Update of the position paper on arterial hypertension and erectile dysfunction.
Adrenergic beta-Antagonists
/ therapeutic use
Antihypertensive Agents
/ therapeutic use
Arteries
/ physiopathology
Atherosclerosis
/ complications
Cardiology
/ standards
Cardiovascular Diseases
/ complications
Coronary Artery Disease
/ physiopathology
Endothelium
/ physiopathology
Erectile Dysfunction
/ complications
Humans
Hypertension
/ complications
Impotence, Vasculogenic
/ complications
Male
Nebivolol
/ therapeutic use
Penile Erection
/ drug effects
Phosphodiesterase 5 Inhibitors
/ therapeutic use
Risk Factors
Sexual Dysfunction, Physiological
/ chemically induced
Societies, Medical
Testosterone
/ therapeutic use
Journal
Journal of hypertension
ISSN: 1473-5598
Titre abrégé: J Hypertens
Pays: Netherlands
ID NLM: 8306882
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
pubmed:
20
2
2020
medline:
18
5
2021
entrez:
20
2
2020
Statut:
ppublish
Résumé
: Sexual health is an integral part of overall health, and an active and healthy sexual life is an essential aspect of a good life quality. Cardiovascular disease and sexual health share common risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking) and common mediating mechanisms (endothelial dysfunction, subclinical inflammation, and atherosclerosis). This generated a shift of thinking about the pathophysiology and subsequently the management of sexual dysfunction. The introduction of phosphodiesterase type 5 inhibitors revolutionized the management of sexual dysfunction in men. This article will focus on erectile dysfunction and its association with arterial hypertension. This update of the position paper was created by the Working Group on Sexual Dysfunction and Arterial Hypertension of the European Society of Hypertension. This working group has been very active during the last years in promoting the familiarization of hypertension specialists and related physicians with erectile dysfunction, through numerous lectures in national and international meetings, a position paper, newsletters, guidelines, and a book specifically addressing erectile dysfunction in hypertensive patients. It was noted that erectile dysfunction precedes the development of coronary artery disease. The artery size hypothesis has been proposed as a potential explanation for this observation. This hypothesis seeks to explain the differing manifestation of the same vascular condition, based on the size of the vessels. Clinical presentations of the atherosclerotic and/or endothelium disease in the penile arteries might precede the corresponding manifestations from larger arteries. Treated hypertensive patients are more likely to have sexual dysfunction compared with untreated ones, suggesting a detrimental role of antihypertensive treatment on erectile function. The occurrence of erectile dysfunction seems to be related to undesirable effects of antihypertensive drugs on the penile tissue. Available information points toward divergent effects of antihypertensive drugs on erectile function, with diuretics and beta-blockers possessing the worst profile and angiotensin receptor blockers and nebivolol the best profile.
Identifiants
pubmed: 32073535
doi: 10.1097/HJH.0000000000002382
pii: 00004872-202007000-00004
doi:
Substances chimiques
Adrenergic beta-Antagonists
0
Antihypertensive Agents
0
Phosphodiesterase 5 Inhibitors
0
Nebivolol
030Y90569U
Testosterone
3XMK78S47O
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1220-1234Références
NCD Risk Factor Collaboration (NCD-RisC)Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet 2017; 389:37–55.
Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidlines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 2018; 36:1953–2041.
Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. Overview, meta-analyses, and metaregression analyses of randomized trials. J Hypertens 2014; 32:2285–2295.
Brunstrom M, Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Intern Med 2018; 178:28–36.
Manolis A, Doumas M. Sexual dysfunction: the ’prima ballerina’ of hypertension-related quality-of-life complications. J Hypertens 2008; 26:2074–2084.
Doumas M, Boutari C. Erectile dysfunction: definition and size of the problem. In: Camm AJ, Lüscher TF, Maurer G, Serruys PW, editors. The ESC Textbook of cardiovascular medicine. Oxford: Oxford University Press; 2018.
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. Management of arterial hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007; 25:1105–1187.
Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, et al. European Society of HypertensionReappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27:2121–2158.
ESH/ESC Task Force for the Management of Arterial Hypertension2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens 2013; 31:1925–1938.
Manolis AJ, Doumas M, Viigimaa M, Narkiewitz K. Hypertension and sexual dysfunction. European Society of Hypertension Scientific Newsletter: update on Hypertension Management, 8, 2007.
Manolis AJ, Doumas M, Viigimaa M, Narkiewitz K. Hypertension and sexual dysfunction. European Society of Hypertension Scientific Newsletter: Update on Hypertension Management. 2011. p. 32.
Viigimaa M, Doumas M, Vlachopoulos C, Anyfanti P, Wolf J, Narkiewicz K, Mancia G. European Society of Hypertension Working Group on sexual dysfunctionHypertension and sexual dysfunction: time to act. J Hypertens 2011; 29:403–407.
Viigimaa M, Vlachopoulos C, Doumas M. Erectile dysfunction in hypertension and cardiovascular disease. Switzerland:Springer, Cham; 2015.
Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365:217–223.
Chow CK, Teo KK, Rangarajan S, Islam S, Gupta R, Avezum A, et al. PURE (Prospective Urban Rural Epidemiology) Study investigatorsPrevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA 2013; 310:959–968.
Catala-Lopez F, Feigin VL, Fernandes JC, Ng M, Biryukov S, Marczak L, et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990-2015. JAMA 2017; 317:165–182.
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Prospective Studies CollaborationAge-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360:1903–1913.
Vishram JK, Borglykke A, Andreasen AH, Jeppesen J, Ibsen H, Jørgensen T, et al. MORGAM ProjectImpact of age on the importance of systolic and diastolic blood pressures for stroke risk: the MOnica, Risk, Genetics, Archiving, and Monograph (MORGAM) project. Hypertension 2012; 60:1117–1123.
Brown DW, Giles WH, Greenlund KJ. Blood pressure parameters and risk of fatal stroke, NHANES II mortality study. Am J Hypertens 2007; 20:338–341.
Lawes CM, Rodgers A, Bennett DA, Parag V, Suh I, Ueshima H, et al. Asia Pacific Cohort Studies CollaborationBlood pressure and cardiovascular disease in the Asia Pacific region. J Hypertens 2003; 21:707–716.
Feldman HA, Goldstein I, Hatzichristou G, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151:54–61.
Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts Male Aging Study. J Urol 2000; 163:460–463.
Braun M, Wassmer G, Klotz T, Reifenrath B, Mathers M, Engelmann U. Epidemiology of erectile dysfunction: results of the ‘Cologne Male Survey’. Int J Impot Res 2000; 12:305–311.
Martin-Morales A, Sanchez-Cruz JJ, Saenz de Tejada I, Rodriguez-Vela L, Jimenez-Cruz JF, Burgos-Rodriguez R. Prevalence and independent risk factors for erectile dysfunction in Spain: results of the Epidemiologia de la Disfuncion Erectil Masculina Study. J Urol 2001; 166:569–574.
Marumo K, Nakashima J, Murai M. Age-related prevalence of erectile dysfunction in Japan: assessment by the International Index of Erectile Function. Int J Urol 2001; 8:53–59.
Mak R, de Backer G, Kornitzer M, De Meyer JM. Prevalence and correlates of erectile dysfunction in a population-based study in Belgium. Eur Urol 2002; 41:132–138.
Akkus E, Kadioglou A, Esen A, Doran S, Ergen A, Anafarta K, Hattat H. Turkish Erectile Dysfunction Prevalence Study GroupPrevalence and correlates of erectile dysfunction in Turkey: a population-based study. Eur Urol 2002; 41:298–304.
Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. Sexual function in men older than 50 years of age: results from the Health Professionals Follow-up Study. Ann Intern Med 2003; 139:161–168.
Mirone V, Ricci E, Gentile V, Basile Fasolo C, Parazzini F, et al. Determinants of erectile dysfunction risk in a large series of Italian men attending andrology clinics. Eur Urol 2004; 45:87–91.
Shiri R, Koskimaki J, Hakkinen J, Tammela TLJ, Huhtala H, Hakama M, Auvinen A. Effects of age, comorbidity and lifestyle factors on erectile function: Tampere Ageing Male Urological Study (TAMUS). Eur Urol 2004; 45:628–633.
Ponholzer A, Temml C, Mock K, Marszalek M, Obermayr R, Madersbacher S. Prevalence and risk factors for erectile dysfunction in 2869 men using a validated questionnaire. Eur Urol 2005; 47:80–86.
Rosen RC, Fischer WA, Eardley I, Niederberger C, Nadel A, Sand M, 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. Curr Med Res Opin 2004; 20:607–617.
Nicolosi A, Moreira ED Jr, Shirai M, Bin Mohd Tambi MI, Glasser DB. Epidemiology of erectile dysfunction in four countries: cross-national study of the prevalence and correlates of erectile dysfunction. Urology 2003; 61:201–206.
McKinlay JB. The worldwide prevalence and epidemiology of erectile dysfunction. Int J Impot Res 2000; 12: (Suppl 4): S6–S11.
Kubin M, Wagner G, Fugl-Meyer AR. Epidemiology of erectile dysfunction. Int J Impot Res 2003; 15:63–71.
Holden CA, McLachlan RI, Pitts M, Cumming R, Wittert G, Agius PA, et al. Men in Australia, Telephone Survey (MATeS) I: a national survey of the reproductive health and concerns of middle aged and older Australian men. Lancet 2005; 366:218–224.
Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281:537–544.
Grimm RH, Grandits GA, Prineas RJ, McDonald RH, Lewis CE, Flack JM, et al. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women: Treatment of Mild Hypertension Study (TOMHS). Hypertension 1997; 29 (1 Pt 1):8–14.
Riley AJ, Steiner JA, Cooper R, McPherson CK. The prevalence of sexual dysfunction in male and female hypertensive patients. J Sex Marital Ther 1987; 2:131–138.
Bulpitt CJ, Dollery CT, Carne S. Changes in symptoms in hypertensive patients after referral to hospital clinic. Br Heart J 1976; 38:121–128.
Bauer GE, Baker J, Hunyor SN, Marshall P. Side-effects of antihypertensive treatment: a placebo-controlled study. Clin Sci Mol Med Suppl 1978; 4:341s–344s.
Croog SH, Levine S, Sudilovsky A, Baume RM, Clive J. Sexual symptoms in hypertensive patients. A clinical trial of antihypertensive medications. Arch Intern Med 1988; 148:788–794.
Doumas M, Douma S. Sexual dysfunction in essential hypertension: myth or reality? J Clin Hypertens 2006; 8:269–274.
Doumas M, Tsiodras S, Tsakiris A, Douma S, Chounta A, Papadopoulos A, et al. Female sexual dysfunction in essential hypertension: a common problem being uncovered. J Hypertens 2006; 24:2387–2392.
Doumas M, Tsakiris A, Douma S, Grigorakis A, Papadopoulos A, Hounta A, et al. Factors affecting the increased prevalence of erectile dysfunction in Greek hypertensive compared with normotensive subjects. J Androl 2006; 27:469–477.
Bohm M, Baumhakel M, Teo K, Sleight P, Probstfield J, Gao P, et al. ONTARGET/TRANSCEND Erectile Dysfunction Substudy InvestigatorsErectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation 2010; 121:1439–1446.
Thomas HN, Evans GW, Berlowitz DR, Chertow GM, Conroy MB, Foy CG, et al. SPRINT Study GroupAntihypertensive medications and sexual function in women: baseline data from the SBP intervention trial (SPRINT). J Hypertens 2016; 34:1224–1231.
Koutsampasopoulos K, Vogiatzis I, Ziakas A, Papadopoulos C, Imprialos KP, Stavropoulos K, et al. Right ventricular function and sexual function: exploring shadows in male and female patients with heart failure. J Sex Med 2019; 16:1199–1211.
Sánchez-Cruz JJ, Cabrera-León A, Martín-Morales A, Fernández A, Burgos R, Rejas J. Male erectile dysfunction and health-related quality of life. Eur Urol 2003; 44:245–253.
Fujisawa M, Sawada K, Okada H, Arakawa S, Saito S, Kamidono S. Evaluation of health-related quality of life in patients treated for erectile dysfunction with viagra (sildenafil citrate) using SF-36 score. Arch Androl 2002; 48:15–21.
Litwin MS, Nied RJ, Dhanani N. Health-related quality of life in men with erectile dysfunction. J Gen Intern Med 1998; 13:159–166.
Intili H, Nier D. Self-esteem and depression in men who present with erectile dysfunction. Urol Nurs 1998; 18:185–187.
Vlachopoulos C, Jackson G, Stefanadis C, Montorsi P. Erectile dysfunction in the cardiovascular patient. Eur Heart J 2013; 34:2034–2046.
Araujo AB, Travison TG, Ganz P, Chiu GR, Kupelian V, Rosen RC, et al. Erectile dysfunction and mortality. J Sex Med 2009; 6:2445–2454.
Schouten BW, Bohnen AM, Bosch JL, Bernsen RM, Deckers JW, Dohle GR, Thomas S. Erectile dysfunction prospectively associated with cardiovascular disease in the Dutch general population: results from the Krimpen Study. Int J Impot Res 2008; 20:92–99.
Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA, et al. Erectile dysfunction and subsequent cardiovascular disease. JAMA 2005; 294:2996–3002.
Banks E, Joshy G, Abhayaratna WP, Kritharides L, Macdonald PS, Korda RJ, Chalmers JP. Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalization and all-cause mortality: a prospective cohort study. PLoS Med 2013; 10:e1001372.
Dong JY, Zhang YH, Qin LQ. Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies. J Am Coll Cardiol 2011; 58:1378–1385.
Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaouridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes 2013; 6:99–109.
Jackson G, Boon N, Eardley I, Kirby M, Dean J, Hackett G, et al. Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus. Int J Clin Pract 2010; 64:848–857.
Jackson G, Nehra A, Miner M, Billups KL, Burnett AL, Buvat J, et al. The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician. Int J Clin Pract 2013; 67:1163–1172.
Montorsi P, Ravagnani PM, Vlachopoulos C. Clinical significance of erectile dysfunction developing after acute coronary event: exception to the rule or confirmation of the artery size hypothesis? Asian J Androl 2015; 17:21–25.
Nehra A, Jackson G, Miner M, Billups KL, Burnett AL, Buvat J, et al. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc 2012; 87:766–778.
Montorsi P, Ravagnani PM, Galli S, Salonia A, Briganti A, Werba JP, Montorsi F. Association between erectile dysfunction and coronary artery disease: matching the right target with the right test in the right patient. Eur Urol 2006; 50:721–731.
Vlachopoulos C, Ioakeimidis N, Stefanadis C. Biomarkers, erectile dysfunction, and cardiovascular risk prediction: the latest of an evolving concept. Asian J Androl 2015; 17:17–20.
Rosen R, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49:822–830.
Cappelleri JC, Rosen RC. The Sexual Health Inventory for Men (SHIM): a 5-year review of research and clinical experience. Int J Impot Res 2005; 17:307–1319.
Steinke EE, Mosack V, Barnason S, Wright DW. Progress in sexual counseling by cardiac nurses, 1994 to 2009. Heart Lung 2011; 40:e15–e24.
Steinke EE. How can heart failure patients and their partners be counseled on sexual activity? Curr Heart Fail Rep 2013; 10:262–269.
Manolis A, Pittaras A, Lazaridis A, Doumas M. Viigimaa M, Vlachopoulos C, Doumas M. Sexual counseling for patients with cardiovascular disease. Erectile dysfunction in hypertension and cardiovascular disease. Cham, Switzerland:Springer; 2015. 231–239.
Viigimaa M. Viigimaa M, Vlachopoulos C, Doumas M. Lifestyle modification in erectile dysfunction and hypertension. Erectile dysfunction in hypertension and cardiovascular disease. Cham, Switzerland:Springer; 2015. 167–174.
Pourmand G, Alidaee MR, Rasuli S, Maleki A, Mehrsai A. Do cigarette smokers with erectile dysfunction benefit from stopping?: a prospective study. BJU Int 2004; 94:1310–1313.
Sighinolfi MC, Mofferdin A, De Stefani S, Micali S, Cicero AF, Bianchi G. Immediate improvement in penile hemodynamics after cessation of smoking: previous results. Urology 2007; 69:163–165.
Zabelina DL, Erickson AL, Kolotkin RL, Crosby RD. The effect of age on weight-related quality of life in overweight and obese individuals. Obesity (Silver Spring) 2009; 17:1410–1413.
Demir T. Prevalence of erectile dysfunction in patients with metabolic syndrome. Int J Urol 2006; 13:385–388.
Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D’Andrea F, et al. Effect of lifestyle changes on erectile dysfunction in obese men. JAMA 2004; 291:2978–2984.
Dallal RM, Chernoff A, O’Leary MP, Smith JA, Braverman JD, Quebbemann BB. Sexual dysfunction is common in the morbidly obese male and improves after gastric bypass surgery. J Am Coll Surg 2008; 207:859–864.
Rosenblatt A, Faintuch J, Cecconello I. Sexual hormones and erectile function more than 6 years after bariatric surgery. Surg Obes Relat Dis 2013; 9:636–640.
Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr 2010; 92:1189–1196.
Meldrum DR, Gambone JC, Morris MA, Ignarro LJ. Multifaceted approach to maximize erectile function and vascular health. Fertil Steril 2010; 94:2514–2520.
Ignarro LJ, Byrns RE, Sumi D, de Nigris F, Napoli C. Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biologic actions of nitric oxide. Nitric Oxide 2006; 15:93–102.
Nicolosi A, Glasser DB, Moreira ED, Villa M. Erectile Dysfunction Epidemiology Cross National Study GroupPrevalence of erectile dysfunction and associated factors among men without concomitant diseases: a population study. Int J Impot Res 2003; 15:253–257.
Hsiao W, Shrewsberry AB, Moses KA, Johnson TV, Cai AW, Stuhldreher P, et al. Exercise is associated with better erectile function in men under 40 as evaluated by the International Index of Erectile Function. J Sex Med 2012; 9:524–530.
Wang W, Wang JQ, Wan F, Yang L. Physical exercise improves erectile function in young and middle-aged men. Zhonghua Nan Ke Xue 2014; 20:1086–1089.
Ettala OO, Syvänen KT, Korhonen PE, Kaipia AJ, Vahlberg TJ, Boström PJ, Aarnio PT. High-intensity physical activity, stable relationship, and high education level associate with decreasing risk of erectile dysfunction in 1,000 apparently healthy cardiovascular risk subjects. J Sex Med 2014; 11:2277–2284.
Rosen RC, Wing RR, Schneider S, Wadden TA, Foster GD, West DS, et al. Erectile dysfunction in type 2 diabetic men: relationship to exercise fitness and cardiovascular risk factors in the Look AHEAD trial. J Sex Med 2009; 6:1414–1422.
Simon RM, Howard L, Zapata D, Frank J, Freedland SJ, Vidal AC. The association of exercise with both erectile and sexual function in black and white men. J Sex Med 2015; 12:1202–1210.
Pohjantähti-Maaroos H, Palomäki A, Hartikainen J. Erectile dysfunction, physical activity and metabolic syndrome: differences in markers of atherosclerosis. BMC Cardiovasc Disord 2011; 11:36.
Compostella L, Compostella C, Truong LV, Russo N, Setzu T, Iliceto S, Bellotto F. History of erectile dysfunction as a predictor of poor physical performance after an acute myocardial infarction. Eur J Prev Cardiol 2017; 24:460–467.
Ioakeimidis N, Samentzas A, Vlachopoulos C, Aggelis A, Stefanadis C, Tousoulis D. Chronotropic incompetence and dynamic postexercise autonomic dysfunction are associated with the presence and severity of erectile dysfunction. Ann Noninvasive Electrocardiol 2016; 21:256–262.
Lamina S, Okoye CG, Dagogo TT. Therapeutic effect of an interval exercise training program in the management of erectile dysfunction in hypertensive patients. J Clin Hypertens (Greenwich) 2009; 11:125–129.
Lamina S, Okoye CG, Dagogo TT. Managing erectile dysfunction in hypertension: the effects of a continuous training programme on biomarker of inflammation. BJU Int 2009; 103:1218–1221.
Kałka D, Domagała Z, Rusiecki L, Karpiński Ł, Gebala J, Kolęda P, et al. Heart rate recovery, cardiac rehabilitation and erectile dysfunction in males with ischaemic heart disease. Anatol J Cardiol 2016; 16:256–263.
Kalka D, Domagala ZA, Kowalewski P, Rusiecki L, Koleda P, Marciniak W, et al. Effect of endurance cardiovascular training intensity on erectile dysfunction severity in men with ischemic heart disease. Am J Mens Health 2015; 9:360–369.
Condorelli RA, Calogero AE, Di Mauro M, Mongioì LM, Russo GI, Morgia G, et al. Effects of tadalafil treatment combined with physical activity in patients with low onset hypogonadism: results from a not-randomized single arm phase 2 study. Aging Male 2016; 19:155–160.
Kirilmaz U, Guzel O, Aslan Y, Balci M, Tuncel A, Atan A. The effect of lifestyle modification and glycemic control on the efficiency of sildenafil citrate in patients with erectile dysfunction due to type-2 diabetes mellitus. Aging Male 2015; 18:244–248.
Maio G, Saraeb S, Marchiori A. Physical activity and PDE5 inhibitors in the treatment of erectile dysfunction: results of a randomized controlled study. J Sex Med 2010; 7:2201–2208.
Ambrosioni E, Leonetti G, Pessina AC, Rappelli A, Trimarco B, Zanchetti A. Patterns of hypertension management in Italy: results of a pharmacoepidemiological survey on antihypertensive therapy. Scientific Committee of the Italian Pharmacoepidemiological Survey on Antihypertensive Therapy. J Hypertens 2000; 18:1691–1699.
Gregoire JP, Moisan J, Guibert R, Ciampi A, Milot A, Gaudet M, Côté I. Determinants of discontinuation of new courses of antihypertensive medications. J Clin Epidemiol 2002; 55:728–735.
Rosen RC. Sexual dysfunction as an obstacle to compliance with antihypertensive therapy. Blood Press Suppl 1997; 1:47–51.
Harmon G, Lefante J, Krousel-Wood M. Overcoming barriers: the role of providers in improving patient adherence to antihypertensive medications. Curr Opin Cardiol 2006; 21:310–315.
Fergus IV. Antihypertensive pharmacotherapy: adverse effects of medications promote nonadherence. J Cardiometab Syndr 2009; 4:E1–E3.
Voils CI, Sandelowski M, Dahm P, Blouin R, Bosworth HB, Oddone EZ, Steinhauser KE. Selective adherence to antihypertensive medications as a patient-driven means to preserving sexual potency. Patient Prefer Adherence 2008; 2:201–206.
McLaughlin T, Harnett J, Burhani S, Scott B. Evaluation of erectile dysfunction therapy in patients previously nonadherent to long-term medications: a retrospective analysis of prescription claims. Am J Ther 2005; 12:605–611.
Adverse reactions to bendrofluazide, propranolol for the treatment of mild hypertensionReport of Medical Research Council Working Party on mild to moderate hypertension. Lancet 1981; 2:539–543.
Wassertheil-Smoller S, Blaufox MD, Oberman A, Blaufox MD, Davis B, Langford H. Effect of antihypertensives on sexual function and quality of life: the TAIM study. Ann Intern Med 1991; 114:613–620.
Lindholm LH, Persson M, Alaupovic P, Carlberg B, Svensson A, Samuelsson O. Metabolic outcome during 1 year in newly detected hypertensives: results of the antihypertensive treatment and lipid profile in a north of Sweden efficacy evaluation (ALPINE study). J Hypertens 2003; 21:1563–1574.
Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo: the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med 1993; 328:914–921.
Korhonen PE, Ettala O, Kautiainen H, Kantola I. Factors modifying the effect of blood pressure on erectile function. J Hypertens 2015; 33:975–980.
Baumhakel M, Schimmer N, Kratz M, Hackett G, Jackson G, Böhm M. Cardiovascular risk, drugs and erectile function - a systematic analysis. Int J Clin Pract 2011; 65:289–298.
Fogari R, Zoppi A, Poletti L, Marasi G, Mugellini A, Corradi L. Sexual activity in hypertensive men treated with valsartan or carvedilol: a crossover study. Am J Hypertens 2001; 14:27–31.
Fogari R, Preti P, Derosa G, Marasi G, Zoppi A, Rinaldi A, Mugellini A. Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men. Eur J Clin Pharmacol 2001; 58:177–180.
Van Bortel LM, Bulpitt CJ, Fici F. Quality of life and antihypertensive effect with nebivolol and losartan. Am J Hypertens 2005; 18:1060–1066.
Chen Y, Cui S, Lin H, Xu Z, Zhu W, Shi L, et al. Losartan improves erectile dysfunction in diabetic patients: a clinical trial. Int J Impot Res 2012; 24:217–220.
Yang L, Yu J, Ma R, Zhao F, Lin X, Liu P, et al. The effect of combined antihypertensive treatment (felodipine with either irbesartan or metoprolol) on erectile function: a randomized controlled trial. Cardiology 2013; 125:235–241.
Ma R, Yu J, Xu D, Yang L, Lin X, Zhao F, Bai F. Effect of felodipine with irbesartan or metoprolol on sexual function and oxidative stress in women with essential hypertension. J Hypertens 2012; 30:210–216.
Llisterri JL, Lozano Vidal JV, Aznar Vicente J, Argaya Roca M, Pol Bravo C, Sanchez Zamorano MA, Ferrario CM. Sexual dysfunction in hypertensive patients treated with losartan. Am J Med Sci 2001; 321:336–341.
Baumhäkel M, Schlimmer N, Böhm M. DO-IT InvestigatorsEffect of irbesartan on erectile function in patients with hypertension and metabolic syndrome. Int J Impot Res 2008; 20:493–500.
Manolis A, Doumas M. Erectile function in cardiovascular disease and hypertension: the role of nebivolol. J Hypertens Open Access 2016; 5:2.
Toblli JE, Stella I, Mazza ON, Ferder L, Inserra F. The effect of different antihypertensive drugs on cavernous tissue in experimental chronic renal insufficiency. J Nephrol 2006; 19:419–428.
Toblli J, Stella I, Néstor Mazza O, Ferder L, Inserra F. Protection of cavernous tissue in male spontaneously hypertensive rats. Beyond blood pressure control. Am J Hypertens 2004; 17:516–522.
Toblli JE, Cao G, Casas G, Mazza ON. In vivo and in vitro effects of nebivolol on penile structures in hypertensive rats. Am J Hypertens 2006; 19:1226–1232.
Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, et al. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signalling. J Sex Med 2010; 7:2681–2697.
Reidenbach C, Schwinger RH, Steinnitz D, Kehe K, Thiermann H, Klotz T, et al. Nebivolol induces eNOS activation and NO-liberation in murine corpus cavernosum. Life Sci 2007; 80:2421–2427.
Baumhakel M, Schlimmer N, Buyukafsar K, Arikan O, Böhm M. Nebivolol, but not metoprolol, improves endothelial function of the corpus cavernosum in apolipoprotein E-knockout mice. J Pharmacol Exp Ther 2008; 325:818–823.
Cordero A, Bertomeu-Martinez V, Mazon P, Fácila L, Bertomeu-González V, Conthe P, et al. Erectile dysfunction in high-risk hypertensive patients treated with beta-blockers agents. Cardiovasc Ther 2010; 28:15–22.
Cordero A, Bertomeu-Martínez V, Mazón P, Fácila L, González-Juanatey JR. Erectile dysfunction may improve by blood pressure control in patients with high-risk hypertension. Postgrad Med 2010; 122:51–56.
Brixius K, Middeke M, Lichtenthal A, Jahn E, Schwinger RH. Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men. Clin Exp Pharmacol Physiol 2007; 34:327–331.
Boydak B, Nalbantgil S, Fici F, Nalbantgil I, Zoghi M, Ozerkan F, et al. A randomized comparison of the effects of nebivolol and atenolol with and without chlorthalidone on the sexual function of hypertensive men. Clin Drug Invest 2005; 25:409–416.
Gur O, Gurkan S, Yumun G, Turker P. The comparison of the effects of nebivolol and metoprolol on erectile dysfunction in the cases with coronary artery bypass surgery. Ann Thorac Cardiovasc Surg 2017; 23:91–95.
Della Chiesa A, Pfiffner D, Meier B, Hess OM. Sexual activity in hypertensive men. J Hum Hypertens 2003; 17:515–521.
Düsing R. Effect of the angiotensin II antagonist valsartan on sexual function in hypertensive men. Blood Press Suppl 2003; 2:29–34.
Doumas M, Tsakiris A, Douma S, Grigorakis A, Papadopoulos A, Hounta A, et al. Beneficial effects of switching from beta-blockers to nebivolol on the erectile function of hypertensive patients. Asian J Androl 2006; 8:177–182.
Martin SA, Atlantis E, Lange K, Taylor AW, O’Loughlin P, Wittert GA. Florey Adelaide Male Ageing StudyPredictors of sexual dysfunction incidence and remission in men. J Sex Med 2014; 11:1136–1147.
Margel D, Cohen M, Livne PM, Pillar G. Severe, but not mild, obstructive sleep apnea syndrome is associated with erectile dysfunction. Urology 2004; 63:545–549.
Shin HW, Rha YC, Han DH, Chung S, Yoon IY, Rhee CS, et al. Erectile dysfunction and disease-specific quality of life in patients with obstructive sleep apnea. Int J Impot Res 2008; 20:549–553.
Heruti R, Shochat T, Tekes-Manova D, Ashkenazi I, Justo D. Association between erectile dysfunction and sleep disorders measured by self-assessment questionnaires in adult men. J Sex Med 2005; 2:543–550.
Budweiser S, Enderlein S, Jorres RA, Hitzl AP, Wieland WF, Pfeifer M, Arzt M. Sleep apnea is an independent correlate of erectile and sexual dysfunction. J Sex Med 2009; 6:3147–3157.
Teloken PE, Smith EB, Lodowsky C, Freedom T, Mulhall JP. Defining association between sleep apnea syndrome and erectile dysfunction. Urology 2006; 67:1033–1037.
Goncalves MA, Guilleminault C, Ramos E, Palha A, Paiva T. Erectile dysfunction, obstructive sleep apnea syndrome and nasal CPAP treatment. Sleep Med 2005; 6:333–339.
Schulz R, Bischof F, Galetke W, Gall H, Heitmann J, Hetzenecker A, et al. German Sleep Apnea Research Network (GERSAN)CPAP therapy improves erectile function in patients with severe obstructive sleep apnea. Sleep Med 2019; 53:189–194.
Cruz IA, Drummond M, Winck JC. Obstructive sleep apnea symptoms beyond sleepiness and snoring: effects of nasal APAP therapy. Sleep Breath 2012; 16:361–366.
Perimenis P, Karkoulias K, Konstantinopoulos A, Alchanatis M, Perimeni PP, Athanasopoulos A, Spyropoulos K. The impact of long-term conventional treatment for overlap syndrome (obstructive sleep apnea and chronic obstructive pulmonary disease) on concurrent erectile dysfunction. Respir Med 2007; 10:210–216.
Margel D, Tal R, Livne PM, Pillar G. Predictors of erectile function improvement in obstructive sleep apnea patients with long-term CPAP treatment. Int J Impot Res 2005; 17:186–190.
Budweiser S, Luigart R, Jorres RA, Kollert F, Kleemann Y, Wieland WF, et al. Long-term changes of sexual function in men with obstructive sleep apnea after initiation of continuous positive airway pressure. J Sex Med 2013; 10:524–531.
Campos-Juanatey F, Fernandez-Barriales M, Gonzalez M, Portillo-Martin JA. Effects of obstructive sleep apnea and its treatment over the erectile function: a systematic review. Asian J Androl 2017; 19:303–310.
Perimenis P, Karkoulias K, Konstantinopoulos A, Perimeni PP, Katsenis G, Athanasopoulos A, Spyropoulos K. Sildenafil versus continuous positive airway pressure for erectile dysfunction in men with obstructive sleep apnea: a comparative study of their efficacy and safety and the patient's satisfaction with treatment. Asian J Androl 2007; 9:259–264.
Perimenis P, Karkoulias K, Markou S, Gyftopoulos K, Athanasopoulos A, Barbalias G, et al. Erectile dysfunction in men with obstructive sleep apnea syndrome: a randomized study of the efficacy of sildenafil and continuous positive airway pressure. Int J Impot Res 2004; 16:256–260.
Li X, Dong Z, Wan Y, Wang Z. Sildenafil versus continuous positive airway pressure for erectile dysfunction in men with obstructive sleep apnea: a meta-analysis. Aging Male 2010; 13:82–86.
Pastore AL, Palleschi G, Ripoli A, Silvestri L, Maggioni C, Pagliuca G, et al. Severe obstructive sleep apnoea syndrome and erectile dysfunction: a prospective randomised study to compare sildenafil vs. nasal continuous positive airway pressure. Int J Clin Pract 2014; 68:995–1000.
Melehan KL, Hoyos CM, Hamilton GS, Wong KK, Yee BJ, McLachlan RI, et al. Randomized trial of CPAP and vardenafil on erectile and arterial function in men with obstructive sleep apnea and erectile dysfunction. J Clin Endocrinol Metab 2018; 103:1601–1611.
Wallis RM, Corbin JD, Francis SH, Ellis P. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 1999; 83:3C–12C.
Chrysant SG, Chrysant GS. The pleiotropic effects of phosphodiesterase 5 inhibitors on function and safety in patients with cardiovascular disease and hypertension. J Clin Hypertens (Greenwich) 2012; 14:644–649.
Carson CC, Burnett AL, Levine LA, Nehra A. The efficacy of sildenafil citrate (Viagra) in clinical populations: an update. Urology 2002; 60: (2 Suppl 2): 12–27.
Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol 2002; 53: (Suppl 1): 5S–12S.
Gupta M, Kovar A, Meibohm B. The clinical pharmacokinetics of phosphodiesterase-5 inhibitors for erectile dysfunction. J Clin Pharmacol 2005; 45:987–1003.
Montorsi F, Padma-Nathan H, Buvat J, Schwaibold H, Beneke M, Ulbrich E, et al. Vardenafil Study GroupVardenafil Study Group. Earliest time to onset of action leading to successful intercourse with vardenafil determined in an at-home setting: a randomized, double-blind, placebo-controlled trial. J Sex Med 2004; 1:168–178.
Montorsi F, Verheyden B, Meuleman E, Jünemann KP, Moncada I, Valiquette L, et al. Long-term safety and tolerability of tadalafil in the treatment of erectile dysfunction. Eur Urol 2004; 45:339–344.
Viigimaa M, Vlachopoulos C, Lazaridis A, Doumas M. Management of erectile dysfunction in hypertension: Tips and tricks. World J Cardiol 2014; 6:908–915.
Sanford M. Avanafil: a review of its use in patients with erectile dysfunction. Drugs Aging 2013; 30:853–862.
Aranda P, Ruilope LM, Calvo C, Luque M, Coca A, Gil de Miguel A. Erectile dysfunction in essential arterial hypertension and effects of sildenafil: results of a Spanish national study. Am J Hypertens 2004; 17:139–145.
Park HJ, Park NC, Shim HB, Park JK, Lee SW, Park K, et al. An open-label, multicenter, flexible dose study to evaluate the efficacy and safety of Viagra (sildenafil citrate) in Korean men with erectile dysfunction and arterial hypertension who are taking antihypertensive agents. J Sex Med 2008; 5:2405–2413.
Pickering TG, Shepherd AM, Puddey I, Glasser DB, Orazem J, Sherman N, Mancia G. Sildenafil citrate for erectile dysfunction in men receiving multiple antihypertensive agents: a randomized controlled trial. Am J Hypertens 2004; 17 (12 Pt 1):1135–1142.
Albuquerque DC, Miziara LJ, Saraiva JF, Rodrigues US, Ribeiro AB, Wajngarten M. Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs. Int Braz J Urol 2005; 31:342–353.
van Ahlen H, Wahle K, Kupper W, Yassin A, Reblin T, Neureither M. Safety and efficacy of vardenafil, a selective phosphodiesterase 5 inhibitor, in patients with erectile dysfunction and arterial hypertension treated with multiple antihypertensives. J Sex Med 2005; 2:856–864.
Kloner RA, Brown M, Prisant LM, Collins M. Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Sildenafil Study Group. Am J Hypertens 2001; 14:70–73.
Kloner RA, Sadovsky R, Johnson EG, Mo D, Ahuja S. Efficacy of tadalafil in the treatment of erectile dysfunction in hypertensive men on concomitant thiazide diuretic therapy. Int J Impot Res 2005; 17:450–454.
Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. American Heart Association Statistics Committee, Stroke Statistics SubcommitteeHeart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 2017; 135:e146–e603.
Boulton AJ, Selam JL, Sweeney M, Ziegler D. Sildenafil citrate for the treatment of erectile dysfunction in men with type II diabetes mellitus. Diabetologia 2001; 44:1296–1301.
Stuckey BG, Jadzinsky MN, Murphy LJ, Montorsi F, Kadioglu A, Fraige F, et al. Sildenafil citrate for treatment of erectile dysfunction in men with type 1 diabetes: results of a randomized controlled trial. Diabetes Care 2002; 25:2159–2164.
Young JM, Bennett C, Gilhooly P, Wessells H, Ramos DE. Efficacy and safety of sildenafil citrate (Viagra) in black and Hispanic American men. Urology 2002; 60: (2 suppl 2): 39–48.
Hellstrom WJ, Gittelman M, Karlin G, Segerson T, Thibonnier M, Taylor T, Padma-Nathan H. Vardenafil for treatment of men with erectile dysfunction: efficacy and safety in a randomized, double-blind, placebo-controlled trial. J Androl 2002; 23:763–771.
Goldstein I, Young JM, Fischer J, Bangerter K, Segerson T, Taylor T. Vardenafil Diabetes Study GroupVardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double blind placebo-controlled fixed-dose study. Diabetes Care 2003; 26:777–783.
Ziegler D, Merfort F, van Ahlen H, Yassin A, Reblin T, Neureither M. Efficacy and safety of flexible-dose vardenafil in men with type-1 diabetes and erectile dysfunction. J Sex Med 2006; 3:883–891.
Valiquette L, Montorsi F, Auerbach S. Vardenafil Study GroupFirst-dose success with vardenafil in men with erectile dysfunction and associated comorbidities: RELY-I. Int J Clin Pract 2006; 60:1378–1385.
Valiquette L, Montorsi F, Auerbach S. Vardenafil demonstrates first-dose success and reliability of penetration and maintenance of erection in men with erectile dysfunction: RELY-II. Can Urol Assoc 2008; 2:187–195.
Stief C, Porst H, Saenz De Tejada I, Ulbrich E, Beneke M. Vardenafil Study GroupSustained efficacy and tolerability with vardenafil over 2 years of treatment in men with erectile dysfunction. Int J Clin Pract 2004; 58:230–239.
Miner M, Gilderman L, Bailen J, Cook D, Dawson K, Stanislaus M, et al. Vardenafil in men with stable statin therapy and dyslipidemia. J Sex Med 2008; 5:1455–1467.
Sperling H, Gittleman M, Norenberg C, Ulbrich E, Ewald S. Efficacy and safety of orodispersible vardenafil formulation for the treatment of erectile dysfunction in elderly men and those with underlying conditions: an integrated analysis of two pivotal trials. J Sex Med 2011; 8:261–271.
Goldstein I, Kim E, Steers WD, Pryor JL, Wilde DW, Natanegara F, et al. Efficacy and safety of tadalafil in men with erectile dysfunction with a high prevalence of comorbid conditions: results from MOMENTUS: multiple observations in men with erectile dysfunction in National Tadalafil Study in the US. J Sex Med 2007; 4:166–175.
Saenz De Tejada I, Anglin G, Knight JR, Emmick JT. Effects of tadalafil on erectile dysfunction in men with diabetes. Diabetes Care 2002; 25:2159–2164.
Corona G, Rastrelli G, Burri A, Jannini EA, Maggi M. The safety and efficacy of Avanafil, a new 2(nd) generation PDE5i: comprehensive review and meta-analysis. Expert Opin Drug Saf 2016; 15:237–247.
Conti CR, Pepine CJ, Sweeny M. Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. Am J Cardiol 1999; 83:29C–34C.
DeBusk RF, Pepine CJ, Glasser DB, Shpilsky A, DeRiesthal H, Sweeny M. Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease. Am J Cardiol 2004; 93:147–153.
Olsson AM, Persson CA. Swedish Sildenafil Investigators GroupEfficacy and safety of sildenafil citrate for the treatment of erectile dysfunction in men with cardiovascular disease. Int J Clin Pract 2001; 55:171–176.
Katz SD, Parker JD, Glasser DB, Bank AJ, Sherman N, Wang H, Sweeney M. Efficacy and safety of sildenafil citrate in men with erectile dusfunction and chronic heart failure. Am J Cardiol 2005; 95:36–42.
Van Ahlen H, Zumbe J, Stauch K, Hanish JU. The real-life safety and efficacy of vardenafil (REALISE) study: results in men from Europe and overseas with erectile dysfunction and cardiovascular or metabolic conditions. J Sex Med 2010; 7:3161–3169.
Feenstra J, van Drie-Pierik RJ, Laclé CF, Stricker BH. Acute myocardial infarction associated with sildenafil. Lancet 1998; 352:957–958.
Morales A, Gingell C, Collins M, Wicker PA, Osterloh IH. Clinical safety of oral sildenafil (Viagra) in the treatment of erectile dysfunction. Int J Impot Res 1998; 10:69–74.
Conti CR, Pepine CJ, Sweeny M. Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischaemic heart disease. Am J Cardiol 1999; 83:29C–34C.
Kloner RA. Cardiovascular risk and sildenafil. Am J Cardiol 2000; 86: (suppl): 57F–61F.
Sakir SAW, Wilton LV, Boshier A, Layton D, Heeley E. Cardiovascular events in users of sildenafil: results from first phase of prescription event monitoring in England. BMJ 2001; 322:651–652.
Mittleman MA, Maclure M, Glasser DB. Evaluation of acute risk for myocardial infarction in men treated with sildenafil citrate. Am J Cardiol 2005; 96:443–446.
Wysowski DK, Farinas E, Swartz L. Comparison of reported and expected deaths in sildenafil (Viagra) users. Am J Cardiol 2002; 89:133–134.
Tsertsvadze A, Yazdi F, Fink HA, MacDonald R, Wilt TJ, Bella AJ, et al. Oral sildenafil citrate (Viagra) for erectile dysfunction: a systematic review and meta-analysis of harms. Urology 2009; 74:831.e8–836.e8.
Kloner RA, Jackson G, Hutter AM, Mittleman MA, Chan M, Warner MR, et al. Cardiovascular safety update of tadalafil: retrospective analysis of data from placebo-controlled and open-label clinical trials of tadalafil as needed, three times per week or once a day dosing. Am J Cardiol 2006; 97:1778–1784.
Hazell L, Boshier A, Harris S, Wilton LV, Shakir SA. An observational cohort study investigating the cardiovascular safety of tadalafil when prescribed in primary care in England: mortality due to ischaemic heart disease. BJU International 2007; 99:387–393.
Lowe G, Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012; 9:265–270.
Webb DJ, Muirhead GJ, Wulff M, Sutton A, Levi R, Dinsmore WW. Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina. J Am Coll Cardiol 2000; 36:25–31.
Vardenafil - summary of product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_ _Product_Information/human/000475/WC500039992.pdf. (Accessed 18 August 2018)
Patterson D, Kloner R, Effron M, Emmick J, Bedding A, Warner M, et al. The effect of tadalafil on the time to exercise-induced myocardial ischaemia in subjects with coronary artery disease. Br J Clin Pharmacol 2005; 60:459–468.
Kloner RA, Hutter AM, Emmick JT, Mitchell MI, Denne J, Jackson G. Time course of the interaction between tadalafil and nitrates. J Am Coll Cardiol 2003; 42:1855–1860.
Emmick JT, Stuewe SR, Mitchel LM. Overview of the cardiovascular effects of tadalafil. Eur Heart J Suppl 2002; 4:1132–1147.
Oliver JJ, Bell K, Leckie SM, Webb DJ. Interaction between glyceryl trinitrate and sildenafil citrate (Viagra) may last less than four hours. Int J Impot Res 2002; 14: (Suppl 3): 522.
Guillaume M, Lonsdale F, Darstein C, Jimenez MC, Mitchell MI. Hemodynamic interaction between a daily dosed phosphodiesterase 5 inhibitor, tadalafil, and the alpha-adrenergic blockers, doxazosin and tansulosin, in middle-aged healthy male subjects. J Clin Pharmacol 2007; 47:1303–1310.
Giuliano F, Kaplan SA, Cabanis MJ, Astruc B. Hemodynamic interaction study between the alpha1-blocker alfuzosin and the phosphodiesterase-5 inhibitor tadalafil in middle-aged healthy male subjects. Urology 2006; 67:1199–1204.
Kloner RA. Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions. Am J Cardiol 2005; 96:42M–46M.
Kloner RA, Jackson G, Emmick JT, Mitchell MI, Bedding A, Warner MR, Pereira A. Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men. J Urol 2004; 172:1935–1940.
Nieminen T, Tammela TL, Koobi T, Kähönen M. The effects of tamsulosin and sildenafil in separate and combined regimens on detailed hemodynamics in patients with benign prostatic enlargement. J Urol 2006; 176:2551–2556.
Goldfischer E, Kowalczyk JJ, Clark WR, Brady E, Shane MA, Dgetluck N, Klise SR. Hemodynamic effects of once-daily tadalafil in men with signs and symptoms of benign prostatic hyperplasia on concomitant a1-adrenergic antagonist therapy: results of a randomized, double-blind, placebo-controlled trial. Urology 2012. 875–882.
Bancroft J. The endocrinology of sexual arousal. J Endocrinol 2005; 186:411–427.
Anderson RA, Bancroft J, Wu FC. The effects of exogenous testosterone on sexuality and mood of normal men. J Clin Endocrinol Metab 1992; 75:1503–1507.
Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 2009; 55:121–130.
Corona G, Rastelli G, Monami M, Guay A, Buvat J, Sforza A, et al. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol 2011; 165:687–701.
Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol 2011; 96:3007–3019.
Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 2005; 60:1451–1457.
Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 2007; 82:29–39.
Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systemic review and meta-analysis. J Clin Endocrinol Metab 2010; 95:2560–2575.
Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363:109–122.
Vigen R, O’Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013; 310:1829–1836.
Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. Increased risk of nonfatal myocardial infarction following testosterone therapy prescription in men. PLoS One 2014; 9:e85805.
Traish AM, Guay AT, Morgentaler A. Death by testosterone? We think not! J Sex Med 2014; 11:624–629.
Kloner RA. Testosterone and cardiovascular health: safety of treatment of hypogonadism. Sex Med Rev 2015; 3:56–62.
Shores MM, Smith NL, Fosberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012; 97:2050–2058.
Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol 2013; 169:725–773.
Anderson JL, May HT, Lappe DL, Bair T, Le V, Carlquist JF, Muhlestein JB. Impact of testosterone replacement therapy on myocardial infarction, stroke, and death in men with low testosterone concentration in an integrated healthcare system. Am J Cardiol 2016; 117:794–799.
Cheetham TC, Ann JJ, Jacobsen SJ, Sidney S, Quesenberry CP, VanDenEeden SK. Association of testosterone replacement with cardiovascular outcomes among men with androgen deficiency. JAMA Intern Med 2017; 177:491–499.
Wallis CJ, Lo K, Lee Y, Krakowsky Y, Garbens A, Satkunasivam R, et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol 2016; 363:498–506.
Sharma R, Oni QA, Gupta K, Chen G, Sharma M, Dawn B, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J 2015; 36:2706–2715.
Haring R, Zhaoyang T, Xanthakis V, Coviello A, Sullivan L, Bhasin S, et al. Association of sex steroids, gonadotrophins, and their trajectories with clinical cardiovascular disease and all-cause mortality in elderly men from the Framingham Heart Study. Clin Endocrinol 2013; 78:629–634.
Montorsi F, Briganti A, Salonia A, Rigatti P, Margonato A, Macchi A, et al. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur Urol 2003; 44:360–364.
Vlachopoulos C, Rokkas K, Ioakeimidis N, Aggeli C, Michaelides A, Roussakis G, et al. Prevalence of asymptomatic coronary artery disease in men with vasculogenic erectile dysfunction: a prospective angiographic study. Eur Urol 2005; 48:996–1002.
Montorsi P, Ravagnani PM, Galli S, Rotatori F, Briganti A, Salonia A, et al. The artery size hypothesis: a macrovascular link between erectile dysfunction and coronary artery disease. Am J Cardiol 2005; 96:19M–23M.
Imprialos KP, Stavropoulos K, Doumas M, Tziomalos K, Karagiannis A, Athyros VG. Sexual dysfunction, cardiovascular risk and effects of pharmacotherapy. Curr Vasc Pharmacol 2018; 16:130–142.
Silvestri A, Galetta P, Cerquetani E, Marazzi G, Patrizi R, Fini M, Rosano GM. Report of erectile dysfunction after therapy with beta-blockers is related to patient knowledge of side effects and is reversed by placebo. Eur Heart J 2003; 24:1928–1932.
Cocco G. Erectile dysfunction after therapy with metoprolol: the Hawthorne effect. Cardiology 2009; 112:174–177.
Doumas M, Viigimaa M, Papademetriou V. Combined antihypertensive therapy and sexual dysfunction: terra incognita. Cardiology 2013; 125:232–234.