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Chapter 32 - Hypogonadism in the Male

Evaluation and Treatment

from Section 5 - Medical and Surgical Management of Issues of Male Health

Published online by Cambridge University Press:  06 December 2023

By
Parviz K. Kavoussi  and
G. Luke Machen
Edited by
Douglas T. Carrell ,
Alexander W. Pastuszak  and
James M. Hotaling
Douglas T. Carrell
Affiliation:
Utah Center for Reproductive Medicine
Alexander W. Pastuszak
Affiliation:
University of Utah
James M. Hotaling
Affiliation:
Utah Center for Reproductive Medicine
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Summary

Knowledge of the anatomy and physiology of the hypothalamic-pituitary-gonadal axis is paramount for the understanding and management of hypogonadism in men. Although the definition of hypogonadism may seem elusive, there is a framework to assist with the diagnosis once a history, physical examination, and appropriate lab testing are obtained. There are a number of treatment options to consider with their associated risks and benefits.

Keywords

hypogonadismhypothalamic-pituitary-gonadal axistestosterone
Type
Chapter
Information
Men's Reproductive and Sexual Health Throughout the Lifespan
An Integrated Approach to Fertility, Sexual Function, and Vitality
 , pp. 251 - 263
Publisher: Cambridge University Press
Print publication year: 2023

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References

Krsmanovic, LZ, Hu, L, Leung, PK, Feng, H, Catt, KJ. The hypothalamic GnRH pulse generator: multiple regulatory mechanisms. Trends Endocrinol Metab. 2009;20(8):402–408.CrossRefGoogle ScholarPubMed
Dufau, ML, Catt, KJ. Gonadotropin receptors and regulation of steroidogenesis in the testis and ovary. Vitam Horm. 1978;36:461–592.CrossRefGoogle ScholarPubMed
Wahlstrom, T, Huhtaniemi, I, Hovatta, O, Seppala, M. Localization of luteinizing hormone, follicle-stimulating hormone, prolactin, and their receptors in human and rat testis using immunohistochemistry and radioreceptor assay. J Clin Endocrinol Metab. 1983;57(4):825–830.Google Scholar
Hayes, FJ, Seminara, SB, Decruz, S, Boepple, PA, Crowley, WF, Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab. 2000;85(9):3027–3035.Google Scholar
Morishima, A, Grumbach, MM, Simpson, ER, Fisher, C, Qin, K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995;80(12):3689–3698.Google ScholarPubMed
Matsumoto, AM, Bremner, WJ. Modulation of pulsatile gonadotropin secretion by testosterone in man. J Clin Endocrinol Metab. 1984;58(4):609–614.Google Scholar
Sheckter, CB, Matsumoto, AM, Bremner, WJ. Testosterone administration inhibits gonadotropin secretion by an effect directly on the human pituitary. J Clin Endocrinol Metab. 1989;68(2):397–401.Google Scholar
Anawalt, BD, Bebb, RA, Matsumoto, AM, et al. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction. J Clin Endocrinol Metab. 1996;81(9):3341–3345.Google Scholar
O’Connor, AE, De Kretser, DM. Inhibins in normal male physiology. Semin Reprod Med. 2004;22(3):177–185.CrossRefGoogle ScholarPubMed
Stocco, DM, Clark, BJ. The role of the steroidogenic acute regulatory protein in steroidogenesis. Steroids. 1997;62(1):29–36.Google Scholar
Winters, SJ, Troen, P. Testosterone and estradiol are co-secreted episodically by the human testis. J Clin Invest. 1986;78(4):870–873.Google Scholar
Axelsson, J, Ingre, M, Akerstedt, T, Holmback, U. Effects of acutely displaced sleep on testosterone. J Clin Endocrinol Metab. 2005;90(8):4530–4535.Google Scholar
Saez, JM. Leydig cells: endocrine, paracrine, and autocrine regulation. Endocr Rev. 1994;15(5):574–626.CrossRefGoogle ScholarPubMed
Jarow, JP, Zirkin, BR. The androgen microenvironment of the human testis and hormonal control of spermatogenesis. Ann N Y Acad Sci. 2005;1061:208–220.CrossRefGoogle ScholarPubMed
Federman, DD. The biology of human sex differences. N Engl J Med. 2006;354(14):1507–1514.Google Scholar
Russell, DW, Wilson, JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25–61.Google Scholar
Mahendroo, MS, Mendelson, CR, Simpson, ER. Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem. 1993;268(26):19463–19470.Google Scholar
Dunn, JF, Nisula, BC, Rodbard, D. Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab. 1981;53(1):58–68.Google Scholar
Mulhall JP, TL, Brannigan, RE, Kurtz, EG, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200:423–432.Google Scholar
Wang, C, Nieschlag, E, Swerdloff, R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009;30(1):1–9.Google Scholar
Emmelot-Vonk, MH, Verhaar, HJ, Nakhai-Pour, HR, Grobbee, DE, van der Schouw, YT. Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males’ Symptoms rating scale (AMS) questionnaires. Clin Endocrinol (Oxf). 2011;74(4):488–494.CrossRefGoogle Scholar
Zitzmann, M. Pharmacogenetics of testosterone replacement therapy. Pharmacogenomics. 2009;10(8):1341–1349.CrossRefGoogle ScholarPubMed
Corona, G, Rastrelli, G, Forti, G, Maggi, M. Update in testosterone therapy for men. J Sex Med. 2011;8(3):639–654; quiz 655.Google Scholar
Diver, MJ, Imtiaz, KE, Ahmad, AM, Vora, JP, Fraser, WD. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol (Oxf). 2003;58(6):710–717.Google Scholar
Wu, FC, Tajar, A, Beynon, JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123–135.Google Scholar
Bhasin, S, Pencina, M, Jasuja, GK, et al. Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts. J Clin Endocrinol Metab. 2011;96(8):2430–2439.Google Scholar
Vesper, HW, Bhasin, S, Wang, C, et al. Interlaboratory comparison study of serum total testosterone [corrected] measurements performed by mass spectrometry methods. Steroids. 2009;74(6):498–503.CrossRefGoogle ScholarPubMed
Petak, SM, Nankin, HR, Spark, RF, et al. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients – 2002 update. Endocr Pract. 2002;8(6):440–456.Google Scholar
Mulligan, T, Frick, MF, Zuraw, QC, Stemhagen, A, McWhirter, C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60(7):762–769.Google Scholar
Lewis, RW, Mills, TM. Effect of androgens on penile tissue. Endocrine. 2004;23(2–3):101–105.Google Scholar
Morelli, A, Filippi, S, Mancina, R, et al. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology. 2004;145(5):2253–2263.Google Scholar
Podlasek, CA, Mulhall, J, Davies, K, et al. Translational perspective on the role of testosterone in sexual function and dysfunction. J Sex Med. 2016;13(8):1183–1198.CrossRefGoogle Scholar
Traish, AM, Park, K, Dhir, V, Kim, NN, Moreland, RB, Goldstein, I. Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology. 1999;140(4):1861–1868.Google Scholar
Davila, HH, Rajfer, J, Gonzalez-Cadavid, NF. Corporal veno-occlusive dysfunction in aging rats: evaluation by cavernosometry and cavernosography. Urology. 2004;64(6):1261–1266.Google Scholar
Swaab, DF. Sexual differentiation of the brain and behavior. Best Pract Res Clin Endocrinol Metab. 2007;21(3):431–444.Google Scholar
Azad, N, Pitale, S, Barnes, WE, Friedman, N. Testosterone treatment enhances regional brain perfusion in hypogonadal men. J Clin Endocrinol Metab. 2003;88(7):3064–3068.Google Scholar
Hoffman, RM, Hunt, WC, Gilliland, FD, Stephenson, RA, Potosky, AL. Patient satisfaction with treatment decisions for clinically localized prostate carcinoma: results from the Prostate Cancer Outcomes Study. Cancer. 2003;97(7):1653–1662.Google Scholar
Potosky, AL, Reeve, BB, Clegg, LX, et al. Quality of life following localized prostate cancer treated initially with androgen deprivation therapy or no therapy. J Natl Cancer Inst. 2002;94(6):430–437.CrossRefGoogle ScholarPubMed
Ng, E, Woo, HH, Turner, S, Leong, E, Jackson, M, Spry, N. The influence of testosterone suppression and recovery on sexual function in men with prostate cancer: observations from a prospective study in men undergoing intermittent androgen suppression. J Urol. 2012;187(6):2162–2166.Google Scholar
Corona, G, Isidori, AM, Buvat, J, et al. Testosterone supplementation and sexual function: a meta-analysis study. J Sex Med. 2014;11(6):1577–1592.Google Scholar
Corona, G, Rastrelli, G, Morgentaler, A, Sforza, A, Vannucci, E, Maggi, M. Meta-analysis of results of testosterone therapy on sexual function based on international index of erectile function scores. Eur Urol. 2017;72(6):1000–1011.Google Scholar
Rastrelli, G, Guaraldi, F, Reismann, Y, et al. Testosterone replacement therapy for sexual symptoms. Sex Med Rev. 2019;7(3):464–475.Google Scholar
Maggi, M, Heiselman, D, Knorr, J, Iyengar, S, Paduch, DA, Donatucci, CF. Impact of testosterone solution 2% on ejaculatory dysfunction in hypogonadal men. J Sex Med. 2016;13(8):1220–1226.CrossRefGoogle ScholarPubMed
Nieschlag, E, Nieschlag, S. ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019;180(6):R201–R212.Google Scholar
Swerdloff, RS, Dudley, RE. A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men. Ther Adv Urol. 2020;12:1756287220937232.Google Scholar
Giagulli, VA, Triggiani, V, Corona, G, et al. Evidence-based medicine update on testosterone replacement therapy (TRT) in male hypogonadism: focus on new formulations. Curr Pharm Des. 2011;17(15):1500–1511.CrossRefGoogle ScholarPubMed
Banks, WA, Morley, JE, Niehoff, ML, Mattern, C. Delivery of testosterone to the brain by intranasal administration: comparison to intravenous testosterone. J Drug Target. 2009;17(2):91–97.CrossRefGoogle Scholar
Rogol, AD, Tkachenko, N, Badorrek, P, Hohlfeld, JM, Bryson, N. Phase 1 pharmacokinetics and phase 3 efficacy of testosterone nasal gel in subjects with seasonal allergies. Can Urol Assoc J. 2018;12(7):E349–E356.Google Scholar
Zitzmann, M, Nieschlag, E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol. 2000;161(1–2):73–88.Google Scholar
Wang, C, Harnett, M, Dobs, AS, Swerdloff, RS. Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial. J Androl. 2010;31(5):457–465.Google Scholar
Kaminetsky, JC, McCullough, A, Hwang, K, Jaffe, JS, Wang, C, Swerdloff, RS. A 52-week study of dose adjusted subcutaneous testosterone enanthate in oil self-administered via disposable auto-injector. J Urol. 2019;201(3):587–594.CrossRefGoogle ScholarPubMed
Snyder, PJ, Peachey, H, Berlin, JA, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000;85(8):2670–2677.Google Scholar
Bhasin, S, Basaria, S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab. 2011;25(2):251–270.Google Scholar
Wang, C, Swerdloff, RS, Iranmanesh, A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab. 2000;85(8):2839–2853.Google Scholar
Carani, C, Scuteri, A, Marrama, P, Bancroft, J. The effects of testosterone administration and visual erotic stimuli on nocturnal penile tumescence in normal men. Horm Behav. 1990;24(3):435–441.Google Scholar
Cunningham, GR, Hirshkowitz, M, Korenman, SG, Karacan, I. Testosterone replacement therapy and sleep-related erections in hypogonadal men. J Clin Endocrinol Metab. 1990;70(3):792–797.Google Scholar
Isidori, AM, Giannetta, E, Greco, EA, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63(3):280–293.Google Scholar
Srinivas-Shankar, U, Roberts, SA, Connolly, MJ, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010;95(2):639–650.Google Scholar
Basaria, S, Coviello, AD, Travison, TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109–122.CrossRefGoogle ScholarPubMed
Zarrouf, FA, Artz, S, Griffith, J, Sirbu, C, Kommor, M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;15(4):289–305.CrossRefGoogle ScholarPubMed
Cunningham, GR, Toma, SM. Clinical review: Why is androgen replacement in males controversial? J Clin Endocrinol Metab. 2011;96(1):38–52.Google Scholar
Sih, R, Morley, JE, Kaiser, FE, Perry, HM, 3rd, Patrick, P, Ross, C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab. 1997;82(6):1661–1667.Google Scholar
Coviello, AD, Kaplan, B, Lakshman, KM, Chen, T, Singh, AB, Bhasin, S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914–919.Google Scholar
Hanafy, HM. Testosterone therapy and obstructive sleep apnea: is there a real connection? J Sex Med. 2007;4(5):1241–1246.Google Scholar
Guay, AT, Jacobson, J, Perez, JB, Hodge, MB, Velasquez, E. Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit? Int J Impot Res. 2003;15(3):156–165.Google Scholar
Katz, DJ, Nabulsi, O, Tal, R, Mulhall, JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012;110(4):573–578.Google Scholar
Krzastek, SC, Sharma, D, Abdullah, N, et al. Long-term safety and efficacy of clomiphene citrate for the treatment of hypogonadism. J Urol. 2019;202(5):1029–1035.Google Scholar
Wheeler, KM, Sharma, D, Kavoussi, PK, Smith, RP, Costabile, R. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev. 2019;7(2):272–276.Google Scholar
Delemarre, EM, Felius, B, Delemarre-van de Waal, HA. Inducing puberty. Eur J Endocrinol. 2008;159(Suppl. 1):S9–S15.Google Scholar
Buchter, D, Behre, HM, Kliesch, S, Nieschlag, E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol. 1998;139(3):298–303.Google Scholar
Raman, JD, Schlegel, PN. Aromatase inhibitors for male infertility. J Urol. 2002;167(2 Pt 1):624–629.Google Scholar
Dadhich, P, Ramasamy, R, Scovell, J, Wilken, N, Lipshultz, L. Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men. Indian J Urol. 2017;33(3):236–240.CrossRefGoogle ScholarPubMed
Ramasamy, R, Masterson, TA, Best, JC, et al. Effect of Natesto on reproductive hormones, semen parameters and hypogonadal symptoms: a single center, open label, single arm trial. J Urol. 2020;204(3):557–563.Google Scholar
Kavoussi, PK MG, Gilkey, M, Hunn, C, et al. Converting men from clomiphene citrate to Natesto for hypogonadism improves libido, maintains semen parameters, and reduces estradiol. Urology. 2021;148:141–144.Google Scholar
Tanrikut, C, Goldstein, M, Rosoff, JS, Lee, RK, Nelson, CJ, Mulhall, JP. Varicocele as a risk factor for androgen deficiency and effect of repair. BJU Int. 2011;108(9):1480–1484.Google Scholar
Li, F, Yue, H, Yamaguchi, K, et al. Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis. Int J Urol. 2012;19(2):149–154.Google Scholar
Chen, X, Yang, D, Lin, G, Bao, J, Wang, J, Tan, W. Efficacy of varicocelectomy in the treatment of hypogonadism in subfertile males with clinical varicocele: a meta-analysis. Andrologia. 2017;49(10):e12778. https://doi.org/10.1111/and.12778.Google Scholar
Ahmed, AF, Abdel-Aziz, AS, Maarouf, AM, Ali, M, Emara, AA, Gomaa, A. Impact of varicocelectomy on premature ejaculation in varicocele patients. Andrologia. 2015;47(3):276–281.Google Scholar
Abdel-Meguid, TA, Farsi, HM, Al-Sayyad, A, Tayib, A, Mosli, HA, Halawani, AH. Effects of varicocele on serum testosterone and changes of testosterone after varicocelectomy: a prospective controlled study. Urology. 2014;84(5):1081–1087.CrossRefGoogle ScholarPubMed
Zohdy, W, Ghazi, S, Arafa, M. Impact of varicocelectomy on gonadal and erectile functions in men with hypogonadism and infertility. J Sex Med. 2011;8(3):885–893.Google Scholar
Najari, BB, Introna, L, Paduch, DA. Improvements in patient-reported sexual function after microsurgical varicocelectomy. Urology. 2017;110:104–109.Google Scholar
Huggins, C. Effect of orchiectomy and irradiation on cancer of the prostate. Ann Surg. 1942;115(6):1192–1200.Google Scholar
Morgentaler, A, Traish, A. The history of testosterone and the evolution of its therapeutic potential. Sex Med Rev. 2020;8(2):286–296.Google Scholar
Roddam, AW, Allen, NE, Appleby, P, Key, TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008;100(3):170–183.Google Scholar
Marks, LS, Mazer, NA, Mostaghel, E, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA. 2006;296(19):2351–2361.Google Scholar
Khera, M, Bhattacharya, RK, Blick, G, Kushner, H, Nguyen, D, Miner, MM. Changes in prostate specific antigen in hypogonadal men after 12 months of testosterone replacement therapy: support for the prostate saturation theory. J Urol. 2011;186(3):1005–1011.Google Scholar
Davidson, E, Morgentaler, A. Testosterone therapy and prostate cancer. Urol Clin North Am. 2016;43(2):209–216.Google Scholar
Morgentaler, A, Traish, AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55(2):310–320.Google Scholar
Wallis, CJ, Lo, K, Lee, Y, et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol. 2016;4(6):498–506.Google Scholar
Thompson, IM, Pauler, DK, Goodman, PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004;350(22):2239–2246.Google Scholar
Salonia, A, Abdollah, F, Capitanio, U, et al. Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy. Clin Cancer Res. 2012;18(13):3648–3657.Google Scholar
San Francisco, IF, Rojas, PA, DeWolf, WC, Morgentaler, A. Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int. 2014;114(2):229–235.Google Scholar
Leon, P, Seisen, T, Cussenot, O, et al. Low circulating free and bioavailable testosterone levels as predictors of high-grade tumors in patients undergoing radical prostatectomy for localized prostate cancer. Urol Oncol. 2015;33(9):384.e21–27.Google Scholar
Ahlering, TE, My Huynh, L, Towe, M, et al. Testosterone replacement therapy reduces biochemical recurrence after radical prostatectomy. BJU Int. 2020;126(1):91–96.Google Scholar
Sarosdy, MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer. 2007;109(3):536–541.Google Scholar
Balbontin, FG, Moreno, SA, Bley, E, Chacon, R, Silva, A, Morgentaler, A. Long-acting testosterone injections for treatment of testosterone deficiency after brachytherapy for prostate cancer. BJU Int. 2014;114(1):125–130.Google Scholar
Pastuszak, AW, Khanna, A, Badhiwala, N, et al. Testosterone therapy after radiation therapy for low, intermediate and high risk prostate cancer. J Urol. 2015;194(5):1271–1276.Google Scholar
Kacker, R, Hult, M, San Francisco, IF, et al. Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results. Asian J Androl. 2016;18(1):16–20.Google Scholar
Morgentaler, A, Lipshultz, LI, Bennett, R, Sweeney, M, Avila, D, Jr., Khera, M. Testosterone therapy in men with untreated prostate cancer. J Urol. 2011;185(4):1256–1260.Google Scholar
Debruyne, FM, Behre, HM, Roehrborn, CG, et al. Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men. BJU Int. 2017;119(2):216–224.Google Scholar
Kohn, TP, Mata, DA, Ramasamy, R, Lipshultz, LI. Effects of testosterone replacement therapy on lower urinary tract symptoms: a systematic review and meta-analysis. Eur Urol. 2016;69(6):1083–1090.Google Scholar
Yabe, S, Kato, H, Mizukawa, S, et al. Predictive factors for outcomes of patients undergoing endoscopic therapy for bile leak after hepatobiliary surgery. Dig Endosc. 2017;29(3):353–361.Google Scholar
LeBrasseur, NK, Lajevardi, N, Miciek, R, Mazer, N, Storer, TW, Bhasin, S. Effects of testosterone therapy on muscle performance and physical function in older men with mobility limitations (the TOM trial): design and methods. Contemp Clin Trials. 2009;30(2):133–140.Google Scholar
Vigen, R, O’Donnell, CI, Baron, AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829–1836.Google Scholar
Traish, AM, Guay, AT, Morgentaler, A. Death by testosterone? We think not! J Sex Med. 2014;11(3):624–629.Google Scholar
Ho, PM, Baron, AE, Wierman, ME. Deaths and cardiovascular events in men receiving testosterone: reply. JAMA. 2014;311(9):964–965.Google Scholar
Finkle, WD, Greenland, S, Ridgeway, GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE. 2014;9(1):e85805.Google Scholar
Morgentaler, A, Miner, MM, Caliber, M, Guay, AT, Khera, M, Traish, AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90(2):224–251.Google Scholar
Ohlsson, C, Barrett-Connor, E, Bhasin, S, et al. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. J Am Coll Cardiol. 2011;58(16):1674–1681.Google Scholar
Araujo, AB, Dixon, JM, Suarez, EA, Murad, MH, Guey, LT, Wittert, GA. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(10):3007–3019.Google Scholar
Bojesen, A, Juul, S, Gravholt, CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003;88(2):622–626.Google Scholar
Fruhmesser, A, Kotzot, D. Chromosomal variants in Klinefelter syndrome. Sex Dev. 2011;5(3):109–123.Google Scholar
Hotaling, JM. Genetics of male infertility. Urol Clin North Am. 2014;41(1):1–17.Google Scholar
Ross, A, Bhasin, S. Hypogonadism: its prevalence and diagnosis. Urol Clin North Am. 2016;43(2):163–176.Google Scholar
Loebenstein, M, Thorup, J, Cortes, D, Clasen-Linde, E, Hutson, JM, Li, R. Cryptorchidism, gonocyte development, and the risks of germ cell malignancy and infertility: a systematic review. J Pediatr Surg. 2020;55(7):1201–1210.Google Scholar
Rochira, V, Diazzi, C, Santi, D, et al. Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study. Andrology. 2015;3(2):298–308.Google Scholar
Zaid, MIA, Menendez, AG, Charif, OE, et al. Adverse health outcomes in relationship to hypogonadism (HG) after platinum-based chemotherapy: a multicenter study of North American testicular cancer survivors (TCS). J Clin Oncol. 2017;35(18_suppl):LBA10012–LBA10012.Google Scholar
Dode, C, Hardelin, JP. Kallmann syndrome. Eur J Hum Genet. 2009;17(2):139–146.Google Scholar
Fechner, A, Fong, S, McGovern, P. A review of Kallmann syndrome: genetics, pathophysiology, and clinical management. Obstet Gynecol Surv. 2008;63(3):189–194.CrossRefGoogle ScholarPubMed
Hardelin, JP, Dode, C. The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Sex Dev. 2008;2(4–5):181–193.Google Scholar
Smeets, DF, Hamel, BC, Nelen, MR, et al. Prader-Willi syndrome and Angelman syndrome in cousins from a family with a translocation between chromosomes 6 and 15. N Engl J Med. 1992;326(12):807–811.Google Scholar
de Vries, F, Bruin, M, Lobatto, DJ, et al. Opioids and their endocrine effects: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2020;105(4):1020–1029.Google Scholar
Rasmussen, JJ, Selmer, C, Ostergren, PB, et al. Former abusers of anabolic androgenic steroids exhibit decreased testosterone levels and hypogonadal symptoms years after cessation: a case-control study. PLoS ONE. 2016;11(8):e0161208.Google Scholar
Buvat, J. Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. 2003;15(5):373–377.Google Scholar
Carter, JN, Tyson, JE, Tolis, G, Van Vliet, S, Faiman, C, Friesen, HG. Prolactin-screening tumors and hypogonadism in 22 men. N Engl J Med. 1978;299(16):847–852.Google Scholar
Patel, SS, Bamigboye, V. Hyperprolactinaemia. J Obstet Gynaecol. 2007;27(5):455–459.Google Scholar
Corona, G, Monami, M, Rastrelli, G, et al. Testosterone and metabolic syndrome: a meta-analysis study. J Sex Med. 2011;8(1):272–283.Google Scholar
Wu, FC, Tajar, A, Pye, SR, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93(7):2737–2745.Google Scholar
Feldman, HA, Longcope, C, Derby, CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002;87(2):589–598.Google Scholar
Fink, HA, Ewing, SK, Ensrud, KE, et al. Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab. 2006;91(10):3908–3915.Google Scholar
Diem, SJ, Greer, NL, MacDonald, R, et al. Efficacy and safety of testosterone treatment in men: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2020;172(2):105–118.Google Scholar

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