MANAGING MALE SEXUAL DYSFUNCTION
From An Evidence-Based Approach to Common Problems in Urology presented by the University of California, San
Francisco, School of Medicine
| VARICOCELES AND INFERTILITY: ARE THEY RELATED ? Jonathan P. Jarow, MD, Professor of Urology, Radiology,
Pathology, and Reproductive Biology, Johns Hopkins University, School of Medicine, Baltimore, MD
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| Varicoceles and infertility: epidemiologic data obtained from infertility clinics and physical examinations performed
on school children and military recruits questionable
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 | Animal data: mimic human condition; showed unilateral varicoceles exert bilateral effect on testicular temperature,
blood flow, and histology; effect on testes—not neurologically or immunologically mediated; reversible by varicocele
repair; conclusion—data support hypothesis that varicoceles damage testes
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| Human data: varicoceles associated with reduction in—ipsilateral testicular volume, regardless of fertility status;
testicular growth in adolescents; semen parameters; key observations—semen parameters improve with varicocele
repair; men with varicoceles fertile (men with large varicoceles only subjects with reduced fertility
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| Effect of varicoceles over time: among adolescents—varicoceles can reduce testicular volume and cause progressive
decline in semen quality; varicocele repair can promote catch-up growth in testis and improve semen quality;
among adults—assessment of asymptomatic military personnel with varicoceles provided no strong evidence that individuals
who enter adulthood with varicoceles and normal fertility status become infertile over time
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| Impact of varicocele size: data show—varicocele size does affect outcome, ie, magnitude of improvement in
sperm count correlates directly with size of variocele repaired; patients do not benefit from repair of subclinical varicoceles;
physical examination—cornerstone of diagnosis; large varicoceles visible; medium varicoceles palpable;
small varicoceles only palpable with Valsalva maneuver; subclinical varicoceles—no gold standard diagnostic tool
available
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| Conclusions: many men with varicoceles remain fertile; varicoceles do not appear to exert progressive effect on most
fertile adults, but do exert deleterious effect on some adolescents; varicocele repair improves testicular function in
most men, and is reasonable alternative when objective evidence of testicular damage exists
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| Management recommendations: annual monitoring of semen parameters sufficient if patient asymptomatic and
has normal baseline semen parameters (can be continued until end of reproductive life); do not look for or treat subclinical
varicoceles in subfertile men (improvement after varicocele repair directly proportional to size of varicocele)
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| EVALUATION OF AZOOSPERMIA —Paul J. Turek, MD, Associate Professor and Academy of Medical Editors Endowed
Chair, Department of Urology, University of California, San Francisco, School of Medicine
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| Basic infertility evaluation: initially, medical history, physical examination, and semen analysis; if male parameters
normal, evaluate female partner; if semen analysis abnormal, perform hormonal evaluation, eliminate presence of gonadotoxins,
and base additional evaluation on semen analysis; point—history of paternity best predictor of fertility
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| Azoospermia: obstructed patients can be reconstructed or undergo intracytoplasmic sperm injection [ICSI]); nonobstructed
patients usually managed by assisted reproductive technique (ART; occasionally, patient can be managed by
other means, eg, individual with Kallmann syndrome)
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| Initial approach to azoospermia: centrifuged pellet semen analysis reduces sampling error and facilitates diagnosis
of nonobstructed azoospermia (NOA) or oligospermia (ie, 1 of every 5 men with supposed azoospermia have
sperm in semen sample); presence of sperm precludes obstruction; physical examination detects palpable vas deferens;
if vas deferens impalpable, patient has genetic condition and requires ART; if palpable, continue algorithm
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| Congenital absence of vas deferens (CAVD): usually bilateral and unreconstructable; constitutes mesonephric
duct problem; patients with CAVD—always have caput epididymidis (remaining portion of epididymidis may be
missing); may lack sections or entire length of scrotal vas; do well with sperm aspiration procedures; have 60% to
80% incidence of cystic fibrosis (CF) gene mutation; CAVD considered “form fruste” of CF because patients—
have underpenetrated version of CF; generally do not have typical CF mutations; may have nasal polyps; generally do
not have pancreatic insufficiency; genetic counseling—need to educate patient about risk of having child with CF
and impalpable vas deferens following ART; potential for litigation associated with problem; physician should—
make sure patient has vas deferens (vas may be thin); approach situation as though performing vasectomy examination
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| Men with palpable vas deferens
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| Follicle-stimulating hormone (FSH) and testosterone evaluation: performed initially; if FSH elevated, patient—
unobstructed; may have small testes producing too little sperm, eg, 60% of men without sperm in ejaculate and
NOA may have sperm in testicles; if FSH normal, patient—may be obstructed and require biopsy; may not have
normal sperm production, eg, men with maturation arrest histology can have normal-sized testes, normal FSH, and
germ cell elements that do not progress to sperm; if FSH low, patient—may require evaluation for prolactinoma or
thyroid and adrenal gland problems; requires magnetic resonance imaging (MRI) of pituitary or computed tomography
(CT) of sella turcica
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| Additional aspects: Y chromosome microdeletion or karyotype—present in one third of men with NOA; of these
men, 30% have sperm on biopsy and >50% have sperm on more extensive testing; biopsy—facilitates prognostic
evaluation; if sperm present on biopsy, sperm retrieval possible; mapping (fine needle aspiration [FNA]) or
microdissection—next level of evaluation; if negative, donor insemination or adoption indicated; ability to find
sperm depends on sampling intensity; either evaluation approach may prove better than biopsy
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| Men with obstructive azoospermia: CF mutation in one third of cases; 5-thymidine (5T) gene variant—detected
with CF mutation analysis; presence may provide clue in men with no apparent blockage
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| Epididymal reconstruction: option for epididymal obstruction; if sperm absent on biopsy, more extensive evaluation
indicated; in patients undergoing surgery—obtain biopsy ahead of time; perform vasography when obstruction
confirmed; epididymal vasostomy standard end-to-side technique; invagination technique—uses vest sutures in
epididymis; easier to learn and faster to perform than standard epididymal vasostomy; durable repair achieves
higher patency rate more quickly than standard approach
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| Hypogonadotropic hypogonadism: may be present in man with low levels of FSH, luteinizing hormone (LH), and
testosterone; if no prolactinoma found—evaluate other parts of pituitary axis; consider referral to endocrinologist for
assessment of thyroid, growth hormone, or adrenocorticotropic hormone [ACTH] level; in general, obtain MRI of pituitary;
pointers—most patients treatable but not curable; if prolactin elevated (in absence of tumor), administer
dopamine agonist; if tumor visible—remove lesion with transphenoidal resection (these patients can be cured); when
pituitary begins to fail, recovery can be achieved by administering clomiphene citrate (Clomid); factors causing hypogonadotropic
hypogonadism—Kallmann syndrome (panhypopituitarism and anosmia); Prader-Willi syndrome
(rare chromosomal abnormality); Bardet-Biedl syndrome (retinitis pigmentosa); cerebellar ataxia (speech and gait
problems); sickle cell anemia (sludging in pituitary and testicle); β-thalassemia (iron overload); hemochromatosis
(look for polycythemia and iron overload); gonadotropin therapy—achieves low but fertile sperm levels; requires
patient to bank sperm and pursue options that will help him stop injections and resume testosterone therapy; duration
of testosterone therapy does not effect outcome
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| Men with low ejaculate volume and azoospermia: if vas palpable, perform transrectal ultrasonography
(TRUS); if TRUS normal, investigate other reasons for problem, eg, testosterone; if evaluation abnormal, look for
ejaculatory duct obstruction that requires treatment; points—TRUS too sensitive to be used as sole basis for proceeding
directly to transurethral incision and/or resection of ejaculatory ducts (TURED); other evaluation tools—seminal
vesiculography; aspiration of sperm from seminal vesicles; point—surgery performed when chromotubation confirms
obstruction
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| ERECTILE DYSFUNCTION: REVIEW OF AMERICAN UROLOGICAL ASSOCIATION (AUA) MANAGEMENT
GUIDELINES— Hunter Wessells, MD, Professor of Urology, University of Washington School of Medicine; Chief of
Urology, Harborview Medical Center, Seattle, WA
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| Evaluation of erectile dysfunction (ED): identify organic comorbidities and psychosexual dysfunctions;
comorbidities—diabetes has highest association with ED; obesity (defined as body mass index [BMI] >30); heart disease
combines with other comorbidities to exert deleterious effect; caveats—risk for ED increases with body mass and
waistline; although exercise in general can reduce risk for ED, bicycling may contribute to development of ED; data
suggest ED may be harbinger of cardiovascular event
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| Recommendations: apply appropriate treatment in stepwise fashion; balance treatment efficacy against degree of invasiveness
and risk; involve patient’s partner in management process; experience and judgment of physician must be
considered when selecting management approach
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| Phosphodiesterase type 5 (PDE5) inhibitors
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| Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra): work well; time-to-onset important, depending on
whether patient wants rapid onset or long “window of opportunity”; time to maximum serum concentration (Cmax)
and half-lives—short for sildenafil and vardenafil; long for tadalafil; patient preference and efficacy—odds of refilling
initial PDE5 prescription markedly lower for vardenafil and tadalafil; options when patient unresponsive—
before switching to different PDE5 inhibitor, determine whether trial adequate, eg, with sildenafil, ask about consumption
of fatty foods; some clinicians suggest drug should be tried ≥8 times before evaluating efficacy
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| Cardiovascular risks: before administering drugs, determine cardiovascular status of patient, ie, determine whether
individual uses nitrates or α-blockers; visual disturbance and nonarteritic anterior ischemic optic neuropathy
(NAION)—ischemic optic neuritis; can lead to blindness; associated with cardiovascular disease and may have
parallel association with ED; discuss with patient who has history of severe loss of vision; high-risk patients—
have unstable angina and congestive heart failure (CHF); should not receive treatment for ED until cardiac condition
stabilizes; therapy contraindicated in any patient taking nitrates; diabetes and hypertension—risks vary
among racial groups; diabetics with no complications can achieve good erection rate with sildenafil; if patient has 1
or 2 complications, erection rate worsens
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| When PDE5 blocker fails: educate patient about alternatives; decision to switch to different PDE5 inhibitor depends
on physician’s experience and patient’s needs
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| Options: alprostadil (prostaglandin E1; PGE1) intraurethral suppositories (Muse [Medicated Urethral System for
Erection])—reliability and reproducibility of effect poor; initial trial dose must be supervised by health care professional;
intracavernosal injection (ICI) therapy—initial trial dose also must be supervised by health care professional;
inform patient about risk of priapism; vacuum device—must contain vacuum limiter to prevent excessive
pressure increases within cylinder; avoid—trazodone; yohimbine; herbal therapies; testosterone supplementation
when serum testosterone levels normal
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| Penile implants: warn patient about penile shortening
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| Prosthetic surgery: contraindicated if infection present; provides antibiotic coverage for gram-negative and gram-positive
organisms; options—combination of cefazolin and aminoglycoside (vancomycin if patient allergic to cefazolin);
fluoroquinolone; before surgery—look for new infections; shave site; perform 10-min “scrub and paint”; place
orthopedic extremity drape with gasket; surgery—antibiotic-impregnated implant not proven conclusively to provide
superior protection against infection; with redo surgery, clean device; postoperatively—prevent swelling,
bruising, and hematoma with closed-suction drainage overnight; antibiotics for 7 days
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| Vascular dysfunction: options—arterial surgery in select patients; venous outflow procedures not recommended;
surgical techniques—never discard entirely; use in select patients, ie, unique mechanisms of injury can cause site-
specific venoocclusive dysfunction
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| Pharmacologic issues: lack of new drugs may be related to—concern over safety; lower profits for pharmacologic
companies; coated implants—not as rigorously evaluated as drugs; different regulatory environment for devices vs
drugs; disconnect between patient needs and pharmacotherapy—current drugs do not address connection between
brain-related desire and physical arousal; melanocyte-stimulating hormone (MSH) analogue PT-141 [Bremelanotide;
investigational] may increase sexual arousal by addressing activity in brain and genitalia
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Educational Objectives
| The goal of this program is to improve the management of male sexual dysfunction. After hearing and assimilating this
program, the clinician will be better able to:
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| 1. Determine how varicoceles affect testicular function and semen quality in adolescents and men.
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| 2. Assess the clinical merits of performing centrifuged pellet semen analysis on azoospermic men.
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| 3. Evaluate and manage azoospermia in the patient with congenital absence of the vas deferens, palpable vas deferens,
obstructive azoospermia, hypogonadotropic hypogonadism, or low ejaculate volume.
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| 4. Explore the role of phosphodiesterase type 5 (PDE5) inhibitors in the management of erectile dysfunction.
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| 5. Perform successful penile implantation surgery.
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Suggested Reading
Chehval MJ, Purcell MH: Deterioration of semen parameters over time in men with untreated varicocele: evidence
of progressive testicular damage. Fertil Steril 57:174, 1992; Jarow JP: Effects of varicocele on male fertility. Hum
Reprod Update 7:59, 2001; Jarow JP: Induction of spermatogenesis in azoospermic men after varicocele repair. J
Urol 170:676, 2003; Matthews GJ et al: Induction of spermatogenesis and achievement of pregnancy after microsurgical
varicocelectomy in men with azoospermia and severe oligoasthenospermia. Fertil Steril 70:71, 1998; Montague
DK et al: Chapter 1: The management of erectile dysfunction: an AUA update. J Urol 174:230, 2005; Practice
Committee of the American Society for Reproductive Medicine: Report on varicocele and fertility. Fertil
Steril 86 Suppl:S93-5, 2006; Shefi S, Turek PJ: Definition and current evaluation of subfertile men. Int Braz J Urol
32:385, 2006; Turek PJ: Practical approaches to the diagnosis and management of male infertility. Nat Clin Pract
Urol 2:226, 2005; Turek PJ et al: Diagnostic findings from testis fine needle aspiration mapping in obstructed and
nonobstructed azoospermic men. J Urol 163:1709, 2000; Wessells H: Exploring cause and effect relationships in male
sexual dysfunction. J Urol 171:1609, 2004; Wessells H et al: The penile implant for erectile dysfunction. J Sex Med
1:98, 2004.
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. The following has
been disclosed: Dr. Turek is affiliated with Auxilium Pharmaceuticals; Dr. Wessells is affiliated with Endocare, Palatin
Technologies, and Pfizer.
Drs. Jarow, Turek, and Wessells were recorded at An Evidence-Based Approach to Common Problems in Urology,
presented February 3-4, 2006, in San Francisco, by the University of California, San Francisco, School of Medicine.
The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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