Efficacy and Safety of Tadalafil for the Treatment of Erectile Dysfunction: Results of Integrated Analyses

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Oct 2002Efficacy and Safety of Tadalafil for the Treatment of Erectile Dysfunction: Results of Integrated Analyses Gerald B. Brock, Chris G. McMahon, K.K. Chen, Timothy Costigan, Wei Shen, Vish Watkins, Greg Anglin, and Steve Whitaker Gerald B. BrockGerald B. Brock Financial interest and/or other relationship with Lilly-ICOS, Pfizer, Bayer and Tap. More articles by this author , Chris G. McMahonChris G. McMahon Financial interest and/or other relationship with Lilly/ICOS. More articles by this author , K.K. ChenK.K. Chen Financial interest and/or other relationship with Eli Lilly and Company. More articles by this author , Timothy CostiganTimothy Costigan Financial interest and/or other relationship with Eli Lilly and Company. More articles by this author , Wei ShenWei Shen Financial interest and/or other relationship with Eli Lilly and Company. More articles by this author , Vish WatkinsVish Watkins Financial interest and/or other relationship with Eli Lilly and Company. More articles by this author , Greg AnglinGreg Anglin Financial interest and/or other relationship with Eli Lilly and Company. More articles by this author , and Steve WhitakerSteve Whitaker Financial interest and/or other relationship with ICOS Corporation.Accepted for publication April 26, 2002.Supported by Lilly ICOS LLC. More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)64442-4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We conducted integrated analyses of the efficacy and safety of tadalafil, a potent, selective phosphodiesterase 5 inhibitor, for the treatment of erectile dysfunction. Materials and Methods: A total of 1,112 men with a mean age of 59 years (range 22 to 82) and mild to severe erectile dysfunction of various etiologies were randomized to placebo or tadalafil, taken as needed without food or alcohol restrictions, at fixed daily doses of 2.5 mg., 5 mg., 10 mg., or 20 mg. in 5 randomized, double-blind, placebo controlled trials lasting 12 weeks. The 3 co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function and the proportion of “yes” responses to questions 2 and 3 of the Sexual Encounter Profile. Additional efficacy instruments included a Global Assessment Question. Results: Compared with placebo, tadalafil significantly enhanced all efficacy outcomes. Patients receiving 20 mg. tadalafil experienced a significant mean improvement of 7.9 in International Index of Erectile Function erectile function domain score from baseline (p <0.001 versus placebo), 75% of intercourse attempts (Sexual Encounter Profile question 3, a secondary efficacy outcome) were successfully completed (p <0.001 versus placebo) and 81% reported improved erections at end point compared with 35% in the control group (p <0.001). Tadalafil was consistently efficacious across disease severities and etiologies, as well as in patients of all ages. Tadalafil was well tolerated, and headache and dyspepsia were the most frequent adverse events. Conclusions: Tadalafil was effective and well tolerated in this patient population. References 1 : The worldwide prevalence and epidemiology of erectile dysfunction. Int J Impot Res2000; 12: S6. Crossref, Medline, Google Scholar 2 : Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol1994; 151: 54. Link, Google Scholar 3 Impotence. NIH Consens Statement1992; 10: 1. Google Scholar 4 : Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med1998; 338: 1397. Crossref, Medline, Google Scholar 5 : When patients request the impotence pill. Postgrad Med1998; 104: 55. Crossref, Medline, Google Scholar 6 : Cyclic GMP and mechanisms of vasodilation. Pharmacol Ther1989; 41: 479. Crossref, Medline, Google Scholar 7 : Molecular mechanism of cGMP-mediated smooth muscle relaxation. J Cell Physiol2000; 184: 409. Crossref, Medline, Google Scholar 8 : Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun1990; 170: 843. Crossref, Medline, Google Scholar 9 : On-demand IC351 (Cialis) enhances erectile function in patients with erectile dysfunction. Int J Impot Res2001; 13: 2. Crossref, Medline, Google Scholar 10 : The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology1997; 49: 822. Crossref, Medline, Google Scholar 11 : Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology1999; 54: 346. Crossref, Medline, Google Scholar 12 Sáenz de Tejada I. Anglin G. Emmick J. Effects of tadalafil on erectile dysfunction in men with diabetes. Unpublished data Google Scholar 13 Porst H. Padma-Nathan H. Rosen R. Giuliano F. Anglin G. Varanese L. Duration of responsiveness to tadalafil in the treatment of erectile dysfunction: a randomized controlled trial. Unpublished data Google Scholar 14 : Health outcomes variables important to patients in the treatment of erectile dysfunction. J Urol1998; 159: 1541. Link, Google Scholar From the Department of Surgery, Division of Urology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada, the Australian Centre for Sexual Health, St. Luke’s Hospital Complex, Sydney, New South Wales, Australia, Taipei Veterans General Hospital, Taipei, Taiwan, Eli Lilly and Company, Indianapolis, Indiana, and ICOS Corporation, Bothell, Washington© 2002 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited by Alkhawaja B, Al-Akayleh F, Al-Khateeb A, Nasereddin J, Ghanim B, Bolhuis A, Jaber N, Al-Remawi M and Qinna N (2023) Deep Eutectic Liquids as a Topical Vehicle for Tadalafil: Characterisation and Potential Wound Healing and Antimicrobial ActivityMolecules, 10.3390/molecules28052402, VOL. 28, NO. 5, (2402) Corona G, Cucinotta D, Di Lorenzo G, Ferlin A, Giagulli V, Gnessi L, Isidori A, Maiorino M, Miserendino P, Murrone A, Pivonello R, Rochira V, Sangiorgi G, Stagno G, Foresta C, Lenzi A, Maggi M and Jannini E (2023) The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunctionJournal of Endocrinological Investigation, 10.1007/s40618-023-02015-5 Wang X, Kong D, Huang T, Xu F, Tang M, Deng Z and Lin S (2022) Flavoprotein StnP2 Catalyzes the β-Carboline Formation during the Streptonigrin BiosynthesisACS Chemical Biology, 10.1021/acschembio.2c00704, VOL. 17, NO. 12, (3499-3506), Online publication date: 16-Dec-2022. Lin C, Pattraraachachai J, Pawa K and Wongyai S (2022) A preliminary study of the efficacy of the polyherbal preparation Sao Thong Tai for erectile dysfunction among elderly men: a double-blind, randomized controlled trialClinical Phytoscience, 10.1186/s40816-022-00341-4, VOL. 8, NO. 1, Online publication date: 1-Dec-2022. Lee M, Lee J, Sohn S, Lee S, Jeong T and Kim S (2022) Effect of low-dose tadalafil once daily on glycemic control in patients with type 2 diabetes and erectile dysfunction: a randomized, double-blind, placebo-controlled pilot studyDiabetology & Metabolic Syndrome, 10.1186/s13098-022-00825-w, VOL. 14, NO. 1, Online publication date: 1-Dec-2022. Onyeji I and Clavijo R (2022) Testosterone replacement therapy and erectile dysfunctionInternational Journal of Impotence Research, 10.1038/s41443-021-00512-w, VOL. 34, NO. 7, (698-703), Online publication date: 1-Nov-2022. Ahmed S, Alalawi A, Shehata A, Alqurshi A, Alahmadi Y and S. M. Ali H (2022) Fabric phase sorptive extraction coupled with UPLC-ESI-MS/MS method for fast and sensitive quantitation of tadalafil in a bioequivalence studySaudi Pharmaceutical Journal, 10.1016/j.jsps.2022.06.001, VOL. 30, NO. 8, (1143-1152), Online publication date: 1-Aug-2022. von Büren M, Rodler S, Wiesenhütter I, Schröder F, Buchner A, Stief C, Gratzke C, Wülfing C and von Büren J (2022) Digital Real-world Data Suggest Patient Preference for Tadalafil over Sildenafil in Patients with Erectile DysfunctionEuropean Urology Focus, 10.1016/j.euf.2021.04.019, VOL. 8, NO. 3, (794-802), Online publication date: 1-May-2022. Porst H (2022) Diagnostik und medikamentöse Therapie der erektilen Dysfunktion Die Urologie, 10.1007/978-3-642-41168-7_153-2, (1-10), . Bromby A, Modgil V and Pearce I (2021) Diagnosis and management of erectile dysfunctionTrends in Urology & Men's Health, 10.1002/tre.817, VOL. 12, NO. 5, (12-17), Online publication date: 1-Sep-2021. Bakr A, El-Sakka A and El-Sakka A (2020) Considerations for prescribing pharmacotherapy for the treatment of erectile dysfunctionExpert Opinion on Pharmacotherapy, 10.1080/14656566.2020.1851365, VOL. 22, NO. 7, (821-834), Online publication date: 3-May-2021. Minagawa T, Oguchi T, Saitou T, Fukazawa A, Hashida I, Koiwai K, Iijima K, Kato H, Ogawa T and Ishizuka O (2021) Impact of low‐dose tadalafil on adverse events after low‐dose‐rate brachytherapy for prostate cancer: A bi‐center randomized open‐label trialInternational Journal of Urology, 10.1111/iju.14487, VOL. 28, NO. 4, (432-438), Online publication date: 1-Apr-2021. Towe M, El-Khatib F, Osman M, Huynh L, Carrion R, Ward S, Reisman Y, Serefoglu E, Pastuszak A and Yafi F (2020) “Doc, if it were you, what would you do?”: a survey of Men’s Health specialists’ personal preferences regarding treatment modalitiesInternational Journal of Impotence Research, 10.1038/s41443-020-0263-3, VOL. 33, NO. 3, (303-310), Online publication date: 1-Apr-2021. Rokach A and Patel K (2021) Sexual dysfunctions Human Sexuality, 10.1016/B978-0-12-819174-3.00009-7, (235-285), . Press B and Honig S (2021) Use of Stem Cells in the Treatment of Erectile Dysfunction Stem Cell Therapy for Vascular Diseases, 10.1007/978-3-030-56954-9_16, (347-365), . Kim S (2020) Legal retirement age of sexual life in Korean menKorean Journal of Sexual Health, 10.34224/kjsh.2020.4.1.9, VOL. 4, NO. 1, (9-18) da Cruz N, Polizelli M, Cezar L, Cardoso E, Penha F, Farah M, Rodrigues E and Novais E (2020) Effects of phosphodiesterase type 5 inhibitors on choroid and ocular vasculature: a literature reviewInternational Journal of Retina and Vitreous, 10.1186/s40942-020-00241-0, VOL. 6, NO. 1, Online publication date: 1-Dec-2020. Guillén V, Rueda J, Lopez-Argumedo M, Solà I and Ballesteros J (2020) Apomorphine for the Treatment of Erectile Dysfunction: Systematic Review and Meta-AnalysisArchives of Sexual Behavior, 10.1007/s10508-020-01817-5, VOL. 49, NO. 8, (2963-2979), Online publication date: 1-Nov-2020. Kedia G, Ückert S, Tsikas D, Becker A, Kuczyk M and Bannowsky A (2020) The Use of Vasoactive Drugs in the Treatment of Male Erectile Dysfunction: Current ConceptsJournal of Clinical Medicine, 10.3390/jcm9092987, VOL. 9, NO. 9, (2987) Akinyede A, Nwaiwu O, Fasipe O, Olusanya A, Olayemi S and Akande B (2020) A prospective study of the effect of antihypertensive medications on the sexual functions of hypertensive adult male patientsFuture Science OA, 10.2144/fsoa-2020-0030, VOL. 6, NO. 6, Online publication date: 1-Jul-2020. Navabi S, Khosravifar M, Navabi S and Heydari R (2019) Acute pancreatitis induced by Tadalafil: a case reportClinical Journal of Gastroenterology, 10.1007/s12328-019-01070-x, VOL. 13, NO. 3, (459-464), Online publication date: 1-Jun-2020. Mitidieri E, Cirino G, d’Emmanuele di Villa Bianca R and Sorrentino R (2020) Pharmacology and perspectives in erectile dysfunction in manPharmacology & Therapeutics, 10.1016/j.pharmthera.2020.107493, VOL. 208, (107493), Online publication date: 1-Apr-2020. Wang Y, Geng L, He C and Yuan S (2019) Chinese herbal medicine combined with tadalafil for erectile dysfunction: a systematic review and meta‐analysisAndrology, 10.1111/andr.12696, VOL. 8, NO. 2, (268-276), Online publication date: 1-Mar-2020. Kim K, Jeong T and Moon H (2020) Effect of daily tadalafil on reported outcomes in patients with erectile dysfunction and depressive symptomsMedicine, 10.1097/MD.0000000000020546, VOL. 99, NO. 23, (e20546) Marcon J and Stief C (2020) Practical Guidelines for the Treatment of Erectile Dysfunction and Peyronie’s Disease Urologic Principles and Practice, 10.1007/978-3-030-28599-9_21, (357-392), . Cazzaniga W, Capogrosso P, Boeri L, Montorsi F and Salonia A (2020) Pharmacology of Male Sexual Function Urologic Principles and Practice, 10.1007/978-3-030-28599-9_10, (159-174), . Luo S, Liu Y, Lambrecht M, Ortwine D, DiPasquale A, Liang J, Wang X, Zbieg J and Li J (2019) cis -Selective synthesis of 1,3-disubstituted tetrahydro-β-carbolines from N -sulfonyl N , S -acetals Organic & Biomolecular Chemistry, 10.1039/C9OB01796H, VOL. 17, NO. 43, (9510-9513) Gul M and Serefoglu E (2019) An update on the drug safety of treating erectile dysfunctionExpert Opinion on Drug Safety, 10.1080/14740338.2019.1659244, VOL. 18, NO. 10, (965-975), Online publication date: 3-Oct-2019. Bayraktar Z and Albayrak S (2019) Efficacy and safety of combination of tadalafil and aspirin versus tadalafil or aspirin alone in patients with vascular erectile dysfunction: a comparative randomized prospective studyInternational Urology and Nephrology, 10.1007/s11255-019-02211-4, VOL. 51, NO. 9, (1491-1499), Online publication date: 1-Sep-2019. McMahon C (2019) Current diagnosis and management of erectile dysfunctionMedical Journal of Australia, 10.5694/mja2.50167, VOL. 210, NO. 10, (469-476), Online publication date: 1-Jun-2019. Alvani A, Jouyban A and Shayanfar A (2019) The effect of surfactant and polymer on solution stability and solubility of tadalafil-methylparaben cocrystalJournal of Molecular Liquids, 10.1016/j.molliq.2019.02.080, VOL. 281, (86-92), Online publication date: 1-May-2019. Le T, Tsambarlis P and Hellstrom W (2018) Pharmacodynamics of the agents used for the treatment of erectile dysfunctionExpert Opinion on Drug Metabolism & Toxicology, 10.1080/17425255.2019.1560421, VOL. 15, NO. 2, (121-131), Online publication date: 1-Feb-2019. Wareham L, Dordea A, Schleifer G, Yao V, Batten A, Fei F, Mertz J, Gregory-Ksander M, Pasquale L, Buys E and Sappington R (2019) Increased bioavailability of cyclic guanylate monophosphate prevents retinal ganglion cell degenerationNeurobiology of Disease, 10.1016/j.nbd.2018.09.002, VOL. 121, (65-75), Online publication date: 1-Jan-2019. Gholamzadeh P (2019) The Pictet–Spengler Reaction: A Powerful Strategy for the Synthesis of Heterocycles , 10.1016/bs.aihch.2018.09.002, (153-226), . Wei Y, Ling Y, Su M, Qin L, Zhang J, Gao Y and Qian S (2018) Characterization and Stability of Amorphous Tadalafil and Four Crystalline PolymorphsChemical and Pharmaceutical Bulletin, 10.1248/cpb.c18-00450, VOL. 66, NO. 12, (1114-1121), Online publication date: 1-Dec-2018. Ethans K, Casey A, Tarhoni M, Nankar M and Entcheva S (2018) A randomized double-blind, placebo-controlled, cross-over trial assessing the effect of tadalafil (Cialis) on the cardiovascular response in men with complete spinal cord injury above the sixth thoracic level: A Pilot StudySpinal Cord Series and Cases, 10.1038/s41394-018-0137-9, VOL. 4, NO. 1 Kim J, Kim M and Baek I (2018) Enhanced Bioavailability of Tadalafil after Intranasal Administration in Beagle DogsPharmaceutics, 10.3390/pharmaceutics10040187, VOL. 10, NO. 4, (187) Burnett A, Nehra A, Breau R, Culkin D, Faraday M, Hakim L, Heidelbaugh J, Khera M, McVary K, Miner M, Nelson C, Sadeghi-Nejad H, Seftel A and Shindel A (2018) Erectile Dysfunction: AUA GuidelineJournal of Urology, VOL. 200, NO. 3, (633-641), Online publication date: 1-Sep-2018. Wareham L, Buys E and Sappington R (2018) The nitric oxide-guanylate cyclase pathway and glaucomaNitric Oxide, 10.1016/j.niox.2018.04.010, VOL. 77, (75-87), Online publication date: 1-Jul-2018. Maruca-Sullivan P, Kleinfeld S and Wilkins K (2018) Treatment Approaches to Sexual Dysfunction in Late LifeCurrent Treatment Options in Psychiatry, 10.1007/s40501-018-0147-z, VOL. 5, NO. 2, (255-274), Online publication date: 1-Jun-2018. Kałka D, Gebala J, Smoliński R, Rusiecki L, Pilecki W and Zdrojowy R (2017) Low-energy Shock Wave Therapy—A Novel Treatment Option for Erectile Dysfunction in Men With Cardiovascular DiseaseUrology, 10.1016/j.urology.2017.05.030, VOL. 109, (19-26), Online publication date: 1-Nov-2017. Wang Y, Madsen A, Diness F and Meldal M (2017) Diversity-Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with PeptidesChemistry - A European Journal, 10.1002/chem.201702900, VOL. 23, NO. 56, (13869-13874), Online publication date: 9-Oct-2017. Patel J, Lee E, Mena-Hurtado C and Walker C (2017) Evaluation and Management of Erectile Dysfunction in the Hypertensive PatientCurrent Cardiology Reports, 10.1007/s11886-017-0889-z, VOL. 19, NO. 9, Online publication date: 1-Sep-2017. Leiber C (2017) Erektile DysfunktionErectile dysfunctionDer Urologe, 10.1007/s00120-017-0355-y, VOL. 56, NO. 4, (519-529), Online publication date: 1-Apr-2017. Price D (2016) Sexual Function in Men and Women with Diabetes Textbook of Diabetes, 10.1002/9781118924853.ch49, (716-730) Garcia F, Chung E and Brock G (2016) Drug therapy for erectile dysfunction Male Sexual Dysfunction, 10.1002/9781118746509.ch19, (172-193) Lu M, Xing H, Yang T, Yu J, Yang Z, Sun Y and Ding P (2016) Dissolution enhancement of tadalafil by liquisolid techniquePharmaceutical Development and Technology, 10.1080/10837450.2016.1189563, VOL. 22, NO. 1, (77-89), Online publication date: 2-Jan-2017. Majzoub A, El Bardisi H and Arafa M (2017) Treating Erectile Dysfunctions The Diagnosis and Treatment of Male Infertility, 10.1007/978-3-319-56547-7_13, (201-225), . Parisi T, Pechnick R and IsHak W (2017) Sex and Pharmacological Sexual Enhancement The Textbook of Clinical Sexual Medicine, 10.1007/978-3-319-52539-6_26, (387-411), . Kucuk E, Tahra A, Bindayi A and Onol F (2016) Erectile dysfunction patients are more satisfied with penile prosthesis implantation compared with tadalafil and intracavernosal injection treatmentsAndrology, 10.1111/andr.12237, VOL. 4, NO. 5, (952-956), Online publication date: 1-Sep-2016. Zurawin J, Stewart C, Anaissie J, Yafi F and Hellstrom W (2016) Avanafil for the treatment of erectile dysfunctionExpert Review of Clinical Pharmacology, 10.1080/17512433.2016.1212655, VOL. 9, NO. 9, (1163-1170), Online publication date: 1-Sep-2016. Boeri L, Capogrosso P, Ventimiglia E, Serino A, La Croce G, Russo A, Damiano R, Montorsi F and Salonia A (2016) Avanafil - a further step to tailoring patient needs and expectationsExpert Review of Clinical Pharmacology, 10.1080/17512433.2016.1195261, VOL. 9, NO. 9, (1171-1181), Online publication date: 1-Sep-2016. Jamnagerwalla J, Howard L, Vidal A, Moreira D, Castro-Santamaria R, Andriole G and Freedland S (2016) The Association between Phosphodiesterase Type 5 Inhibitors and Prostate Cancer: Results from the REDUCE StudyJournal of Urology, VOL. 196, NO. 3, (715-720), Online publication date: 1-Sep-2016. Cuzin B (2016) Alprostadil cream in the treatment of erectile dysfunction: clinical evidence and experienceTherapeutic Advances in Urology, 10.1177/1756287216644116, VOL. 8, NO. 4, (249-256), Online publication date: 1-Aug-2016. Baek J and Cho C (2015) Transdermal delivery of tadalafil using a novel formulationDrug Delivery, 10.3109/10717544.2015.1077291, VOL. 23, NO. 5, (1571-1577), Online publication date: 12-Jun-2016. Teich A, Sakurai M, Patel M, Holman C, Saeed F, Fiorito J, Arancio O and Koldamova R PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic DiseaseJournal of Alzheimer's Disease, 10.3233/JAD-151104, VOL. 52, NO. 1, (295-302) Sennath Joseph Arul A S (2016) PREVENTION OF TADALAFIL INDUCED BACKACHE IN ERECTILE DYSFUNCTION PATIENTSJournal of Evolution of Medical and Dental Sciences, 10.14260/jemds/2016/332, VOL. 5, NO. 27, (1410-1412), Online publication date: 4-Apr-2016. Irkilata L, Aydin H, Ozer I, Aydin M, Demirel H, Moral C and Atilla M (2016) The efficacy of udenafil in end-stage renal disease patients undergoing hemodialysisRenal Failure, 10.3109/0886022X.2015.1128840, VOL. 38, NO. 3, (357-361), Online publication date: 15-Mar-2016. Li H, Gao T and Wang R (2016) The role of the sexual partner in managing erectile dysfunctionNature Reviews Urology, 10.1038/nrurol.2015.315, VOL. 13, NO. 3, (168-177), Online publication date: 1-Mar-2016. Ventimiglia E, Capogrosso P, Montorsi F and Salonia A (2016) The safety of phosphodiesterase type 5 inhibitors for erectile dysfunctionExpert Opinion on Drug Safety, 10.1517/14740338.2016.1131818, VOL. 15, NO. 2, (141-152), Online publication date: 1-Feb-2016. Corona G, Rastrelli G, Burri A, Jannini E and Maggi M (2016) The safety and efficacy of Avanafil, a new 2 nd generation PDE5i: comprehensive review and meta-analysis Expert Opinion on Drug Safety, 10.1517/14740338.2016.1130126, VOL. 15, NO. 2, (237-247), Online publication date: 1-Feb-2016. Choi H, Shim E, Shon J, Jung J, Ghim J, Ryu J, Bae K and Shin J (2016) Effects of mirodenafil on the hemodynamics in hypertensive patients taking amlodipineTranslational and Clinical Pharmacology, 10.12793/tcp.2016.24.2.90, VOL. 24, NO. 2, (90), . Bhasin S and Basson R (2016) Sexual Dysfunction in Men and Women Williams Textbook of Endocrinology, 10.1016/B978-0-323-29738-7.00020-4, (785-830), . Porst H (2016) Diagnostik und medikamentöse Therapie der erektilen Dysfunktion Die Urologie, 10.1007/978-3-642-39940-4_153, (1513-1521), . Bennett N (2016) Oral Prescription Therapy for Erectile Dysfunction Contemporary Treatment of Erectile Dysfunction, 10.1007/978-3-319-31587-4_12, (163-173), . Yang H, Ho C, Zhao P, Su D and Seftel A (2016) Geriatric Sexuality Primer of Geriatric Urology, 10.1007/978-1-4939-4928-1_12, (163-227), . Hatzichristou D, d’Anzeo G, Porst H, Buvat J, Henneges C, Rossi A, Hamidi K and Büttner H (2015) Tadalafil 5 mg once daily for the treatment of erectile dysfunction during a 6-month observational study (EDATE): impact of patient characteristics and comorbiditiesBMC Urology, 10.1186/s12894-015-0107-5, VOL. 15, NO. 1, Online publication date: 1-Dec-2015. Ceballos M, Álvarez Villarraga J, Silva Herrera J, Uribe J and Mantilla D (2015) Guía de disfunción eréctil. Sociedad Colombiana de UrologíaUrología Colombiana, 10.1016/j.uroco.2015.04.006, VOL. 24, NO. 3, (185.e1-185.e22), Online publication date: 1-Dec-2015. Baek J, Pham C, Myung C and Cho C (2015) Tadalafil-loaded nanostructured lipid carriers using permeation enhancersInternational Journal of Pharmaceutics, 10.1016/j.ijpharm.2015.09.054, VOL. 495, NO. 2, (701-709), Online publication date: 1-Nov-2015. Mehanna M, Motawaa A and Samaha M (2014) Nanovesicular carrier-mediated transdermal delivery of tadalafil: i- formulation and physicsochemical characterizationDrug Development and Industrial Pharmacy, 10.3109/03639045.2014.900075, VOL. 41, NO. 5, (714-721), Online publication date: 4-May-2015. Wobst J, Kessler T, Dang T, Erdmann J and Schunkert H (2015) Role of sGC-dependent NO signalling and myocardial infarction riskJournal of Molecular Medicine, 10.1007/s00109-015-1265-3, VOL. 93, NO. 4, (383-394), Online publication date: 1-Apr-2015. Ryu J, Kim W, Koh Y, Piao S, Jin H, Lee S, Choi M, Shin H, Kwon M, Jung K, Koh G and Suh J (2015) Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through healthy cavernous angiogenesis in a hypercholesterolemic mouseScientific Reports, 10.1038/srep09222, VOL. 5, NO. 1 Burns P, Rosen R, Dunn M, Baygani S and Perelman M (2015) Treatment Satisfaction of Men and Partners Following Switch from On-Demand Phosphodiesterase Type 5 Inhibitor Therapy to Tadalafil 5 mg Once DailyThe Journal of Sexual Medicine, 10.1111/jsm.12818, VOL. 12, NO. 3, (720-727), Online publication date: 1-Mar-2015. McCarthy B and Pierpaoli C (2013) Sexual Challenges With Aging: Integrating the GES Approach in an Elderly CoupleJournal of Sex & Marital Therapy, 10.1080/0092623X.2013.831004, VOL. 41, NO. 1, (72-82), Online publication date: 2-Jan-2015. Gigant N, Honraedt A, Gras E and Gillaizeau I (2014) Efficient Cross-Coupling of Dioxazaborocanes with α-Phosphate EnamidesEuropean Journal of Organic Chemistry, 10.1002/ejoc.201402927, VOL. 2014, NO. 35, (7889-7894), Online publication date: 1-Dec-2014. Hatzimouratidis K, Buvat J, Büttner H, Vendeira P, Moncada I, Boehmer M, Henneges C and Boess F (2014) Psychosocial outcomes after initial treatment of erectile dysfunction with tadalafil once daily, tadalafil on demand or sildenafil citrate on demand: results from a randomized, open-label studyInternational Journal of Impotence Research, 10.1038/ijir.2014.15, VOL. 26, NO. 6, (223-229), Online publication date: 1-Nov-2014. Buvat J, Hatzichristou D, Boess F, Büttner H, Gehchan N, Henneges C and Porst H (2014) Continuation and effectiveness of tadalafil once daily during a 6‐month