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:

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

o 2% of men in their 40s
o 25% of men in their 60s
o 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
 ED is a clinical syndrome or symptom, and the diagnosis is based on the patient’s
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):
o Diagnostic and statistical manual of mental disorders. 4th ed. Washington,
DC: American Psychiatric Association; 2000:545-7
o 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/μL

o Differential count:
 Neutrophils—segmented: 1,800 to 7,800/μL
 Neutrophils—bands: 0 to 700/μL
 Lymphocytes: 1,000 to 4,800/μL
 Monocytes: 0 to 800/μL
 Eosinophils: 0 to 450/μL
 Basophils: 0 to 200/μL
 Erythrocyte count: 3.9 to 5.5 × 106/μL
 Hemoglobin: 14.0 to 17.5 g/dL
 Hematocrit: 41% to 50%
 Platelet count: 150 to 350 × 103/μL

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-pituitary-testis 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 μg/dL
 Free thyroxine: 0.9 to 2.3 ng/dL
 TSH: 2 to 11 μU/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 pudendal and inferior epigastric arteriography

Description

 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 with stenotic lesions indicate atherosclerotic disease

 Involves radiation exposure

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 α-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 the pharmacokinetics of mirtazapine
 The oral clearance of mirtazapine is reduced in elderly patients

 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 life-threatening

hypotension
 Dose adjustment is required when taken concomitantly with α-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 μg initially; increase dose by 2.5 to 5 μg increments, according to

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

Intra-urethral:

 125 to 250 μg 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 μg). 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
0.17-0.98, 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 patient’s 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 first-choice 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

 Mayo Clinic:
o Erectile dysfunction
o Erectile dysfunction: a sign of heart disease?
o Erectile dysfunction and diabetes: take control today
o Erectile dysfunction: Viagra and other oral medications
 American Urological Association:
o Erectile dysfunction: primary treatment options
o Surgical management of erectile dysfunction
 Cleveland Clinic:
o 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 4.62-
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

Alprostadil enhances erectile function with minor side effects.

 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 μg). 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 0.97-
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
References
Evidence references
1. 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. 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. 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. 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. 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. 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 isn’t 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; with inhibited sexual excitement;
impotence
 607.84 Impotence of organic origin