Erectile Dysfunction (ED)

Invited lecture delivered by Dr Sujoy Dasgupta in a Webinar organized by Sexual medicine Committee of FOGSI (Federation of Obstetric and Gynaecological Societies of India), held in February, 2022

1. Dr Sujoy Dasgupta MBBS (Gold Medalist, Hons ) MS (OBGY- Gold Medalist) DNB (New Delhi) MRCOG (London) Advanced ART Course for Clinicians (NUHS, Singapore) Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata Visiting Consultant, RSV Hospital, Kolkata Bhagirathi Neotia Women and Child Care centre Woodlands Multispeciality Hospital, Kolkata Managing Committee Member, Bengal Obstetric & Gynaecological Society ( BOGS ) Secretary, Subfertility and Reproductive Endocrinology Committee , BOGS Executive Committee Member, Indian Fertility Society ( IFS )- West Bengal Chapter Executive Committee Member, Indian Society for Assisted Reproduction ( ISAR )- Bengal Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019 Erectile Dysfunction (ED)

2. ED- an opportunity

3. Underlying Reasons for ED Vasculogenic - Commonest cause Generalized vascular diseases - dyslipidaemia , diabetes, coronary artery disease, peripheral vasculopathy , smoking, hypertension Focal/ partial pelvic and penile arterial occlusive disease- Veno -occlusive diseases Major pelvic surgery or radiotherapy (pelvis or retroperitoneum )- Neurogenic Central causes- Degenerative disorders (multiple sclerosis, Parkinson’s disease, Alzheimer disease), spinal cord trauma or diseases, CVA , tumours Peripheral causes- Diabetic neuropathy, peripheral neuropathy, chronic renal disease, major surgery (in pelvis, retroperitoneum , colorectal and urethra) Anatomical Phimosis , fracture penis, Peyronie’s disease, hypospadias , epispadias , micropenis , penile cancer Trauma Injury to Spinal cord & brain, radical prostectomy , penile fracture, perineal trauma Endocrine Hypogonadism , DM, Thyroid and Adrenal disorders, Hyperprolactinaemia Drugs induced Antihypertensives , Beta blockers, Antipsychotics, Antiarrhythmic , Anticancer Psychogenic cause Preexisting psychological disorders- Anxiety, depression Relationship conflict Performance issues Sexual dysfunction in female partner Infertility, Timed intercourse Infrequent intercourse- Sex abuse Socioeconomic condition- Decreased income and professional stress

4. Physical or Psychological ED? Physical Psychological Gradual Onset Sudden onset Progressive Off and on In all situations/ partners In some particular situations Inadequate response to PDE5-i Good response to PDE5-i Better erection in standing position than in lying down Precipitating/ psyological factors Morning erection low Morning erection suggests but cannot always confirm psychological eitiology

5. Definition of ED (DSM-V) the recurrent inability to achieve an erection, the inability to maintain an adequate erection, and/or a noticeable decrease in erectile rigidity during partnered sexual activity. symptoms must have persisted for at least 6 months and must have occurred on at least 75% of occasions.

6. Prevalence 1/3 of the men at any point of their lives Increases with age The exact prevalence of ED may be difficult to determine? “Massachusetts Male Aging Study “( MMAS )- 52% “European Male Ageing Study” ( EMAS )- 6% to 64%, (average 30%) 50% of the young men had severe ED

7. Evaluation Medical history Sexual history Addiction Drug history Lifestyle- Smoking, alcohol, anabolic steroid, Bicycle riding >3 hours in young men Hypogonadism - fatigue, loss of energy, cognitive defects, bone pain LUTS - frequency, urgency, hesitancy Psychological screening “During the past month have you often been bothered by feeling down, depressed or hopeless” “During the past month have you often been bothered by little interest or pleasure, doing things?” Cardiac risks

8. Princeton III Consensus Age Hypertension Type 1 and type 2 DM Smoking Dyslipidaemia Sedentary lifestyle Family history of premature cardiovascular disease

9. All men with ED are “Cardiac Patients”

10. International Index of Erectile Function ( IIEF ) Questionnaire

11. International Index of Erectile Function (IIEF-5) Question 1 2 3 4 5 1. How would you rate your confidence that you could get and keep an erection ? Very Low Low Moderate High Very High 2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration ? 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) Always or Almost always 3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner ? 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) Always or Almost always 4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse ? Extremely difficult Very difficult Difficult Slightly difficult Not d ifficult 5. When you attempted sexual intercourse, how often was it satisfactory for you ? 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) Always or Almost always

12. How severe is the ED? Severe ED (5-7) Moderate (8-11) Mild to moderate ED (12-16) Mild ED (17-21) No ED (22-25). 

13. Physical Examination Genital Examination Especially if there are rapid onset of pain and bending of the penis during erection, symptoms of hypogonadism Penis- Peyronie’s disease, pre-malignant or malignant genital lesions Phimosis - especially for diabetics Testes- size, consistency Digital rectal examination ( DRE ) - not routine (only if there LUTS or ejaculatory dysfunction or before TRT ) Comfortable atmosphere Look beyond genitals Other systems Secondary sexual chanracteristics BMI, BP, HR- if not checked in last 3-6 months Vascular and neurological systems- peripheral pulse, levator ani tone

14. Investigations Routine/ Minimal HbA1c Lipid profile- if not assessed in the last 12 months Total testosterone 8-11 AM in the fasting condition- an abnormal test must be repeated after 2-3 weeks Further LH - In suspected hypogonadism   Prolactin - If low testosterone and low or low to normal LH - In case of unexplained elevation of prolactin , evaluation for other endocrine disorders (including pituitary MRI) Serum estradiol - If gynaecomastia or breast symptoms- if this man wishes to father the baby, for whom testosterone supplementation should not be used, Semen analysis- Not routine (before TRT , if future fertility is considered)

15. Advanced Testing

16. Duplex ultrasound of the penis

17. Interpretation of Doppler

18. Before starting treatment Explanation Rationale of investigations Stepwise management Risk of cardiac disease Role of partner

19. Non-Pharmacological Therapy Sex Education- To remove the myths and misconceptions ( Vaishnav et al., 2020). Pelvic floor Exercise - It helps to improve the erectile function ( Dorey , et al., 2004; Rival and Clapeau 2017). Homework assignment of the couple- Nnongenital sensate focus, genital sensate focus and vaginal containment (Masters and Johnson, 1970). Couple therapy- The PLISSIT model (Permission giving, Limited Information, Specific Suggestion and Intensive Sex therapy) ( Annon , 1976) Cognitive behaviour therapy (CBT)- to allay anxiety and improve sexual relationship (Burnett et al., 2018).

20. Phosphodiesterase -V inhibitors

21. Before starting PDE5i Exclude possible reversible cause s- Hypogonadism , DM, Psychiatric illness Cardiac evaluation Non-pharmacological therapy, Pelvic floor exercise and lifestyle changes Explanation about the drug Act ONLY after adequate sexual stimulation Wait for some time (according to the medicine he is taking)- at least 15-30 minutes Fatty meal impairs the absorption of sildenafil and vardenafil , but not tadalafil . And avanafil Absolute contraindications- Concomitant use of nitrate Dose adjustment- In men with hepatic and renal impairment, age >65 years and taking drugs which inhibit cytochromoe enzyme ( ritonavir , eryhthromycine etc) For men with BHP - If taking alpha-blockers, the PDE-5i should be taken after/ before alpha-blockers with a gap of at least 4-6 hours. Consider Tadalafil .

22. Choice of drugs

23. If PDE-5-I fails Lack of efficacy Response rate 63-75 % “ Non-responder ”- if he fails to respond to the drug taken on at least 6-8 occasions with maximum dose and after adequate sexual stimulation Incorrect use Taking unlicensed drug- The active components may vary considerably in between the preparations Lack of adequate sexual stimulation Failure to wait after taking the medicines- Fatty food- - sildenafil and vardenafil Undiagnosed reversible cause- Psychogenic disorder, DM, hypogonadism , hypothyroid, hyperprolactinaemia

24. Next step Frequent dosing regime- Regular use of PDE-5i can salvage 50% of non-responders ( Tadalafil 5 mg per day) Combining different PDE-5i- regular medication with long acting drug ( tadalafil ) along with on-demand intake of short acting medicines ( sildenafil )- without increasing the side effects Changing to different PDE-5i- Can sometimes help Further investigations- duplex Doppler ultrasound, arteriography and dynamic infusion cavernosometry Lifestyle changes- weight, smoking, alcohol, sedentary lifestyle Exclude reversible causes

25. Hypogonadism and ED

26. Testosterone Replacement therapy ( TRT )

27. Vacuum Erection Device ( VED )

28. VED Advantages Effective in all types of ED, particularly where PDE-5i-s have failed or are contraindicated For men who want drug-free or infrequent intercourse Satisfaction rate 35-84% The long term compliance is better than ICI Disadvantages Penis may look bluish and may feel cold to touch because of obstructed venous outflow Pain, bruising, numbness Ejaculation failure, unless ring is released Rarely serious risk of skin necrosis, which can be avoided by removing the ring within 30 minutes after intercourse Contraindications- bleeding disorders or taking anticoagulants

29. 2 nd line of treatment

30. ICI - pros and cons Initial satisfaction rate as high as 94%. Efficacy 70-80% Requires in office training Insertion site pain (PGE1) Priapism - report if erection >4 hrs Contraindications- Hypersensitivity to PG, risk of priapism , bleeding disorder

31. Medical urethral System for Erection (MUSE) PG-E1 pellet (0.5-1 mg) is placed within the urethra followed by massaging that area The response-rate 56-65% Compliance is low Burning and painful sensation in the urethra Rarely priapism and fibrosis are rare UTI - for faulty technique Transfer to female partner

32. 3 rd Line of Treatment Penile Implants/ Prostheses Penile Revascularization surgery

33. Penile Prosthesis Suitable mainly for men with organic ED, caused by diabetes, pelvic surgery and post- priapism Particularly suitable for Peyronie’s disease Satisfaction rate up to 92-100%, (better than oral PDE-5i, ICI and MUSE) Return to “normal” sex life without repeated drug therapy “Irreversible” and invasive nature Must be medically fit with BMI <30 Needs expertise Complications-infection, cylinder erosion, auto-inflation, pump, reservoir migration Contraindications- Systemic, cutaneous and urinary tract infections

34. Penile revascularization Suitable candidates Young men (<55 years) Non-diabetic Non-smokers Not having concomitant venous leak (very important) Post-traumatic ED- best prognosis Contraindications Multifocal arterial disease Veno -occlusive diseases

35. Inferior epigastric artery is anastomosed with dorsal artery of penis Success rate up to 80% Overall satisfaction rate is much lower than IPP Complications- inguinal hernia, glans hyperaemia and shunt thrombosis

36. Newer Therapies Oral agents- ROCK inhibitors and soluble guanylyl cyclase activators- for men resistant to the oral PDE-5i therapies (under investigation) Topical therapy- PG-E1 gel 300 µg (phase III trial) Low-Intensity Extracorporal Shock Wave Therapy- can induce neovascularization in men resistant to PDE-5i treatment- needs further research Regenerative medicine - growth factors, gene therapy, stem cells and tissue engineering Penile PRP (platelet-rich-plasma)- Some clinics are claiming high success rate

37. References

38. Take home ED is curable but often undertreated Thorough evaluation is needed Most men do well with oral PDE5-I Few men require advanced investigations and treatment

39. Thank You