Erectile Dysfunction. Dr Mampedi Bogoshi

Transcription

1 Erectile Dysfunction Dr Mampedi Bogoshi February 26,

2 Erectile Dysfunction What is ED? ED: Erectile dysfunction is defined as the inability to achieve and/or maintain a penile erection sufficient for satisfactory sexual activity ED is the most thoroughly studied sexual dysfunction in men and the most common sexual complaint of men presenting to healthcare providers In talking to patients, it is better to refer to their symptoms as erection problems Erectile dysfunction and erection problems are both preferable terms to impotence, which, when used colloquially, has emotive or derogatory implications Albersen M, Mwamukonda, KB, Shindel AW, et al. Evaluation and treatment of erectile dysfunction. Med Clin N Am. 2011;95: ; NIH Consensus Statement. Impotence. 1992;10(4):

3 Prevalence The reluctance of many men to admit to suffering from erection problems causes difficulties in determining its prevalence Worldwide prevalence of ED is between 10% and 20%, and it is strongly correlated with aging Among younger men, 8% of 20- to 29-year-olds and 11% of men ages experience ED Approximately 52% of men ages experience ED 71% of men over 70 experience ED This may be due to: Increased incidence of diseases that cause ED Use of treatments that can cause ED Estimated prevalence for 2025 = 300M men worldwide Laumann EO, A Nicolosi, DB Glasser, et al. Sexual problems among women and men aged y: prevalence and correlates identified in the global study of sexual attitudes and behaviors. Int J Impot Res. 2005;17:39 57; Nicolosi A, Laumann EO, Glasser DB, et al. Sexual behavior and sexual dysfunctions after age 40: the global study of sexual attitudes and behaviors. Urology. 2004;64: ; Saigal CS, Wessells H, Pace J, et al. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166: ; Lue TF. Erectile dysfunction. N Engl J Med. 2000;342: ; Rosen RC, Fisher WA, Eardley I, et al. The multinational men s attitudes to life events and sexuality(males) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Cur Med Res Opin. 2004;20(5): ; Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol. 1994;151(1):54-61; Porst H, Buvat J. Standard Practice in Sexual Medicine. 2006; Uckert S, Mayer ME, Stief CG et al. The future of the oral pharmacotherapy of male erectile dysfunction: things to come. Expert Opin Emerg Drugs. 2007;12(2):

4 ED in men over 55 years Age Prevalence >55 47% >75 78% + Diabetes 50% + Hypertension 34% Thompson IM, Tangen CM, Goodman PJ, et al. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005;294: ; Saigal CS, Wessells H, Pace J, et al. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166:

5 Erectile Dysfunction Causes of ED Penile erection requires: Neural transmission of pro-erectile impulses Intact arterial blood flow supply Functional erectile tissue in the corpus cavernosum Anything that impairs any of these three processes will have an impact on erectile function A normal erection relies on a combination of psychogenic, hormonal, neurological, and vascular factors These are broadly divided into psychogenic causes and organic causes ED is generally multifactorial Albersen M, Mwamukonda, KB, Shindel AW, et al. Evaluation and treatment of erectile dysfunction. Med Clin N Am. 2011;95: ; Foresta C, Caretta N, Corona G, et al. Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart. Int J Androl. 2008;32: ; Lue TF. Erectile dysfunction. N Engl J Med. 2000;342: ; Bortolotti A, Parazzini F, Colli E, et al. The epidemiology of erectile dysfunction and its risk factors. Int J Androl. 1997;20:

6 Erectile Dysfunction ED is multifactorial Lue TF. Erectile dysfunction. N Engl J Med. 2000;342: ; Bortolotti A, Parazzini F, Colli E, et al. The epidemiology of erectile dysfunction and its risk factors. Int J Androl. 1997;20: ; Hatzimouratidis K, Amar E, Eardley I, et al. Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. Eur Urol. 2010;57: ; Moreno-Pe rez O, Escoín C, Serna-Candel C, et al. Risk factors for sexual and erectile dysfunction in HIV-infected men: the role of protease inhibitors. AIDS. 2010;24: ; Saigal CS, Wessells H, Pace J, et al. Predictors and prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166: ; Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin North Am. 1995;22:

7 Erectile Dysfunction Lifestyle and ED Lifestyle factors have been associated with ED in both cross-sectional and longitudinal studies Obesity and sedentary lifestyle are clear-cut risk factors for ED Smoking and alcohol consumption have also been implicated in some studies to date Higher levels of sedentary behaviour have been strongly linked to the occurrence of ED in aging men Intervening on cardiovascular and lifestyle factors may have broader benefits beyond restoration of erectile function Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3:

8 Erectile Dysfunction Surgery Pelvic surgery (e.g., radical prostatectomy) can damage the neural transmission and lead to ED General surgery and trauma these can cause erection problems because of spinal lesion (e.g., spinal cord injury). Only 25% of men with complete lower cord lesions can achieve an erection. In addition to ED, they may also have impaired ejaculation and orgasm. Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005;32:

9 Erectile Dysfunction Other medical conditions and drugs Other medical conditions These tend to affect the vascular and/or neurological supply to the penis; e.g., multiple sclerosis, Parkinson s disease, stroke, diabetes, hypertension, and cardiovascular disease Drugs Some drugs directly cause erection problems (iatrogenic cause), but many treat diseases that are themselves associated with ED Antihypertensives and hypertension Antidepressants and depression Lipid-lowering drugs and raised cholesterol Recreational/illicit drugs can also cause erection problems Wespes E, Amar E, Eardley I, et al. Erectile dysfunction and premature ejaculation. Guidelines on Male Sexual Dysfunction. 2010; Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3:28-36; Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin North Am. 1995;22: ; Bang-Ping J. Sexual dysfunction in men who abuse illicit drugs: a preliminary report. J Sex Med. 2009;6:

10 Erectile Dysfunction Medications associated with ED Cardiovascular drugs Psychotropic drugs Recreational drugs Thiazide diuretics Beta blockers Anxiolytics and hypnotics Spironolactone Calcium blocks antagonists testosterone synthesis Tricyclic antidepressants and competitively binds to androgen receptors Centrally acting agents Selective serotonin reuptake Methyldopa Clonidine, reserpine Ganglion blockers Digoxin Lipid lowering agents ACE inhibitors Major tranquillizers inhibitors Others Cimetidine and ranitidine Metoclopramide Decreases libido and causes impotence through elevation Carbamazepine of serum prolactin and blocking of androgen receptors Alcohol Marijuana Amphetamines Development Cocaine of a peripheral autonomic neuropathy, and behavioral changes Anabolic steroids Heroin Endocrine drugs Antiandrogens Oestrogens LHRH: luteinizing hormonereleasing hormone analogues Testosterone Foresta C, Caretta N, Corona G, et al. Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart. Int J Androl. 2008;32: ; Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin North Am. 1995;22: ; Krane RJ et al. N Engl J Med. 1989;321:

11 Erectile Dysfunction Illicit drug use and ED Illicit drugs such as cocaine and amphetamines are often seen as aphrodisiacs, but can cause erection problems In a survey of 701 male drug abusers (mean age 34 years), 36% reported ED Other forms of sexual dysfunction reported were decreased sexual desire (39%) and increased ejaculation latency (50%) ED was most commonly seen with heroin use, followed by amphetamine and MDMA: 3,4-methylenedioxy-methamphetamine ( ecstasy ) use Bang-Ping J. Sexual dysfunction in men who abuse illicit drugs: a preliminary report. J Sex Med. 2009;6:

12 Prevalence of co-morbidities (%) Erectile Dysfunction ED is linked to serious health problems 70 No ED ED 64 *P< High blood pressure Heart trouble or angina* High cholesterol Diabetes* Depression* Any of these N=23,416 Rosen RC, Fisher WA, Eardley I, et al. The multinational men s attitudes to life events and sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Cur Med Res Opin. 2004;20(5):

13 Prevalence of co-morbidities (%) Erectile Dysfunction Cardiovascular disease is the most common co-morbid condition in men with ED 70 No ED ED 64 *P< High blood pressure Heart trouble or angina* High cholesterol Diabetes* Depression* Any of these N=23,416 Rosen RC, Fisher WA, Eardley I, et al. The multinational men s attitudes to life events and sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population. Cur Med Res Opin. 2004;20(5):

14 The Link between ED and Cardio vascular disease ED often occurs before other vascular diseases The artery size theory ED manifests earlier than cardiovascular disease because the smaller penile arteries reach critical narrowing, with insufficient blood flow, earlier than larger vessels (Threshold for symptom development is 50% lumen.) Early Late Footnotes Penile artery 1-2 mm ED Coronary artery 3-4 mm Angina/infarction Carotid artery 5-7 mm Stroke Femoral artery 6-8 mm Claudication Montorsi P, Ravagnani PM, Galli S, et al. The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Am J Cardiol. 2005;96(suppl):19M 23M. 14

15 Erectile Dysfunction Endothelial dysfunction, ED, and CVD: cardiovascular disease ED and CVD share aetiologies as well as pathophysiology (endothelial dysfunction), and evidence suggests that the degree of ED correlates with severity of CVD ED may be a predictive symptom of CVD in otherwise asymptomatic patients ED may precede a cardiovascular event by as much as five years in otherwise asymptomatic patients A man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise Schwartz BG, Economides C, Mayeda GS, et al. The endothelial cell in health and disease: its function, dysfunction, measurement and therapy. Int J Impot Res. 2010;22:77 90; Thompson IM, Tangen CM, Goodman PJ, et al. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005;294: ; Hodges JD, Kirby M, Solanki J, et al. The temporal relationship between erectile dysfunction and cardiovascular disease. Int J Clin Pract. 2007;61(12) ; Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3:

16 Erectile Dysfunction Cardiovascular risk Men with organic ED should have their cardiac risk factors addressed ED is significantly associated with cardiovascular risk factors. These include: hypertension raised cholesterol (hyperlipidaemia) diabetes smoking There is a degree of cardiac risk associated with sexual activity, so it is crucial to assess the CV risk according to Second Princeton Consensus The risk is small (~1% for myocardial infarction) and low compared with many other risks most patients will encounter (e.g. watching football) Men should be strongly advised to discuss CV risk factors with a physician if they have not already done so Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3:28-36; Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol. 1994;151(1):54-61; Chi JS, Kloner RA. Stress and myocardial infarction. Heart. 2003;89:

17 Erectile Dysfunction Stratification of CV risk in the ED patient (Second Princeton Consensus) Princeton II evaluation algorithm Jackson G, Rosen RC, Kloner RA, et al. The Second Princeton Consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. J Sex Med. 2006;3:

18 Erectile Dysfunction Diabetes 20-85% of men with diabetes suffer from ED (ranging from mild to complete) In the Massachusetts Male Aging Study, ED was three times more common in diabetic men vs nondiabetic men ED occurs earlier in men with diabetes compared with men who do not have diabetes The risk of ED increases: The longer diabetes is present If the condition is inadequately controlled (raised blood glucose and HbA 1C ) Men with diabetes should be advised to discuss their condition with a physician if they have not already done so Boulton AJ, Selam J-L, Sweeney M, et al. Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus. Diabetologia. 2001;44: ; De Barardis, Franciosi M, Belfiglio M, et al. Erectile dysfunction and quality of life in Type 2 diabetic patients. Diabetes Care. 2002;25: ; Roth A, Kalter-Leibovici O, Kerbis Y, et al. Prevalence and risk factors for Erectile dysfunction in men with diabetes, hypertension, or both diseases: a community survey among 1,412 Israeli men. Clin Cardiol. 2003;26:

19 Erectile Dysfunction Depression Men with depression are twice as likely to experience moderate to severe ED as men who are not depressed There is evidence for a direct link between ED and depressive symptoms Antidepressant drugs such as the tricyclics and SSRIs can also cause ED Men with depression should be advised to discuss their condition with a physician if they have not already done so Goldstein I. The mutually reinforcing triad of depressive symptoms, cardiovascular disease, and erectile dysfunction. Am J Cardiol. 2000;86(suppl):41F 45F; Araujo AB et al. The relationship between depressive symptoms and male erectile dysfunction: cross-sectional results from the Massachusetts male aging study. Psychosom Med. 1998;60: ; Foresta C, Caretta N, Corona G, et al. Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart. Int J Androl. 2008;32:

20 Erectile Dysfunction Prostate Men with enlarged prostates can also suffer from erection problems ED is underdiagnosed in patients consulting urologists for benign prostatic hyperplasia The incidence of ED after transurethral resection of the prostate is 14% ED is very often seen after radical prostatectomy 44-75% of patients experience symptoms Radiation therapy for localized prostate cancer can cause erection problems in ~75% of patients Men with prostate problems should be advised to discuss their condition with a physician if they have not already done so Hosel CE, Woll EM, Burkart M, et al. Erectile dysfunction (ED) is prevalent, bothersome and underdiagnosed in patients consulting urologists for benign prostatic syndrome (BPS). Eur Urol. 2005;47: ; Taher A. Erectile dysfunction after transurethral resection of the prostate: incidence and risk factors. World J Urol. 2004;22: ; Matthew AG, Goldman A, Trachtenberg J, et al. Sexual dysfunction after radical prostatectomy prevalence, treatments, restricted use of treatments and distress. J Urol. 2005;174: ; Brown MW, Brooks JP, Albert PS, et al. An analysis of erectile function after intensity modulated radiation therapy for localized prostate carcinoma. Prostate Cancer Prostatic Dis. 2007;10:

21 Erectile Dysfunction Impact on quality of life Men with ED experience low self-esteem, diminished confidence, and relationship problems Partners often have feelings of rejection, unattractiveness, and guilt Improvements in erection hardness with ED oral treatment have shown to improve satisfaction with sex life, love and romance, and overall health An awareness of the impact of ED on quality of life (QoL) can help health care providers: Empathize and communicate effectively with sufferers Appreciate the value of appropriate treatment Althof SE. Quality of life and erectile dysfuntion. Urology. 2002;59: ; Cappelleri JC, Bell SS, Althof SE, et al. Comparison between sildenafil-treated subjects with erectile dysfunction and control subjects on the self-esteem and relationship questionnaire. J Sex Med. 2006;3: ; Speckens AEM, Hengeveld MW, Nijeholt GL, et al. Psychosexual functioning of partners of men with presumed non-organic erectile dysfunction: cause or consequence of the disorder? Arch Sex Behav. 1995;24(2): ; Montorsi F, Padma-Nathan H, Glina S. Erectile function and assessments of erection hardness correlate positively with measures of emotional well-being, sexual satisfaction, and treatment satisfaction in men with erectile dysfunction treated with sildenafil citrate(viagra ). Urology. 2006;68(suppl 3A):

22 Erectile Dysfunction Summary ED is the most thoroughly studied sexual dysfunction in men and the most common sexual complaint of men presenting to health care providers ED is common and increases with age ED shares several risk factors with cardiovascular disease Men with an enlarged prostate can also suffer from erection problems ED can have a negative impact on the patient as well as his partner Men with ED should be encouraged to talk to their doctor NIH Consensus Statement. Impotence. 1992;10(4):1 33; Nicolosi A, Laumann EO, Glasser DB, et al. Sexual behavior and sexual dysfunctions after age 40: the global study of sexual attitudes and behaviors. Urology. 2004;64: ; Schwartz BG, Economides C, Mayeda GS, et al. The endothelial cell in health and disease: its function, dysfunction, measurement and therapy. Int J Impot Res. 2010;22:77 90; Hosel CE, Woll EM, Burkart M, et al. Erectile dysfunction (ED) is prevalent, bothersome and underdiagnosed in patients consulting urologists for benign prostatic syndrome (BPS). Eur Urol. 2005;47: ; Althof SE. Quality of life and erectile dysfuntion. Urology. 2002;59: ; Cappelleri JC, Bell SS, Althof SE, et al. Comparison between sildenafil-treated subjects with erectile dysfunction and control subjects on the self-esteem and relationship questionnaire. J Sex Med. 2006;3: ; Speckens AEM, Hengeveld MW, Nijeholt GL, et al. Psychosexual functioning of partners of men with presumed non-organic erectile dysfunction: cause or consequence of the disorder? Arch Sex Behav. 1995;24(2):

23 Diagnosis and Treatment of ED February 26,

24 Diagnosis and Treatment of ED Diagnosis of ED Basic workup includes: Medical history Psychological history Sexual history Physical examination Laboratory tests Medical and psychological histories should be taken for both patients and their partners Wespes E, Amar E, Eardley I, et al. Erectile dysfunction and premature ejaculation. Guidelines on Male Sexual Dysfunction

25 Diagnosis and Treatment of ED Assessment of erection problems by validated tools Clinical trials use a number of self-assessment methods to quantify ED and treatment response, including: IIEF: International Index of Erectile Function, 15 items in five domains and the abbreviated five-item SHIM: Sexual Health Inventory for Men questionnaires EHS: Erection Hardness Score, four-point scale grading the hardness of the erection QEQ: Quality of Erection Questionnaire, six-question, patient-reported outcome measure for evaluating satisfaction with the quality of erections in terms of hardness, onset, and duration SEAR: Self-Esteem and Relationship Questionnaire, the 14-item SEAR questionnaire is a brief, self-administered, disease-specific scale for assessing the relevant psychosocial manifestations of ED, specifically patient-reported outcomes of self-esteem, confidence, and relationships Mulhall J, Althof SE, Brock GB, et al. Erectile dysfunction: monitoring response to treatment in clinical practice recommendations of an international study panel. J Sex Med. 2007;4: ; Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998;338: ; Rosen RC, Althof SE, Giuliano. Research instruments for the diagnosis and treatment of patients with erectile dysfunction. Urology. 2006;68(Suppl 3A):6-16; Lowy M, Collins S, Bloch M, et al. Quality of erection questionnaire correlates: change in erection quality with erectile function, hardness, and psychosocial measures in men treated with sildenafil for erectile dysfunction. J Sex Med. 2007;4:83-92; Porst H, Gilbert C, Collins S, et al. Development and validation of the quality of erection questionnaire. J Sex Med. 2007;4: ; Althof SE, Cappelleri JC, Shpilsky A, et al. Treatment responsiveness of the self-esteem and relationship questionnaire in erectile dysfunction. Urology. 2003;61: ; Cappelleri JC, Althof SE, Siegel RL, et al. Development and validation of the self-esteem and relationship (SEAR) questionnaire in erectile dysfunction. Int J Impot Res. 2004;16:

26 Diagnosis and Treatment of ED Erection Hardness Score The EHS is a robust, validated, single-item patient-reported outcome for evaluating erection hardness Improvements in erection hardness have correlated with a restoration of confidence in the ED patient You can educate sufferers to use the EHS to assess the severity of their ED An expert panel defined the maximum score 4 as the main goal in the treatment of ED EHS 1 EHS 2 EHS 3 EHS 4 Penis is larger but not hard Penis is hard, but not hard enough for penetration Penis is hard enough for penetration, but not completely hard Penis is completely hard and fully rigid Mulhall J, Althof SE, Brock GB, et al. Erectile dysfunction: monitoring response to treatment in clinical practice recommendations of an international study panel. J Sex Med. 2007;4: ; Mulhall JP, Goldstein I, Bushmakin AG, et al. Validation of the erection hardness score. J Sex Med. 2007;4:

27 Rigidity is Important to Patients - Mullhall et al. Patient ED Treatment Success Sexual Satisfaction Confidence/Self-Esteem Healthcare Professional Optimal Erection Hardness Partner Source: Mulhall JP et al. J Sex Med. 2007;4:

28 Erection Hardness Score (EHS) IIEF Severe ED 6-10 Moderate ED Mild ED No ED Penis is larger but not hard Penis is hard but not hard enough for penetration Penis is hard enough for penetration but not completely hard Penis is completely hard and fully rigid Sources: Goldstein I et al. N Engl J Med. 1998;338: ; Mulhall JP et al. J Sex Med. 2007;4:

29 Rigidity is Important to Patients A shift from EHS Grade 3 at baseline to EHS Grade 4 at the EOT is accompanied by significant improvements in intercourse and relationship satisfaction An international panel of experts convened to evaluate data clinical trials involving > men with ED, concerning the role of erection hardness in defining the response to treatment with PDE5 therapy Tools International Index of Erectile Function (IIEF), Self-Esteem and Relationship Questionnaire (SEAR) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS Index scores) Mulhall J, et al. 2007

30 Studies also show Studies show that erection hardness is important to patients A total of 307 men were randomised to sildenafil or placebo EHS 3 or 4 had increased by 40% for sildenafil vs. 11% for placebo (p<0.0001) Improvement in function, emotional well-being, and satisfaction was greatest in men with completely hard erections and correlated positively with other measures of hardness (Kadioglu A. et al. 2007)

31 Evaluation and Management of ED Early detection Patient should see a doctor for a full assessment Directed investigations( e.g. psychiatric, testosterone levels, prostate check, cardiovascular work-up) Partner interaction the spouse plays an important role and should be actively involved in management Rigorous follow-up to ensure compliance Specialist referral when necessary 31

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33 Concerns About Other Therapies in ED Management 33

34 Alternative treatments Date 34

35 Concerns About Other Therapies in ED Management What are alternative treatments? An alternative treatment is a health treatment that is not classified as standard Western medical practice Alternative supplements may include: herbal medicines nutritional supplements acupuncture 35 Alternative Treatments for ED: Web MD. 23 Feb Available from: Accessed Dec 12, 2012.

36 Herbal therapy Date 36

37 Concerns About Other Therapies in ED Management What are herbal supplements? Herbal supplements may be called many things: herbal medicines plant preparations nutritional supplements alternative medicines complementary medicines traditional medicines What are some herbal supplements for ED? Asian ginseng Ginkgo biloba Alternative Treatments for ED: Web MD. 23 Feb Available from: Accessed Dec 12,

38 Cumulative number of papers published through 2013 Concerns About Other Therapies in ED Management Body of evidence for plant preparations for the treatment of ED is very weak Medline search* Plant preparations Tadalafil Vardenafil Sildenafil *Data collected following a Medline search using the following terms: sildenafil, tadalafil, vardenafil and plant preparations/therapeutic use AND erectile dysfunction/drug therapy [MAJR]. Search was limited to humans and clinical trials. Results updated through June Medline Search Papers file:///users/eddecker/desktop/adams%20&%20knight/mod%209/plant%20preparations% webarchive. Accessed November 18,

39 Concerns About Other Therapies in ED Management More evidence is needed before herbal medicines play a role in ED treatment Most herbal preparation testing has been done in animals Randomized controlled trials in humans are scarce Many herbal therapies appear to have potential benefits, and similarly, the health risks of various phytotherapeutic compounds need to be elucidated To really understand if they have value there need to be properly designed human trials to assess the efficacy and safety 39 Ho CCK, Tan HM. Rise of herbal and traditional medicine in erectile dysfunction management. Curr Urol Rep. 2011;12:

40 Concerns About Other Therapies in ED Management Existing evidence on adverse events associated with dietary supplements A one-year prospective surveillance study of dietary supplement related poison control center calls in 2006 showed: 275 calls Sympathomimetic toxicity was most common, with caffeine products accounting for 47%, and yohimbe products accounting for 18% of supplement-related symptomatic cases Suspected drug-herb interactions occurred in 6 cases Most supplement-related adverse events were minor 40 Haller C, Kearney T, Bent S, et al. Dietary supplement adverse events: report of a one-year poison center surveillance project. J Med Toxicol. 2008;4:84-92.

41 Concerns About Other Therapies in ED Management Some herbal products contain PDE5 inhibitors Twenty-six herbal products were tested by the US FDA laboratory for the presence of known PDE5 inhibitors or previously identified synthetic analogues Synthentic analogues include sildenafil citrate, tadalafil, vardenafil hydrochloride trihydrate, methisosildenafil, homosildenafil, piperidenafil, thiosildenafil, and thiomethisosildenafil Fifteen of 26 of the herbal products actually contained a PDE5 inhibitor or analogue 42% 58% Contained ED drug or analogue Did not contain analogue 41 Gryniewicz CM, Reepmeyer JC, Kauffman JF, et al. Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry. J Pharm Biomed Anal. 2009;49:

42 Concerns About Other Therapies in ED Management Some herbal products contain PDE5 inhibitors In a separate study, 17 herbal dietary supplements were assessed by a laboratory in France Eight of the 17 preparations contained sildenafil or an analogue (including a previously unidentified [and unstudied] propoxyphenyl-thiohydroxyhomosildenafil analogue in two of eight preparations) 22% 78% Contained ED drug or analogue Did not contain analogue 42 Balayssac S, Trefi S, Gilard V, et al. 2D and 3D DOSY 1H NMR, a useful tool for analysis of complex mixtures: application to herbal drugs or dietary supplements for erectile dysfunction. J Pharm Biomed Anal

43 Concerns About Other Therapies in ED Management One study shows that the effectiveness of the tested herbal treatment may be due to presence of PDE5 inhibitors One study comparing an herbal supplement to sildenafil citrate in 32 ED patients showed: Similar efficacy between products in the open-label portion But in the subsequent double-blind portion comparing the herbal supplement to placebo: The herbal product had no effect on ED The supplier of the natural product confirmed that the product in the first batch (used for open-label phase) was adulterated with a PDE5 inhibitor. 43 Corte s-gonza lez JR, Arratia-Maqueo JA, Gómez-Guerra LS, et al. The use of Butea superba (Roxb.) compared to sildenafil for treating erectile dysfunction. BJU Int. 2009;105:

44 Concerns About Other Therapies in ED Management Herbal therapies may carry potential risks The Medicines and Healthcare Products Regulatory Agency (MHRA) from the UK advises consumers not to buy 'herbal' remedies sold as a treatment for erectile dysfunction. Evidence from around the world suggests that such products are often adulterated with random quantities of pharmaceutical substances. Risks can include serious harm and even death. Their website also contains lists of dozens of specific ED herbal remedy products that carry known risks 44 MHRA website. Herbal sexual dysfunction products warnings and alerts. Available at: oductswarningsandalerts/index.htm. Accessed Dec 12, 2012.

45 Concerns About Other Therapies in ED Management Summary: Herbal supplements Natural does not always mean safe Very little evidence to determine their efficacy A surprising number contain PDE5 inhibitors which may be why some of them work 45 Balayssac S, Trefi S, Gilard V, et al. 2D and 3D DOSY 1H NMR, a useful tool for analysis of complex mixtures: application to herbal drugs or dietary supplements for erectile dysfunction. J Pharm Biomed Anal Gryniewicz CM, Reepmeyer JC, Kauffman JF, et al. Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry. J Pharm Biomed Anal. 2009;49: MacKay D. Nutrients and botanicals for erectile dysfunction: examining the evidence. Alt Med Rev. 2004;9:4-16.

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