Erectile Dysfunction and Scleroderma: Evaluation and Managament
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This document provides information on erectile dysfunction (ED) in patients with scleroderma. It defines ED and scleroderma, noting that 41.6% of scleroderma patients experience moderate to severe ED. ED in scleroderma is associated with more severe organ involvement. The document reviews the physiology of erections, risk factors for ED, and how scleroderma impacts penile blood vessels and smooth muscle function. It outlines the evaluation of ED, including history, exam, questionnaires, and potential labs/imaging. Finally, the document discusses treatment options for ED, including oral medications, injections, devices, and penile implants.
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Erectile Dysfunction and Scleroderma: Evaluation and Managament
- 1. Erectile Dysfunction in Scleroderma Evaluation & Management N. Bennett, MD, FACS Associate Professor of Urology, Department of Urology, Northwestern University, Feinberg School of Medicine Co-Director Andrology Fellowship
- 2. DISCLOSURES – CONFLICTS OF INTEREST 10/20/2016 2 I have no disclosures or COI
- 4. Erectile Dysfunction and SCC • Importance of ED • Definition of ED • Definition of SCC • Intersection of ED and SCC • Risk Factors / Pathophysiology • Evaluation History/Physical Labs • Treatment • Conclusions Agenda
- 5. Importance of Sexual Health • Important to overall health and quality of life • A fundamental human right • Satisfaction provides many benefits to patients and their partners • 35% men ages 40-70 reported ED in MMAS Older men 3x more likely to report ED, decreased libido • ED: 1 in 5 visits to urologist Johannes et al, J Urol 2000 Laumann et al, JAMA 1999 “40% of 40-year-olds, 70% of 70-year-olds” Proceedings of a Regional Consultation convened by Pan American Health Organization (PAHO). World Health Organization (WHO) in collaboration with the World Association for Sexology (WAS). May 19-22, 2000; Antigua Guatemala, Guatemala.
- 6. Definition of Erectile Dysfunction (ED) The inability to achieve or maintain an erection sufficient for sexual intercourse. • May include: Inability to initiate an erection Inability to get hard enough for penetration Inability to maintain an erection to the completion of intercourse • May be associated with Orgasm problems Ejaculation problems Penile shape issues (curvature)
- 7. Definition of Scleroderma Scleroderma, or systemic sclerosis (SSc), is a chronic multisystem autoimmune disease characterized by: 1. Vasculopathy (blood vessel disease) 2. Diffuse fibrosis of skin and various internal organs, 3. Immune abnormalities.
- 8. Erectile Dysfunction Is Frequent In Systemic Sclerosis And Associated With Severe Disease: A Study Of The EULAR Scleroderma Trial And Research Group • Prospective, 22 centers in 13 countries Starting in 2009 • Performed using the multinationaldatabase of the EULAR Scleroderma Trial and Research (EUSTAR) group. • 130 patients • Men given the International Index of Erectile Function-5 (IIEF-5), a self-administered questionnaire Foocharoen et al. Arthritis Research & Therapy 2012, 14:R37
- 9. EUSTAR Results 41.6 % - Moderate or Severe ED
- 10. EUSTAR Results • In the majority of patients, the erectile problem started after the onset of SSc In 90.1% of SSc patients after the onset of Raynaud's phenomenon In 82.1% of men after the manifestation of the first non-Raynaud's symptom of SSc. • The presence of ED was also associated with more severe organ involvement in SSc.
- 15. Physiology of Erection • Arterial dilation (nitric oxide mediated) and increase in penile artery inflow • Venous compression • Tunical expansion • Penile rigidity
- 16. Mechanism of Erection • Arterial dilation (nitric oxide mediated) and increase in penile artery inflow • Venous compression • Tunical expansion • Penile rigidity
- 18. Mechanism of Erection • Inside the body there are several kinds of muscle: • Skeletal muscle is what we see at the Olympics -- bulging biceps, and so on. • Cardiac muscle powers the heart. • Smooth muscle can be found in things like blood vessels, the intestines and the stomach, and it usually acts involuntarily. • Smooth muscle plays a key role in every erection,
- 19. Physiology of Erection The a cons from Smo arter the a the p Smooth Muscle • Contracted smooth muscle - keeps blood from entering. • Relaxed smooth muscle – allows blood to enter the penis
- 20. What Does This Have To Do With Scleroderma Scleroderma, or systemic sclerosis (SSc), is a chronic multisystem autoimmune disease characterized by: 1. Vasculopathy (blood vessel disease) 2. Diffuse fibrosis of skin and various internal organs, 3. Immune abnormalities.
- 21. Penile Vessels in Scleroderma • In scleroderma, the blood vessels are abnormal • The wall of the vessel is thickened, fibrotic • Decreased blood flow • Smooth muscle cells in the vessel wall cannot relax properly
- 24. Causes Of ED
- 26. Pathophysiology of ED • Loss of innervation to corpora – Impair SM relaxation and penile blood flow • Lower motor neuron (pelvic ganglia and cavernous nerve) • Upper motor neuron (spinal cord and brain) Example • Radical pelvic surgery – nerve injury (traction, transection, electrocautery) • Diabetes – autonomic neuropathy – progressive demyelination • Spinal cord injury – trauma, compression by bone , hematoma, tumor or disc material, spinal arterial ischemia Neurologic
- 27. Pathophysiology of ED • Hypertension (blood pressure >130/85) • Hypertriglyceridemia (> 150 mg/dL) • Low high-density lipoprotein (< 40 mg/dL) • Diabetes (fasting blood sugar > 110 mg/dL) • Obesity (body mass index > 30 & waist circumference >40 inches) • Tobacco use • Lack of exercise (< 3 metabolic equivalents per week) All independently associated with risk of ED Vascular
- 29. Pathophysiology of ED • 5-alpha reductase inhibitors • Antiandrogens • LH-RH Agonists/Antagonists • Antihypertensives Beta-blockers Thiazides Spironolactone ACE-I CCB • Statins • H2 blockers – acid reflux • Psychiatric SSRI Tricyclics Benzo Antipsychotics • Phenytoin • Digoxin • Opioids • Steroids Medications
- 31. Erectile Function History • Onset • Duration • Rigidity (0-10 or 1-4) • Rigidity during partnered relations versus masturbation • Ability to attain erection sufficient for penetration • Sustainability of erection • Presence and rigidity of nocturnal erections • Use of any prior erectogenic therapies • Issues with libido, ejaculation, orgasm, penile deformity
- 32. Psychosexual History • Identify (or rule out) psychological and interpersonal factors that affect erectile function. Depression External stressors (work, finances) Interpersonal conflict • Sexual dysfunction is a condition of the couple Ask about the status of the patient's partner(s): • Gender • Duration of relationship, Legal/Marital status • Partner health and sexual problems.
- 33. Physical Exam Pearls • BMI and waist circumference are independent predictors of ED. • Examine chest for gynecomastia • Assess 2ndry sex characteristics for hypogonadism – beard, pubic hair • Penis Flaccid stretch, skin lesions, hypospadias In stretch, eval for Peyronie’s dorsally and ventrally • Scrotum Testis location, testis size, consistency • Digital Rectal Exam Prostate pathology Bulbocavernous reflex (Osinski’s reflex) • absent in up to 30%
- 34. SHIM • 1-7 – Severe ED • 8-11 – Moderate ED • 12-16 – Mild/moderate ED • 17-21 – Mild ED • 22-25 – No ED Sexual Health Inventory forMen Rosen et al, Int J Impot Res 1999 Name: _____________________________ DOB:_______________ DOV:__________________ SHIM Score PATIENT INSTRUCTIONS: Sexual health is an important part of an individual's overall physical and emotional well-being. Erectile dysfunction, also known as impotence, is one type of very common medical condition affecting sexual health. Fortunately, there are many different treatment options for erectile dysfunction. This questionnaire is designed to help you and your doctor identify if you may be experiencing erectile dysfunction. If you are, you may choose to discuss treatment options with your doctor. Each question has several possible responses. Circle the number of the response that best describes your own situation. Please be sure that you select one and only one response for each question. OVER THE PAST 6 MONTHS: 1. How do you rate your confidence that you could get and keep an erection? Very low Low Moderate High Very high 1 2 3 4 5 2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration (entering your partner)? No sexual activity Almost never or none A few times (much less than half the time) Sometimes (about half the time) Most times (much more than half the time) Almost always or always 0 1 2 3 4 5 3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner? Did not attempt intercourse Almost never or none A few times (much less than half the time) Sometimes (about half the time) Most times (much more than half the time) Almost always or always 0 1 2 3 4 5 4. During sexual intercourse how difficult was it to maintain your erection to completion of intercourse? Did not attempt intercourse Extremely difficult Very difficult Difficult Slightly difficult Not difficult 0 1 2 3 4 5 5. When you attempted sexual intercourse, how often was it satisfactory for you? Did not attempt intercourse Almost never or never A few times (much less than half the time) Sometimes (about half the time) Most times (much more than half the time) Almost always or always 0 1 2 3 4 5 SCORE: __________ Add the numbers corresponding to questions 1 - 5. If your score is 21 or less, you may want to speak to your doctor.
- 35. Investigations • Chem 7 - optional but highly recommended • Early morning total testosterone level, • Fasting lipids • Fasting glucose • Hemoglobin A1C (HbA1C) • Thyroid function – selected patients • Prostate specific antigen (PSA) – selected patients Laboratory Studies
- 37. Investigations Cavernosometry/Cavernosography • Best assessment of venous leak • Injection of vasoactive agent • Saline infused at constant rate • Change in corporal pressure measured Pudendal Angiography • Internal pudendal arteriography • Indicated in patients with arterial insufficiency & prior to penile revascularization surgery Vascular Studies
- 39. A Urologist’s Timeline of ED Treatment 2000s Men’s Health 1970’s Penile Implant 1998 sildenafil 1960’s Sexual Therapy
- 40. Erectile Dysfunction - Treatment • Phase I Oral medication - PDE-5 Inhibitors • Phase II Intraurethral suppository Intracavernosal injection Vacuum Erection Device • Phase III Penile prosthesis • Optimize/correct comorbidities Control diabetes Manage hyperlipidemia Treat T deficiency Lifestyle modification: weight loss, smoking cessation, exercise
- 41. PDE5i PDE5i Oral Medications • Types sildenafil vardenafil tadalafil avanafil • Prevent breakdown of cGMP ↑ smooth muscle relaxation PDE-5 inhibitors Phosphodiesterase in present in highconcentration in penilesmooth muscle
- 42. Oral Medications • Advantages 60-70% effective Well-tolerated • Disadvantages Cost Stress of taking the pill • Contraindications: Nitrates,Amyl Nitrite Those in whom sexual intercourse is inadvisable due to cardiovascular risk factors…..2 flights of stairs. Caution with α-blockers, HIV meds PDE-5 inhibitors
- 43. Adverse Events • Flushed face • Headache • Nasal congestion • Gastric reflux • Muscle/back pain PDE-5inhibitors
- 44. Oral Medications - Instructions • Avoid alcohol first time • Wait minimum 2 hours (4 hours for tadalafil) • Stimulation of brain and penis required • Need 3-4 separate encounters to determine true efficacy • Lack of spontaneity due to waiting might be an issue with oral vs. injectable medication PDE-5Inhibitors
- 45. Why do men stop oral treatment? • Inadequate instructions, dose too low • Ineffective with severe venous leak or neurogenic ED • Expensive • Side effects – reflux, headache • Attitude of patient, fear, perception of quality of erection • Lack of confidence in the medication • Unreceptive partner PDE-5inhibitors
- 46. Intraurethral Suppository • Alprostadil (PGE1) Promotes NO synthesis smooth muscle relaxation penile vasodilation • Advantages Administered per urethra ~80% effective • Disadvantages Urethral pain, hypotension, hematuria May trigger uterine contractions in female partner • Study results 66% of 1511 patients had erections in office 65% had successful intercourse at home vs. 18.6% with placebo • Overall success reported was 30% to 60% Padma-Nathan H, et al. N Engl J Med. 1997;336:1-7.
- 47. Intracavernosal Injections • Alprostadil (PGE1) • Bimix/TriMix/Quadmix Phentolamine Papaverine PGE1 Atropine • Advantages 85+% effective Easy for diabetics • Disadvantages Priapism Corporal fibrosis
- 48. Intraurethral Gels • Contains papaverine, phenolamine, alprostadil in a gel matrix. • Concentration of alprostadil is quite high 500-2000 mcg. • Same side effects as alprostadil: pain, hypotension, hematuria • In a 2009 study of men s/p RRP and no PDE5i response, 100% achieved tumescence with trimix gel. • 40% achieved penetration quality erections. Trimix Gel Marmar,J et al.J UrolVol.179, No.8(Supp).pp. 431
- 49. Vacuum Erection Device (VED) • Lack of interest in drug therapy • Specific contraindications to drug therapy • Patient preference • Aspiration of venous blood into the penis • Venous constriction ring necessary at base of penis
- 50. Vacuum Erection Device (VED) • Requires manual dexterity1 • Instructional video and/or in-office teaching1 • 30-minute maximum duration of constriction is advised to prevent penile ischemia1 • Precautions necessary in patients on anticoagulant therapy or those easily bruised1,2 1. Montague DK, et al, for the AUA Clinical Guidelines Panel on Erectile Dysfunction. J Urol. 1996;156:2007-2011. 2. Levine LA, Dimitriou RJ. Urol Clin North Am. 2001;28:335-341.
- 51. Vacuum Erection Device (VED) • Efficacy1 Uniformly produces erection Reported satisfaction rate ~55% (at 2 years)2 • Advantages2,3 On-demand use No systemic side effects • Disadvantages2,3 Cumbersome Unnatural erection Possible side effects may include • Petechiae/ecchymosis • Penile pain • Ejaculatoryblockage • Numbness • Penile hinging
- 52. Penile Prosthesis • Ideal for men who have tried other treatments without success. • On the market for over 30 years • 25,000 penile implants per year. • 300,000 implants to date • High patient and partner satisfaction • 3 types of devices from 2 companies
- 54. Take-home Message • Those with scleroderma have worse ED earlier in life • Optimization of medical issues • Lifestyle modification is KEY. What is good for the heart is good for the penis • Many medical and surgical treatment options Many require patience and open-mindedness
- 55. Erectile Dysfunction in Scleroderma N. Bennett, MD, FACS Associate Professor of Urology, Department of Urology, Northwestern University, Feinberg School of Medicine Co-Director Andrology Fellowship
- 56. Erectile Dysfunction in Scleroderma Evaluation and Management N. Bennett, MD, FACS Associate Professor of Urology, Department of Urology, Northwestern University, Feinberg School of Medicine Co-Director Andrology Fellowship