hypogonadism
(testicular failure), hyperprolactinemia, and hypothalamic-pituitarytestis axis dysfunction and in those taking anabolic steroids (eg,
athletes). It is increased in some patients with certain testicular
tumors

A low testosterone level should prompt a repeat morning

determination as well as prolactin, FSH, and LH testing. Evaluation of
FSH and LH can help determine whether low testosterone levels are
due to testicular failure or to pituitary dysfunction
Of total testosterone (the entire amount of circulating testosterone),
one portion is free, another portion is weakly bound to proteins
such as albumin, and the remaining one is tightly bound to steroid
hormone binding globulin (SHBG)
SHBG is produced in the Sertoli cells of the testicle.
Hyperthyroidism, liver disease, elevated estrogen, and older age
increase SHBG, thus decreasing free, unbound, and biologically active
testosterone

Prolactin
Description

Venous blood sample to evaluate for hyperprolactinemia

Normal range

Prolactin: <400 mU/L (400-600 mU/L is mildly elevated; levels

>2,000-3,000 mU/L suggest prolactinoma)

Comments

Prolactin is a peptide secreted from the pituitary gland and involved

in sexual gratification in men
Prolactin decreases circulating testosterone; levels should be drawn
in the presence of low libido, loss of hair, visual problems, headaches,
gynecomastia, and a low testosterone level
Mildly elevated levels may be due to normal physiologic events such
as sleeping, stress, or following coitus
Some chronic medical conditions such as renal or liver failure can
increase serum prolactin
Higher prolactin levels may be due to more serious causes, such as
tumor in the hypothalamic/pituitary axis, and require immediate
referral to a specialist for evaluation
Several different physiologic or pathologic states can cause elevated
prolactin levels
Many drugs can also increase prolactin levels (eg, cimetidine,
metoclopramide, and methyldopa)

Plasma FSH
Description

Venous blood sample for hormone assay

Normal range

FSH: 4 to 25 IU/L

Comments

High FSH levels are found in patients with primary testicular failure.
This can be due to developmental defects during testicular growth,
such as testicular agenesis, or to testicular injury from mumps,
trauma, radiation, chemotherapy, or some autoimmune diseases. It
may be low in patients with hypopituitarism
FSH may be falsely elevated in patients taking cimetidine, digitalis,
and levodopa and falsely low in those taking phenothiazines and
hormone treatments
Reference values are dependent on many factors, including patient
age and test method; consult local guidelines

Serum LH levels
Description

Venous blood sample for hormone assay

Normal range

LH: 5 to 25 IU/L

Comments

Levels can be decreased in severe illness

Laboratory technique may affect results

Thyroid function tests, including TSH

Description

Venous blood sample for evaluation of thyroid function

Normal ranges

Thyroxine: 4 to 12 g/dL
Free thyroxine: 0.9 to 2.3 ng/dL
TSH: 2 to 11 U/mL

Comments

Primary test used in the diagnosis of thyroid dysfunction, which can

be subtle, especially in elderly men; it is important to screen for this
Increased TSH levels occur in primary hypothyroidism and other
diseases
Abnormally low TSH levels occur in hyperthyroidism
TSH is released from the anterior pituitary in response to
thyrotropin-releasing hormone from the hypothalamus and, in turn,
stimulates the thyroid gland to secrete thyroxine and triiodothyronine
In one study evaluating endocrine dysfunction as a cause of ED, 6%
were found to have hypothyroidism

Nocturnal penile tumescence and rigidity testing

Description

Detects erections during rapid-eye-movement sleep

A simple ring is placed around the penis. Any erection meeting
pressure criteria during the night will cause the ring to break. The
rings are coupled to an electronic sensor, which measures
characteristics of erections, such as duration and strength

Normal result

Expansion of the penile circumference by 15 to 30 mm

Comments

Noninvasive, but inconvenient to perform because it requires

overnight observation
Implies organic rather than psychogenic causation for ED but is
nonspecific regarding exact etiology
Vascular insufficiency or neurogenic or endocrine abnormality may
cause an abnormal result
Multiple confounders, such as dream content, sleep disturbances,
and neurologic conditions may affect results
Poorly correlates with sexual performance

Combined intracavernosal injection and stimulation

Description

Intracavernosal injection (usually with alprostadil) into the penile

corpora followed by masturbatory stimulation to achieve an erection

Normal result

Erection with stimulation

Comments

A good erection during this test rules out veno-occlusive disease but
not arterial insufficiency
A poor response can be caused by inadequate dosing or faulty
administration of alprostadil, veno-occlusive disease, arterial
insufficiency, or extreme anxiety
A poor response can also be seen in persons with underlying
psychologic or neurologic dysfunction who do not respond to
stimulation
Lack of standard dosing for alprostadil may complicate
administration of the test (titration of drug to sufficient dose for
erectile response is usually required)

Penile duplex Doppler sonography

Description

Doppler ultrasound images of vascular flow to the penis beginning 5

to 10 minutes after intracavernosal injection of vasodilating
medication
The 5 to 10 Hz transducer is utilized to measure arterial flow, peak
systolic velocity, cavernous artery diameter, cavernous artery end
diastolic velocity, and venous outflow

Normal ranges

Peak systolic velocity >30 cm/s

Sum of right- and left-peak systolic velocities should be >50 to 60
cm/s
Normal flaccid cavernous artery diameter is 0.3 to 0.4 mm; normal
erect diameter is 0.7 to 1.2 mm

Comments

Objective measure of erectile flow dynamics

Differentiates among the different vascular causes of ED

Arteriogenic insufficiency is suspected if cavernous artery diameter

is less than 0.7 mm
The deep dorsal vein will normally be visible on ultrasound imaging
when the patient has an erection. This result should not be confused
with veno-occlusive dysfunction and is an expected finding

Cavernosometry and cavernosography

Description

Cavernosography is usually performed with cavernosometry and

involves infusion of radiographic contrast into the penile corpora
A needle is inserted into a penile corpora through which heparinized
saline is infused, and a second needle inserted into the opposite
penile corpora to measure intracavernosal pressure
The heparinized saline flow required to achieve and maintain an
intracavernosal pressure of 150 mm Hg is recorded
The heparinized saline flow is stopped, and the amount of time for
intracavernosal pressure to decline to 105 mm Hg is measured
(intracavernosal pressure decay)

Normal results

Flow to maintain intracavernosal pressure of 150 mm Hg should be

<3 mL/min
Intracavernosal pressure decay of 45 mm Hg should be >30 s
Minimal or no venous leakage from corpora should be evident on
cavernosography

Comments

Distinguishes ED caused by arterial insufficiency from that related to

excessive venous runoff
Veno-occlusive
dysfunction
is
considered
present
when
intracavernosal pressure cannot be increased to the level of systemic
mean arterial pressure
Anteroposterior and oblique radiographs can be used to visualize
the location of a possible venous leak

Bilateral internal
arteriography
Description

pudendal

and

inferior

epigastric

Radiography
of
penile
vasculature
following
intravenous
administration of contrast
Indicated in young men with suspected arterial insufficiency who are
candidates for revascularization procedure

Normal result

Patent vessels without stenosis or shunting

Comments

Obliterated, tortuous vessels

atherosclerotic disease
Involves radiation exposure

with

stenotic

lesions

indicate

Differential diagnosis
Given that ED is a symptom with multiple etiologies, there is no true differential diagnosis.
Evaluation focuses on defining the underlying etiology of the patient's ED, which may
be psychogenic, endocrine, vascular, neurologic, traumatic, or iatrogenic.

Consultation
Referral to a urologist is appropriate in complicated presentations or when the cause of ED
cannot be established.

Treatment

Summary approach

The goal of ED treatment is restoration of erectile function adequate

for sexual penetration and maintenance of an erection without
premature detumescence
Immediate referral is mandatory if serious, life-threatening
underlying disease is detected
Address
underlying
treatable
causes
first:
For
example,depressionshould be investigated and treated, if necessary,
with bupropion or mirtazapine
First-line therapy for all types of ED is a phosphodiesterase-5
inhibitor . Sildenafil , vardenafil , and tadalafil all appear to have equal efficacy;
however, they differ in their onset of action and duration of action.
Phosphodiesterase-5 inhibitors require appropriate sexual stimulation
in order to work effectively. Variability of response to each agent
mandates that if one agent does not work, another may be tried with
success. Patients suitable for and willing to try phosphodiesterase-5
inhibitors
have a high degree of satisfaction. Use of

phosphodiesterase-5 inhibitors is contraindicated in patients taking

nitrate therapy, and they should be used with caution in patients
taking -blockers
Intracavernosal or transurethral alprostadil is the medication of choice
for penile self-injection
Second-line therapies for all types of ED include vacuum-constriction
erection devices or penile injections, depending on patient preference
Lifestyle changes (eg, reducing alcohol and tobacco consumption) may
also improve erectile function
Many patients with psychogenic ED benefit from psychotherapy , which
can be carried out simultaneously with pharmacologic therapy
If second-line therapies are not effective, surgical intervention
(eg, penile prosthesis and arterial revascularization ) may be considered
Outcome of therapy depends on the cause of ED and is linked to the
severity and chronicity of the underlying disease
Complementary therapies (eg, Chinese medicine and Korean red
ginseng) have not been found to have success in treatment of ED
Older injectable agents including papaverine, phentolamine, or a
mixture of both drugs have fallen out of favor for treatment of ED

Medications
Bupropion
Indication

Bupropion is indicated for depression

Dose information

100 mg orally twice daily initially

May increase to 100 mg 3 times daily after 3 days
Maximum daily dose: 450 mg; maximum single dose: 150 mg

Major contraindications

Anorexia nervosa
Bulimia nervosa
MAOI therapy
Seizure disorder
Seizures

Comments

Increased risk of suicidality, worsening depression, and depressive

behavior in patients up to 24 years of age

Mirtazapine
Indication

Mirtazapine is indicated for depression

Dose information

Adult: 15 mg/d orally initially; increase dose gradually every 1 to 2

weeks
Maximum: 45 mg/d

Comments

Gender,
age,
and
organ
dysfunctions
may
affect
pharmacokinetics of mirtazapine
The oral clearance of mirtazapine is reduced in elderly patients

the

Phosphodiesterase-5 inhibitors
Indication

First-line therapy for all types of non-psychogenic ED

Dose information
Sildenafil :

Initial dosage 50 mg orally

Patient can self-titrate in increments of 25 mg to achieve maximal
benefit

Vardenafil :

Initial dosage 10 mg orally

Patient can self-titrate in increments of 5 mg to achieve maximal
benefit

Tadalafil :

Initial dosage 10 mg orally

Patient can self-titrate in increments of 5 mg to achieve maximal
benefit

Major contraindications

Nitrate/nitrite therapy

Comments

Concomitant use of nitrates or nitric oxide may precipitate lifethreatening hypotension

Dose adjustment is required when taken concomitantly with blockers or CYP3A4inhibitors

Evidence
Sildenafil enhances erectile function with minor side effects.

A systematic review of 27 randomized, controlled trials (RCTs) and

6,659 men found sildenafil was more likely than placebo to lead to
successful sexual intercourse. Specific adverse events with sildenafil
included flushing (12%), headache (11%), dyspepsia (5%), and visual
disturbances (3%). Sildenafil was not associated with serious
cardiovascular events or death. [1] Level of evidence: 1

Flexible dose vardenafil is effective for treatment of ED.

An RCT studied 323 patients randomly assigned to vardenafil 10 mg

orally or placebo. After 4 weeks, patients could switch to 5 or 20 mg,
or remain on 10 mg for an additional 4 weeks. Symptom scores
improved significantly in men on vardenafil compared with placebo at
weeks 4, 8, 12, and last observation carried forward (LOCF) (P< .005)
when compared to placebo. The authors concluded that vardenafil
produced substantial improvements in erectile function in men with
ED and was well-tolerated. [2] Level of evidence: 2

Sildenafil and tadalafil are effective in sexual dysfunction resulting from the use of
antidepressants.

A systematic review of 15 RCTs including 904 men found the

addition of sildenafil to be an effective strategy for men with
antidepressant-induced ED. In men with ED, the addition of sildenafil
resulted in less sexual dysfunction at endpoint on rating scales
including the International Index of Erectile Function (IIEF; WMD
19.36, 95% CI 15.00-23.72). There was no significant difference in
dropout rates between sildenafil and placebo. One trial found that the
addition of bupropion led to improved symptom scores (WMD 0.88,
95% CI 0.21-1.55). One trial found that the addition of tadalafil was
associated with greater improvement in erectile function than
placebo (WMD 8.10; 95% CI 4.62-11.68). [3] Level of evidence: 1

Phosphodiesterase-5 inhibitors are effective in sexual dysfunction resulting from type 1 and
type 2 diabetes mellitus.

A systematic review of 8 RCTs including 1,717 men found evidence

that phosphodiesterase-5 inhibitors improve ED in men with diabetes.
Overall, 80% of the participants had type 2 diabetes mellitus.
Mortality was not reported in any of the included trials. Adverse
cardiovascular effects were reported in one study. Headache was the
most frequent adverse event reported, flushing was the second most
common event, with upper respiratory tract complaints and flu-like
syndromes, dyspepsia, myalgia, abnormal vision, and back pain also
reported in a descending order of frequency. The overall risk ratio for
developing any adverse reaction was 4.8 (CI 95% 3.74-6.16) in the
phosphodiesterase-5
inhibitors
arm
as
compared
to
the
control. [4] Level of evidence: 1

References
Alprostadil
Indication

Alprostadil is a second-line therapy for all types of ED

Dose information
Intracavernosal:

1.25 to 2.5 g initially; increase dose by 2.5 to 5 g increments,

according to response, up to a maximum of 60 g/dose
Maximum: 3 doses/wk with at least 24 h between doses

Intra-urethral:

125 to 250 g initially; increase dose according to response

Maximum: 2 doses/d

Major contraindications

Balanitis
Females
Hypospadia
Infants
Leukemia
Multiple myeloma
Neonates
Penile implants
Penile structural abnormality

Peyronie disease
Polycythemia
Sickle cell disease
Thrombocytosis
Urethral stricture
Urethritis

Comments

Reports of prolonged erection and priapism, both of which should be

treated immediately if they persist for more than 4 hours
Reports of penile fibrosis, including Peyronie disease. Discontinue
treatment in patients who develop penile angulation, cavernosal
fibrosis, or Peyronie disease (intracavernosal)

Evidence

A systematic review of 4 RCTs including 1,873 patients found

alprostadil-treated men were more likely to report successful sexual
intercourse and at least one orgasm over a 3-month treatment period
than placebo control. The study confirmed the effectiveness and
safety of alprostadil in the treatment of ED and found that it was
beneficial for various etiologies. Adverse effects were not serious and
were proportional to dosage. [5] Level of evidence: 1
An RCT of 296 men found intracavernosal injection of alprostadil
was effective in the treatment of ED and associated with minimal
adverse effects. Higher response rates were obtained with increasing
doses of alprostadil (from 2.5 to 20 g). Responses were recorded in
23% to 38% of men with ED of neurogenic, vasculogenic,
psychogenic, or mixed causes. Penile pain, usually mild, occurred in
50 percent of the patients; prolonged erection occurred in 5 percent;
and frank priapism in 1 percent. [6] Level of evidence: 2
An RCT of 44 patients compared intracavernosal alprostadil versus
vacuum devices and found that there were no significant differences
between the groups in ability to attain erection; however, the ability
to attain orgasm was significantly better in the alprostadil group, and
overall satisfaction was rated significantly better with alprostadil by
the men and their partners. Men under 60 years of age and those
with ED of less than 12 months' duration were more likely to favor
alprostadil. [7]Level of evidence: 3

References
Non-drug treatments
Vacuum-constriction devices
Description

A cylindrical vacuum pump is placed over the penis and air is drawn
from the cylinder, causing blood to flow into the penis
When erection is achieved, an occlusive ring is placed around the
penile base to maintain the erection

Indication

Erectile dysfunction

Complications

Priapism, hematoma, retarded ejaculation, numb penis, penile pain

The penile ring used in conjunction with most vacuum devices may
cause urethral injury
These devices should only be used if they have an electronic limiter,
as severe injury may occur with excessive pressure

Comments

The vacuum-pump device may be combined with medical therapy

for maximal benefit
Thirty minutes is the maximum duration of use
Allow 1 hour after removing the occlusive band before repeating use

Evidence

An RCT of 44 patients compared intracavernosal alprostadil versus

vacuum devices and found that there were no significant differences
between the groups in ability to attain erection; however, the ability
to attain orgasm was significantly better in the alprostadil group, and
overall satisfaction was rated significantly better with alprostadil by
the men and their partners. Men under 60 years of age and those
with ED of less than 12 months' duration were more likely to favor
alprostadil. [7]Level of evidence: 3

References
Lifestyle changes
Description

Reducing alcohol consumption and smoking may reduce ED

Indication

Erectile dysfunction

Comments

Patients often benefit from participation in support groups (eg,

smoking cessation classes)
Organizations such as Alcoholics Anonymous may be helpful in
cases of alcohol abuse
Rapid detoxification of heavily dependent alcoholics may result in
withdrawal symptoms

Psychotherapy
Description

Patients with psychogenic ED may benefit from counseling with a

sex therapist or psychiatric professional

Indication

Psychogenic ED

Comments

Underlying metabolic and endocrine causes should always be

addressed, but depression should be considered as a complicating
factor and treated appropriately
Depending on the cause, psychotherapy may also be used
concomitantly with pharmacologic therapy

Evidence

A systematic review of 9 RCTs including 398 men with ED found no

differences in effectiveness between psychosocial interventions
versus local injection and vacuum devices. Group psychotherapy was
more likely than the control group to reduce the number of men with
persistence of ED at 6 months post-treatment (RR 0.40, 95% CI 0.170.98, N=100; NNT 1.61, 95% CI 0.97-4.76). In a meta-analysis that
compared group therapy plus sildenafil citrate versus sildenafil, men
randomly assigned to receive group therapy plus sildenafil showed
significant improvement of successful intercourse and were less likely

than those receiving only sildenafil to drop out. [8] Level of evidence:
1

References
Penile prosthesis and arterial revascularization
Description

Surgical intervention is generally reserved for failures of

conservative therapy
Penile prostheses have evolved from non-inflatable, malleable
devices to 2- and 3-piece inflatable prostheses. The newer penile
prostheses allow the user to control whether the penis is flaccid or
erect
Revascularization is best suited for isolated stenosis or occlusion of
extra-penile arteries; however, long-term results of revascularization
procedures are quite poor

Indication

Erectile dysfunction

Complications

Risks include infection, erosion, and mechanical malfunction, while

successful surgical intervention restores sexual competency
Erosion is more common with non-inflatable than inflatable
prostheses
Infection rate in primary implants is 0% to 3%

Comments

Satisfaction is high for the patient (60%-80%) and the patients

partner (60%-80%)
Proper preoperative counseling is essential with regard to risks,
benefits, and expectations

Special circumstances
Many underlying or coexisting diseases limit the options available to treat ED and may also
modify the achievable goals in the condition.

Comorbidities
Coexisting disease:

Diabetes and vascular disease create major, high-priority medical

problems and may force the problem of ED to be overlooked or set
aside
Any severe chronic illness may significantly limit what can be
achieved in treating ED
Some diseases are relative contraindications to the use of firstchoice drugs (eg, sickle cell anemia , leukemia, and multiple myeloma , which
all predispose to priapism)
Renal insufficiency, hepatic dysfunction, and bleeding disorders can
limit drug options

Coexisting medication:

Some medications are implicated in causing ED

Certain medications necessary to treat other coexisting diseases
may restrict ED treatment options (eg, the use of nitrates to treat
angina precludes the use of phosphodiesterase-5 inhibitors)

Special patient groups:

Elderly men often simply want reassurance that there is no other

serious problem. If they do want treatment, caution must be used
with all of the medications available

Patient satisfaction/lifestyle priorities

Restoration of erectile function adequate for sexual penetration and

maintenance of erection without premature detumescence should be
the goal for patients desirous of sexual activity
Patients suitable for and willing to try phosphodiesterase-5 inhibitors
have a high degree of satisfaction with therapy and few adverse
effects or complications to limit their sexual activity

Consultation
Refer patients not responding to first-line therapy to a urologist and those with difficult and
complicated co-morbid conditions to appropriate sub-specialists.

Follow-up

Follow-up should focus on whether therapy is effective and sexual

intercourse is satisfactory
Prudent usage of medications mandates initial close monitoring of
effectiveness and identification of adverse effects

Plan for review

With medications, ideally the patient should return to report after his
first dose, but at the least he should be seen at weekly intervals until
the treatment goals have been achieved

Prognosis

Prognosis is variable and depends on the etiology, severity, and

chronicity of the underlying disease
For hypogonadism, treatment with testosterone replacement is
effective in 75% to 85% of cases
Overall success with phosphodiesterase-5 inhibitors is 61% to 71%
Intracavernosal injection success ranges from 31% to 72%
Vacuum constriction device satisfaction is found in 27% to 47% of
users

Progression of disease

Generally, disease progresses gradually and in close association

with the severity and chronicity of the underlying causative illness
Systemic disease (eg, diabetes mellitus), neurogenic disorders,
endocrine disorders, and cardiovascular disease are commonly
associated with ED and should be treated, as appropriate

Therapeutic failure:

Assess for noncompliance with chosen therapy (eg, adverse effects)

Reassess for occult underlying cause
Assess other therapeuticoptions(eg, surgery)

Recurrence:

Recurrence may be due to therapeutic failure (may be

noncompliance) or the development/recurrence of an underlying
cause
Often requires referral to appropriate specialist (depending on
cause)

Clinical complications

Priapism due to phosphodiesterase-5 inhibitor therapy is a rare

consequence of treatment. It requires prompt evaluation and
treatment to prevent permanent fibrotic injury to the penile corpora
and vascular supply

Failure to respond to priapistic episodes of greater than 4 hours'

duration may severely compromise subsequent sexual function and
treatment of the condition

Patient education

The increasing incidence of ED in men as they age should be

explained to the patient, ideally with his partner present
When medications are prescribed, it is important that their possible
adverse effects are fully discussed
Emphasis on smoking cessation and moderation in alcohol intake is
appropriate for both erectile function and overall health

Online information for patients

o
o
o
o

o
o

Mayo Clinic:
Erectile dysfunction
Erectile dysfunction: a sign of heart disease?
Erectile dysfunction and diabetes: take control today
Erectile dysfunction: Viagra and other oral medications

American Urological Association:

Erectile dysfunction: primary treatment options
Surgical management of erectile dysfunction

Cleveland Clinic:
Treating erectile dysfunction: lifestyle changes

Resources
Summary of evidence
Evidence
Sildenafil enhances erectile function with minor side effects.

A systematic review of 27 RCTs and 6,659 men found sildenafil was more
likely than placebo to lead to successful sexual intercourse. Specific adverse
events with sildenafil included flushing (12%), headache (11%), dyspepsia (5%),
and visual disturbances (3%). Sildenafil was not associated with serious
cardiovascular events or death. [1] Level of evidence: 1

Flexible dose vardenafil is effective for treatment of ED.

An RCT studied 323 patients randomly assigned to vardenafil 10 mg orally or

placebo. After 4 weeks, patients could switch to 5 or 20 mg, or remain on 10 mg
for an additional 4 weeks. Symptom scores improved significantly in men on
vardenafil compared with placebo at weeks 4, 8, 12, and last observation carried
forward (LOCF) (P< .005) when compared to placebo. The authors concluded
that vardenafil produced substantial improvements in erectile function in men
with ED and was well-tolerated. [2] Level of evidence: 2

Sildenafil and tadalafil are effective in sexual dysfunction resulting from the use of
antidepressants.

A systematic review of 15 RCTs including 904 men found the addition of

sildenafil to be an effective strategy for men with antidepressant-induced ED.
In men with ED, the addition of sildenafil resulted in less sexual dysfunction at
endpoint on rating scales including the International Index of Erectile Function
(IIEF; WMD 19.36, 95% CI 15.00-23.72). There was no significant difference in
dropout rates between sildenafil and placebo. One trial found that the addition
of bupropion led to improved symptom scores (WMD 0.88, 95% CI 0.21-1.55).
One trial found that the addition of tadalafil was associated with greater
improvement in erectile function than placebo (WMD 8.10; 95% CI 4.6211.68). [3] Level of evidence: 1

Phosphodiesterase-5 inhibitors are effective in sexual dysfunction resulting from

type 1 and type 2 diabetes mellitus.

A systematic review of 8 RCTs including 1,717 men found evidence that

phosphodiesterase-5 inhibitors improve ED in men with diabetes. Overall, 80%
of the participants had type 2 diabetes mellitus. Mortality was not reported in
any of the included trials. Adverse cardiovascular effects were reported in one
study. Headache was the most frequent adverse event reported, flushing was
the second most common event, with upper respiratory tract complaints and
flu-like syndromes, dyspepsia, myalgia, abnormal vision, and back pain also
reported in a descending order of frequency. The overall risk ratio for
developing any adverse reaction was 4.8 (CI 95% 3.74-6.16) in the
phosphodiesterase-5 inhibitors arm as compared to the control. [4] Level of
evidence: 1

Alprostadil enhances erectile function with minor side effects.

A systematic review of 4 RCTs including 1,873 patients found alprostadiltreated men were more likely to report successful sexual intercourse and at
least one orgasm over a 3-month treatment period than placebo control. The
study confirmed the effectiveness and safety of alprostadil in the treatment of
ED and found that it was beneficial for various etiologies. Adverse effects were
not serious and were proportional to dosage. [5] Level of evidence: 1
An RCT of 296 men found intracavernosal injection of alprostadil was
effective in the treatment of ED and associated with minimal adverse effects.
Higher response rates were obtained with increasing doses of alprostadil (from
2.5 to 20 g). Responses were recorded in 23% to 38% of men with ED of
neurogenic, vasculogenic, psychogenic, or mixed causes. Penile pain, usually
mild, occurred in 50 percent of the patients; prolonged erection occurred in 5
percent; and frank priapism in 1 percent. [6]Level of evidence: 2

An RCT of 44 patients compared intracavernosal alprostadil versus vacuum

devices and found that there were no significant differences between the groups
in ability to attain erection; however, the ability to attain orgasm was
significantly better in the alprostadil group, and overall satisfaction was rated
significantly better with alprostadil by the men and their partners. Men under
60 years of age and those with ED of less than 12 months' duration were more
likely to favor alprostadil. [7] Level of evidence: 3

Group psychotherapy significantly improves ED compared to medical therapy alone.

A systematic review of 9 RCTs including 398 men with ED found no

differences in effectiveness between psychosocial interventions versus local
injection and vacuum devices. Group psychotherapy was more likely than the
control group to reduce the number of men with persistence of ED at 6 months
post-treatment (RR 0.40, 95% CI 0.17-0.98, N=100; NNT 1.61, 95% CI 0.974.76). In a meta-analysis that compared group therapy plus sildenafil citrate
versus sildenafil, men randomly assigned to receive group therapy plus
sildenafil showed significant improvement of successful intercourse and were
less likely than those receiving only sildenafil to drop out. [8] Level of evidence:
1

References
References
Evidence references
1.

2.

3.

4.

5.

6.

1. Fink HA, MacDonald R, Rutks IR, et al. Sildenafil for male erectile
dysfunction: a systematic review and meta-analysis. Arch Intern Med.
2002;162:1349-60
View In Article | CrossRef
2. Hatzichristou D, Montorsi F, Buvat J, et al; European Vardenafil Study
Group. The efficacy and safety of flexible-dose vardenafil (levitra) in a broad
population
of
European
men.
Eur
Urol.
2004;45:634-41
View In Article | CrossRef
3. Rudkin L, Taylor MJ, Hawton K. Strategies for managing sexual
dysfunction induced by antidepressant medication. Cochrane Database Syst
Rev.
2004:CD003382
View In Article | CrossRef
4. Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in
patients with diabetes mellitus. Cochrane Database Syst Rev. 2007:CD002187
View In Article | CrossRef
5. Urciuoli R, Cantisani TA, Carlinil M, Giuglietti M, Botti FM. Prostaglandin
E1 for treatment of erectile dysfunction. Cochrane Database Syst Rev.
2004:CD001784
View In Article | CrossRef
6. Linet OI, Ogrinc FG; the Alprostadil Study Group. Efficacy and safety of
intracavernosal alprostadil in men with erectile dysfunction. N Engl J Med.

1996;334:873-7
View In Article | CrossRef
7. 7. Soderdahl DW, Thrasher JB, Hansberry KL. Intracavernosal drug-induced
erection therapy versus external vacuum device in the treatment of erectile
dysfunction.
Br
J
Urol.
1997;79:952-7
View In Article

8.

8. Melnik T, Soares BG, Nasselo AG. Psychosocial interventions for erectile

dysfunction.
Cochrane
Database
Syst
Rev.
2007:CD004825.
View In Article | CrossRef

Guidelines
The American Urological Association has produced the following:

Montague DK, Jarow JP, Broderick GA, et al; Erectile Dysfunction Guideline
Update Panel. The management of erectile dysfunction . Linthicum, MD: American
Urologic Association, Education and Research, Inc.; 2005. Updated 2006.
Reviewed 2011
Montague DK, Jarow JP, Broderick GA, et al; Erectile Dysfunction Guideline
Update Panel. Guideline on the pharmacologic management of premature ejaculation .
Linthicum, MD: American Urological Association, Inc.; 2004. Reviewed 2010

The American Association of Clinical Endocrinologists has produced the following:

Guay AT, Spark RF, Bansal S, et al; American Association of Clinical

Endocrinologists Male Sexual Dysfunction Task Force. American Association of
Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and
treatment of male sexual dysfunction: a couple's problem . Endocr Pract. 2003;9:77-95

The European Association of Urology has produced the following:

Wespes E, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile

dysfunction and premature ejaculation . Arnhem, Netherlands: European
Association of Urology; 2009

Further reading

Lue TF, Giuliano F, Montorsi F, et al. Summary of the recommendations on

sexual dysfunctions in men. J Sex Med. 2004;1:6-23
Erectile Dysfunction. Urol Clin North Am. 2005;32(4)
Basson R, Schultz WW. Sexual sequelae of general medical disorders. Lancet.
2007;369:409-24
Rees PM, Fowler CJ, Maas CP. Sexual function in men and women with
neurological disorders. Lancet. 2007;369:512-25
Traish AM, Goldstein I, Kim NN. Testosterone and erectile function: from
basic research to a new clinical paradigm for managing men with androgen
insufficiency and erectile dysfunction. Eur Urol. 2007;52:54-70

Zimmerman M, Posternak MA, Attiullah N, et al. Why isnt bupropion the

most frequently prescribed antidepressant? J Clin Psychiatry. 2005;66:603-10
Kasper S, Zivkov M, Roes KC, Pols AG. Pharmacological treatment of severely
depressed patients: a meta-analysis comparing efficacy of mirtazapine and
amitriptyline. Eur Neuropsychopharmacol. 1997;7:115-24
Dhar NB, Angermeier KW, Montague DK. Long-term mechanical reliability of
AMS 700CX/CXM inflatable penile prosthesis. J Urol. 2006;176:2599-601
Kostis JB, Jackson G, Rosen R, et al. Sexual dysfunction and cardiac risk (the
Second Princeton Consensus Conference). Am J Cardiol. 2005;96:313-21
Johannes C, et al. Incidence of erectile dysfunction in men 40 to 69 years old:
Longitudinal results from the Massachusetts Male Aging Study. J Urol.
2000;163:460-3

Codes
DSM-IV
302.72 Male erectile disorder

ICD-9 code

302.72 Psychosexual dysfunction;

impotence
607.84 Impotence of organic origin

with

inhibited

sexual

excitement;