Diagnosis and Management of Testosterone Deficiency in men: A review of the European and American Urology Associations

[1] Almeida O.P., Yeap B.B., Hankey G.J., Jamrozik K., Flicker L.: Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch. Gen. Psychiatry, 2008; 65: 283–289 AlmeidaO.P. YeapB.B. HankeyG.J. JamrozikK. FlickerL. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men Arch. Gen. Psychiatry 2008 65 283 289 10.1001/archgenpsychiatry.2007.3318316674 Search in Google Scholar

[2] Araujo A.B., O’Donnell A.B., Brambilla D.J., Simpson W.B., Longcope C., Matsumoto A.M., McKinlay J.B.: Prevalence and incidence of androgen deficiency in middle-aged and older men: Estimates from the Massachusetts Male Aging Study. J. Clin. Endocrinol. Metab., 2004; 89: 5920–5926 AraujoA.B. O’DonnellA.B. BrambillaD.J. SimpsonW.B. LongcopeC. MatsumotoA.M. McKinlayJ.B. Prevalence and incidence of androgen deficiency in middle-aged and older men: Estimates from the Massachusetts Male Aging Study J. Clin. Endocrinol. Metab. 2004 89 5920 5926 10.1210/jc.2003-03171915579737 Search in Google Scholar

[3] Baillargeon J., Urban R.J., Morgentaler A., Glueck C.J., Baillargeon G., Sharma G., Kuo Y.F..: Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clin. Proc., 2015; 90: 1038–1045 BaillargeonJ. UrbanR.J. MorgentalerA. GlueckC.J. BaillargeonG. SharmaG. KuoY.F.. Risk of venous thromboembolism in men receiving testosterone therapy Mayo Clin. Proc. 2015 90 1038 1045 10.1016/j.mayocp.2015.05.01226205547 Search in Google Scholar

[4] Caminiti G., Volterrani M., Iellamo F., Marazzi G., Massaro R., Miceli M., Mammi C., Piepoli M., Fini M., Rosano G.M.: Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J. Am. Coll. Cardiol., 2009; 54: 919–927 CaminitiG. VolterraniM. IellamoF. MarazziG. MassaroR. MiceliM. MammiC. PiepoliM. FiniM. RosanoG.M. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study J. Am. Coll. Cardiol. 2009 54 919 927 10.1016/j.jacc.2009.04.07819712802 Search in Google Scholar

[5] Chao J.K., Hwang T.I., Ma M.C., Kuo W.H., Liu J.H., Chen Y.P., Lin Y.C.: A survey of obesity and erectile dysfunction of men conscripted into the military in Taiwan. J. Sex. Med., 2011; 8: 1156–1163 ChaoJ.K. HwangT.I. MaM.C. KuoW.H. LiuJ.H. ChenY.P. LinY.C. A survey of obesity and erectile dysfunction of men conscripted into the military in Taiwan J. Sex. Med. 2011 8 1156 1163 10.1111/j.1743-6109.2010.02181.x21269394 Search in Google Scholar

[6] Corona G., Mannucci E., Fisher A.D., Lotti F., Petrone L., Balercia G., Bandini E., Forti G., Maggi M.: Low levels of androgens in men with erectile dysfunction and obesity. J. Sex. Med., 2008; 5: 2454–2463 CoronaG. MannucciE. FisherA.D. LottiF. PetroneL. BalerciaG. BandiniE. FortiG. MaggiM. Low levels of androgens in men with erectile dysfunction and obesity J. Sex. Med. 2008 5 2454 2463 10.1111/j.1743-6109.2008.00856.x18494771 Search in Google Scholar

[7] Corona G., Rastrelli G., Monami M., Melani C., Balzi D., Sforza A., Forti G., Mannucci E., Maggi M.: Body mass index regulates hypogonadism-associated CV risk: Results from a cohort of subjects with erectile dysfunction. J. Sex. Med., 2011; 8: 2098–2105 CoronaG. RastrelliG. MonamiM. MelaniC. BalziD. SforzaA. FortiG. MannucciE. MaggiM. Body mass index regulates hypogonadism-associated CV risk: Results from a cohort of subjects with erectile dysfunction J. Sex. Med. 2011 8 2098 2105 10.1111/j.1743-6109.2011.02292.x21561538 Search in Google Scholar

[8] Coviello A.D., Matsumoto A.M., Bremner W.J., Herbst K.L., Amory J.K., Anawalt B.D., Sutton P.R., Wright W.W., Brown T.R., Yan X., Zirkin B.R., Jarow J.P.: Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J. Clin. Endocrinol. Metab., 2005; 90: 2595–2602 CovielloA.D. MatsumotoA.M. BremnerW.J. HerbstK.L. AmoryJ.K. AnawaltB.D. SuttonP.R. WrightW.W. BrownT.R. YanX. ZirkinB.R. JarowJ.P. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression J. Clin. Endocrinol. Metab. 2005 90 2595 2602 10.1210/jc.2004-080215713727 Search in Google Scholar

[9] Crum-Cianflone N.F., Bavaro M., Hale B., Amling C., Truett A., Brandt C., Pope B., Furtek K., Medina S., Wallace M.R.: Erectile dys-function and hypogonadism among men with HIV. AIDS Patient Care STDS, 2007; 21: 9–19 Crum-CianfloneN.F. BavaroM. HaleB. AmlingC. TruettA. BrandtC. PopeB. FurtekK. MedinaS. WallaceM.R. Erectile dys-function and hypogonadism among men with HIV AIDS Patient Care STDS 2007 21 9 19 10.1089/apc.2006.007117263654 Search in Google Scholar

[10] Dohle G.R., Arver S., Bettocchi C., Jones T.H., Kliesch S.: European association of urology guidelines on male hypogonadism: The 2018 update. https://uroweb.org/guideline/male-hypogonadism/ (05.02.2020) DohleG.R. ArverS. BettocchiC. JonesT.H. KlieschS. European association of urology guidelines on male hypogonadism: The 2018 update https://uroweb.org/guideline/male-hypogonadism/ (05.02.2020) Search in Google Scholar

[11] Finkle W.D., Greenland S., Ridgeway G.K., Adams J.L., Frasco M.A., Cook M.B., Fraumeni J.F.Jr, Hoover R.N.: Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One, 2014; 9: e85805 FinkleW.D. GreenlandS. RidgewayG.K. AdamsJ.L. FrascoM.A. CookM.B. FraumeniJ.F.Jr HooverR.N. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men PLoS One 2014 9 e85805 10.1371/journal.pone.0085805390597724489673 Search in Google Scholar

[12] Ford A.H., Yeap B.B., Flicker L., Hankey G.J., Chubb S.A., Handelsman D.J., Golledge J., Almeida O.P.: Prospective longitudinal study of testosterone and incident depression in older men: The Health In Men Study. Psychoneuroendocrinology, 2016; 64: 57–65 FordA.H. YeapB.B. FlickerL. HankeyG.J. ChubbS.A. HandelsmanD.J. GolledgeJ. AlmeidaO.P. Prospective longitudinal study of testosterone and incident depression in older men: The Health In Men Study Psychoneuroendocrinology 2016 64 57 65 10.1016/j.psyneuen.2015.11.01226615472 Search in Google Scholar

[13] Francomano D., Greco E.A., Lenzi A., Aversa A.: CAG repeat testing of androgen receptor polymorphism: Is this necessary for the best clinical management of hypogonadism? J. Sex. Med., 2013; 10: 2373–2381 FrancomanoD. GrecoE.A. LenziA. AversaA. CAG repeat testing of androgen receptor polymorphism: Is this necessary for the best clinical management of hypogonadism? J. Sex. Med. 2013 10 2373 2381 10.1111/jsm.1226823844628 Search in Google Scholar

[14] Garvey W.T., Mechanick J.I., Brett E.M., Garber A.J., Hurley D.L., Jastreboff A.M., Nadolsky K., Pessah-Pollack R., Plodkowski R., Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines: Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr. Pract., 2016; 22: 1–203 GarveyW.T. MechanickJ.I. BrettE.M. GarberA.J. HurleyD.L. JastreboffA.M. NadolskyK. Pessah-PollackR. PlodkowskiR. Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity Endocr. Pract. 2016 22 1 203 10.4158/EP161365.GL27219496 Search in Google Scholar

[15] Gianatti E.J., Dupuis P., Hoermann R., Zajac J.D., Grossmann M.: Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. J. Clin. Endocrinol. Metab., 2014; 99: 3821–3828 GianattiE.J. DupuisP. HoermannR. ZajacJ.D. GrossmannM. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial J. Clin. Endocrinol. Metab. 2014 99 3821 3828 10.1210/jc.2014-187224978674 Search in Google Scholar

[16] Goodman N., Guay A., Dandona P., Dhindsa S., Faiman C., Cunningham G.R., AACE Reproductive Endocrinology Scientific Committee: American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of testosterone and cardiovascular risk. Endocr. Pract., 2015; 21: 1066–1073 GoodmanN. GuayA. DandonaP. DhindsaS. FaimanC. CunninghamG.R. AACE Reproductive Endocrinology Scientific Committee American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of testosterone and cardiovascular risk Endocr. Pract. 2015 21 1066 1073 10.4158/EP14434.PS26355962 Search in Google Scholar

[17] Halabi S., Collins E.G., Thorevska N., Tobin M.J., Laghi F.: Relationship between depressive symptoms and hypogonadism in men with COPD. COPD, 2011; 8: 346–353 HalabiS. CollinsE.G. ThorevskaN. TobinM.J. LaghiF. Relationship between depressive symptoms and hypogonadism in men with COPD COPD 2011 8 346 353 10.3109/15412555.2011.59446521774576 Search in Google Scholar

[18] Hall S.A., Esche G.R., Araujo A.B., Travison T.G., Clark R.V., Williams R.E., McKinlay J.B.: Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J. Clin. Endocrinol. Metab., 2008; 93: 3870–3877 HallS.A. EscheG.R. AraujoA.B. TravisonT.G. ClarkR.V. WilliamsR.E. McKinlayJ.B. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample J. Clin. Endocrinol. Metab. 2008 93 3870 3877 10.1210/jc.2008-0021257965218664536 Search in Google Scholar

[19] Isidori A.M., Buvat J., Corona G., Goldstein I., Jannini E.A., Lenzi A., Porst H., Salonia A., Traish A.M., Maggi M.: A critical analysis of the role of testosterone in erectile function: From pathophysiology to treatment – A systematic review. Eur. Urol., 2014; 65: 99–112 IsidoriA.M. BuvatJ. CoronaG. GoldsteinI. JanniniE.A. LenziA. PorstH. SaloniaA. TraishA.M. MaggiM. A critical analysis of the role of testosterone in erectile function: From pathophysiology to treatment – A systematic review Eur. Urol. 2014 65 99 112 10.1016/j.eururo.2013.08.04824050791 Search in Google Scholar

[20] Jones T.H., Arver S., Behre H.M., Buvat J., Meuleman E., Moncada I., Morales A.M., Volterrani M., Yellowlees A., Howell J.D., Channer K.S., TIMES2 Investigators.: Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care, 2011; 34: 828–837 JonesT.H. ArverS. BehreH.M. BuvatJ. MeulemanE. MoncadaI. MoralesA.M. VolterraniM. YellowleesA. HowellJ.D. ChannerK.S. TIMES2 Investigators Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study) Diabetes Care 2011 34 828 837 10.2337/dc10-1233306403621386088 Search in Google Scholar

[21] Kamischke A., Kemper D.E., Castel M.A., Lüthke M., Rolf C., Behre H.M., Magnussen H., Nieschlag E.: Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy. Eur. Respir. J., 1998; 11: 41–45 KamischkeA. KemperD.E. CastelM.A. LüthkeM. RolfC. BehreH.M. MagnussenH. NieschlagE. Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy Eur. Respir. J. 1998 11 41 45 10.1183/09031936.98.110100419543268 Search in Google Scholar

[22] Kaplan S.A., Lee J.Y., O’Neill E.A., Meehan A.G., Kusek J.W.: Prevalence of low testosterone and its relationship to body mass index in older men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Aging Male, 2013; 16: 169–172 KaplanS.A. LeeJ.Y. O’NeillE.A. MeehanA.G. KusekJ.W. Prevalence of low testosterone and its relationship to body mass index in older men with lower urinary tract symptoms associated with benign prostatic hyperplasia Aging Male 2013 16 169 172 10.3109/13685538.2013.84478624134648 Search in Google Scholar

[23] Kelsey T.W., Li L.Q., Mitchell R.T., Whelan A., Anderson R.A., Wallace W.H.: A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years. PLoS One, 2014; 9: e109346 KelseyT.W. LiL.Q. MitchellR.T. WhelanA. AndersonR.A. WallaceW.H. A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years PLoS One 2014 9 e109346 10.1371/journal.pone.0109346419017425295520 Search in Google Scholar

[24] Kohn T.P., Louis M.R., Pickett S.M., Lindgren M.C., Kohn J.R., Pastuszak A.W., Lipshultz L.I.: Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertil. Steril., 2017; 107: 351–357 KohnT.P. LouisM.R. PickettS.M. LindgrenM.C. KohnJ.R. PastuszakA.W. LipshultzL.I. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy Fertil. Steril. 2017 107 351 357 10.1016/j.fertnstert.2016.10.004529227627855957 Search in Google Scholar

[25] Malkin C.J., Pugh P.J., West J.N., van Beek E.J., Jones T.H., Channer K.S.: Testosterone therapy in men with moderate severity heart failure: A double-blind randomized placebo controlled trial. Eur. Heart J., 2006; 27: 57–64 MalkinC.J. PughP.J. WestJ.N. van BeekE.J. JonesT.H. ChannerK.S. Testosterone therapy in men with moderate severity heart failure: A double-blind randomized placebo controlled trial Eur. Heart J. 2006 27 57 64 10.1093/eurheartj/ehi44316093267 Search in Google Scholar

[26] Martens H.F., Sheets P.K., Tenover J.S., Dugowson C.E., Bremner W.J., Starkebaum G.: Decreased testosterone levels in men with rheumatoid arthritis: Effect of low dose prednisone therapy. J. Rheumatol., 1994; 21: 1427–1431 MartensH.F. SheetsP.K. TenoverJ.S. DugowsonC.E. BremnerW.J. StarkebaumG. Decreased testosterone levels in men with rheumatoid arthritis: Effect of low dose prednisone therapy J. Rheumatol. 1994 21 1427 1431 Search in Google Scholar

[27] Mateo L., Nolla J.M., Bonnin M.R., Navarro M.A., Roig-Escofet D.: Sex hormone status and bone mineral density in men with rheumatoid arthritis. J. Rheumatol., 1995; 22: 1455–1460 MateoL. NollaJ.M. BonninM.R. NavarroM.A. Roig-EscofetD. Sex hormone status and bone mineral density in men with rheumatoid arthritis J. Rheumatol. 1995 22 1455 1460 Search in Google Scholar

[28] Mazzola C.R., Katz D.J., Loghmanieh N., Nelson C.J., Mulhall J.P..: Predicting biochemical response to clomiphene citrate in men with hypogonadism. J. Sex. Med. 2014; 11: 2302–2307 MazzolaC.R. KatzD.J. LoghmaniehN. NelsonC.J. MulhallJ.P.. Predicting biochemical response to clomiphene citrate in men with hypogonadism J. Sex. Med. 2014 11 2302 2307 10.1111/jsm.1259224902614 Search in Google Scholar

[29] Morgentaler A., Miner M.M., Caliber M., Guay A.T., Khera M., Traish A.M.: Testosterone therapy and cardiovascular risk: Advances and controversies. Mayo Clin. Proc., 2015; 90: 224–251 MorgentalerA. MinerM.M. CaliberM. GuayA.T. KheraM. TraishA.M. Testosterone therapy and cardiovascular risk: Advances and controversies Mayo Clin. Proc. 2015 90 224 251 10.1016/j.mayocp.2014.10.01125636998 Search in Google Scholar

[30] Morgentaler A., Zitzmann M., Traish A.M., Fox A.W., Jones T.H., Maggi M., Arver S., Aversa A., Chan J.C., Dobs A.S., Hackett G.I., Hellstrom W.J., Lim P., Lunenfeld B., Mskhalaya G. i wsp.: Fundamental concepts regarding testosterone deficiency and treatment: International expert consensus resolutions. Mayo Clinic Proc., 2016; 91: 881–896 MorgentalerA. ZitzmannM. TraishA.M. FoxA.W. JonesT.H. MaggiM. ArverS. AversaA. ChanJ.C. DobsA.S. HackettG.I. HellstromW.J. LimP. LunenfeldB. MskhalayaG. Fundamental concepts regarding testosterone deficiency and treatment: International expert consensus resolutions Mayo Clinic Proc. 2016 91 881 896 10.1016/j.mayocp.2016.04.00727313122 Search in Google Scholar

[31] Moskovic D.J., Araujo A.B., Lipshultz L.I., Khera M.: The 20-year public health impact and direct cost of testosterone deficiency in U.S. men. J. Sex. Med., 2013; 10: 562–569 MoskovicD.J. AraujoA.B. LipshultzL.I. KheraM. The 20-year public health impact and direct cost of testosterone deficiency in U.S. men J. Sex. Med. 2013 10 562 569 10.1111/j.1743-6109.2012.02944.x23035926 Search in Google Scholar

[32] Mulhall J.P., Trost L.W., Brannigan R.E., Kurtz E.G., Redmon J.B., Chiles K.A., Lightner D.J., Miner M.M., Murad M.H., Nelson C.J., Platz E.A., Ramanathan L.V., Lewis R.W.: Evaluation and management of testosterone deficiency: AUA guideline. J. Urol., 2018; 200: 423–432 MulhallJ.P. TrostL.W. BranniganR.E. KurtzE.G. RedmonJ.B. ChilesK.A. LightnerD.J. MinerM.M. MuradM.H. NelsonC.J. PlatzE.A. RamanathanL.V. LewisR.W. Evaluation and management of testosterone deficiency: AUA guideline J. Urol. 2018 200 423 432 10.1016/j.juro.2018.03.11529601923 Search in Google Scholar

[33] Mulligan T., Frick M.F., Zuraw Q.C., Stemhagen A., McWhirter C.: Prevalence of hypogonadism in males aged at least 45 years: The HIM study. Int. J. Clin. Pract., 2006; 60: 762–769 MulliganT. FrickM.F. ZurawQ.C. StemhagenA. McWhirterC. Prevalence of hypogonadism in males aged at least 45 years: The HIM study Int. J. Clin. Pract. 2006 60 762 769 10.1111/j.1742-1241.2006.00992.x156944416846397 Search in Google Scholar

[34] Muraleedharan V., Marsh H., Kapoor D., Channer K.S., Jones T.H..: 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: 725–733 MuraleedharanV. MarshH. KapoorD. ChannerK.S. JonesT.H.. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes Eur. J. Endocrinol. 2013 169 725 733 10.1530/EJE-13-032123999642 Search in Google Scholar

[35] Nieschlag E., Bouloux P.G., Stegmann B.J., Shankar R.R., Guan Y., Tzontcheva A., McCrary Sisk C., Behre H.M.: An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism. Reprod. Biol. Endocrinol., 2017; 15: 17 NieschlagE. BoulouxP.G. StegmannB.J. ShankarR.R. GuanY. TzontchevaA. McCrary SiskC. BehreH.M. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism Reprod. Biol. Endocrinol. 2017 15 17 10.1186/s12958-017-0232-y534139028270212 Search in Google Scholar

[36] Nieschlag E., Swerdloff R., Behre H.M., Gooren L.J., Kaufman J.M., Legros J.J., Lunenfeld B., Morley J.E., Schulman C., Wang C., Weidner W., Wu F.C.: Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. Int. J. Androl., 2005; 28: 125–127 NieschlagE. SwerdloffR. BehreH.M. GoorenL.J. KaufmanJ.M. LegrosJ.J. LunenfeldB. MorleyJ.E. SchulmanC. WangC. WeidnerW. WuF.C. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations Int. J. Androl. 2005 28 125 127 10.1111/j.1365-2605.2005.00553.x15910536 Search in Google Scholar

[37] Ohlander S.J., Varghese B., Pastuszak A.: Erythrocytosis following testosterone therapy. Sex. Med. Rev., 2017; 61: 1038–1045 OhlanderS.J. VargheseB. PastuszakA. Erythrocytosis following testosterone therapy Sex. Med. Rev. 2017 61 1038 1045 10.1016/j.sxmr.2017.04.001569089028526632 Search in Google Scholar

[38] Pastuszak A.W., Badhiwala N., Lipshultz L.I. Khera M.: Depression is correlated with the psychological and physical aspects of sexual dysfunction in men. Int. J. Impot. Res., 2013; 25: 194–199 PastuszakA.W. BadhiwalaN. LipshultzL.I. KheraM. Depression is correlated with the psychological and physical aspects of sexual dysfunction in men Int. J. Impot. Res. 2013 25 194 199 10.1038/ijir.2013.423466661 Search in Google Scholar

[39] Pugh P.J., Jones R.D., West J.N., Jones T.H., Channer K.S.: Testosterone treatment for men with chronic heart failure. Heart, 2004; 90: 446–447 PughP.J. JonesR.D. WestJ.N. JonesT.H. ChannerK.S. Testosterone treatment for men with chronic heart failure Heart 2004 90 446 447 10.1136/hrt.2003.014639176816115020527 Search in Google Scholar

[40] Ramasamy R., Scovell J.M., Kovac J.R., Lipshultz L.I.: Testosterone supplementation versus clomiphene citrate for hypogonadism: An age matched comparison of satisfaction and efficacy. J. Urol., 2014; 192: 875–879 RamasamyR. ScovellJ.M. KovacJ.R. LipshultzL.I. Testosterone supplementation versus clomiphene citrate for hypogonadism: An age matched comparison of satisfaction and efficacy J. Urol. 2014 192 875 879 10.1016/j.juro.2014.03.08924657837 Search in Google Scholar

[41] Rao P.M., Kelly D.M., Jones T.H.: Testosterone and insulin resistance in the metabolic syndrome and T2DM in men. Nat. Rev. Endocrinol., 2013; 9: 479–493 RaoP.M. KellyD.M. JonesT.H. Testosterone and insulin resistance in the metabolic syndrome and T2DM in men Nat. Rev. Endocrinol. 2013 9 479 493 10.1038/nrendo.2013.12223797822 Search in Google Scholar

[42] Roberts C.K, Chen B.H., Pruthi S., Lee M.L.: Effects of varying doses of testosterone on atherogenic markers in healthy younger and older men. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2014; 306: R118–R123 RobertsC.K ChenB.H. PruthiS. LeeM.L. Effects of varying doses of testosterone on atherogenic markers in healthy younger and older men Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014 306 R118 R123 10.1152/ajpregu.00372.201324305063 Search in Google Scholar

[43] Saad F., Aversa A., Isidori A.M., Zafalon L., Zitzmann M., Gooren L.: Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur. J. Endocrinol., 2011; 165: 675–685 SaadF. AversaA. IsidoriA.M. ZafalonL. ZitzmannM. GoorenL. Onset of effects of testosterone treatment and time span until maximum effects are achieved Eur. J. Endocrinol. 2011 165 675 685 10.1530/EJE-11-0221318884821753068 Search in Google Scholar

[44] Santos M.R., Sayegh A.L., Groehs R.V., Fonseca G., Trombetta I.C., Barretto A.C., Arap M.A., Negrão C.E., Middlekauff H.R., Alves M.J.: Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure. Arq. Bras. Cardiol., 2015; 105: 256–264 SantosM.R. SayeghA.L. GroehsR.V. FonsecaG. TrombettaI.C. BarrettoA.C. ArapM.A. NegrãoC.E. MiddlekauffH.R. AlvesM.J. Testosterone deficiency increases hospital readmission and mortality rates in male patients with heart failure Arq. Bras. Cardiol. 2015 105 256 264 10.5935/abc.20150078459217426200897 Search in Google Scholar

[45] Sato Y., Tanda H., Kato S., Onishi S., Nakajima H., Nanbu A., Nitta T., Koroku M., Akagashi K., Hanzawa T.: Prevalence of major depressive disorder in self-referred patients in a late onset hypogonadism clinic. Int. J. Impot. Res., 2007; 19: 407–410 SatoY. TandaH. KatoS. OnishiS. NakajimaH. NanbuA. NittaT. KorokuM. AkagashiK. HanzawaT. Prevalence of major depressive disorder in self-referred patients in a late onset hypogonadism clinic Int. J. Impot. Res. 2007 19 407 410 10.1038/sj.ijir.390155117460698 Search in Google Scholar

[46] Sharma R., Oni O.A., Chen G., Sharma M., Dawn B., Sharma R., Parashara D., Savin V.J., Barua R.S., Gupta K.: Association between testosterone replacement therapy and the incidence of DVT and pulmonary embolism: A retrospective cohort study of the veterans administration database. Chest, 2016; 150: 563–571 SharmaR. OniO.A. ChenG. SharmaM. DawnB. SharmaR. ParasharaD. SavinV.J. BaruaR.S. GuptaK. Association between testosterone replacement therapy and the incidence of DVT and pulmonary embolism: A retrospective cohort study of the veterans administration database Chest 2016 150 563 571 10.1016/j.chest.2016.05.00727179907 Search in Google Scholar

[47] Stanworth R.D., Akhtar S., Channer K.S., Jones T.H.: The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: TIMES2 sub-study. Eur. J. Endocrinol., 2013; 170: 193–200 StanworthR.D. AkhtarS. ChannerK.S. JonesT.H. The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: TIMES2 sub-study Eur. J. Endocrinol. 2013 170 193 200 10.1530/EJE-13-070324165020 Search in Google Scholar

[48] Sussman E.M., Chudnovsky A., Niederberger C.S.: Hormonal evaluation of the infertile male: Has it evolved? Urol. Clin. North Am., 2008; 35: 147–155 SussmanE.M. ChudnovskyA. NiederbergerC.S. Hormonal evaluation of the infertile male: Has it evolved? Urol. Clin. North Am. 2008 35 147 155 10.1016/j.ucl.2008.01.01018423236 Search in Google Scholar

[49] Taylor F., Levine L.: Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: Efficacy and treatment cost. J. Sex. Med., 2010; 7: 269–276 TaylorF. LevineL. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: Efficacy and treatment cost J. Sex. Med. 2010 7 269 276 10.1111/j.1743-6109.2009.01454.x19694928 Search in Google Scholar

[50] Vandenput L., Mellström D., Karlsson M.K., Orwoll E., Labrie F., Ljunggren Ö., Ohlsson C.: Serum estradiol is associated with lean mass in elderly Swedish men. Eur. J. Endocrinol., 2010; 162: 737–745 VandenputL. MellströmD. KarlssonM.K. OrwollE. LabrieF. LjunggrenÖ. OhlssonC. Serum estradiol is associated with lean mass in elderly Swedish men Eur. J. Endocrinol. 2010 162 737 745 10.1530/EJE-09-069620061331 Search in Google Scholar

[51] Vigen R., O’Donnell C.I., Barón A.E., Grunwald G.K., Maddox T.M., Bradley S.M., Barqawi A., Woning G., Wierman M.E., Plomondon M.E., Rumsfeld J.S., Ho P.M.: Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA, 2013; 310: 1829–1836 VigenR. O’DonnellC.I. BarónA.E. GrunwaldG.K. MaddoxT.M. BradleyS.M. BarqawiA. WoningG. WiermanM.E. PlomondonM.E. RumsfeldJ.S. HoP.M. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels JAMA 2013 310 1829 1836 10.1001/jama.2013.28038624193080 Search in Google Scholar

[52] Wang C., Nieschlag E., Swerdloff R., Behre H.M., Hellstrom W.J., Gooren L.J., Kaufman J.M., Legros J.J., Lunenfeld B., Morales A., Morley J.E., Schulman C., Thompson I.M., Weidner W., Wu F.C. i wsp.: Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur. Urol., 2009; 55: 121–130 WangC. NieschlagE. SwerdloffR. BehreH.M. HellstromW.J. GoorenL.J. KaufmanJ.M. LegrosJ.J. LunenfeldB. MoralesA. MorleyJ.E. SchulmanC. ThompsonI.M. WeidnerW. WuF.C. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations Eur. Urol. 2009 55 121 130 10.1016/j.eururo.2008.08.03318762364 Search in Google Scholar

[53] Wenker E.P., Dupree J.M., Langille G.M., Kovac J., Ramasamy R., Lamb D., Mills J.N., Lipshultz L.I.: The use of HCG-based combination therapy for recovery of spermatogenesis after testosterone use. J. Sex. Med., 2015; 12: 1334–1337 WenkerE.P. DupreeJ.M. LangilleG.M. KovacJ. RamasamyR. LambD. MillsJ.N. LipshultzL.I. The use of HCG-based combination therapy for recovery of spermatogenesis after testosterone use J. Sex. Med. 2015 12 1334 1337 10.1111/jsm.1289025904023 Search in Google Scholar

[54] Wiehle R., Cunningham G.R., Pitteloud N., Wike J., Hsu K., Fontenot G.K., Rosner M., Dwyer A., Podolski J.: Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: Pharmacodynamics and pharmacokinetics. BJU Int., 2013; 112: 1188–1200 WiehleR. CunninghamG.R. PitteloudN. WikeJ. HsuK. FontenotG.K. RosnerM. DwyerA. PodolskiJ. Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: Pharmacodynamics and pharmacokinetics BJU Int. 2013 112 1188 1200 10.1111/bju.12363 Search in Google Scholar

[55] Wiehle R.D., Fontenot G.K., Michael M.S., Willett M.S., Garcia W.D., Podolski J.S.: Enclomiphene citrate stimulates serum testosterone in men with low testosterone within 14 days. J. Men’s Health, 2014; 11: 196–205 WiehleR.D. FontenotG.K. MichaelM.S. WillettM.S. GarciaW.D. PodolskiJ.S. Enclomiphene citrate stimulates serum testosterone in men with low testosterone within 14 days J. Men’s Health 2014 11 196 205 10.1089/jomh.2014.0006 Search in Google Scholar

[56] Wiehle R.D., Fontenot G.K., Wike J., Hsu K., Nydell J., Lipshultz L., ZA-203 Clinical Study Group: Enclomiphene citrate stimulates testosterone production while preventing oligospermia: A randomized phase II clinical trial comparing topical testosterone. Fertil. Steril., 2014; 102: 720–727 WiehleR.D. FontenotG.K. WikeJ. HsuK. NydellJ. LipshultzL. ZA-203 Clinical Study Group Enclomiphene citrate stimulates testosterone production while preventing oligospermia: A randomized phase II clinical trial comparing topical testosterone Fertil. Steril. 2014 102 720 727 10.1016/j.fertnstert.2014.06.004 Search in Google Scholar

[57] World Health Organization Task Force on Methods for the Regulation of Male Fertility: Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil. Steril., 1996; 65: 821–829 World Health Organization Task Force on Methods for the Regulation of Male Fertility Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men Fertil. Steril. 1996 65 821 829 10.1016/S0015-0282(16)58221-1 Search in Google Scholar

[58] Wu F.C., Tajar A., Beynon J.M., Pye S.R., Silman A.J., Finn J.D., O’Neill T.W., Bartfai G., Casanueva F.F., Forti G., Giwercman A., Han T.S., Kula K., Lean M.E., Pendleton N. i wsp.: Identification of late-onset hypogonadism in middle-aged and elderly men. N. Engl. J. Med., 2010; 363: 123–135 WuF.C. TajarA. BeynonJ.M. PyeS.R. SilmanA.J. FinnJ.D. O’NeillT.W. BartfaiG. CasanuevaF.F. FortiG. GiwercmanA. HanT.S. KulaK. LeanM.E. PendletonN. Identification of late-onset hypogonadism in middle-aged and elderly men N. Engl. J. Med. 2010 363 123 135 10.1056/NEJMoa091110120554979 Search in Google Scholar

[59] Xu L., Freeman G., Cowling B.J., Schooling C.M.: Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med., 2013; 11: 108 XuL. FreemanG. CowlingB.J. SchoolingC.M. Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled randomized trials BMC Med. 2013 11 108 10.1186/1741-7015-11-108364845623597181 Search in Google Scholar

[60] Zitzmann M., Mattern A., Hanisch J., Gooren L., Jones H., Maggi M.: IPASS: A study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men. J. Sex. Med., 2013; 10: 579–588 ZitzmannM. MatternA. HanischJ. GoorenL. JonesH. MaggiM. IPASS: A study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men J. Sex. Med. 2013 10 579 588 10.1111/j.1743-6109.2012.02853.x22812645 Search in Google Scholar