Erectile dysfunction in the elderly: An old widespread issue with novel treatment perspectives

International Journal of Endocrinology

Volumn 2014, Issue , 2014, Pages

  Gareri, Pietro ^a   Castagna, Alberto ^b   Francomano, Davide ^c   Cerminara, Gregorio ^d,e   De Fazio, Pasquale ^d,e  

^a ASP Catanzaro   (Italy)

^b AUSL Modena   (Italy)

^c SAPIENZA UNIVERSITY OF ROME   (Italy)

^d UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^e Mater Domini University Hospital   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AVANAFIL; ICARIIN; PHOSPHODIESTERASE V INHIBITOR; PROSTAGLANDIN E1; SILDENAFIL; TADALAFIL; VARDENAFIL; YOHIMBINE;

AGED; AGING; BIPOLAR DISORDER; CARDIOVASCULAR DISEASE; CEREBROVASCULAR ACCIDENT; DEMENTIA; DIABETES MELLITUS; DISABLED PERSON; DRUG EFFICACY; DRUG SAFETY; DRUG USE; EPIDEMIOLOGICAL DATA; ERECTILE DYSFUNCTION; GINSENG; HUMAN; HYPERTENSION; INFLATABLE PENIS PROSTHESIS; LIFESTYLE MODIFICATION; MALE GENITAL SYSTEM SURGERY; MEDICAL DEVICE; MOOD DISORDER; MULTIPLE SCLEROSIS; NONHUMAN; PARKINSON DISEASE; PATHOPHYSIOLOGY; PENIS SURGERY; PRIORITY JOURNAL; REVIEW; SEXUAL BEHAVIOR; SEXUAL COUNSELING; SPINAL CORD INJURY; TREATMENT RESPONSE; VACUUM CONSTRICTION DEVICE;

EID: 84897478167     PISSN: 16878337     EISSN: 16878345     Source Type: Journal    
DOI: 10.1155/2014/878670     Document Type: Review

References (109)

1. Smith L. J., Mulhall J. P., Deveci S., Monaghan N., Reid M. C., Sex after seventy: a pilot study of sexual function in older persons. The Journal of Sexual Medicine 2007 4 5 1247 1253 2-s2.0-34548314478 10.1111/j.1743-6109.2007. 00568.x (Pubitemid 47337668)
2. Bruzziches R., Francomano D., Gareri P., Lenzi A., Aversa A., An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type-5 inhibitors. Expert Opinion on Pharmacotherapy 2013 14 10 1333 1344
3. Lue T. F., Erectile dysfunction. The New England Journal of Medicine 2000 342 24 1802 1813 2-s2.0-0034660235 10.1056/NEJM200006153422407 (Pubitemid 30390241)
4. Solomon H., Man J. W., Jackson G., Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator. Heart 2003 89 3 251 254 2-s2.0-0037370885 (Pubitemid 36241528)
5. Lindau S. T., Schumm L. P., Laumann E. O., Levinson W., O'Muircheartaigh C. A., Waite L. J., A study of sexuality and health among older adults in the United States. England Journal of Medicine 2007 357 8 762 774 2-s2.0-34548060648 10.1056/NEJMoa067423 (Pubitemid 47295643)
6. Feldman H. A., Goldstein I., Hatzichristou D. G., Krane R. J., McKinlay J. B., Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. The Journal of Urology 1994 151 1 54 61 2-s2.0-0028036149 (Pubitemid 24046934)
7. Corona G., Lee D. M., Forti G., O'Connor D. B., Maggi M., O'Neill T. W., Pendleton N., Bartfai G., Boonen S., Casanueva F. F., Finn J. D., Giwercman A., Han T. S., Huhtaniemi I. T., Kula K., Lean M. E. J., Punab M., Silman A. J., Vanderschueren D., Wu F. C. W., Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). The Journal of Sexual Medicine 2010 7 4 1362 1380 2-s2.0-77955150230 10.1111/j.1743-6109.2009.01601.x
8. Holden C. A., McLachlan R. I., Pitts M., Cumming R., Wittert G., Agius P. A., Handelsman D. J., de Kretser D. M., Men in Australia Telephone Survey (MATeS): a national survey of the reproductive health and concerns of middle-aged and older Australian men. The Lancet 2005 366 9481 218 224 2-s2.0-22144441746 10.1016/S0140-6736(05)66911-5 (Pubitemid 40981049)
9. Lindau S. T., Abramsohn E., Gosch K., Patterns and loss of sexual activity in the year following hospitalization for acute myocardial infarction (A U.S. National, Multi-Site Observational Study). The American Journal of Cardiology 2012 109 10 1439 1444
10. Shiri R., Koskimäki J., Häkkinen J., Tammela T. L. J., Huhtala H., Hakama M., Auvinen A., Effects of age, comorbidity and lifestyle factors on erectile function: Tampere Ageing Male Urological Study (TAMUS). European Urology 2004 45 5 628 633 2-s2.0-1842737585 10.1016/j.eururo.2003.11.020 (Pubitemid 38481691)
11. Aversa A., Bruzziches R., Francomano D., Natali M., Gareri P., Spera G., Endothelial dysfunction and erectile dysfunction in the aging man. International Journal of Urology 2010 17 1 38 47 2-s2.0-74049092278 10.1111/j.1442-2042.2009. 02426.x
12. Chiurlia E., D'Amico R., Ratti C., Granata A. R., Romagnoli R., Modena M. G., Subclinical coronary artery atherosclerosis in patients with erectile dysfunction. Journal of the American College of Cardiology 2005 46 8 1503 1506 2-s2.0-26844574414 10.1016/j.jacc.2005.06.068 (Pubitemid 41446186)
13. Gazzaruso C., Solerte S. B., Pujia A., Coppola A., Vezzoli M., Salvucci F., Valenti C., Giustina A., Garzaniti A., Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: a potential protective role for statins and 5-phosphodiesterase inhibitors. Journal of the American College of Cardiology 2008 51 21 2040 2044 2-s2.0-43749101797 10.1016/j.jacc.2007.10.069 (Pubitemid 351689055)
14. Thompson I. M., Tangen C. M., Goodman P. J., Probstfield J. L., Moinpour C. M., Coltman C. A., Erectile dysfunction and subsequent cardiovascular disease. Journal of the American Medical Association 2005 294 23 2996 3002 2-s2.0-29144533834 10.1001/jama.294.23.2996 (Pubitemid 41817661)
15. Albersen M., Orabi H., Lue T. F., Evaluation and treatment of erectile dysfunction in the aging male: a mini-review. Gerontology 2012 58 1 3 14 2-s2.0-84155167230 10.1159/000329598
16. El-Sakka A. I., Yassin A. A., Review: amelioration of penile fibrosis: myth or reality. Journal of Andrology 2010 31 4 324 335 2-s2.0-77957842891 10.2164/jandrol.109.008730
17. Rudner X. L., Berkowitz D. E., Booth J. V., Funk B. L., Cozart K. L., D'Amico E. B., El-Moalem H., Page S. O., Richardson C. D., Winters B., Marucci L., Schwinn D. A., Subtype specific regulation of human vascular α 1-adrenergic receptors by vessel bed and age. Circulation 1999 100 23 2336 2343 2-s2.0-0033534082
18. Christ G. J., Stone B., Melman A., Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men. Canadian Journal of Physiology and Pharmacology 1991 69 7 909 913 2-s2.0-0026075221
19. Browne D., Meeking D., Shaw K., Cummings M., Endothelial dysfunction and pre-symptomatic atherosclerosis in type 1 diabetes-pathogenesis and identification. British Journal of Diabetes and Vascular Disease 2003 3 1 27 34 2-s2.0-0042388044 (Pubitemid 37045605)
20. Vanhoutte P. M., Ageing and endothelial dysfunction. European Heart Journal Supplements 2002 4 A8 A17
21. Musicki B., Kramer M. F., Becker R. E., Burnett A. L., de Tejada I. S., Age-related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis. The Journal of Sexual Medicine 2005 2 3 347 357 2-s2.0-19744372761 10.1111/j.1743-6109.2005.20349.x (Pubitemid 40744375)
22. Wespes E., The ageing penis. World Journal of Urology 2002 20 1 36 39 2-s2.0-0036561825
23. Ferrini M. G., Davila H. H., Valente E. G. A., Gonzalez-Cadavid N. F., Rajfer J., Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media. Cardiovascular Research 2004 61 4 796 805 2-s2.0-1342281658 10.1016/j.cardiores.2003.12.006 (Pubitemid 38249479)
24. Traish A., Kim N., The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. The Journal of Sexual Medicine 2005 2 6 759 770 2-s2.0-28444486296 10.1111/j.1743-6109.2005. 00094.x (Pubitemid 41727389)
25. Hougaku H., Fleg J. L., Najjar S. S., Lakatta E. G., Harman S. M., Blackman M. R., Metter E. J., Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements. American Journal of Physiology-Endocrinology and Metabolism 2006 290 2 E234 E242 2-s2.0-33644867881 10.1152/ajpendo.00059.2005
26. Hak A. E., Witteman J. C. M., de Jong F. H., Geerlings M. I., Hofman A., Pols H. A. P., Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. The Journal of Clinical Endocrinology and Metabolism 2002 87 8 3632 3639 2-s2.0-0036342660 10.1210/jc.87.8.3632 (Pubitemid 34879505)
27. Laughlin G. A., Barrett-Connor E., Bergstrom J., Low serum testosterone and mortality in older men. The Journal of Clinical Endocrinology and Metabolism 2008 93 1 68 75 2-s2.0-38148998650 10.1210/jc.2007-1792
28. Corona G., Rastrelli G., Maseroli E., Forti G., Maggi M., Sexual function of the ageing male. Best Practice & Research: Clinical Endocrinology & Metabolism 2013 27 4 581 601 10.1016/j.beem.2013.05.007
29. 2+ entry mechanisms of coronary vasoconstriction. Arteriosclerosis, Thrombosis, and Vascular Biology 1999 19 4 1034 1040 2-s2.0-0032892341 (Pubitemid 29177353)
30. Ruige J. B., Ouwens D. M., Kaufman J. M., Beneficial and adverse effects of testosterone on the cardiovascular system in men. The Journal of Clinical Endocrinology & Metabolism 2013 98 11 4300 4310
31. Corona G., Gacci M., Baldi E., Mancina R., Forti G., Maggi M., Androgen deprivation therapy in prostate cancer: focusing on sexual side effects. The Journal of Sexual Medicine 2012 9 3 887 902 2-s2.0-84857654914 10.1111/j.1743-6109.2011.02590.x
32. Araujo A. B., Dixon J. M., Suarez E. A., Murad M. H., Guey L. T., Wittert G. A., Endogenous testosterone and mortality in men: a systematic review and meta-analysis. The Journal of Clinical Endocrinology and Metabolism 2011 96 10 3007 3019 2-s2.0-80053558302 10.1210/jc.2011-1137
33. Isidori A. M., Buvat J., Corona G., A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. European Urology 2014 65 1 99 112
34. Corona G., Rastrelli G., Morelli A., Vignozzi L., Mannucci E., Maggi M., Hypogonadism and metabolic syndrome. Journal of Endocrinological Investigation 2011 34 7 557 567 2-s2.0-80054089894 10.3275/7806
35. Corona G., Rastrelli G., Maggi M., Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Practice & Research: Clinical Endocrinology & Metabolism 2013 27 4 557 579
36. Vigen R., O'Donnell C. I., Barón A. E., Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. The Journal of the American Medical Association 2013 310 17 1829 1836 10.1001/jama.2013.280386
37. Martin S., Atlantis E., Wilson D., Clinical and biopsychosocial determinants of sexual dysfunction in middle-aged and older Australian men. The Journal of Sexual Medicine 2013 9 8 2093 2103 10.1111/j.1743-6109.2012.02805.x
38. Foresta C., Caretta N., Corona G., Fabbri A., Francavilla S., Jannini E., Maggi M., Bettocchi C., Lenzi A., Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart. International Journal of Andrology 2009 32 3 198 211 2-s2.0-65549100996 10.1111/j.1365-2605. 2008.00932.x
39. Sachs B. D., The false organic-psychogenic distinction and related problems in the classification of erectile dysfunction. International Journal of Impotence Research 2003 15 1 72 78 2-s2.0-0037300854 10.1038/sj.ijir.3900952 (Pubitemid 36356361)
40. Corona G., Mondaini N., Ungar A., Razzoli E., Rossi A., Fusco F., Phosphodiesterase type 5 (PDE5) inhibitors in erectile dysfunction: the proper drug for the proper patient. The Journal of Sexual Medicine 2011 8 12 3418 3432 2-s2.0-82955203374 10.1111/j.1743-6109.2011.02473.x
41. Vardi M., Nini A., Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database of Systematic Reviews 2007 1 CD002187 2-s2.0-34247891684
42. Corona G., Lee D. M., Forti G., O'Connor D. B., Maggi M., O'Neill T. W., Pendleton N., Bartfai G., Boonen S., Casanueva F. F., Finn J. D., Giwercman A., Han T. S., Huhtaniemi I. T., Kula K., Lean M. E. J., Punab M., Silman A. J., Vanderschueren D., Wu F. C. W., Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). The Journal of Sexual Medicine 2010 7 4 1362 1380 2-s2.0-77955150230 10.1111/j.1743-6109.2009.01601.x
43. Corona G., Monami M., Boddi V., Cameron-Smith M., Lotti F., de Vita G., Melani C., Balzi D., Sforza A., Forti G., Mannucci E., Maggi M., Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction. The Journal of Sexual Medicine 2010 7 5 1918 1927 2-s2.0-77953580306 10.1111/j.1743-6109.2010.01744.x
44. Corona G., Mannucci E., Lotti F., Fisher A. D., Bandini E., Balercia G., Forti G., Maggi M., Pulse pressure, an index of arterial stiffness, is associated with androgen deficiency and impaired penile blood flow in men with ED. The Journal of Sexual Medicine 2009 6 1 285 293 2-s2.0-58149513375 10.1111/j.1743-6109.2008.01059.x
45. Jackson G., Rosen R. C., Kloner R. A., Kostis J. B., The second Princeton consensus on sexual dysfunction and cardiac risk: new guidelines for sexual medicine. The Journal of Sexual Medicine 2006 3 1 28 36 2-s2.0-33645744784 10.1111/j.1743-6109.2005.00196.x
46. Eardley I., Donatucci C., Corbin J., El-Meliegy A., Hatzimouratidis K., McVary K., Munarriz R., Lee S. W., Pharmacotherapy for erectile dysfunction. The Journal of Sexual Medicine 2010 7 1 524 540 2-s2.0-74049143429 10.1111/j.1743-6109.2009.01627.x
47. Jung J.-H., Kam S.-C., Choi S.-M., Jae S.-U., Lee S.-H., Hyun J.-S., Sexual dysfunction in male stroke patients: correlation between brain lesions and sexual function. Urology 2008 71 1 99 103 2-s2.0-38649085291 10.1016/j.urology.2007.08.045 (Pubitemid 351173266)
48. Celik D. B., Poyraz E. C., Bingöl A., Idiman E., Ozakbaş S., Kaya D., Sexual dysfunction n multiple sclerosis: gender differences. Journal of the Neurological Sciences 2013 324 1-2 17 20 10.1016/j.jns.2012.08.019
49. Sakakibara R., Kishi M., Ogawa E., Bladder, bowel, and sexual dysfunction in Parkinson's disease. Parkinson's Disease 2011 2011 21 924605 10.4061/2011/924605
50. Kotková P., Weiss P., Psychiatric factors related to sexual functioning in patients with Parkinson's disease. Clinical Neurology and Neurosurgery 2013 115 4 419 424
51. Bronner G., Vodušek D. B., Management of sexual dysfunction in Parkinson's disease. Therapeutic Advances in Neurological Disorders 2011 4 6 375 383 2-s2.0-82955213570 10.1177/1756285611411504
52. Mendez M. F., Shapira J. S., Hypersexual behavior in frontotemporal dementia: a comparison with early-onset Alzheimer's disease. Archives of Sexual Behavior 2013 42 3 501 519
53. Chen C. Y., Lee C. P., Chen Y., Jiang J. R., Chu C. L., Chen C. L., The correlation between emotional distress and aging males' symptoms at a psychiatric outpatient clinic: sexual dysfunction as a distinguishing characteristic between andropause and anxiety/depression in aging men. Clinical Interventions in Aging 2013 8 635 640 10.2147/CIA.S45190
54. Pastuszak A. W., Badhiwala N., Lipshultz L. I., Khera M., Depression is correlated with the psychological and physical aspects of sexual dysfunction in men. International Journal of Impotence Research 2013 25 5 194 199 10.1038/ijir.2013.4
55. Jeong J.-Y., Lee S. K., Kang Y.-W., Jang S.-N., Choi Y. J., Kim D.-H., Relationship between ED and depression among middle-aged and elderly men in Korea: Hallym aging study. International Journal of Impotence Research 2011 23 5 227 234 2-s2.0-80052750492 10.1038/ijir.2011.32
56. Tan H. M., Tong S. F., Ho C. C. K., Men's health: sexual dysfunction, physical, and psychological health-is there a link? The Journal of Sexual Medicine 2012 9 3 663 671 2-s2.0-84857642554 10.1111/j.1743-6109.2011.02582.x
57. Perelman M. A., Erectile dysfunction and depression: screening and treatment. Urologic Clinics of North America 2011 38 2 125 139 2-s2.0-79957452770 10.1016/j.ucl.2011.03.004
58. Kennedy S. H., Dugré H., Defoy I., A multicenter, double-blind, placebo-controlled study of sildenafil citrate in Canadian men with erectile dysfunction and untreated symptoms of depression, in the absence of major depressive disorder. International Clinical Psychopharmacology 2011 26 3 151 158 2-s2.0-79954611867 10.1097/YIC.0b013e32834309fc
59. Kinzl J. F., Major depressive disorder, antidepressants and sexual dysfunction. Neuropsychiatrie 2009 23 2 134 138 2-s2.0-67650678443
60. Nagaraj A. K., Nizamie H. S., Akhtar S., Sinha B. N., Goyal N., A comparative study of sexual dysfunction due to typical and atypical antipsychotics in remitted bipolar-I disorder. Indian Journal of Psychiatry 2004 46 3 261 266 (Pubitemid 40077047)
61. Hiller W., Rief W., Brähler E., Somatization in the population: from mild bodily misperceptions to disabling symptoms. Social Psychiatry and Psychiatric Epidemiology 2006 41 9 704 712 2-s2.0-33748576914 10.1007/s00127-006-0082-y (Pubitemid 44363759)
62. Lue T. F., Broderick G. A., Evaluation and nonsurgical management of erectile dysfunction and premature ejaculation. Campbell-Walsh Urology 2007 9th Amsterdam, The Netherlands Elsevier
63. Korfage I. J., Pluijm S., Roobol M., Dohle G. R., Schröder F. H., Essink-Bot M.-L., Erectile dysfunction and mental health in a general population of older men. The Journal of Sexual Medicine 2009 6 2 505 512 2-s2.0-59349112147 10.1111/j.1743-6109.2008.01111.x
64. Corona G., Rastrelli G., Monami M., Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. European Journal of Endocrinology 2013 168 6 829 843 10.1530/EJE-12-0955
65. Gupta B. P., Murad M. H., Clifton M. M., Prokop L., Nehra A., Kopecky S. L., The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. Archives of Internal Medicine 2011 171 20 1797 1803 2-s2.0-81355164347 10.1001/archinternmed.2011.440
66. Saltzman E. A., Guay A. T., Jacobson J., Improvement in erectile function in men with organic erectile dysfunction by correction of elevated cholesterol levels: a clinical observation. The Journal of Urology 2004 172 1 255 258 2-s2.0-3242754347
67. Montejo-González A. L., Llorca G., Izquierdo J. A., Ledesma A., Bousoño M., Calcedo A., Carrasco J. L., Ciudad J., Daniel E., De La Gandara J., Derecho J., Franco M., Gomez M. J., Macias J. A., Martin T., Perez V., Sanchez J. M., Sanchez S., Vicens E., SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. Journal of Sex and Marital Therapy 1997 23 3 176 194 2-s2.0-0030734647 (Pubitemid 27514710)
68. Rosen R. C., Lane R. M., Menza M., Effects of SSRIs on sexual function: a critical review. Journal of Clinical Psychopharmacology 1999 19 1 67 85 2-s2.0-0032958811 10.1097/00004714-199902000-00013 (Pubitemid 29047334)
69. Wespes E., Amar E., Hatzichristou D., Hatzimouratidis K., Montorsi F., Pryor J., Vardi Y., EAU guidelines on erectile dysfunction: an update. European Urology 2006 49 5 806 815 2-s2.0-33645794792 10.1016/j.eururo.2006.01.028
70. Albersen M., Shindel A. W., Mwamukonda K. B., Lue T. F., The future is today: emerging drugs for the treatment of erectile dysfunction. Expert Opinion on Emerging Drugs 2010 15 3 467 480 2-s2.0-77955879920 10.1517/14728214.2010. 480973
71. Sildenafil S. P. C., Sildenafil Summary of Product Characteristics. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/ human/000202/WC500049830.pdf
72. Vardenafil S. P. C., Vardenafil Summary of Product Characteristics. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/ human/000475/WC500039992.pdf
73. Jung J., Choi S., Cho S. H., Ghim J.-L., Hwang A., Kim U., Kim B. S., Koguchi A., Miyoshi S., Okabe H., Bae K.-S., Lim H.-S., Tolerability and pharmacokinetics of avanafil, a phosphodiesterase type 5 inhibitor: a single- and multiple-dose, double-blind, randomized, placebo-controlled, dose-escalation study in healthy Korean male volunteers. Clinical Therapeutics 2010 32 6 1178 1187 2-s2.0-77954626094 10.1016/j.clinthera.2010.06.011
74. Fujisawa M., Sawada K., Clinical efficacy and safety of sildenafil in elderly patients with erectile dysfunction. Archives of Andrology 2004 50 4 255 260 2-s2.0-3042808655 10.1080/01485010490448589 (Pubitemid 38858390)
75. Hatzimouratidis K., Hatzichristou D. G., A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs 2005 65 12 1621 1650 2-s2.0-23744435642 10.2165/00003495- 200565120-00003 (Pubitemid 41138985)
76. Bella A. J., Deyoung L. X., Al-Numi M., Brock G. B., Daily administration of phosphodiesterase type 5 inhibitors for urological and nonurological indications. European Urology 2007 52 4 990 1005 2-s2.0-34548297591 10.1016/j.eururo.2007.06.048 (Pubitemid 47334787)
77. Shindel A. W., 2009 update on phosphodiesterase type 5 inhibitor therapy part 1: recent studies on routine dosing for penile rehabilitation, lower urinary tract symptoms, and other indications (CME). The Journal of Sexual Medicine 2009 6 7 1794 1808 2-s2.0-67649887476 10.1111/j.1743-6109.2009.01347.x
78. Konstantinopoulos A., Giannitsas K., Athanasopoulos A., Spathas D., Perimenis P., The impact of daily sildenafil on levels of soluble molecular markers of endothelial function in plasma in patients with erectile dysfunction. Expert Opinion on Pharmacotherapy 2009 10 2 155 160 2-s2.0-65649148693 10.1517/14656560802678211
79. Müller A., Smith L., Parker M., Mulhall J. P., Analysis of the efficacy and safety of sildenafil citrate in the geriatric population. BJU International 2007 100 1 117 121 2-s2.0-34249931429 10.1111/j.1464-410X.2007. 06915.x (Pubitemid 46878564)
80. Shabsigh R., Kaufman J. M., Steidle C., Padma-Nathan H., Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. The Journal of Urology 2004 172 2 658 663 2-s2.0-3142546340 10.1097/01.ju.0000132389.97804.d7 (Pubitemid 38900229)
81. Aversa A., Isidori A. M., Spera G., Lenzi A., Fabbri A., Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction. Clinical Endocrinology 2003 58 5 632 638 2-s2.0-0038670738 10.1046/j.1365-2265.2003.01764.x (Pubitemid 36566807)
82. Sperling H., Debruyne F., Boermans A., Beneke M., Ulbrich E., Ewald S., The POTENT I randomized trial: efficacy and safety of an orodispersible vardenafil formulation for the treatment of erectile dysfunction. The Journal of Sexual Medicine 2010 7 4 1497 1507 2-s2.0-77955254138 10.1111/j.1743-6109.2010. 01806.x
83. Sanford M., Vardenafil orodispersible tablet. Drugs 2012 72 1 87 98 2-s2.0-84055190600 10.2165/11208270-000000000-00000
84. Gittelman M., McMahon C. G., Rodríguez-Rivera J. A., Beneke M., Ulbrich E., Ewald S., The POTENT II randomised trial: efficacy and safety of an orodispersible vardenafil formulation for the treatment of erectile dysfunction. International Journal of Clinical Practice 2010 64 5 594 603 2-s2.0-77949382405 10.1111/j.1742-1241.2010.02358.x
85. Salonia A., Gallina A., Zanni G., Briganti A., Dehò F., Saccà A., Suardi N., Barbieri L., Guazzoni G., Rigatti P., Montorsi F., Acceptance of and discontinuation rate from erectile dysfunction oral treatment in patients following bilateral nerve-sparing radical prostatectomy. European Urology 2008 53 3 564 570 2-s2.0-38749123514 10.1016/j.eururo.2007.08.016 (Pubitemid 351178991)
86. Rosen R., Altwein J., Boyle P., Kirby R. S., Lukacs B., Meuleman E., O'Leary M. P., Puppo P., Robertson C., Giuliano F., Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). European Urology 2003 44 6 637 649 2-s2.0-10744221043 10.1016/j.eururo.2003.08.015 (Pubitemid 37542920)
87. Roehrborn C. G., Lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction, and phosphodiesterase-5 inhibitors. Reviews in Urology 2004 6 3 121 127
88. Andersson K.-E., de Groat W. C., McVary K. T., Lue T. F., Maggi M., Roehrborn C. G., Wyndaele J. J., Melby T., Viktrup L., Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action. Neurourology and Urodynamics 2011 30 3 292 301 2-s2.0-79952749220 10.1002/nau.20999
89. Fujisawa M., Sawada K., Clinical efficacy and safety of sildenafil in elderly patients with erectile dysfunction. Archives of Andrology 2004 50 4 255 260 2-s2.0-3042808655 10.1080/01485010490448589 (Pubitemid 38858390)
90. Carson C. C. III, Cardiac safety in clinical trials of phosphodiesterase 5 inhibitors. American Journal of Cardiology 2005 96 12 37M 41M 2-s2.0-29544447417 10.1016/j.amjcard.2005.07.010 (Pubitemid 43017216)
91. Giuliano F., Donatucci C., Montorsi F., Auerbach S., Karlin G., Norenberg C., Homering M., Segerson T., Eardley I., Vardenafil is effective and well-tolerated for treating erectile dysfunction in a broad population of men, irrespective of age. BJU International 2005 95 1 110 116 2-s2.0-12544256530 10.1111/j.1464-410X.2004.05260.x (Pubitemid 350027199)
92. Borer J., Armstrong P., Proceedings of the 99th meeting of the Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee. May 29th and 30th, 2003. Circulation 2003 107 23, article e9052 2-s2.0-0037562522
93. Corona G., Razzoli E., Forti G., Maggi M., The use of phosphodiesterase 5 inhibitors with concomitant medications. Journal of Endocrinological Investigation 2008 31 9 799 808 2-s2.0-57349196418
94. Gareri P., de Sarro G., Putignano S., Cester A., Gareri P., Principi di farmacologia geriatrica. Geriatria nel territorio. Un metodo per i vecchi, per i medici e per il futuro 2012 Roma, Italy Critical Medicine Publishing s.r.l. 361 404
95. Hedner T., Edgar B., Edvinsson L., Hedner J., Persson B., Pettersson A., Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers. European Journal of Clinical Pharmacology 1992 43 6 651 656 2-s2.0-0026454859 10.1007/BF02284967
96. Lebret T., Hervé J.-M., Gorny P., Worcel M., Botto H., Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. European Urology 2002 41 6 608 613 2-s2.0-0036624720 10.1016/S0302-2838(02)00175-6 (Pubitemid 35333917)
97. Ning H., Xin Z.-C., Lin G., Banie L., Lue T. F., Lin C.-S., Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology 2006 68 6 1350 1354 2-s2.0-33845296134 10.1016/j.urology.2006.09.031 (Pubitemid 44880379)
98. Xu H.-B., Huang Z.-Q., Icariin enhances endothelial nitric-oxide synthase expression on human endothelial cells in vitro. Vascular Pharmacology 2007 47 1 18 24 2-s2.0-34249280557 10.1016/j.vph.2007.03.002 (Pubitemid 46818133)
99. Zhang Z.-B., Yang Q.-T., The testosterone mimetic properties of icariin. Asian Journal of Andrology 2006 8 5 601 605 2-s2.0-33747619425 10.1111/j.1745-7262.2006.00197.x (Pubitemid 44263434)
100. Hellstrom W. J. G., Montague D. K., Moncada I., Carson C., Minhas S., Faria G., Krishnamurti S., Implants, mechanical devices, and vascular surgery for erectile dysfunction. The Journal of Sexual Medicine 2010 7 1 501 523 2-s2.0-74049088979 10.1111/j.1743-6109.2009.01626.x
101. Hatzimouratidis K., Amar E., Eardley I., Giuliano F., Hatzichristou D., Montorsi F., Vardi Y., Wespes E., European Association of Urology E. A. O. U., Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation. European Urology 2010 57 5 804 814 2-s2.0-77953948992
102. Tharyan P., Gopalakrishanan G., Erectile dysfunction. Clinical Evidence 2006 15 1227 1251 2-s2.0-39049191336
103. Harte C. B., Meston C. M., Recreational use of erectile dysfunction medications in undergraduate men in the United States: characteristics and associated risk factors. Archives of Sexual Behavior 2011 40 3 597 606 2-s2.0-79958743002 10.1007/s10508-010-9619-y
104. Korkes F., Costa-matos A., Gasperini R., Reginato P. V., Perez M. D. C., Recreational use of PDE5 inhibitors by young healthy men: recognizing this issue among medical students. The Journal of Sexual Medicine 2008 5 10 2414 2418 2-s2.0-53549108569 10.1111/j.1743-6109.2008.00792.x
105. Schnetzler G., Banks I., Kirby M., Zou K. H., Symonds T., Characteristics, behaviors, and attitudes of men bypassing the healthcare system when obtaining phosphodiesterase type 5 inhibitors. The Journal of Sexual Medicine 2010 7 3 1237 1246 2-s2.0-77950821266 10.1111/j.1743-6109.2009.01674.x
106. Melnik T., The psychological effects of recreational PDE5 inhibitor use. Nature Reviews Urology 2012 9 479 480
107. Puzzo D., Staniszewski A., XianDeng S., Privitera L., Leznik E., Liu S., Zhang H., Feng Y., Palmeri A., Landry D. W., Arancio O., Phosphodiesterase 5 inhibition improves synaptic function, memory, and amyloid- β load in an Alzheimer's disease mouse model. Journal of Neuroscience 2009 29 25 8075 8086 2-s2.0-67649342620 10.1523/JNEUROSCI.0864-09.2009
108. Ghofrani H. A., Osterloh I. H., Grimminger F., Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nature Reviews Drug Discovery 2006 5 8 689 702 2-s2.0-33746584053 10.1038/nrd2030 (Pubitemid 44151606)
109. Albersen M., Weyne E., Bivalacqua T. J., Stem cell therapy for erectile dysfunction: progress and future directions. Sexual Medicine Reviews 2013 1 1 50 64 10.1002/smrj.5