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The Art of Andrology: Optimizing Treatment for Erectile Dysfunction

Professor John Mulhall
Director of the Male Sexual & Reproductive Medicine Program
Memorial Sloan Kettering Cancer Center, New York City, NY, USA
08 Jun 2017
In the practice of sexual medicine, the goal of the treating physician is to help the patient (or the couple) return to satisfactory sexual relations. Healthy sexual activity is important, and many, including the elderly population, report of regular sexual activity.1,2 Erectile dysfunction is an important aspect of sexual health that often goes undetected. Crucial barriers to ED discussion in the clinic are patients’ embarrassment or reluctance to discuss the condition and the lack of knowledge or training on the physicians’ side.3

Sildenafil: Shaping the management of ED
Originally developed as an anti-anginal drug, sildenafil citrate has evolved to an on-demand oral treatment for ED, in which it has demonstrated highly potent and selective inhibition of the enzyme phosphodiesterase type 5 (PDE5).4 Ever since the scientific publication of its use for the treatment of ED in human subjects in the late 1990s,5,6 sildenafil has revolutionized the management of ED. Not only did sildenafil change how physicians perceive sexual health in general,7 it also led to an explosion of research on ED, including the development and validation of several instruments to evaluate ED and its treatment efficacy.8–11 A few other PDE5 inhibitors are now available and Table 1 summarizes the pharmacokinetic profile of these drugs. 

HK-PFR-496b2-ID_table 1

Implications of a Grade 4 erection
The Erection Hardness Score (EHS) is a simple, reliable and patient-reported outcome for scoring erection hardness, because it displays clear differentiation between normal and impaired erectile function as defined by the International Index of Erectile Function (IIEF) questionnaire.11

Grade 4 erection, according to the EHS, implies that the penis is completely hard and fully rigid; it is essentially the desired outcome of ED management. A Grade 4 erection is important because:
  • It is directly correlated to successful sexual intercourse (SSI): the percentage of SSI increases from almost 60% at EHS 3 to 93.1% at EHS 4.16
  • A shift from Grade 3 erection (hard enough for penetration but not completely hard) to Grade 4 is significantly associated with improvements in psychosocial measures such as self-esteem, confidence, and relationship and intercourse satisfaction.17
  • Driving men to greater erectile rigidity appears to translate to lower dropout rates, ie, higher treatment adherence.18
The sildenafil candidate patient
According to the Princeton Consensus Panel, patients who are not taking nitrates of any form, with low cardiac risk, and have enough exercise reserve to resume sexual activity, can receive treatment for ED.19 “Other factors such as sexual dynamics, frequency and predictability of sexual activity, and integratability of treatment with sexual activity, may decide which PDE5 inhibitor is suitable for a particular patient,” said Professor Mulhall. 

Speaking from his own clinical experience, Professor Mulhall noted that sildenafil 100 mg is a good starting dose, and this may be down-titrated to manage any possible side effects or if treatment response is excellent. In the study by Buvat et al,20 patients with ED who were titrated to sildenafil 100 mg had significantly greater improvement in the erectile function domain of the IIEF compared with those on sildenafil 50 mg  (Figure 1). The improvement in erectile function was also correlated with significant improvement in the sexual desire, intercourse satisfaction and overall satisfaction domains of the IIEF. 

HK-PFR-496b2-ID_figure 1

Pooled safety analysis from 67 double-blind placebo-controlled trials involving more than 14,000 men confirms the good tolerability and safety profile of sildenafil 50 mg and 100 mg. Common adverse events with sildenafil are those related to the pharmacology of PDE5 inhibition, such as headache, vasodilation and facial flushing. The rates of these adverse events are higher during the first 4–6 weeks of treatment but decrease markedly thereafter, reaching similar rates as placebo-treated patients (Figure 2).21 As for cardiovascular safety, pooled analysis from more than 120 trials of sildenafil found that the rates of myocardial infarction and cardiovascular death were low and comparable with placebo.22

HK-PFR-496b2-ID_figure 2

Summary
Sildenafil is the first PDE5 inhibitor approved and has shaped the modern management of ED. The use of sildenafil in ED is backed by robust efficacy data; safety analyses revealed that it is well tolerated and does not increase cardiovascular events compared with placebo. Last but not least, optimizing patients’ response to ED treatment requires careful instruction on use of the drug and regular follow-up.

HK-PFR-496b2-ID_tips

References: 
  1. Braun M, et al. Int J Impot Res 2000;12(6):305–311.
  2. Lindau ST, et al. N Engl J Med 2007;357(8):762–774.
  3. Humphery S, Nazareth I. Fam Pract 2001;18(5):516–518.
  4. Ghofrani HA, et al. Nat Rev Drug Discov 2006;5(8):689–702.
  5. Boolell M, et al. Br J Urol 1996;78(2):257–261.
  6. Goldstein I, et al. N Engl J Med 1998;338(20):1397–1404.
  7. Potts A, et al. Sociol Health Illn 2006;28(3):306–329.
  8. Rosen RC, et al. Urology 1997;49(6):822–830.
  9. Althof SE, et al. Urology 1999;53(4):793–799.
  10. Porst H, et al. J Sex Med 2007;4(2):372–381.
  11. Mulhall JP, et al. J Sex Med 2007;4(6):1626–1634.
  12. Seftel AD. Clin Cardiol 2004;27(Suppl I):I14–I19.
  13. Nichols DJ, et al. Br J Clin Pharmacol 2002;53(Suppl 1): 5S–12S.
  14. MIMS Indonesia. Cialis Full Prescribing Information.
  15. MIMS Indonesia. Vardenafil Full Prescribing Information.
  16. Goldstein I, et al. J Sex Med 2008;5(10):2374–2380.
  17. Mulhall J, et al. J Sex Med 2007;4(2):448–464.
  18. Mazzola CR, et al. J Sex Med 2013;10(7):1861–1866.
  19. DeBusk R, et al. Am J Cardiol 2000;86(2):175–181.
  20. Buvat J, et al. BJU Int 2008;102(11):1645–1650.
  21. Giuliano F, et al. Int J Clin Pract 2010;64(2):240–255.
  22. Mittleman MA, et al. Int J Clin Pract 2003;57(7):597–600.
  23. Landén M, et al. J Clin Psychopharmacol 1999;19(3):268–271.
  24. SexHealthMatters.org. Treating Erectile Dysfunction. Available at: http://www.sexhealthmatters.org/erectile-dysfunction/treatingerectile-dysfunction. Accessed 8 Oct 2015.

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Most Read Articles
Elvira Manzano, 16 Jan 2018
Cancer patients at risk for recurrent venous thromboembolism (VTE) are less likely to experience recurrence with rivaroxaban compared with dalteparin, the Select-D trial has shown, ushering in a new standard of care (SoC) for cancer-related VTE.
4 days ago
It appears that urgent repeat endoscopic retrograde cholangiopancreatography (ERCP) predicts failure of plastic stent treatment for biliary strictures (BS) following liver transplant, according to a study.
Roshini Claire Anthony, 4 days ago

The combination of ceftazidime and avibactam proved noninferior to meropenem in adults with nosocomial pneumonia, positioning it as a potential treatment option for this condition, results from the phase III REPROVE* trial show. Nonetheless, the combination was associated with a higher number of safety events compared with meropenem.

Pearl Toh, 18 hours ago
Use of supplemental calcium, vitamin D, or both combined does not seem to lower the risk of fractures in community-dwelling older adults, suggests a meta-analysis.