Cara Liday and Catherine Heyneman
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Identify the structures of the male reproductive system and describe the physiology of a penile erection.
2. Differentiate between organic and psychogenic erectile dysfunction (ED) and describe the etiology and pathophysiology of each.
3. Identify the drug classes most likely to contribute to ED.
4. Define the essential components of history, physical examination, and laboratory data needed to evaluate the patient presenting with ED.
5. Describe current nonpharmacologic and pharmacologic options for treating ED and determine an appropriate first-line therapy for a specific patient.
6. Compare and contrast the benefits and risks for the current phosphodiesterase (PDE) inhibitors.
7. Identify patients with significant cardiovascular risk and recommend an appropriate treatment approach for their ED.
KEY CONCEPTS
Erectile dysfunction (ED) can be classified as organic, psychogenic, or mixed. Many patients may initially have organic dysfunction, but develop a psychogenic component as they cope with their inability to achieve an erection.
In addition to a physical exam, a thorough medical, social, and medication history with emphasis on cardiac disease must be taken before starting any treatment for ED to assess for ability to safely perform sexual activity and to assess for possible drug interactions.
A wide range of treatment options is now available for men with ED. These include medical devices, pharmacologic treatments, lifestyle modifications, surgery, and psychotherapy.
When determining the best treatment for an individual, the role of the clinician is to inform the patient and his partner of all available options while understanding his medical history, desires, and goals. The choice of treatment is primarily left up to the couple, but most often treatment is initiated with the least invasive option and then progresses to more invasive options if needed.
Vacuum erection devices (VEDs) and intracavernosal injections are highly effective for many patients, but side effects, lack of spontaneity, and fear of needles limit their widespread use as first-line therapy.
Effectiveness of the three available phosphodiesterase (PDE) inhibitors is essentially comparable, but differences exist in duration of action and, to a small degree, incidence of side effects and drug interactions.
Androgens are important for general sexual function and libido, but testosterone supplementation is only effective in patients with documented low serum testosterone levels.
INTRODUCTION
Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection sufficient for sexual intercourse. The definition is very subjective due to differences in desired or needed rigidity in patients of different ages and in different types of relationships. Patients may refer to their dysfunction as “impotence,” but the National Institutes of Health Consensus Development Conference recommends that the term “erectile dysfunction” replace the term “impotence” due to confusion with other forms of sexual dysfunction and the negative connotation associated with the term “impotence.”1 Patients may also develop libido or ejaculatory disorders, but these are not considered ED.
EPIDEMIOLOGY AND ETIOLOGY
ED becomes increasingly frequent as men age. Few men report erection problems before the age of 40, but the percentage of men experiencing ED increases to 26% in men aged 50 to 59 years and 40% in men aged 60 to 69 years.2The increase in incidence could be due to physiologic changes that occur with aging, the onset of chronic disease states associated with ED, increased medication use, lifestyle factors, or a combination of the above.
PATHOPHYSIOLOGY
The penis consists of three components, two dorsolateral corpora cavernosa and a ventral corpus spongiosum that surrounds the penile urethra and distally forms the glans penis. The corpora cavernosa consist of blood-filled sinusoidal or lacunar spaces, which are lined with endothelial cells, supported by trabecular smooth muscle, and surrounded by a thick fibrous sheath called the tunica albuginea. The cavernosal arteries, which are branches of the penile artery, penetrate the tunica albuginea and supply blood flow to the penis.
Sympathetic and parasympathetic nerves innervate the penis. In the flaccid state, α2-adrenergic receptors mediate tonic contraction of the arterial and corporal smooth muscles. This maintains high penile arterial resistance and a balance exists between blood flow into and out of the corpora. With sexual stimulation, nerve impulses from the brain travel down the spinal cord to the thoracolumbar ganglia.3 A decrease in sympathetic tone and an increase in parasympathetic activity then occurs, causing a net increase in blood flow into the erectile tissue. Erections may also occur as a result of a sacral nerve reflex arc while patients are sleeping (nocturnal erections). Acetylcholine-mediated parasympathetic activity leads to production of the nonadrenergic-noncholinergic transmitter nitric oxide (NO). By enhancing the activity of guanylate cyclase, NO increases the production of cyclic guanosine monophosphate (cGMP). Vasoactive peptide and prostaglandins E1 and E2 stimulate increased production of cyclic adenosine monophosphate (cAMP). Both cAMP and cGMP ultimately lead to a decrease in calcium concentration within smooth muscle cells of the penile arteries and the sinusoidal spaces, leading to smooth muscle relaxation and increased blood flow. As the sinusoidal spaces become engorged, intracavernosal pressure increases, subtunical venules are compressed, and the penis becomes rigid and elongated (Fig. 51–1).
FIGURE 51–1. Mechanism of erection and sites of action of various treatment modalities for erectile dysfunction (ED). Penile erection is achieved through relaxation of smooth muscle cells lining arterial vessels and sinusoidal spaces in the corpora cavernosa, which leads to increased arterial inflow and pressure, decreased venous outflow, and increased intracavernosal pressure. Smooth muscle relaxation is mediated by intracellular generation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP) via activation of guanylate cyclase by nitric oxide. Treatment modalities for ED (shown in blue) include oral phosphodiesterase type 5 (PDE-5) inhibitors, which inhibit the breakdown of cGMP, and local vasoactive agents. A link between testosterone and nitric oxide synthase has been demonstrated experimentally, but the significance of this observation in humans has not been established (indicated by the dashed line and question mark). Psychotherapy (not shown) may also be effective in selected individuals with ED. (From Ref. 4.)
Detumescence occurs with sympathetic discharge after ejaculation. Sympathetic activity induces smooth muscle contraction of arterioles and vascular spaces leading to a reduction in blood inflow, decompression of the sinusoidal spaces, and enhanced outflow.
Testosterone also plays a significant albeit complex role in erectile function. Testosterone is responsible for much of a man’s libido. With low serum concentrations, libido declines. Additionally, testosterone helps with stabilization of intracavernosal levels of NO synthase, the enzyme responsible for triggering the NO cascade. Interestingly, some patients with low or borderline low serum concentrations of testosterone will have normal erectile function, while some with normal levels will have dysfunction.
Normal penile erections are complex events that require the full function of the vascular, neurologic, and hormonal systems. Anything that affects the function of these systems may lead to ED. ED can be classified as organic, psychogenic, or a mixture of these. Organic dysfunction includes abnormalities in the three systems responsible for a normal erection or may be medication-induced (Tables 51-1 and 51-2). Note that many of the risk factors for ED are the same as risk factors for cardiovascular (CV) disease. In many patients, ED is the first indication of the endothelial dysfunction associated with cardiovascular disease.7 The presence of ED risk factors leads to the assumption that the patient has organic dysfunction. Most commonly, medical conditions that impair arterial flow into or out of the erectile tissue or affect the innervation will be strongly associated with ED. Patients with diabetes mellitus have exceptionally high rates of ED as a result of vascular disease and neuropathy. Additionally, a relationship has been found between low testosterone levels and an increased incidence of metabolic syndrome and type 2 diabetes.8
Psychogenic dysfunction occurs if a patient does not respond to psychological arousal. It occurs in up to 30% of all cases of ED. Common causes include performance anxiety, strained relationships, lack of sexual arousability, and overt psychiatric disorders such as depression and schizophrenia.9 Many patients may initially have organic dysfunction, but develop a psychogenic component as they try to cope with their inability to achieve an erection. It has been estimated that up to 80% of ED cases have an organic cause, with many having a psychogenic component as well.1
Table 51–1 Factors Associated With ED
Chronic medical conditions
Hypertension
Diabetes mellitus
Inflammatory conditions of the prostate
Coronary and peripheral vascular disease
Neurologic disorders (e.g., Parkinson’s disease and multiple sclerosis)
Endocrine disorders (hypogonadism and pituitary, adrenal, and thyroid disorders)
Psychiatric disorders (depression, anxiety, and schizophrenia)
Hyperlipidemia
Renal failure
Liver disease
Penile disease (Peyronie’s disease or anatomic abnormalities)
Surgical procedures
Perineal surgery
Radical prostatectomy
Vascular surgery
Lifestyle
Age
Smoking
Excessive alcohol consumption
Obesity
Poor overall health and reduced physical activity
Trauma
Pelvic fractures
Spinal cord injuries
Table 51–2 Medication Classes Associated With ED
Antihypertensives
β-Blockers (particularly nonselective)
Thiazide diuretics
Centrally acting agents (clonidine, methyldopa, and reserpine)
Spironolactone
α-Blockers
Lipid medications
Gemfibrozil
Antidepressants
Tricyclic antidepressants
Monoamine oxidase inhibitors
Selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors
Antipsychotics
Phenothiazines
Risperidone
Lithium
Anticonvulsants
Carbamazepine Phenytoin
Histamine antagonists
Cimetidine
Antiandrogens and hormones
5α-Reductase inhibitors
Progesterone and estrogen
Recreational drugs
Ethanol
Cocaine
Marijuana
Opiates
From Refs. 3, 5, 6.
TREATMENT
Desired Outcomes
ED is not a life-threatening condition, but left untreated it can be associated with depression, loss of self-esteem, poor self-image, and marital discord.13 The primary goal of therapy is achievement of erections suitable for intercourse and improvement in patient quality of life. Additionally, the ideal therapy should have minimal side effects, be convenient to administer, have a quick onset of action, and have few or no drug interactions.10 In addition to a physical exam, a thorough medical, social, and medication history with emphasis on cardiac disease must be taken before starting any treatment for ED to assess for ability to safely perform sexual activity and to assess for possible drug interactions.
General Approach to Treatment
After determining whether the ED is organic or psychogenic, the initial step in management is to identify associated disease states and lifestyle activities that adversely affect erectile function and treat them optimally. Medications suspected to cause or worsen ED should also be discontinued if possible. In patients with intermediate or high cardiovascular risk, additional testing should occur to determine if sexual activity is safe.
Clinical Presentation and Diagnosis of ED10,11
The introduction of oral medications and direct-to-consumer advertising has made patients feel more comfortable approaching practitioners for treatment advice. Despite this, some patients may only discuss their dysfunction when questioned directly by their provider or if their partner initiates the interaction. Patients may still feel that a loss in erectile function translates into a loss of masculinity.
Possible Signs and Symptoms
• Embarrassment
• Anxiousness
• Anger
• Marital problems
• Low self-confidence or morale
• Full inability to achieve erections
• Ability to achieve partial erections, but not suitable for intercourse
• Erections sufficient for intercourse, but early detumescence
• The problem may have a slow or acute onset, or may wax and wane
Diagnosis
ED may be the presenting symptom of other chronic disease states.
Full medical, social, and medication histories should be taken to determine areas that can cause or exacerbate ED and to assess the patient’s ability to safely perform intercourse.
• Medical history with emphasis on cardiovascular and psychiatric disorders, diabetes, trauma, and surgical procedures
• Social history: smoking, recreational drug use, exercise, and alcohol consumption
• Medication history including prescription, nonprescription, and dietary supplements
PE
• Review for hypogonadism (gynecomastia, testicular atrophy, reduced body hair, increase in body fat)
• Digital rectal exam to determine if prostate is enlarged
• Vital signs
• Abnormalities of the penis or impaired vasculature and nerve function to the penis
Labs
• Thyroid function Fasting lipid panel
• HbA1c Metabolic panel
• Serum testosterone Further cardiac testing if warranted
Determine severity
• Sexual health inventory for men12:
• How do you rate your confidence that you could get and keep an erection?
• When you had erections with sexual stimulation, how often were your erections hard enough for penetration?
• During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?
• During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?
• When you attempted sexual intercourse, how often was it satisfactory for you?
• Questions scored 1 to 5, very low to very high respectively. Score of 21 or less indicates ED likely.
Table 51–3 Common Drug Treatment Regimens for ED
A wide range of treatment options is now available for men with ED. These include medical devices, pharmacologic treatments, lifestyle modifications, surgery, and psychotherapy.
When determining the best treatment for an individual, the role of the clinician is to inform the patient and his partner of all available options while understanding his medical history, desires, and goals. Most often treatment is initiated with the least invasive option and then treatment progresses to more invasive options if needed. Ultimately, the choice of therapy should be individualized, taking into account patient and partner preferences, concomitant disease states, response, administration route, cost, tolerability, and safety. Common drug treatment regimens for ED are listed in Table 51–3.
Patient Encounter, Part 1
A 52-year-old man with type 2 diabetes, hypertension, and dyslipidemia returns to your clinic for follow-up on his chronic disease states. When reviewing his history, he describes problems having satisfactory sexual intercourse. After further questioning, you determine that his dysfunction has progressively gotten worse over the last year. He is quite emotional and states that the problem is distressing and has caused significant marital discord. He wonders about “those ads on television” suggesting a pill.
Based on the available information, how would you classify his ED?
What additional information do you need to determine his ability to safely perform intercourse?
What additional information do you need before establishing an appropriate treatment regimen?
Nonpharmacologic Therapy
Lifestyle Modifications
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
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 noninvasiveness 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.
Prostheses
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.17 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.17 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.18 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
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.20 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 nonarteritic 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 determine the safety of intercourse in patients with cardiovascular disease21,22 (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 α-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
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 intercourse results.23
Alprostadil
Alprostadil is a prostaglandin E1 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 alprostadil 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%,24 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 intracavernosal injections. Patients must be adequately informed of technique, expectations, side effects, and when to seek help. Intracavernosal injections are effective in up to 90% of patients, but side effects, lack of spontaneity, and fear 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.
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 α-adrenergic 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
Yohimbine is an indole alkaloid produced in the bark of yohimbe trees. It selectively inhibits α2-adrenergic receptors in the brain that are associated with libido and penile erection. Because there are only limited data supporting its efficacy, yohimbine is not a recommended treatment for any form of ED.26 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.
Patient Encounter, Part 2: Medical History, Physical Exam, and Diagnostic Tests
PMH: Type 2 diabetes for 15 years; not controlled due to his stressful profession; he often works late, eats on the run, and has no time for exercise. Hypertension for 8 years, currently uncontrolled. Dyslipidemia for 8 years, currently controlled
FH: Father had type 2 diabetes and died of myocardial infarction at the age of 50 years; mother is alive at 75, with no major illnesses
SH: Works long hours as a business executive; drinks alcohol only occasionally, but smokes half a pack of cigarettes per day; has a 20-pack per year history
Meds: Metformin 1,000 mg orally twice daily; metoprolol XL 50 mg orally once daily; simvastatin 20 mg orally once daily
ROS: (-) Morning, nocturnal, or spontaneous erections suitable for intercourse; (-) nocturia, urgency, symptoms of prostatitis; (+) significant life stressors; (+) mild pain in feet
PE:
VS: BP 148/90 mm Hg, p 85 bpm, RR 18/min, T 37°C (98.6°F)
CV: Normal exam
Genital/Rectal: Normal scrotum and testicles w/o masses; penis without discharge or curvature
Labs: Complete metabolic panel, CBC, and thyroid panel within normal limits; lipid panel: total cholesterol, LDL, HDL, triglycerides within normal limits; hemoglobin A1c 8% (0.08), testosterone 700 ng/dL (24 nmol/L)
Given this additional information, what are his risk factors for ED?
Identify treatment goals for this patient.
What pharmacologic and nonpharmacologic alternatives are available for this patient?
An alternative to the oral route is the buccal mucoadhesive system. The Striantbuccal system adheres to the inside of the mouth and the testosterone is absorbed through the oral mucosa and delivered to the systemic circulation. There is no first-pass effect, as the liver is bypassed by this route of administration. Patients apply a 30-mg tablet to the upper gum twice daily. The cost is similar to that of the patch or gel. Side effects unique to this dosage form include oral irritation, bitter taste, and gum edema.
General side effects of testosterone include gynecomastia, dyslipidemia, polycythemia, and acne. Weight gain, hypertension, edema, and exacerbations of congestive heart failure also occur due to sodium retention. Before initiating testosterone, the patient should undergo evaluation for benign prostatic hypertrophy and prostate cancer. Routine follow-up includes yearly prostate-specific antigen, digital rectal exam, hemoglobin and liver function, in addition to assessment of response.
OUTCOME EVALUATION
Successful therapy for ED results in an increase in erections suitable for intercourse, and most importantly in an improvement in the patient’s quality of life. Ideally, the therapy chosen is free of significant adverse effects, discomfort, and inconvenience. Laboratory evaluation and a physical exam are not necessary for evaluation of effectiveness, but may be necessary to determine if adverse events are occurring.
Evaluate satisfaction and effectiveness after a 4-week trial unless the patient initiates follow-up sooner. Some therapies such as intracavernosal injections will require multiple visits over the long term to determine the correct dose and to detect adverse effects. If the initial therapy is not effective, the patient must be further evaluated to determine if the initial assessment of comorbid disease states, type of dysfunction, and patient goals were correct. After ensuring that patient goals are realistic and providing further counseling, providers will then increase the dose of drug if not at maximum, switch to another therapy, or add a therapy if indicated.
Patient Encounter, Part 3: Creating a Treatment Plan
Based on the information available, create a treatment plan for this patient’s ED.
Which of the available options will be your treatments of choice based on degree of invasiveness, ease of use, and side-effect profile?
Perform a cardiovascular risk assessment to determine risk.
What are the safety and efficacy monitoring parameters for the chosen treatment?
Patient Encounter, Part 4
The patient now presents with new-onset chest pain for which his provider has given him a prescription of sublingual nitroglycerin.
What is your treatment of choice based on this new information?
What are the safety and efficacy monitoring parameters for the chosen treatment?
Abbreviations Introduced in This Chapter
Patient Care and Monitoring
1. Assess the patient’s specific symptoms to determine the type of dysfunction. Does the patient have ED or an ejaculatory or libido disorder?
2. If problems are with erectile ability, ask specific questions related to onset, frequency, and sexual relationships. Does the patient history imply psychogenic, organic, or mixed dysfunction?
3. Perform a thorough medical and social history as well as a physical exam to diagnose ED and to determine potential causes that may be treatable.
4. Perform a thorough history of prescription and nonprescription medications. Are any of the patient’s medications associated with ED or are they contraindicated with possible ED therapies?
5. Generally treatment is started with the least invasive option and then progresses to more invasive options, but ultimately patient preference determines the initial therapy.
6. Discontinue medications that may cause ED if possible and optimally treat associated disease states.
7. If the patient is not satisfied, provide further counseling to ensure that they are using the therapy appropriately and that they have realistic goals.
8. Provide patient education with regard to disease state, lifestyle modifications, drug therapy, and device technique:
• The causes of ED
• The fact that therapy will not cure ED, but may be helpful in improving erections; it is important to have realistic expectations
• The appropriate use of medications and devices
• Typical adverse effects
• Drug interactions
• Warning signs and their management (e.g., vision changes, fibrosis, pain, priapism, or hypotension)
• The importance of frequent follow-up with the provider
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
REFERENCES
1. NIH Consensus Conference. NIH Consensus Development Panel on Impotence. JAMA 1993;270:83–90.
2. Bacon CG, Mittleman MA, Kawachi I, et al. Sexual function in men older than 50 years of age: Results from the health professionals follow-up study. Ann Int Med 2003;139:161–168.
3. AACE 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, 2003 update. Endocr Pract 2003;9:77–95.
4. Morgentaler A. A 66-year-old man with sexual dysfunction. JAMA 2004;291:2994–3003.
5. Morales A. Testosterone replacement: When is there a role? Int J Impot Res 2000;12(Suppl 4):S112–S118.
6. Hafez ESE, Hafez SD. Erectile dysfunction: Anatomical parameters, etiology, diagnosis, and therapy. Arch Androl 2005;51:15–31.
7. Billups KL. Sexual dysfunction and cardiovascular disease: Integrative concepts and strategies. Am J Cardiol 2005;96(Suppl):57M–61M.
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