REVIEW ARTICLE core Sree seasons A Comparative Review of the Options for Treatment of Erectile Dysfunction Which Treatment for Which Patient? Konstantinos Hatzimouratidis and Dimitrios G. Hatzichristou Center for Sexual and Reproductive Health, Aristotle University of Thessaloniki, Thessaloniki, Greece Contents Abstract. . #6 ween . 1622 1, Treatment Options for Erectile Dysfunction €D) . 1623 2. Phosphodiesterase Type 5 Inhibitors 1625 21 Soret : SEIT es 211 Pharmacokinetics and Dose | Administration . 1625 212 emcacy 1825 2.1.3 Adverse Events and Discontinuation Rates..... 0.6... ceee eer etree etter ee 1627 2a. atin! Sotltaction toor 22 tadoiot : SIT 2.2.1 Pharmacokinetics and Dose | Administration... sestaaseneneaennene. 1628 202 encacy 1028 223. avers Evenis onc Oscontinuaton Rotes,...s.sjssctoesicesseceseeseecese. 190 2.2.4 Patient Satisfaction, . . . tees . 1630 2.3 Vardenafil 1630 2.3.1 Pharmacokinetics and Dose Administration 7 vce pat . 1630 232 eMncacy vss0 233. adver Evenis onc Dsconinuaton Rotes,..,ssj.sctoasisesnsusvaesnesese. 1098 23.4 Patient Satisfaction. . " . = 1632 3. Centrally Acting Drugs... . . . . tees . 1632 31" apomorphine te2e on pnomecciogy : : SEIT es 3.1.2 Efficacy 1632 213. dveséEvenls onl Dsconination Rote. 00 licnisi ni ETT es 4. Topic maropies : STII os 4,1 Intracavernous Pharmacotherapy . . i see . 1633, 4.1.1 Drugs and Combinations 1633, 42 tticacy : SI 4113. dverse Even Onc Dconinsaton Rots Seaman 4114 he fol of novavemous hjectorsin 2005... SEIS oa 4.2 Intraurethral Pharmacotherapy ... . rere rere tees . - 1635, 48 Other Topco! prarmacomsroples ict 5. Mechantca Bavices SAIS ee 5.1 Vacuum Constriction Devices ¥ 7 H . 1636 52 Pente Prosheses vas? 6. Which Treatment for Which Patient? ... Oma ARO EEA . 1638 6.1. Understanding Individuality in Patients with ED 16381622 Hatzimowratidis & Hatziotristou 62 Vipich Oral Cruat? The Role of the Phyniclanip Dernarwrating Pramacalooical Ditferences 1639 63 Management of Patients Unresponsive to Oral Drugs 1640 64 Treatment Options Other than Oral Drugs 1642 7. Conclusions srr TARO = 1643 Abstract The field of erectile dysfunction (ED) has been revolutionised over the last two decades. Several treatment options are available today, most of which are asso ated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken in order to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDES) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice of most physicians and patients for the treatment of ED. PDES inhibitors have differences in their pharmacologi- cal profiles, the most obvious being the long duration of action of tadalafil, but there are no data supporting superiority for any one of them in terms of efficacy or safety. Sublingual apomorphine has limited efficacy compared with the PDES inhibitors, and its use is limited to patients with mild ED. Treatment failures with coral drugs may be due to medication, clinician and patient issues, The physician needs to address all of these issues in order to identify true treatment failures. Patients who are truly unresponsive to oral drugs may be offered other treatment options. Intracavernous injections of alprostadil alone, or in combination with other vasoactive agents (papaverine and phentolamine), remain an excellent treatment option, with proven efficacy and safety over time. Topical pharmacotherapy is appealing in nature, but currently available formulations have limited ef Vacuum constriction devices may be offered mainly to elderly patients with ‘occasional intercourse attempts, as younger patients show lited preference because of the unnatural erection that is associated with this treatment modality. Penile prostheses are generally the last treatment option offered, because of invasiveness, cost and non-reversibility; however, they are associated with high salisfaction rates in properly selected patients All treatment options are associated with particular strengths and weaknesses. A patient-centred approach based on patient needs and expectations is necessary for the management of ED. The clinician must educate the patient and provide a supportive environment for shared decision making. The management strategy must be supplemented by careful follow-up in order to identify changes in patient health and relationship/emotional status that may necessitate treatment optimisa- tion. Erectile dysfunction (ED) has been one of the more rapidly growing fields in medicine over the mellitus and hyperlipidaemia, Smoking, the absence of physical exercise, and obesity are lifestyle risk past 20 years. The prevalence of ED is high, and ED is expected to affect 322 million men by the year 2025." The prevalence increases with age and other risk factors such as cardiovascular disease, diabetes ©2008 Ads Dota information BY. Al ihe reserved factors for ED.! ED is associated with a high in dence of depressive symptoms and has a profound negative impact on the quality of life of patients and their partners.) rugs 2006: 08 012)‘Treatment Options for Erectile Dysfunction 1623 -veral options for the treatment of ED with no identifiable cause have been added to the armamen- tarium of physicians over the past 20 years (see table 1). The advent of new oral drugs has revolutionised treatment for ED." Older treatment modalities, such as penile prostheses and intracavernous injections of vasoactive drugs, underwent improvements in terms of administration, dosage, or technical items (e.g. autoinjectors, battery-operated vacuum constriction devices, pre-connected penile prosthesis). The liter- ature on treatment options is rapidly growing, presenting data that are often difficult to interpret in clinical practice.!© Optimal therapy for patients with ED may be challenging.!”! Treatment endpoints for assessing efficacy and safety are certainly important but cannot be extrapolated to every patient!) A MEDLINE search was conducted using the keywords ‘erectile dysfunction” and ‘treatment’. This search revealed 1571 relevant references (as at April 2005). This review provides a critical assess- ment of all currently available treatment options for ED, with a particular focus on selection of the appropriate treatment for a given individual as part of a patient-centred model of care. 1, Treatment Options for Erectile Dysfunction (ED) ED is potemtially reversible when specilic aetio- logical or lifestyle determinants can be addressed |! These include specific endocrinopathies (e.g. hypogonadism, hyperprolactinaemia). pelvic or per- ineal trauma, drugs (e.g. antihypertensives, antide~ pressants, antiandrogens, recreational drugs), lifes- tyle and psychosocial factors. Hypogonadism is a potentially reversible cause of ED." It may occur either as a result of primary failure (primary hypogonadism) or secon- dary to pituitary or hypothalamic causes (hypogo- nadotrophic hypogonadism). The prevalence of hy- pogonadism increases with age, due to both testicu- lar and pituitary failure, Treatment is based on testosterone replacement by parenteral or topical (patch or gel) delivery. Administration of testoster- ‘one is contraindicated in men with a history of prostate disorders or with symptoms of bladder out- testicu ©2008 Ads Dota information BY. Al ihe reserved let obstruction, Prior to initiating testosterone re- placement therapy, a digital rectal examination and serum prostate-specific antigen (PSA) should be performed. Patients receiving androgen therapy should be monitored for a clinical response, as well as undergoing intermittent measurements of serum testosterone levels. liver function status, PSA and serum haematocrit levels. Patients with hyperpro- lactinaemia must undergo an evaluation of the hypo- thalamic/pituitary area (magnetic resonance imag- ing is the preferred imaging modality) for a hor- ing tumour (prolactinoma). ‘Treatment nomas is based on the administration of (eg. bromocriptine, dopamine cabergoline), Surgical treatment of prolactinoma reserved for large tumours that fail to respond to agonists medical therapy Pelvic or perineal trauma may be associated with focal arterial occlusive lesions which can be docu- mented by pharmacoarteriography. The associated ED may be amenable to reconstructive microvascu- lar surgery in selected patients (young men, <40 years of age, without concomitant vascular risk fac- tors).""| The revascularisation procedure usually employs the inferior epigastric artery as a donor artery to the corpora cavernosa via the dorsal artery and its penetrating branches. It is associated with long-term success rates ranging between 25% and 80% 121 ED may be secondary to drug therapy, and lifes- tyle and psychosocial factors. Alterations in drug dosages or classes (whenever possible) may be of benefit in a relatively small number of patients, especially those taking antihypertensives (B-adre- noceptor antagonists [B-blockers] or diuretics). Lifestyle factors, including obesity, cigarette smok- ing, alcoholism or substance abuse, may require priority management specific to the particular issue. Psychosocial factors include relationship issues (e.g partner conflict), mood problems and depression, or other psychosexual dysfunctions, Good medical practice recognises the value of altering modifiable risk factors, However, such alterations are frequent ly insufficient to reverse ED completely, and the rugs 2006: 08 012)