Nonpharmacologic Therapy Lifestyle Modifications

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Lifestyle modifications should always be addressed in the management of ED. A healthy diet, increase in regular physical activity and weight loss are associated with higher International Index of Erectile Dysfunction (IIED) scores and an improvement in erectile function.14 The clinician should recommend smoking cessation, reduction in excessive alcohol intake, and discontinuation of illicit drug use.


Psychotherapy is an appropriate treatment approach for patients with psychogenic or mixed dysfunction. It should address immediate causes of dysfunction, and if possible the partner should attend sessions as well. Effectiveness is not well documented for organic dysfunction unless combined with other therapies. Advantages include nonin-vasiveness and partner participation, while disadvantages include increased cost and time commitment.

Vacuum Erection Devices

Vacuum erection devices (VEDs) induce erections by creating a vacuum around the penis; the negative pressure draws blood into the penis by passively dilating arteries and engorging the corpora cavernosa. The erection is maintained with a constriction band placed at the base of the penis to reduce venous outflow (Fig. 51-2). They may be used as often as desired, but it is recommended that the constriction band not be left in place longer than 30 minutes at a time.

FIGURE 51-2. Available devices and prostheses used to treat ED. (From Ref. 15.)

VEDs are one of the most effective treatment modalities for ED. They have a success rate of greater than 90% in obtaining an erection sufficient for coitus and are considered a first-line noninvasive therapy.16 Rigidity may be improved by using a double pump technique in which the vacuum is applied for a couple of minutes, removed, then reapplied for another few minutes. Higher efficacy rates can also be achieved by combining VEDs with other therapies.

Onset of action is slow at around 30 minutes, which limits spontaneity. In addition, patients and partners may complain of a cold, lifeless, discolored penis that has a hinge-like feel. Painful ejaculation or inability to ejaculate are additional adverse effects. VEDs are contraindicated in persons with sickle cell disease and should be used with caution in patients on oral anticoagulants or who have bleeding disorders due to the increased possibility of priapism.


Penile prostheses are semi-rigid malleable or inflatable rods, which are inserted surgically into the corpus cavernosa to allow erections (Fig. 51-2). The malleable rods are rigid at all times, but may be bent into position by the patient when desired. The inflatable prostheses remain flaccid until the pump within the scrotum moves fluid from a reservoir to the cylinders within the penis. Detumescence is achieved when the fluid is then transferred back to the reservoir by activating a release button.

Because prostheses are the most invasive treatment available, they are only considered in patients who do not respond to medications or external devices, or those who have significant adverse effects from other therapies. Patient satisfaction rates

can be as high as 95% with partner satisfaction rates just slightly lower. The primary risk of insertion is infection, although this only happens in 3% of first-time prostheses. Semi-rigid malleable rods may interfere with urination, are difficult to conceal, and

have a higher likelihood of erosion. Most devices need replacement after 10 to 15 years.

Pharmacologic Therapy Phosphodiesterase Type 5 Inhibitors

Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) act by selectively inhibiting phosphodiesterase (PDE) type 5, an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP, smooth muscle relaxation is induced, leading to an erection (Fig. 51-1). However, the PDE inhibitors are only effective in the presence of sexual stimulation to drive the NO/cGMP system, making them facilitators of an erection, not initiators. Patients must be informed of the need for sexual stimulation to induce an erection, as it will not occur spontaneously.

® Effectiveness of the three available PDE inhibitors is essentially comparable, but differences exist in duration of action and, to a small degree, incidence of side effects and drug interactions (Table 51-4). Review of available data for each individual agent shows a 50% to 80% response rate depending on the dose of agent used and the etiology of dysfunction. Response rates tend to be lower in patients with radical prostatectomy as well as those with diabetes, severe nerve damage, or severe vascular disease.1 While efficacy rates appear to be similar between agents, there are some data to suggest continuation rates are higher and patient preference greater with tadalafil.19 The PDE inhibitors are considered first-line therapies due to high efficacy rates, convenience of dosing, and minimal severe adverse effects.

Table 51-4 Comparison of PDE Inhibitors

Sildenafil (Viagra)

Tadalafil (Calls)

Vardenafil ILevltra)

Available sUcnglhn

100-mq Nbi

2.5-, 10'. mg tubs

2.^, 5\ 10', 20'f»g tabs.

Inlli ji dosag? healthy

SOmg up to onoe dally taken

10 mg up to once daily taken

10 mg uplooncedity taten

jnHulli ifiiyj

1 ticxii prk^f [■:] il ,k '■.. il y

1 iKXir pxici if if :<u.d <i( 1 rvity

1 hour pfkH 10 iO^u Ji OCi ivity

a 2.5 mg daily al the same

lint fjtli <Jjy

Dosing rarxio for healthy




Oduli Ifillf)

Dosage in the eldeily

Ji mg every day

10mg everyday

S mg everyday

Oowje In iwal impfliimwH

50 met Wl1 tncprterarrt

^ nnq every day Invjderice* are)

i-2t) mg everyday

?5 (HQ &tty dJy {S^Cii'j

Dosjtjp in hepolE

li mg evef y day


5-10 mg'


I ¡me lo onart

30 minutes

li minutes

luaslltan 1 Iuiii

Onwr dftojvd hy hfcjh fit





(Nation oi effect

U|i rii^ rwuis

Up 1o J6 hours

Uplo4 hours


■8 hctin



CftV* ImaiCfi


CrP3A4 (majofj

CVP3CS flminor}

CYP3A5 (miivji]

CVPX ih>inor)

Cllnkally relevant dnjg Hrtialev. póteme Inhibitors, Nkrslei, a Mofijffi', apofe Nihatei.arwLsiliythmlr agenté

inSeiatlioTO d/ok" jnUuníuli. diuilunyiilvtrylhromyun o. bbckef^evylhinmytai

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'Sfktlivcd, bkjctefi ¿n 0.4 mg ijmiukTsin fvpiy dayíarc jpí jict» iah.* in ccmbnutkjfi v*i;Mddjldli:

VjMjenjíil can caust QT inle<vjl pnokjmjiliort ltiii efíat I in corobinaiit«! wil li tei tain an(ia«rii/Lhmic igenK can lend (t> hie 1tiiea;pnirK|

The most dramatic difference among the three agents is tadalafil's extended duration of action, earning it the nickname "the weekender drug." While sildenafil and vardenafil have average half-lives of 3 to 4 hours, tadalafil's half-life is approximately 18 hours. The extended half-life allows for more spontaneous sexual activity over a couple of days, but may increase the duration of adverse effects and likelihood of drug interactions. Tadalafil has been approved for use as a daily medication at a lower dose (2.5-5 mg) than the as-needed dose. The dosing efficacy appears to be similar to as-needed dosing, but cost will be prohibitive for many patients.

The most common side effects experienced with PDE inhibitors include headache, facial flushing, nasal congestion, dyspepsia, myalgia, back pain, and, rarely, priapism. Vardenafil and sildenafil may also cause difficulty in discriminating blue from green, bluish tones in vision, or difficulty seeing in dim light due to cross-reactivity with PDE 6 in the retina. Labeling for all PDE inhibitors includes a warning about non-arteritic ischemic optic neuropathy (NAION) in a small number of patients. This is a condition in which blood flow is blocked to the optic nerve. If patients experience sudden or decreased vision loss they should call a health care provider immediately.

Concern exists about the safety of renewing sexual activity and using PDE inhibitors in patients with cardiovascular disease. Because of the numerous adverse cardiovascular events reported after the release of sildenafil, a management approach was developed to give recommendations for the use of PDE inhibitors as well as to de-

21 22

termine the safety of intercourse in patients with cardiovascular disease ' (Table 51-5). In addition to the inherent risk of renewing sexual activity, PDE inhibitors can lead to significant hypotension. Patients taking organic nitrates are the most at risk, as these drugs potentiate the drop in blood pressure. All three PDE inhibitors are absolutely contraindicated in patients taking any form of nitrate, whether scheduled or sublingual for acute situations. Caution should be used when using a PDE inhibitor in patients taking a-blockers due to an increased risk of hypotension. In addition, the labeling for vardenafil contains a precautionary statement about the possibility of QT prolongation with the use of the drug. Other drug interactions and cautions vary slightly between agents and are described in Table 51-4.

Table 51-5 Recommendations of the Second Princeton Consensus Conference for Cardiovascular Risk Stratification of Patients Being Considered for PDE Inhibitor Therapy litk. CJtfrgary Pfricrlptiprt ai Pirlfil f CpndHHirt»

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Lùw risk hUVi Aiymptonutic Cvwtlh Iki Unci1 rni

(khh fat iv ascese

H.ii wfll CtKliULHIiXl hypinernion H.n mikJl ïtible an^ra

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HiHtmcdtfiie. swwe jnginj a I«™ myocarilLHi!il.iu rifiniv iunke mithin lhe past 6

ha moderAie t(*vj«iivt OMÎT failure ÎNYHA CUS? ID High risk Hb üraUWi? or symploruilk anglnj, dœiahf Uoolmiiiïl

Hinnyjonrrülltd hyt>c<iensk)n Hi; WvW faille (NYK*|Q|W III Of W)

HikJ j kxctU rriyotdrdu' ¡rtarillBAH Mrota; within lliii |HSr Î

He high rü* uitdiK intythmüs

Has. otiWiMCtîwe HrpeirnjphK cif(1io«nyt;fiirhy

PjtM?n1 trah Lie itanlfd on fly inhlbimr

^riom tfioifcl undcfçioiornpteijeafilioviicijlsr ï*aii«y And treadmill stneis fo»it (a (îcrpi m iv IdIc?aiï f to int itdscd myecantiüi ccrmmptton »vxtiK*d wiih inrrmdHl ¿ahilty

I'lJt inhibitor fetonrrairpdiidSod, uwual irtrcouru! JiookJ bedtfcntd

ClV CArilitwAu'.iUr; NiHA, Mwr Ttirk Hfuri Awoildiian Ctit,priUipHodi(K.[«i.

FujiuM- II.

The introduction of the oral PDE inhibitors has dramatically changed the treatment of ED. Direct-to-consumer advertising has informed patients of the availability of oral drugs for treatment. However, patients must be fully informed of side effects, drug interactions, mechanism of action, and dosing before being prescribed the medication. In addition, they need to understand the need for sexual stimulation to achieve the desired result and that a single trial is not adequate. It is estimated that six to eight attempts with a medication and specific dose may be needed before successful inter-

course results.


Alprostadil is a prostaglandin Ei analog that induces an erection by stimulating adenyl cyclase, which leads to an increase in smooth muscle relaxation, rapid arterial inflow, and increased penile rigidity. Alprostadil is available as an intracavernosal injection (Caverject or Edex) or a transurethral suppository (MUSE, medicated urethral system for erection), but the injectable form is more effective (Fig. 51-3). Both forms of al-

prostadil are considered more invasive than oral medications or VEDs, and are therefore second-line therapies.

MUSE consists of a urethral pellet of alprostadil with an applicator. Onset of action is within 5 to 10 minutes and it is effective for 30 to 60 minutes. Initial dose titration should occur in a physician's office to ensure correct dose and prevent adverse events.

Although effectiveness rates in clinical trials have been as high as 65%, its success in practice has been lower.25 Aching in the penis, testicles, legs, and perineum; warmth or burning sensation in the urethra, minor urethral bleeding or spotting, priapism, and lightheadedness are all possible adverse effects. In addition, partners may experience vaginal burning or itching. Disadvantages include lower effectiveness, high cost, adverse effects, complicated insertion technique, and a contraindication against use with a pregnant partner unless using a condom.

Alprostadil injected into the corpus cavernosum is the more effective route and is the only FDA-approved injection for ED. The onset of action is similar to transurethral alprostadil, but duration varies with dose and must be titrated in a physician's office to achieve an erection lasting no more than 1 hour. Injections should be done into one side of the penis directly into the corpus cavernosum, and then the penis should be massaged to distribute the drug. Because of cross-circulation, both corpora will become erect when massaging. Education is extremely important with intracav-ernosal injections. Patients must be adequately informed of technique, expectations, side effects, and when to seek help. Intracavernosal injections are effective in up to 90% ofpatients, but side effects, lack of spontaneity, andfear of needles limit their widespread use as first-line therapy, and therefore this therapy is most appropriate for patients in long-term stable relationships. Adverse effects include pain with injection, bleeding or bruising at the injection site, fibrosis, or priapism. Use with caution in patients with sickle cell disease, those on anticoagulants, or those who have bleeding disorders, due to an increased risk of priapism and bleeding.

Alprostadil Administration

FIGURE 51-3. Intraurethral and intracavernosal administration of alprostadil. (From Ref. 15.) Papaverine and Phentolamine

Papaverine and phentolamine are non-FDA-approved agents used for intra-cavernosal injection. Papaverine is a nonselective PDE inhibitor that induces an erection by relaxing smooth muscle and increasing blood flow. Phentolamine is a competitive a-adren-ergic receptor antagonist that increases arterial inflow by opposing arterial constriction. Both drugs are rarely used alone, and are most often mixed in various concentrations with alprostadil for increased effectiveness and in an effort to reduce adverse effects with smaller doses of each medication. Patients typically must see a specialist for use of these medications in mixtures, as the providers are the most likely to compound them and adjust dosages.


Yohimbine is an indole alkaloid produced in the bark of yohimbe trees. It selectively inhibits a2-adrenergic receptors in the brain that are associated with libido and penile erection. Because there are only limited data sup63orting its efficacy, yohimbine is not a recommended treatment for any form of ED. Adverse effects of the drug include nausea, irritability, headaches, anxiety, tachycardia, and hypertension.

Testosterone Supplementation

Androgens are important for general sexual function and libido, but testosterone supplementation is only effective in patients with documented low serum testosterone levels. In patients with hypogonadism, testosterone replacement is the initial treatment of choice, as it corrects decreased libido, fatigue, muscle loss, sleep disturbances, and depressed mood. Improvements in ED may occur, but they should not be expected to occur in all patients. The initial trial should be for 3 months. At that time, re-evaluation and the addition of another ED therapy is warranted. Dosage forms include oral, intramuscular, topical patches or gel, an implanted pellet, and a buccal tablet.

Injectable esters of testosterone offer the most inexpensive replacement option. Testosterone cypionate and enanthate have the longest duration of action and are therefore the preferred agents. There are several drawbacks associated with parenteral testosterone including the need to administer deep intramuscular injections every 2 to 4 weeks. In addition, levels of hormone are well above physiologic values within the first few days. Concentrations then decline and eventually dip below physiologic levels just before the next dose. These extreme changes in concentration lead to mood swings and a reduced sense of well-being.5

Treatment with topical products is attractive to patients due to convenience, but they tend to be more expensive than the injections. Testosterone patches and gels are administered daily and result in serum levels within the physiologic range during the 24-hour dosing period.5 Most patients prefer the nonscrotal patch or the gel because the scrotal patch requires shaving of the area, and the patch has a tendency to fall off. Care must be taken with the use of the gel to wash hands thoroughly after use and avoid baths or showers within 5 to 6 hours of application. The most common side effects of topical testosterone are dermatologic reactions caused by the absorption enhancers.

Oral testosterone products are also available for supplementation. Unfortunately, testosterone has poor oral bio-availability and undergoes extensive first-pass metabolism. Alkylated derivatives such as methyltestosterone and fluoxymesterone have been formulated to compensate for these problems, but this modification makes them considerably more hepatotoxic. This adverse effect makes oral replacement undesirable and this route of administration should not be used.

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Dealing With Erectile Dysfunction

Dealing With Erectile Dysfunction

Whether you call it erectile dysfunction, ED, impotence, or any number of slang terms, erection problems are something many men have to face during the course of their lifetimes.

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