IT’S IN THE MALE
| UPDATE ON SEXUAL DYSFUNCTION —Dana A. Ohl, MD, Professor, Department of Urology, and Head, Division of Andrology and Microsurgery, University of Michigan Medical School, Ann Arbor |
| Prevalence of erectile dysfunction (ED): 10% psychogenic; in 1 study, 50% of men 40 to 70 yr of age had some degree of ED; other studies show lower rates, based on definition of ED |
| Evaluation: history; physical examination; laboratory testing; specialized testing; history—onset, duration, degree of impairment, structural changes, cardiovascular risk assessment (must be evaluated); organic—gradual onset (eg, atherosclerosis); risk factors present (eg, diabetes, hypertension [HTN], age) consistent across all types of sexual activity; orgasm with flaccid penis indicates vascular problem; psychogenic—sudden onset, risk factors absent, sleep erections present, orgasm absent; nocturnal penile tumescence (NPT) monitoring used for patients who do not accept psychogenic causation; with normal RigiScan NPT test (60% rigidity, >15 min duration), patient referred to sex therapist; drugs—antihypertensives and antidepressants (selective serotonin reuptake inhibitors [SSRIs]); some SSRIs change brain chemistry, making it unfavorable for sexual activity and ability to achieve climax; inability to achieve climax most common side effect of SSRIs; antihypertensive drugs (eg, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium-channel blockers) lower blood pressure and decrease perfusion pressure in penile arteries; physical examination—adequate testosterone (virilization), gross vascular disease, neurologic examination; laboratory tests—testosterone has profound effect on penile tissue function; studies indicate nitric oxide synthase in genitourinary tract androgen-dependent; check other hormones if testosterone low (<50% of lower limit of normal range); treat as independent problem; thyroid function; assess and treat cardiovascular risks (eg, fasting glucose, lipid profile, hemoglobin [Hb]A1C ) |
| Vascular causes of ED: HTN, hypercholesterolemia, and diabetes cause structural changes in penile arteries, atherosclerosis, and endothelial dysfunction; arterial stenosis and impaired vasodilation lead to arterial insufficiency; impaired smooth muscle relaxation due to corporal veno-occlusive dysfunction leads to excessive outflow and reduced inflow in penis |
| Cardiovascular risk assessment and treatment: Princeton Consensus Conference Guidelines provide clinical evaluation for cardiovascular risk and sexual activity; low-risk—<3 cardiovascular risk factors, controlled HTN, uncomplicated past myocardial infarction (MI), class I heart failure, successful coronary revascularization (eg, stent or coronary artery bypass graft), mild valvular disease, mild stable angina; intermediate-risk—3 risk factors, moderate stable angina, recent MI (2ע wk), class II heart failure, or other manifestations of peripheral vascular disease; high-risk— unstable angina, uncontrolled HTN, class III or IV heart failure, MI <2 wk ago, severe arrhythmias, severe vascular disease; treatment for low-risk—phosphodiesterase type 5 (PDE5) inhibitor, vacuum device; high-risk—abstain from sexual activity until cardiac condition stabilized; intermediate-risk—get cardiac evaluation |
| Specialized testing: color Doppler ultrasonography (US) for vascular assessment, RigiScan NPT, penile arteriography in selected patients; not required for most patients; testing performed to assess and alter ED therapy course (eg, pelvic injury in young accident victim undergoing revascularization); testing characterizes systemic diseases—color Doppler US, normal values (inflow >30 cm/sec, end diastolic velocity <5 cm/sec, resistive index 0.80, normal erection with provocative testing); penile arteriography; duplex US |
| Therapies for ED: surgical (eg, penile prostheses); few indications for revascularization; penile injections with vasoactive substances; vacuum erection devices (not well accepted by patients); Food and Drug Administration (FDA)-approved injectables; intraurethral agents (prostaglandin E1 [PGE1]); newer PDE5 inhibitors; penile tissue function affected by androgen status; unlikely that testosterone alone will cure ED; studies show testosterone may convert nonresponder to responder of other therapies (eg, PDE5 inhibitors); rescue may be as high as 60%; avoid testosterone overdose |
| Mechanism of action of PDE5 inhibitors: cause accumulation of cyclic guanosine monophosphate (cGMP) and prolonged smooth muscle response; PDE5 inhibition occurs systemically, but importance in comparison to other PDE enzymes quite small; importance of PDE5 in penile tissue significant |
| Phosphodiesterases: 11 families; type 5 most important in penis; PDE5 inhibitors highly selective for PDE5 group; cross-reactivity exists with PDE6 (in retina) and PDE 11 (in skeletal muscle, heart, testis, pituitary, and sperm cells) |
PDE5 Inhibitors | Names: sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis) highly specific; 60% efficacy; 80% improvement of erection; order of potency (high to low)—vardenafil, sildenafil, tadalafil; bioavailability, protein binding, and dosing affect potency (eg, 100 mg sildenafil maximum dose vs 20 mg vardenafil); vardenafil and sildenafil have similar time to maximum plasma concentration (1 hr); 4-hr half-life; tadalafil takes 2 hr to reach maximum plasma concentration, 18-hr half-life in young individuals |
| Adverse effects: sildenafil most crossreactive; PDE 6 in retina causes bluish discoloration of vision; less reactivity with vardenafil; no visual discoloration with tadalafil; tadalafil inhibits PDE 11 at doses given for sexual dysfunction; role of PDE 11 unknown; systemic effects—vasodilatory side effects (eg, headaches, flushing, rhinitis, heartburn due to gastroesophageal reflux from relaxation of smooth muscle); specific adverse effects—visual changes (sildenafil), muscle pain (tadalafil), etiology unknown; cardiovascular safety—studies indicate no statistical difference between placebo and sildenafil in serious cardiovascular events per 100 patient-years of exposure (4.9 vs 3.9) |
| Drug interactions: nitrates contraindicated for all agents; cause profound drop in blood pressure in some patients when combined with PDE5 inhibitors; wash-out factor—3 half-lives; 24 hr for sildenafil, 2 days for tadalafil; α-blocker factors—for sildenafil, separate dose by 4 hr; contraindicated for tadalafil, except for 0.4 mg tamsulosin (Flomax); vardenafil contraindicated for all α–blockers and >0.4 mg Flomax |
| Advantages: oral therapy high priority for patients; difference between satisfaction rate and patients’ wishes to continue using drugs (as opposed to penile injections); well tolerated |
| Disadvantages: less effective than other treatments (eg, penile prosthesis); cannot be used with nitrates; time; cost |
| Other studies: cardioprotective effects—in study of sildenafil vs placebo, time to limiting angina, time to angina, and exercise duration statistically improved in sildenafil group; similar studies with vardenafil; drugs originally designed as antianginal agents; provide patients with good instructions for taking medications; time of onset—faster than previously experienced (eg, 14 min with sildenafil, 11 min with vardenafil); caution patients that more rapid time of onset could occur; after radical prostatectomy—sildenafil improved erectile function and well tolerated |
| Penile implants: self-contained inflatable devices and malleable implants have role in some patients; for satisfaction, patient must have 3-piece inflatable device with reservoir, scrotal pump, and cylinders; fluid from cylinders can be transferred to reservoir (for flaccidness); transfer large amount of fluid into cylinders from reservoir to create large, firm erection; other devices do not provide same effect |
| Surgical technique: approach controversial; infrapubic—familiar; easy reservoir placement; potential injury to dorsal penile nerve; takes longer than penoscrotal approach; penoscrotal—faster; potentially limits infection rate; easy dissection to dilate corporal bodies; penile nerves not in surgical field; numbness rate close to zero; blind reservoir placement; setup—lone star retractor; hook in meatus stretches and lifts corporal bodies; small penoscrotal incision; sutures can be placed in corporal body; easy dilation; reservoir placement tricky; make incision and reach through fascia to place reservoir; technique learned quickly |
Penile Prosthesis Improvements: in laboratory, parylene coating increased durability (American Medical Devices); lock-out reservoir (Mentor Corporation) prevents autoinflation
| Complications: malfunction, erosion, pain, and infection; prevent infection using shorter surgical time (penoscrotal approach), preoperative antibiotics (eg, vancomycin [Vancocin], gentamicin), aseptic technique, laminar flow in operating room, irrigation of surgical site; incidence of infection 1% to 3% |
| Management of infection: remove device; reinserting device results in scar tissue and shrinkage; difficult to reinsert device; Mulcahy salvage procedure—remove device, perform irrigation series, reprep and replace in same operative setting; 80% effective without need to completely remove device; protocol—remove all prosthetic parts and foreign material; irrigate wound with 7 solutions; completely change operative drapes, instruments, gowns, and gloves; insert new prosthesis (no drains); oral antibiotics for 1 mo; antibiotic irrigations—1) vancomycin-gentamicin solution, half- strength hydrogen peroxide to break down bacterial biofilm, half-strength povidone-iodine (Betadine); 2) pressure wash with vancomycin-gentamicin (speaker eliminates this step; causes edema); 3) in reverse order, reprep and reinsert device |
| Coated implants: AMS has rifampin and minocycline (InhibiZone) bonded to device; Mentor has Titan (hydrophilic coating to resist bacterial adherence and formation of biofilm); InhibiZone leaches out into tissue locally over extended period (primarily during first wk); Titan coating (polyvinyl perilodine) pulls antibiotic irrigation into coating; satisfaction rates for implants—remain high |
| CRYPTORCHIDISM: CURRENT MANAGEMENT STRATEGIES —Steven G. Docimo, MD, Professor of Urology, University of Pittsburgh School of Medicine, and Chief, Division of Urology, Children’s Hospital of Pittsburgh |
| Undescended testis: includes several diagnoses; true undescended testis, ectopic testis, ascended testis, nonpalpable testis; surgical approach tailored to specific task |
| True undescended testis: exists along path of testicular descent; processus vaginalis must be patent (last step of testicular descent); on physical examination, will not remain in scrotum even momentarily (retractile testis will); associated with epididymal anomalies |
| Ectopic testis: more common than true undescended testis; defined by gubernacular attachment, most commonly in superficial inguinal pouch; original definition required that testis be beyond external ring, but testis can be higher than that; less likely, but can still have patent processus vaginalis |
| Testicular ascent: recognized as common only fairly recently; testis documented to be scrotal and later undescended; well documented phenomenon; not uncommon, sometimes predictable |
| Categories: infantile—rarely reported; testis documented to be descended, but ascends during first year of life; true undescended testis with patent hernia; childhood true ascent—in older children with anatomy of true undescended testis; patent processus vaginalis and shortened cord structures draw testis up out of scrotum; ectopic ascent—probably most common form; lax ectopic attachments allow testis to hang in scrotum; as child grows, attachments draw testis out of scrotum to undescended position; some have fibrous processus, but as child grows, testicle pulled out of scrotum; does not respond to hormone therapy; postsurgical ascent—testis caught in scar tissue from previous operation, ascends with linear growth; can occur after hernia repair or orchidopexy; challenging surgical problem; will not descend spontaneously or respond to hormone therapy; registry in Netherlands confirmed that 74% of undescended testis were ascended testis, rather than primary undescended testis |
| Surgical intervention for palpable testis: classical inguinal incision; high scrotal orchidopexy (Bianchi)— approach not popular, but selectively used in patients with palpable ectopic testis or ascended testis (less likely to have patent processus vaginalis); also used in patients with surgical testicular ascent; low scrotal approach—horizontal scrotal (dartos pouch) incision; expose and open processus; dissect cord to external ring; probe processus; use inguinal incision if patent; if hernia not present, divide processus for length; rationale—scrotal incision necessary for either approach; transcrotal control of testis makes hernia repair more intuitive; scrotal incision more cosmetic, less morbid; quick procedure if inguinal hernia not present |
Nonpalpable Testis | Defined by clinical description: includes abdominal testis, peeping testis, vanishing testis, and atrophic testis (nubbins) |
| Traditional operations for abdominal testis: extended inguinal orchidopexy, transabdominal approach, Fowler- Stephens orchidopexy (spermatic vessels divided), 2-stage orchidopexy, testicular autotransplantation; meta-analysis—low testis had higher success rate (lack of atrophy and intrascrotal position); intra-abdominal testis had 74% success rate; Fowler- Stephens approach had 66% to 67% success rate; advantage to preserving spermatic vessels and advantage to operating before 6 yr of age; success of operation not as high as expected; technique important; success rate of one study—transabdominal orchidopexy (97%), Fowler-Stephens orchidopexy (74%), overall success (84%), orchidectomies (16%); data reaffirm benefit of maintaining intact vessels |
| Diagnostic laparoscopy: standard approach if testis not palpable during examination under anesthesia; scrotal exploration if any palpable tissue present in scrotum; if hemosiderin deposit or nubbin found, do not perform laparoscopy; traditionally used to define open surgical approach to testicles; findings—vessels and vas deferens meeting and exiting internal ring, blind-ending vessels, and vas deferens (vanishing testis; no need to proceed further); intra-abdominal testis (found 50%), absent testis (50%) |
| Therapeutic laparoscopy: laparoscopic one-stage and staged orchidopexies; success rates according to study— primary orchidopexy (97%), single-stage Fowler-Stephens (74%), staged Fowler-Stephens (88%); becoming gold standard |
Educational Objectives
| The purpose of this program is to provide the listener with information on the nature and management of erectile dysfunction (ED). After hearing and assimilating this program, the clinician will be better able to: |
 | 1. Summarize the etiology of ED. |
| 2. Describe the examination and treatment of the patient with ED. |
| 3. Discuss the mechanism of action, types, and drug interactions of phosphodiesterase type 5 (PDE5) inhibitors. |
| 4. Cite some recent advances in the use of penile prostheses. |
| 5. Review the etiology and management of cryptorchidism. |
Discussed on This Program
Gentamicin (several trade names) Povidone iodine [Betadine] Sildenafil [Viagra] Tadalafil [Cialis] Vancomycin [Vancocin, Vancocin IV, Lyphocin, Vancocin HCl, Vancocin HCl Pulvules, Vancoled, Vancomycin HCL] Vardenafil [Levitra]
Suggested Reading
Abouassaly R, Montague DK: Penile prosthesis coating and the reduction of postoperative infection Curr Urol Rep 5:460, 2004; Arroteia KF et al: Does orchidopexy revert the histological alterations in epididymal and vas deferens caused by cryptorchidism? Arch Androl 51:109, 2005; Ben-Meir D, Hutson JM: Re: Successful outpatient management of the nonpalpable intra-abdominal testis with staged Fowler-Stephens orchiopexy J Urol 173:2206, 2005; Carson CC 3rd: Efficacy of antibiotic impregnation of inflatable penile prostheses in decreasing infection in original implants Urol 171:1611, 2004; Chattaraj S: Male erectile dysfunction: therapy and drug delivery IDrugs 4:684, 2001; Darouiche RO: Treatment of infections associated with surgical implants N Engl J Med 350:1422, 2004; Guvenc BH et al: Advantages of video-assisted approach in detecting epididymal anomalies and treatment of nonpalpable testis Urol Int 74:127, 2005; Henry GD et al: Penile prosthesis cultures during revision surgery: a multicenter study J Urol 172:153, 2004; Henry GD et al: Revision washout decreases penile prosthesis infection in revision surgery: a multicenter study J Urol 173:89, 2005; Hirshkowitz M, Schmidt MH: Sleep-related erections: Clinical perspectives and neural mechanisms Sleep Med Rev 9:311, 2005; Hutson JM, Hasthorpe S: Testicular descent and cryptorchidism: the state of the art in 2004 J Pediatr Surg 40:297, 2005; Israilov S et al: Treatment program for erectile dysfunction in patients with cardiovascular diseases Am J Cardiol 93:689, 2004; Jensen JB et al: Clinical experience with the mentor alpha-1 inflatable penile prosthesis: report on 65 patients Scand J Urol Nephrol 39:69, 2005; Koksal M et al: The effects of sildenafil on ocular blood flow Acta Ophthalmol Scand 83:355, 2005; Kostis JB et al: Sexual Dysfunction and Cardiac Risk (the Second Princeton Consensus Conference) Am J Cardiol 96:313, 2005; Lepor NE: Vascular disease and erectile dysfunction Rev Cardiovasc Med 6:127, 2005; Milbank AJ, Montague DK: Surgical management of erectile dysfunction Endocrine 23:161, 2004; Moncada I et al: Current role of penile implants for erectile dysfunction Curr Opin Urol 14:375, 2004; Montague DK et al: Chapter 1: The management of erectile dysfunction: an AUA update J Urol 174:230, 2005; Montorsi F et al: Penile implants in the era of oral drug treatment for erectile dysfunction BJU Int 94:745, 2004; Patil KK et al: Laparoscopy for impalpable testes BJU Int 95:704, 2005; Redman JF: The ascending (acquired undescended) testis: a phenomenon? BJU Int 95:1165, 2005; Reffelmann T, Kloner RA: Pharmacotherapy of erectile dysfunction: focus on cardiovascular safety Expert Opin Drug Saf 4:531, 2005; Schmittenbecher P: Hormonal cryptorchidism therapy: Systematic review with metanalysis of randomised clinical trials J Pediatr Surg 40:896, 2005; Shabsigh R, Perelman MA: Health issues of men: prevalence and correlates of erectile dysfunction Urol 174:662, 2005; Shimizu T et al: Erectile dysfunction following nerve-sparing radical retropubic prostatectomy and its treatment with sildenafil Int J Urol 12:552, 2005; Sun P, Swindle R: Are men with erectile dysfunction more likely to have hypertension than men without erectile dysfunction? A naturalistic national cohort study J Urol 174:244, 2005; Van Ahlen H et al: The real-life safety and efficacy of vardenafil: an international post-marketing surveillance study—results from 29 358 German patients J Int Med Res 33:337 200.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, Dr. Ohl has disclosed that he is a consultant for Bayer, GlaxoSmithKline, Pfizer, Lilly, ICDS, Mentor, AMS, and Solvay.
Dr. Ohl was recorded at Updates in Urological Health: Advanced Diagnosis and Treatment of Urological Disorders, held November 24, 2004, in Dearborn, Michigan, sponsored by the University of Michigan School of Medicine. Dr. Docimo was recorded at Urology 2004: New Solutions for Old Problems, held November 12-14, 2004, in Los Angeles, sponsored by Cedars-Sinai Medical Center of Los Angeles. The Audio-Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.
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