ISSUES IN MALE SEXUAL DYSFUNCTION
Educational Objectives
| The goal of this program is to improve the management of erectile dysfunction (ED) and problems of intimacy after
prostate cancer. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Describe the etiology of and risk factors for ED.
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| 2. Summarize the pathophysiology of ED and the role of the endothelium of the penile vasculature in ED.
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| 3. List the most commonly prescribed phosphodiesterase-5 (PDE-5) inhibitors and review their mechanism of action.
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| 4. Discuss the organic and psychogenic causes of ED after treatment of prostate cancer, and how these relate to
impaired sexual function.
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| 5. Explain how patients’ attitudes such as denial and avoidance and physician’s time constraints and embarrassment
often form barriers to treatment of ED and resolution of intimacy problems after prostate cancer treatment.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, the following has been disclosed: Dr. White is a stockholder of
Johnson & Johnson, Merck, and Eli Lilly and has financial relationships with Pfizer and GlaxoSmithKline. Dr. Kingsberg is a
consultant and investigator for Procter & Gamble, an investigator for Boehringer-Ingelheim, on the Speakers’ Bureau for Eli
Lilly, and a consultant, speaker, and investigator for Solvay.
Acknowledgements
Dr. White addressed Current Concepts in Men’s Health 2007, presented August 2-5, 2007, in Lake George, NY, by
Albany Medical College and the Urological Institute of Northeastern New York. Dr. Kingsberg lectured at Duke Prostate
Cancer Symposium, Patient Centered Outcomes Research in Prostate Cancer, presented April 27, 2007, in Research
Triangle Park, NC, by the Division of Urologic Surgery of Duke University Medical Center and the American
Urological Association. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in
the production of this program.
| ERECTILE DYSFUNCTION: CURRENT AND FUTURE TRENDS IN MANAGEMENT —Mark D. White, MD, Associate
Professor of Surgery (Urology), Albany Medical College and Urological Institute of Northeastern New York, Albany,
NY
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Overview
| Drug therapy: 3 phosphodiesterase-5 (PDE-5) inhibitors dominate market; sales have plateaued and now declining; only
≈10% of affected men seek treatment; use of prostheses and other surgical therapies increasing
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| Etiology: old notions changing; all antihypertensives do not cause or contribute to erectile dysfunction (ED); angiotensin-
converting enzyme (ACE) inhibitors and some angiotensin antagonists may have beneficial effect on corpora and may
improve erectile function; β-blockers, calcium channel blockers, and diuretics may not be as detrimental to erectile
function as previously thought
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| Risk factors: age >65 yr; diabetes; prevalence higher than expected in men with lower urinary tract symptoms or history
of stroke; hypertension; pelvic surgery; use of calcium channel blockers; tobacco use less associated with ED than
originally thought; lower prevalence of ED with use of—statin drugs (may contribute to improvement of corporal function;
long-term use may protect against ED); β-blockers as well as red wine may be protective; other risk factors—
depression; myocardial infarction (MI); early presentation of ED significant prognostic marker for cardiovascular disease
(CVD)
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| Patient and physician factors: lack of efficacy or partial efficacy leads to failure to refill prescriptions for PDE-5 drugs;
ED underdiagnosed, underscreened, and undertreated
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| Endothelial dysfunction: new name for ED; higher risk for damage to vascular endothelium in patients with metabolic
syndrome; cascade of events in which ED one of final steps; longer-term damage predisposes to CVD; role of
endothelium—need substances that modulate vascular tone and blood flow; cavernous nerves produce nitric oxide (NO);
individual variation in response to endothelial stimulation; eventually, genetic testing will predict response to drug therapy;
patients with impaired endothelium and impaired corporal smooth muscle progress to ED; CVD present in 5% to
56% of men with ED; study data show that among patients undergoing angiography for CVD, >50% had ED before diagnosis
of CVD, and that two-thirds of them had 3-yr gap between noticing ED and CVD diagnosis or event; obesity—65%
of United States population overweight or obese; altered lipid metabolism; 50% risk for ED in diabetics; unknowns—
whether ED marker for more global vascular disease; which patients with ED will respond to vasoactive medications
(those who do not respond have more severe cardiac disease and more severe ED)
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| Metabolic syndrome: term coined in 1998 by World Health Organization (WHO); includes glucose intolerance, obesity,
hypertension, and changes in lipid balance; independent predictors include hypertension, hypercholesterolemia, obesity
(body mass index [BMI] >30); metabolic syndrome may predict abdominal aortic aneurysms; possible role for C-
reactive protein (CRP), especially cardiac fraction
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| PDE-5 inhibitors: human genome has 21 PDE genes that encode for 11 protein families; cyclic guanosine monophosphate
(cGMP) causes relaxation of vascular smooth muscle; PDE-5 inhibitors found during search for antihypertensive
drugs; did not work well for blood pressure (BP) control, but male patients reported improved erectile function; as result,
sildenafil (Viagra) developed; sexual stimulation causes release of NO from nerves and endothelial cells in penis;
localization—PDE-5 in corpus cavernosum, vascular smooth muscle, skeletal muscle, and platelets; PDE-11 in skeletal
muscle, heart, and vascular muscle; PDE-6 involved in blue color vision in retina; other potential uses of sildenafil—
Raynaud’s phenomenon and pulmonary hypertension; may also be useful in congestive heart failure (CHF); may prevent
apoptosis and left ventricular dysfunction in chemotherapy-induced cardiotoxicity; autologous fat—potential use for
growing new corporal cells that can be transplanted into penis to remodel corpora
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| Massachusetts Male Aging Study: looked at population prevalence of ED at given time; 1290 men, 40 to 70 yr of
age; 48% had no ED, while 52% had some degree of ED, ie, complete (10%), moderate, or minimal; treatment—≈90%
never seek care; 10% seek or receive treatment (5% on sildenafil, vardenafil, or tadalafil; remainder on other forms of
treatment)
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| Penile vasculature: erection caused by compression of subtunical venules so that blood trapped in corpora (mediated by
cGMP); oxidative stress on endothelium impairs production of NO; causes of oxidative stress include cigarette smoking,
obesity, high fat intake, sedentary lifestyle, and psychologic stress; decreased production of NO sign of endothelial damage
(vasculogenic ED) and happens well before other signs or markers of damage; endothelial damage translates to vascular
damage, which may cause atherosclerotic changes; ED marker for comorbid diseases, eg, hypertension, cardiac disease, dyslipidemia,
diabetes, depression (more prevalent in men with ED)
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| Case: man 38 yr of age with family history of CVD diagnosed with CVD and ED—in history, look for possible psychogenic
and drug causes; screen for hypogonadism; take sexual history (eg, desire, ejaculation, premature ejaculation); psychosocial
history, eg, anxiety, life stressors, relationship issues; genital examination (look for Peyronie’s disease); neurologic
examination (test rectal tone); look for cardiac risk factors; according to Princeton Consensus Conference, if patient can
walk a mile without shortness of breath, stress test not needed before prescribing PDE-5 inhibitor; laboratory tests—
morning testosterone for hypogonadism; prostate-specific antigen (PSA) if clinically indicated; cardiac risk, ie, high-density
lipoprotein (HDL) and low-density lipoprotein (LDL); most men with metabolic syndrome have low HDL and high
LDL, and may have glucose intolerance
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| Communication: patients—may not talk about ED because of embarrassment, misconceptions about treatment, own or
partner’s lack of interest, and/or fear of side effects; physicians—lack of awareness, embarrassment, lack of skills, and
concern about time-consuming nature of ED management; cascade effect—patients talk to physician and may fill prescription,
but only small percentage continue using medication
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| Role of urologist: surgical treatments for ED; injection therapy and its complications; androgen replacement therapy;
screening; classification of patients by cardiac risk factors
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| PDE-5 inhibitors: work by preventing degradation of cGMP, thereby preventing relaxation of smooth muscle and loss
of erection; 3 drugs differ by half-life and effect of fat ingestion; sildenafil—fatty meal causes ≈30% decrease in effective
concentration; half-life ≈4 hr; vardenafil—18% to 50% decrease in concentration with fatty meal; half-life ≈4 hr;
tadalafil—no change in concentration with fat ingestion; longest half-life (17.5 hr); delayed response (up to 36 hr); mean
for success—60% to 70% with any of 3 drugs; with sildenafil, 65% had successful intercourse attempts; side effects—
tadalafil has slightly higher risk for back pain (due to PDE-11 activity); headache, flushing, rhinitis, nasal congestion; abnormal
vision with sildenafil (due to PDE-6 cross-reactivity); sildenafil and tadalafil have only modest effect on BP and
no real association with MI or death rate; use of nitrates contraindicated when patients on PDE-5 drugs
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| Other agents: no libido-enhancing agents; dopamine agonists not viable because of side effects of hypotension and fainting;
prostaglandin injections (Caverject, Eject; adding α-blockers being studied)
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| Market: 30 to 60 million men, but epidemiologic calculation may be incorrect; pharmaceutical companies spending large
amounts of money on marketing; speaker opines that older men face 2 problems drugs cannot cure, 1) no one particularly
wants to have sex with them, and 2) they have outgrown it anyway
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| In pipeline: avanafil—PDE-5 inhibitor with short half-life (1.5 hr); testosterone replacement—for hypogonadism; noninjectable,
nonoral formulations, ie, gels; premature ejaculation and ED—inhaled formulations; injectable and intranasal
modes of delivery; dapoxetine (antidepressant for premature ejaculation) not approved by Food and Drug
Administration (FDA), but soon available in Europe; tramadol (Ultram; pain reliever) increases ejaculatory latency from
1 min to 8 min (off-label use)
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| INTIMACY AFTER PROSTATE CANCER —Sheryl A. Kingsberg, PhD, Associate Professor, Case Western Reserve University
School of Medicine, and Chief, Division of Behavioral Medicine, Department of Obstetrics and Gynecology, University
Hospitals MacDonald Women’s Hospital, Cleveland, OH
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| Sex and aging: prostate cancer population; “viagratization of America”—has changed face of sexuality; graying of
America—has changed image and expectations of midlife; research and treatment of sexual problems now “out of the
closet”
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| Male sexual dysfunctions: disorders of arousal (primarily ED); disorders of desire; disorders of ejaculation and orgasm;
others, eg, Peyronie’s disease
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| ED: defined as inability to achieve or maintain penile erection sufficient for satisfactory sexual performance (not necessarily
intercourse); may be psychogenic, organic, or mixed; >600,000 new cases annually
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| Statistics: 50% of women and 31% of men 18 to 59 yr of age have sexual dysfunction; in this age range, premature ejaculation
most prevalent problem; definition of “premature” problematic since based on subjective perception (average
length of intercourse 3-5 min)
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| Causes of ED: psychogenic—depression, performance anxiety, and relationship problems; psychosocial issues; psychologic
distress; all can relate to prostate cancer; organic—age alone may contribute to ED; prostate cancer; even when
problem primarily organic, psychologic component present; after prostate cancer—ED most common side effect of treatment;
others include difficulty reaching orgasm, dry orgasms, weaker or less satisfying orgasms, decreased desire, and
sexual pain
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| Treatment of prostate cancer
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| Surgery: nerve-sparing radical prostatectomy has less impact on sexual function, but even nerve-sparing surgery may
cause temporary ED; early penile rehabilitation—not standard of care, but used after nerve-sparing and non-nerve-
sparing surgery; gets men back to sexual activity sooner, to prevent muscle atrophy and fibrosis; getting couple back to
being sexual earlier has important impact on success; devices for rehabilitation—constriction devices; medicated urethral
system for erection (MUSE); intracavernosal injections; PDE-5 inhibitors (can be used in combination with other
options; not covered by Medicare)
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| Radiation, hormone therapy, and chemotherapy: also affect sexual function
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| Patient attitudes: body image—as important for men after prostate cancer as for women after breast or gynecologic
cancer; idea of having cancer (being diseased) has negative impact on body image and willingness to be sexual; effect
on partner—partner may be worried and have depression and anxiety about partner having life-threatening illness; performance
anxiety—once ED has occurred, even if treatment successful, performance anxiety occurs
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| National study: 48% of participants surveyed reported sexual activity at least once monthly; 79% of men and 66% of
women said sex important component of relationship
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| Pfizer study: surveyed 26,000 men and women 40 to 80 yr of age in 29 countries; 57% of men and 51% of women reported
sexual activity 1 to 6 times weekly (higher than average in United States, which is ≈3 times monthly)
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| Barriers to treatment: medical anxiety—low percentage of men with ED seek treatment; often due to poor communication
with partner (women often make appointments); attitude that “real men don’t go to the doctor”; some men afraid
physician will be condescending or dismissive; some men afraid treatment will not work for them; fear that partner will
not want sex; reasons for not seeking treatment—belief that ED part of normal aging; hope that ED will go away; embarrassment
about discussing ED; minimization, eg, “it doesn’t happen that often”
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| Denial and avoidance: driven by performance anxiety; involves lack of communication and misunderstanding between
partners; unintended result significant impact on relationship; impact of satisfactory sex on marriage relatively small
(15%-20% positive effect), but impact of sexual problems inordinately large
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| Physicians’ attitudes: time constraints; embarrassment; lack of awareness of associated comorbid conditions; lack of relationship
of ED to survival; patients do not bring up topic unless physician does
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| Components of desire: drive—spontaneous sexual interest; biologic; depends on androgens; people born with certain
level of drive (tends to be higher in men because of higher testosterone levels); declines with age (relative to original
amount); affected by medications (eg, antihypertensives, antidepressants); beliefs and values—cultural and social beliefs
that increase or decrease interest in being sexual; motivation—most important; all psychologic and interpersonal factors
that create willingness to bring body to sexual experience
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| Masters and Johnson model: linear; works relatively well for men; more complicated for women (nonlinear); with aging,
fewer women thinking about sex, but most open to it due to desire for emotional intimacy
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| Psychologic concepts: essential for reinitiation of sexuality after surgery; self-perception theory—people make attributions
about own attitudes by observing external behavior; may lead to misunderstanding between partners; obligation—
once sex feels like obligation, it is no longer fun (sense of pressure and resentment get in way)
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| Woman’s sexual function: when man who has not been sexual due to ED undergoes successful treatment, woman may
not be physically ready because of vaginal dryness, genital atrophy, and lack of elasticity
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Suggested Reading
Beckman TJ et al: Evaluation and medical management of erectile dysfunction. Mayo Clin Proc 81:385, 2006;
Bruner DW et al: The sexual impact of cancer and cancer treatments in men. Nurs Clin North Am 42:555, 2007; Burnett
AL et al: Erectile function outcome reporting after clinically localized prostate cancer treatment. J Urol 178:597,
2007; Carson CC 3rd: Phosphodiesterase type 5 inhibitors: state of the therapeutic class. Urol Clin North Am 34:507,
2007; Harrod HL: A piece of my mind. An essay on desire. JAMA 289:813, 2003; Khera M et al: The role of testosterone
replacement therapy following radical prostatectomy. Urol Clin North Am 34:549, 2007; Kostis JB et al: Sexual
dysfunction and cardiac risk (the Second Princeton Consensus Conference). Am J Cardiol 96:313, 2005; Kupelian V et
al: Erectile dysfunction as a predictor of the metabolic syndrome in aging men: results from the Massachusetts Male Aging
Study. J Urol 176:222, 2006; Kupelian V et al: Is there a relationship between sex hormones and erectile dysfunction?
Results from the Massachusetts Male Aging Study. J Urol 176:2584, 2006; Lindau ST et al: A study of sexuality and
health among older adults in the United States. N Engl J Med 357:762, 2007; Matthew AG et al: Sexual dysfunction after
radical prostatectomy: prevalence, treatments, restricted use of treatments and distress. J Urol 174:2105, 2005; McMahon
CN et al: Treating erectile dysfunction when PDE5 inhibitors fail. BMJ 332:589, 2006; McVary KT: Clinical
practice. Erectile dysfunction. N Engl J Med 357:2472, 2007; Melman A: Gene therapy for male erectile dysfunction.
Urol Clin North Am 34:619, 2007; Michl UH et al: Prediction of postoperative sexual function after nerve sparing radical
retropubic prostatectomy. J Urol 176:227, 2006; Schover LR et al: Defining sexual outcomes after treatment for localized
prostate carcinoma. Cancer 95:1773, 2002; Seftel AD et al: Office evaluation of male sexual dysfunction. Urol Clin
North Am 34:463, 2007; Travison TG et al: The natural progression and remission of erectile dysfunction: results from
the Massachusetts Male Aging Study. J Urol 177:241, 2007; Zippe CD et al: Penile rehabilitation following radical prostatectomy:
role of early intervention and chronic therapy. Urol Clin North Am 34:601, 2007.
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