management of erectile dysfunction

1. Erectile dysfunction-
Management
Dr S.K Plash
Moderator-Dr Kumar Madhavan

2. Treatment considerations.
Total expenditures for OPD clinical management of ED (exclusive of pharmaceutical costs) in the
United States in the year 2000 approximated $330 million.
9th most costly among the most frequent urologic diagnoses.
The American Urological Association (AUA) ED guideline panel has endorsed shared decision
making as the state of the art in ED management.
Role of partner interview.
Follow-up care is an essential part of ED management and should not be overlooked.
Primary basis is to ensure continual success with the therapeutic outcome.
Treatment discontinuation occurs at high rates among patients who are not reassessed regularly.

3. Treatment considerations
Current recommendations –
Adhere to a shared decision-making approach to therapy.
All therapeutic options are presented to the patient with
advantages and disadvantages of each.
The perceived risks and benefits based on the patient’s clinical
situation should be presented and weighed to make an informed
decision.

5. Treatment considerations.
Lifestyle modification
Medication change
Psychosexual therapy
Hormonal therapy
Pharmacologic therapy
Medical device
Surgery

6. Lifestyle modification improves erectile
dysfunction.
Discontinuation of smoking
Increasing exercise and weight control
Mediterranean diets and calorie restriction improves ed in men with metabolic syndrome.
No-nose saddle for occupational bicycle riders-reduces ed risk by reducing perineal trauma.
The mechanisms of this effect may include reduced cardiovascular risk factors, increased serum
testosterone levels, and overall improved mood and self-esteem.

7. Medication change
Changing antihypertensive medications like thiazide diuretics and beta blockers
to CCB,ARB,ACE inhibitors.
Patients suffering adverse sexual dysfunction effects from the use of
SSRIs (e.g., ED, retarded ejaculation), treatment strategies such as drug
substitution (e.g., bupropion, nefazodone, buspirone, mirtazapine),drug
holidays, SSRI dosage reduction, watchful waiting, and administration of
PDE5 inhibitors have enabled sexual function recovery.

8. Psychosexual therapy
A variety of interventions are used: systematic anxiety
reduction/desensitization,interpersonal therapy, cognitive-behavior therapy, sex
education, couples’ communication and sexual skills training.
Collaborative efforts with a mental health clinician who has expertise in
psychosexual therapy may be necessary.

9. Hormonal therapy
Testosterone replacement.
Alternative hormonal replacement
Hyperprolactinemia treatment.

10. Testosterone replacement
Evaluating serum testosterone levels before and during treatment is imperative,
efficacy of testosterone therapy is best judged by clinical response rather than a precise
testosterone determination.
Current recommendations suggest that a short (e.g., 3-month) therapeutic trial is justified,
and, in the absence of a response, testosterone administration should be discontinued.
Potential adverse effects of androgen therapy (i.e., erythrocytosis, sleep apnea, urinary
symptoms, prostate cancer progression risk, gynecomastia, acne) should be recognized.
No causal relationship between testosterone and cardiovascular events.

11. Testosterone replacement
Monitoring of patients on therapy consists of:-
Baseline assessment- includes digital rectal examination and serum PSA testing
along with laboratory evaluation (i.e,hemoglobin/hematocrit levels, liver
function tests, cholesterol level, and lipid profile) followed by the assessment of
treatment efficacy after 3 to 6 months and annually thereafter to ascertain
symptom response and any adverse events.
Short-acting preparations- preferred for the initial treatment of patients so
that therapy can be discontinued on the occasion of an adverse event.
Various routes: intramuscular, subcutaneous, transdermal (patch and gel),
buccal, and oral.

12. Testosterone replacement
Intramuscular-
Testosterone enanthate(Testoviron) 250 mg or Cypionate (Testocyp) 200 mg every 2-3 weeks-
deep intramuscular leads to supraphysiologic levels of testosterone for first 72 hrs, f/b decline to
subphysiologic levels by 10 to 12 days.
Alternative dosing of 100 mg every 7 to 10 days can be considered in situations in which
patients experience symptomatic mood changes or sexual fluctuations associated with
documented early low testosterone level troughs.
Testosterone propionate (Testop) 200 mg every 2-3 days becoz of short half life.
Testosterone undecanoate(cernos) depot formulation 1000 mg every 10 weeks, used in
Europe.

13. Testosterone replacement
Subcutaneous preparation-Pellets offer a subcutaneous, long-acting depot formulation of testosterone.
Testopel is a pellet containing 75 mg of testosterone.
Dosing usually is 2 to 6 pellets (150 to 450 mg testosterone) implanted subcutaneously every 3 to 6
months.
Transdermal-patches and gels, with a delivery approach that intentionally simulates normal circadian
levels of testosterone.
When patients apply medication in the morning, higher initial absorption mimics normal diurnal variation.
Testoderm TTS represented an alternative formulation avoiding the inconveniences of the scrotal
application. Applied to the arm, back, or buttock as a 5-mg patch.
Androderm, an alternative product, delivers 2.5 or 5 mg of testosterone daily.
Both patches have been associated with itching, chronic skin irritation, and allergic contact
dermatitis.

14. Testosterone replacement
AndroGel (testosterone 1% gel) is a topical gel pack that contains 50,
75, or 100 mg of testosterone, with only 10% of the drug being absorbed
during a 24-hour period.Applied once daily in the morning to clean, dry
skin on the shoulders, upper arms, or abdomen.
Axiron (testosterone 2% solution) is another transdermal product
approved by the US FDA, consisting of 30 mg of testosterone applied to
each axilla once daily using a metered applicator.
Testosterone nasal gel (Natesto) is applied to the nostrils. The
recommended dosage of Natesto is 11 mg of testosterone (2 pump
actuations; 1 actuation per nostril) administered intranasally two to three
times daily for a total daily dose of 22 to 33 mg.

15. Testosterone replacement
Buccal- Striant is a tabletlike, mucoadhesive treatment system (30 mg of testosterone)
that continuously delivers medication. It is applied twice daily to the gum tissue above
the incisors, allowing testosterone to be absorbed through the buccal mucosa.
Oral - Limited, liver toxicity of testosterone (i.e., hepatitis, cholestatic jaundice,
hepatomas, hemorrhagic liver cysts, and hepatocellular carcinoma) related to the large
doses necessary to achieve normal serum levels.
Large doses (>200 mg/day) are required orally because much of the administration is
rendered
metabolically inactive during the “first-pass” circulation through the liver.
Not FDA approved.

19. Alternative hormonal therapies
DHT-A therapeutic DHT gel is available at a dose of 125 to 250 mg/day,
yielding plasma DHT levels comparable with physiologic testosterone
levels.
Dehydroepiandrosterone (DHEA)- a hormone supplement with
androgen-like and estrogen-like effects, has been used, although limited
evidence exists showing it improves sexual function.
Human chorionic gonadotropin (hCG) has been found to increase total
and free testosterone and estradiol 50% above baseline.
Because of insufficient evidence about the therapeutic benefits and
adverse effects of alternative replacement therapies in older men
with testosterone deficiency, they are not currently recommended
for use.

20. Hyperprolactinemia treatment
The therapeutic objective, rather, is to identify and address the underlying cause, which
may then ameliorate ED.
Offending drugs, such as estrogens, morphine, sedatives, and neuroleptics, should be
discontinued.
A prolactin-secreting adenoma should be treated medically and, if necessary, surgically.
Bromocriptine, a dopamine agonist that lowers prolactin level and restores testosterone
to normal, reduces the size of the tumor.
Neurosurgical ablation becomes necessary if the therapeutic response to medication
does not occur or visual effects are noted in association with optic nerve compression.

21. Pharmacologic therapy
Central acting
1.pro erectile-D2 agonists in medial hypothalamus
2.opposing anti erectile-5ht1a/2 antagonists.
Peripherally acting
1.pro erectile-increasing cAMP/cGMP synthesis.
2.opposing anti-erectile-PDE-5 inhibitors.

22. Oral therapy
Orally administered medication for ED meets many of the attributes of
“ideal therapy,” which include convenience, simplicity, and
noninvasiveness.

23. Phosphodiesterase Type 5
Inhibitors.
Sildenafil citrate (Viagra,Pfizer) in 1998.
Vardenafil hydrochloride (Levitra,Bayer) in
2003.
Tadalafil (Cialis,Lilly) in 2003.
Avanafil (Stendra,Vivus) in 2012.

24. PDE5i
MOA- Block PDE5, which degrades cGMP ,the downstream effector
of nitric oxide.
NO causes corporal smooth muscle relaxation required for
erection.
These medications augment but do not induce the erectile
response.
Sexual stimulation is required for NO release from penile nerve
endings and vascular endothelium.

25. PDE5i
Sildenafil and Vardenafil- cross react with PDE6 in retina- cause
visual disturbances.
Tadalafil-longer half life, longer therapeutic window and more
convenience.
All have equivalent efficacy and tolerability.
Successful intercourse rates of 70%.

27. Patients are instructed to take on demand 30-60
minutes before intended sexual activity.
Daily dosing regimen approved for Tadalafil.

28. Optimization of effect
Applying sexual stimulation properly as a prerequisite for nitric
oxide release.
Reducing food intake, which may delay drug absorption.
Escalating drug dosing as needed.
Correcting or improving adverse health conditions (e.g.,
glycemic control, hyperlipidemic control, androgen
replacement), which affect drug efficacy, has also been
demonstrated as potentially beneficial.

30. Precautions.
Cardiovascular risk assessment and stabilization should be considered for all
men before the institution of PDE5 inhibitor therapy.
Nitrate use in any form (e.g., sublingual nitroglycerin, isosorbide dinitrate,)
represents an absolute contraindication.
Past use of nitrates, that is, more than 2 weeks before the use of PDE5
inhibitors, is not considered a contraindication.
If angina occurs during sexual activity when using a PDE5 inhibitor, patients
should cease this activity and seek emergency care immediately.
Inform medical personnel that a PDE5 inhibitor was taken and should avoid
nitroglycerin use for a period of 24 hours for sildenafil and vardenafil and 48
hours for tadalafil.

31. Precautions
If acute MI occurs with the use of PDE5 inhibitors, usual therapies, with the exception of
organic nitrates, may be administered.
If hypotension results from PDE5 inhibitor use, patients should be placed in the Trendelenburg
position and given intravenous fluids along with administration of α-adrenergic agonists (e.g.,
phenylephrine) as needed.
Refractory hypotension warrants intra-aortic balloon counterpulsation, as specified by the
American College of Cardiology/American Heart Association guidelines.
No pharmacologic antidote to the PDE5 inhibitor/nitrate interaction exists.
Caution is advised when PDE5 inhibitors are co-administered with α-adrenergic blockers,
because
both agents are vasodilators with blood pressure–lowering effects.

32. Side effects
Headache (7% to 16%)
Dyspepsia (4% to 10%),
Flushing (4% to10%).
Myalgia/back pain (0 to 3%)
Nasal congestion (3% to 4%),
Visual disturbances (e.g., photophobia, blue vision) (0 to 3%).
NAION (non arteritic anterior optic neuropathy)-sudden blindness-case reports in HTN,DM and
dyslipidemic patients.

33. Other oral therapies
Alpha adrenergic antagonists- Phentolamine mesylate-non specific alpha adrenergic receptor
antagonist-
produce corporeal smooth muscle relaxation by blocking the postsynaptic alpha 1 adrenergic
receptor-
further investigation required.
yohimbine hydrochloride-central effects on the mediation of penile erection operating as an α2-
adrenoreceptor antagonist the drug does not appear to enable successful sexual intercourse any
better than placebo in men with confirmed organic ED.
its modest results suggest that it may be best limited to men with psychogenic ED-dose-5.4 mg
thrice daily for a month).

34. Other oral therapies
Dopaminergic agonists-Apomorphine-
-activating D1 and D2 receptors at a central level within the paraventricular nucleus of the brain-
administered in sublingual form with a dosage range of 2, 4, and 6 mg, and it has no erectile
efficacy if it is swallowed.Not FDA approved.
Melanocortin receptor agonists- Melanotan.-NOT FDA approved.
Others-
Trazodone-(Desyrel) is an antidepressant that has been associated with priapism, prompting its
“off-label” investigation as a possible treatment for ED, L-arginine, Limaprost, Naltrexone.
Not FDA approved.

35. Intracavernosal injection
It was discovered in 1982 that vasoactive agents, delivered by injection into the penis, induced
erections.
Three medications are used regularly in clinical practice: alprostadil, papaverine, and
phentolamine.
Administered clinically as a single agent (i.e.,monotherapy) or in various combinations (e.g.,
bimix, trimix).
Combination therapy offers a synergistic mechanism of the vasoactive agents to elicit maximal
erectile responses, particularly among patients who have failed monotherapy.
A general rule of thumb is to start with a small dose of medication, especially in patients with
non-vasculogenic forms of ED.

37. Alprostadil- prostaglandin E1.- causes smooth
muscle relaxation
It currently is the only FDA-approved injectable medication for ED, locally metabolized by 96%
within 60 minutes and does not appreciably enter the peripheral Circulation.
At dosages of 10 to 20 μg, alprostadil produces full erections in 70% to 80% of patients with ED.
S/E- Pain at the injection site or during erection (in 11% of patients), hematoma/
ecchymosis (1.5%), prolonged erection/priapism (1% to 5%), and penile fibrotic lesions (2%).
ADVANTAGE - lower incidences of prolonged erection, systemic side effects, and penile fibrosis.
DISADVANTAGE- higher incidence of painful erection and higher cost, and, after reconstitution
into liquid from powder, alprostadil has a shortened half-life if not refrigerated.

38. Papaverine
Alkaloid isolated from the opium poppy, is a nonspecific PDE inhibitor-causes smooth muscle
relaxation.
Metabolized in the liver, plasma half-life is 1 to 2 hours.
Its general efficacy in promoting penile erection after intracavernosal administration is
approximately 60%.
Advantage- Inexpensive, stable at room temp.
Disadvantage- liver enzyme elevations, priapism risk (up to 35%), and penile fibrosis risk (1% to
33%), which have led to its abandonment as monotherapy.

39. Phentolamine
Also used orally.
ERECTOGENIC EFFECT-mediated by blocking the (antierectile) postsynaptic α1-adrenergic
receptor.(Alpha adrenergic antagonist).
limited success when administered intracavernosally as a sole agent.
short plasma half-life (30 minutes).
S/E-systemic hypotension, reflex tachycardia, nasal congestion, and gastrointestinal upset.

40. VIP
disappointing effects when administered alone,
Although if combined with other drugs such as papaverine and phentolamine, erection
responses were elicited.
VIP, in combination with phentolamine (Invicorp), is currently being sought for regulatory
approval in the United States.

41. Contraindications of ici use
-men with psychological instability.
-a history or risk for priapism.
-histories of severe coagulopathy or unstable cardiovascular disease.
 -reduced manual dexterity (although the partner can be trained in the
injection technique)
-use of monoamine oxidase inhibitors (because of the risk of precipitating a
life-threatening hypertensive crisis in the event that an intracavernosal α-
adrenergic agonist is used to reverse apriapic episode).

42. Intraurethral suppositories.
Medication absorbed into spongiosa from urethra,later passes into cavernosa.
A synthetic formulation of prostaglandin E1 was developed and FDA approved it in November
1996 as MUSE (Medicated Urethral System for Erection).
a suppository inserted into the urethral opening dispenses a semisolid pellet (1 × 3 mm) of
alprostadil (125-, 250-, 500-, and 1000-μg doses) into the distal urethra (3 cm from the external
urethral meatus).
50 % response rate. among responders-70% sexual intercourse possible.
ACTIS-adjustable penile constriction band-fda approved-enhance local retention and effect of
medication.

44. Intraurethral suppositories.
ALIBRA- transurethral bimix –consist of alprostadil and prazosin.-increase at home responder
rate from 47% with alprostadil alone to 70% with ALIBRA.
PDE5i> ICI>SUPPOSITORY.
Main indications-Patients who are nonresponsive to PDE5 inhibitors resulting from damage of
the autonomic penile nerve supply (e.g., radical prostatectomy, cystectomy, and trauma) or
those who wish to use the therapy in combination with PDE5 inhibitors.
Rare indication- soft (cold) glans syndrome, which may occur after penile prosthesis
implantation or as a clinical entity.

45. MUSE-Side effects.
MC- local urogenital pain (approximately one-third of patients) and minor urethral
bleeding (5%), hypotension (3%), dizziness (4%), and priapism (0.1%).
Contraindication- known hypersensitivity to alprostadil, abnormal penile anatomy, and
conditions that increase the risk of priapism.
MUSE seems safe for female partners, producing only a 5.8% incidence of vaginal burning or
itching, although it should not be used without a condom for intercourse with a pregnant
woman.

46. Transdermal/topical pharmacotherapy.
Alprostadil has been a more promising prospect, alprostadil 0.3% in combination
with a proprietary permeation enhancer, referred to as Vitaros and alprostadil
combined with NexACT, referred to as Alprox-TD.

47. Medical devices
For those patients who do not respond to or who decline oral or local vasoactive
pharmacotherapeutic options, vacuum erection device therapy may be alternatively explored.
PRINCIPLE- to mechanically create negative pressure surrounding the penis to engorge it with
blood and then restrain blood egress from the organ to maintain the erection-like effect.
Consists of a usually clear plastic suction cylinder and vacuum-generating source (manual or
battery-operated pump) in one piece.
It is placed directly over the flaccid penis and operated, and after the penis is erected an elastic
constriction ring or band is positioned at the base of the penis; then the vacuum is released and
the device is removed.

49. Medical devices
The cylinder has a pressure-release valve designed to prevent penile injury from
excessive negative pressure.
It is recommended that the ring should not be left in place for longer than 30 minutes.
Efficacy rate as high as 90% but lower satisfaction rate- 30% to 70%.
Complications - penile pain and numbness, difficult ejaculation, petechiae, ecchymosis, skin
necrosis, fourniers gangrene.
Patients receiving anticoagulant therapy (e.g., aspirin, warfarin) and patients with bleeding
disorders should use the device with caution.

50. Surgery
Surgery is often applied in the face of penile injury resulting from genital or pelvic trauma, penile
structural deformity occurring in association with Peyronie disease, or possibly cavernosal
fibrosis secondary to prolonged ischemic priapism or infection.
They are also considered when medical therapy for ED is contraindicated, unsuccessful, or
undesirable.
1 -Penile revascularization.
2 -Penile prosthesis surgery.

51. Penile revascularization surgery.
Arterial revascularization.
Venous reconstruction.

52. Arterial revascularization
Creating an anastomosis of the inferior epigastric artery either to the corpus cavernosum
directly or to vascular conduits of the penis such as the dorsal artery (i.e., revascularization), the
deep dorsal vein (i.e., arterialization), or the deep dorsal vein with venous ligation(i.e.,
arterialization with venous reconstruction).
Success depends on careful patient selection.
Penile arteriography is required to establish a penile arterial anatomic defect.
Other organic causes of ED (e.g., venous incompetence) that would limit surgical success should
be excluded.

53. Arterial revascularization
Inclusion criteria for arterial surgery:
Age less than 55 years, nonsmoker, nondiabetic, absence of venous leakage, and radiographic
confirmation of stenosis of the internal pudendal artery .
The highest success rates are reported in young men (less than 30 years of age) with isolated
arterial stenosis after perineal or pelvic trauma.
Complications-Glans hyperemia (13%), shunt thrombosis (8%), and inguinal hernias (6.5%).

54. Venous reconstruction
Venous reconstruction was proposed to prevent pathologic blood egress from penis (i,e to
correct venoocclusive ED).
Ligating or embolizing penile veins (e.g., superficial dorsal vein, deep dorsal vein, crural vein) or
surgically compressing the penile crura (e.g., crural plication/ligation, pericavernoplasty).
Currently considered investigational.

55. Alternate therapies
Low-intensity extracorporeal shock wave therapy (Li-ESWT),stem cell therapies, and platelet-
rich plasma have been proposed as an effective, noninvasive treatment option for ED among
men who respond poorly to PDE5 inhibitors.
MOA- in animal models erectile function improved by promoting regeneration of nerves,
endothelium, and smooth muscle of the penis.

56. Dornier aries

57. Penile prosthesis surgery.
NA Borgoraz (1936)-used rib cartilage to fashion a rigid implant.
Dr Brantley scott (1973) 3 piece inflatable device.
Dr Hernan Carrion,Dr Michael small(1974)-Semi rigid prosthesis.

58. Penile prosthesis surgery-indications
Failure/rejection of more conservative therapies.
Peyronies disease in which ed coexists with penile deformity.
Irreversible organic etiology of ed.
Penile fibrosis.
Post priapism ed unresponsive to other therapies.
Phalloplasty after radical penile surgery for cancer/gender change surgery.
Psychological impotence after failure of all other treatment.

59. Types of prosthesis
1)Semirigid rod- Malleable rods and Positional devices.
2)Inflatable (hydraulic) devices ---OF TWO TYPES---2 PIECE AND 3 PIECE.
Today there are two vendors of penile implants in the United States: Boston Scientific and
Coloplast.
The three-piece inflatable implant is composed of two cylinders with one placed in each corpus
cavernosum. These are connected by tubing to a pump located in the scrotum, which, in turn, is
connected to an abdominal reservoir.
The function of the pump is to transfer fluid between the reservoir and the cylinders.
Because fluid can be totally evacuated from the cylinders, the penis becomes very loose in the
flaccid state. These two features, alternating exceptional rigidity and flaccidity, make the three-
piece inflatable group the most popular device among implanting urologists and patients.

62. Models available
Boston Scientific markets three models of the three-piece inflatable device:
(1)AMS 700 LGX , which expands in girth and may increase in length up to 25%
(2)AMS 700 CX and
(3)AMS 700 CXR, which increase in girth only.
The CXR is a narrower version of the CX.
Coloplast sells two versions of a three-piece inflatable implant, the Titan, and a narrower
congener, the Titan narrow, which increase in girth only.
The two-piece inflatable implant, the Ambicor of Boston Scientific, comprises a scrotal
pump and two cylinders, one placed in each corporal body.

66. Semirigid rod implants.
There are currently two types of malleable semirigid rod implants, the Tactra of Boston
Scientific and the Genesis of Coloplast.
The Tactra is composed of a nickel-titanium alloy (nitinol) core surrounded by a silicone outer
coat.
The core of the Genesis is individual braided silver wire strands, and it likewise has a silicone
outer cover.
Both malleable devices are provided in fixed girth sizes.
The firmness of the erection depends on the intrinsic rigidity of the cylinders and the amount of
dead space in the erectile chambers surrounding the cylinders. Less dead space provides greater
rigidity.

69. Advantages of semirigid devices
Relatively inexpensive
Easy to implant
Relatively low mechanical failure rate
Easy to use.

70. Drawbacks of semirigid devices.
Simulate a constant erection(do not permit flaccidity)
Maybe difficult to conceal
Do not increase penile girth
Quality of erection decreases over time
Distal tip of device more likely to atrophy/migrate toward distal glans and to erode through
meatus

71. Inflatable prosthesis-advantage
Permit girth as well length expansion.
Penile flaccidity when not in use.
Act and feel more like a natural erection: three piece device is more rigid when inflated, more
flaccid when deflated.

72. Potential contraindications
Situational ed
Ed resulting from relationship conflict
Potentially reversible ed
Inability to follow instructions
Hygiene issue and skin cleanliness
Non compliance with current medications
Spinal cord injury
Uncontrolled diabetes.

73. Complications
Infection-1-3 %
Device malfunction
Erosion
Cylinder extrusion.
Cylinder aneurysm
S-shaped penile deformity
Poor glans support
Scrotal hematoma
Penile necrosis

77. Patient satisfaction
Patient satisfaction with penile prosthetic implantation is highest among all of the treatments
for ed.