Erectile Dysfunction

Erectile Dysfunction

Definition

  • Erectile Dysfunction (ED) is defined as the inability to achieve or maintain an erection sufficient for sexual intercourse.

Physiology of Normal Erection

  • A normal erection requires the full function of vascular, neurologic, and hormonal systems.
  • Key components include:
    • Decreased sympathetic tone and increased parasympathetic tone.
    • Net increase of blood flow into the erectile tissue.
    • Acetylcholine-mediated parasympathetic activity.
    • Nitric oxide: increases cGMP (cyclic guanosine monophosphate).
    • PGE1 & PGE2: increases cAMP (cyclic adenosine monophosphate).
    • cGMP & cAMP lead to decreased calcium concentration in smooth muscle cells of the penile arteries and sinusoidal spaces, resulting in smooth muscle relaxation.

Classification of Erectile Dysfunction

  • Organic:
    • Any abnormalities in the vascular, neurologic, or hormonal systems responsible for normal erection.
    • Endothelial dysfunction: impairs arterial flow to erectile tissue.
    • Conditions affecting innervation.
  • Psychogenic:
    • Lack of response to arousal.
    • Associated with psychiatric disorders (including anxiety), strained relationships.
    • Anxiety leads to sympathetic stimulation, causing smooth muscle contraction of arterioles and vascular spaces in erectile tissue.
    • May initially have organic ED, but psychogenic ED can develop in response.
  • Mixed:
    • Combination of organic and psychogenic factors.
  • Medication-Induced:
    • Caused by various medications (organic).

Medication-Induced ED

  • Antihypertensives:
    • B-blockers
    • Thiazide diuretics
    • Centrally-acting agents (Clonidine, methyldopa)
    • Spironolactone
    • α-blockers
  • Lipid Lowering Agents:
    • Gemfibrozil
  • Antidepressants:
    • TCAs (Tricyclic Antidepressants)
    • MAOIs (Monoamine Oxidase Inhibitors)
    • SSRIs (Selective Serotonin Reuptake Inhibitors)
  • Antipsychotics:
    • Phenothiazines
    • Risperidone
    • Lithium
  • Anticonvulsants:
    • Carbamazepine
    • Phenytoin
  • Anti-androgens & Hormones:
    • 5-reductase inhibitors
    • Progesterone/Estrogen
  • Other:
    • Cimetidine (Tagamet®)
    • Spironolactone (Aldactone®)
  • Recreational Substances:
    • Ethanol
    • Cocaine
    • Marijuana

Evaluation of ED

  • Medical History:
    • Complete medical history with psychosocial issues.
  • Physical Exam:
  • Labs:
    • Total & free serum testosterone
    • Serum glucose
    • Fasting lipid panel
    • Thyroid function panel
    • PSA (Prostate-Specific Antigen)
  • Questionnaire:
    • The International Index of Erectile Dysfunction

Risk Factors for ED

  • Chronic Medical Conditions:
    • Cardiovascular (CV): Hypertension, coronary & peripheral vascular disease, hyperlipidemia.
    • Neurologic disorders (Parkinson’s).
    • Endocrine (Diabetes, thyroid, pituitary dysfunction).
    • Psychiatric disorders (depression, anxiety).
    • Other: renal failure, liver disease, penile disease (Peyronie’s), or anatomic abnormalities.
  • Surgical Procedures:
    • Perineal surgery, radical prostatectomy, vascular surgery.
  • Lifestyle:
    • Smoking, excessive alcohol consumption, obesity, poor overall health & reduced physical activity.
  • Trauma:
    • Pelvic fractures, Spinal cord injuries.

Nonpharmacologic Treatment of ED

  • Identify associated disease states & lifestyle factors that may adversely affect erectile function.
  • Rx meds: discontinue if possible, consider dosage reduction or medication change.
  • Encourage healthy diet and physical activity, maintenance of healthy body weight.
  • Smoking cessation, discontinue excessive ETOH & illicit drug use.
  • Psychotherapy:
    • For psychogenic or mixed ED.
  • Vacuum Erection Devices (pumps)
  • Prosthesis:
    • Surgical; invasive techniques used for refractory ED or if contraindications to pharmacologic therapy.

Pharmacologic Treatment of ED

  • Phosphodiesterase (PDE) Type 5 Inhibitors
    • MoA: Selective inhibition of PDE-5, inducing smooth muscle relaxation
      • PDE type 5: enzyme that breaks down cGMP
    • "Erection Facilitators"-Only effective in the presence of sexual stimulation to drive the nitric oxide/cGMP system
    • Adverse Effects:
      • HA, facial flushing, nasal congestion, dyspepsia
      • Rare- priapism (seek medical care for erection > 4 hours)
      • Changes in vision, difficulty in blue-green discrimination
      • Label warning: non-arteritic ischemic optic neuropathy (NAION)- Blood flow is blocked to the optic nerve (sudden decrease in vision)

PDE 5 Inhibitors-Cardiovascular Disease Risk

  • Low Risk:
    • Asymptomatic CV Disease
    • Well-controlled HTN
    • Mild, stable angina, MI > 6 weeks ago
    • PDE Inhibitors can be used in most cases
  • Moderate Risk:
    • > 3 risk factors for CAD
    • Moderate, stable angina
    • Recent MI or CVA within last 6 weeks
    • Complete CV workup (including stress test) to determine tolerance to increase myocardial oxygen demand associated with physical activity
  • High Risk:
    • Unstable or symptomatic angina (despite treatment)
    • Poorly controlled HTN
    • Moderate to severe valvular heart disease, MI within 2 weeks
    • PDE Inhibitors are CONTRAINDICATED

PDE Inhibitors: Drug Interactions

  • CONTRAINDICATED with nitrates
    • Contraindicated with PRN dosing & scheduled dosing of nitrates
  • Caution with α-blocker therapy
    • increases risk of hypotension & possible QT prolongation
  • CYP 450 3A4 Inhibitors/inducers –
    • cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, saquinavir, & grapefruit juice
  • Ethanol-increases risk of hypotension with excessive ETOH intake

PDE-5 Inhibitors

  • Sildenafil (Viagra®)
    • Doses: 25mg, 50mg, 100mg
    • Start at 50mg taken about 1 hour prior to sexual activity; Max frequency is once per day; absorption may be reduced/delayed with high fat meal
  • Vardenafil (Levitra®)
    • Doses: 2.5mg, 5mg, 10mg, 20mg
    • Start at 10mg taken about 1 hour before sexual activity; absorption may be reduced/delayed with high fat meal
  • Vardenafil (Staxyn®)
    • Doses: 10mg ODT
    • 10mg PO 1 hour prior to sexual activity
  • Tadalafil (Cialis®)
    • Doses: 2.5, 5, 10, & 20mg
    • Start on 10mg-can be taken without regard to meals (extent & rate of absorption is not significantly affected)
    • Take at least 30 min prior to anticipated sexual activity
    • Maximum dosing frequency is once per day
    • Erectile function may be improved for up to 36 hours following 1 dose
    • Approved for daily use-2.5 mg taken daily at the same time (without regard to timing of sexual activity
  • Avanafil (Stendra®)
    • Doses: 50, 100, 200mg
    • Start with 50mg – 30 min prior to sexual activity

Alprostadil

  • Class-Prostaglandin E1 analog
  • MoA-Induces erection by stimulating cAMP & causing smooth muscle relaxation & rapid arterial inflow
  • Dosage forms:
    • Injection
    • Urethral suppositories

Alprostadil (Caverject, Edex®)

  • Intracavernosal injection (Caverject®, Edex®)
    • Injectable is more effective than suppository
    • Dosage titration in office
    • Achieve an erection for no longer than 1 hour
    • Injected into one side of the penis directly into the corpus cavernosum then massaged to distribute the medication
    • Effective in 90% of patients
    • Adverse Effects
      • Injection: pain with injection, bleeding or bruising at the injection site, fibrosis, priapism
      • Caution in patients with sickle cell disease or on anticoagulant therapy

Alprostadil (MUSE®)

  • Transurethral suppository (MUSE®)
  • Medicated urethral system for erection
  • Urethral pellet of alprostadil with an applicator
  • Onset/Duration
    • Onset-5-10 minutes; Duration-30-60 minutes
  • Titration of dosage of both forms in physician’s office to ensure correct dose, but avoid excessive adverse effects
  • Adverse Effects
    • Aching in the penis, testicles, legs, perineum, warmth or burning sensation of the urethera, minor uretheral bleeding or spotting, priapism, lightheadedness
    • Cannot be used during sexual intercourse with pregnant partner (unless condom is used)
    • Partner may also experience burning or itching

Testosterone Supplementation

  • Androgens Important for general sexual function & libido
  • Testosterone supplementation is only effective for treatment of ED in patients with low serum testosterone levels
  • Usually not used as monotherapy
  • Routes of administration
    • Oral, IM, Topical patches or gel, buccal tablet
  • Adverse Effects
    • Gynecomastia, dyslipidemia, acne, weight gain, hypertension, edema
  • Monitoring
    • Prior to treatment: evaluate for BPH & prostate cancer
    • Yearly PSA, DRE, LFTs, lipid panel
  • Testosterone (AndroGel, Depo-Testosterone, Aveed)

Other ED Treatment

  • Papaverine
    • Vasodilator – nonspecific PDE inhibitor
    • Labeled use for relief of peripheral ischemia associated with arterial spasm
    • Off-label use for ED; lack of clinical data for safety & efficacy
    • AE: priapism, corporal fibrosis, hypotension, hepatotoxicity
  • Yohimbine (Yocon®)
    • Herbal product
    • central α-blocker
    • increases catecholamines & improves mood
    • Use: Unlabeled/Investigational Treatment of SSRI-induced sexual dysfunction; impotence; may have activity as an aphrodisiac
    • Adverse Effects
      • Nausea, irritability, HA, anxiety, tachycardia, hypertension