Male hypogonadism with its systemic complications
DOI:
https://doi.org/10.12775/JEHS.2020.10.09.020Keywords
hypogonadism, systemic complications, prostate cancer, cardiovascular risk, metabolic syndromeAbstract
Introduction and purpose: Total lack of testosterone or its level lower than 9-12 mmol/L (250-350 ng/dL) of serum in men is called hypogonadism. Due to the importance of testosterone in male body, hypogonadism usually causes a variety of symptoms, mostly of sexual nature – lack of libido, erectile dysfunction, infertility and associated psychological problems, it can though be the cause of more dangerous changes in the male body. The purpose of this study is to review possible systemic complications of male hypogonadism (with the emphasis on hypogonadotropic hypogonadism) apart from those sex-related.
State of knowledge: The lack of testosterone and gonadotropins was proven to cause a number of negative changes in different systems and various clinical situations. It can negatively impact the condition of skeletal system. Although testosterone is widely thought to increase cardiovascular risk some studies show that the hypogonadism has a negative impact on it as well. Some studies hypothesised the role of hypogonadism in anaemia development, but generally it isn’t taken into account in investigation of this condition. Some studies show the impact of hypogonadism on higher risk of some metabolic and endocrine diseases. The most interesting conclusions were found in literature on oncological implications of testosterone and lack of it. It turns out that there is a number of studies showing the positive impact of relatively higher testosterone concentrations while androgen deprivation therapy is the main therapeutic option in advanced prostate cancer.
Conclusions: Due to very unpleasant and possibly dangerous complications of hypogonadism endocrinologists should stay alert to signs of hypogonadism to be able to start testosterone replacement in the right moment.
References
A. W. Tiegs, J. Landis, N. Garrido, R. T. Scott, and J. M. Hotaling, ‘Total Motile Sperm Count Trend Over Time: Evaluation of Semen Analyses From 119,972 Men From Subfertile Couples’, Urology, vol. 132, pp. 109–116, 2019, doi: 10.1016/j.urology.2019.06.038.
H. Levine et al., ‘Temporal trends in sperm count: a systematic review and meta-regression analysis’, Hum. Reprod. Update, vol. 23, no. 6, pp. 646–659, 01 2017, doi: 10.1093/humupd/dmx022.
J.-F. Chen, P.-W. Lin, Y.-R. Tsai, Y.-C. Yang, and H.-Y. Kang, “Androgens and Androgen Receptor Actions on Bone Health and Disease: From Androgen Deficiency to Androgen Therapy,” Cells, vol. 8, no. 11, p. 1318, Oct. 2019.
S. Movérare et al., “Differential effects on bone of estrogen receptor α and androgen receptor activation in orchidectomized adult male mice,” Proc. Natl. Acad. Sci. U. S. A., vol. 100, no. 23, pp. 13573–13578, Nov. 2003.
E. Seeman, “Sexual Dimorphism in Skeletal Size, Density, and Strength,” J. Clin. Endocrinol. Metab., vol. 86, no. 10, pp. 4576–4584, Oct. 2001.
J. S. Finkelstein et al., “Gonadal steroid-dependent effects on bone turnover and bone mineral density in men,” J. Clin. Invest., vol. 126, no. 3, pp. 1114–1125, Mar. 2016.
P. J. Snyder et al., “Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone a controlled clinical trial,” JAMA Intern. Med., vol. 177, no. 4, pp. 471–479, Apr. 2017.
Francis, “The effects of testosterone on osteoporosis in men,” Clin. Endocrinol. (Oxf)., vol. 50, no. 4, pp. 411–414, Apr. 1999.
M. N. Özbek, H. Demirbilek, R. T. Baran, and A. Baran, “Bone mineral density in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism,” JCRPE J. Clin. Res. Pediatr. Endocrinol., vol. 8, no. 2, pp. 163–169, Jun. 2016.
E. M. Wong, A. Lehman, P. Acott, J. Gillis, D. L. Metzger, and S. Sirrs, “Hypogonadotropic hypogonadism in males with glycogen storage disease type 1,” in JIMD Reports, vol. 36, Springer, 2017, pp. 79–84.
M. K. Lindberg et al., “Estrogen receptor α, but not estrogen receptor β, is involved in the regulation of the OPG/RANKL (osteoprotegerin/receptor activator of NF-κB ligand) ratio and serum interleukin-6 in male mice,” J. Endocrinol., vol. 171, no. 3, pp. 425–433, 2001.
L. J. Robinson et al., “FSH-receptor isoforms and FSH-dependent gene transcription in human monocytes and osteoclasts,” Biochem. Biophys. Res. Commun., vol. 394, no. 1, pp. 12–17, Mar. 2010.
K. Y. Chin, “The relationship between follicle-stimulating hormone and bone health: Alternative explanation for bone loss beyond oestrogen?,” International Journal of Medical Sciences, vol. 15, no. 12. Ivyspring International Publisher, pp. 1373–1383, 2018.
J. Wang et al., “Follicle-stimulating hormone increases the risk of postmenopausal osteoporosis by stimulating osteoclast differentiation,” PLoS One, vol. 10, no. 8, Aug. 2015.
J. G. Cannon, B. Kraj, and G. Sloan, “Follicle-stimulating hormone promotes RANK expression on human monocytes,” Cytokine, vol. 53, no. 2, pp. 141–144, Feb. 2011.
H. M. Behre, S. Kliesch, E. Leifke, T. M. Link, and E. Nieschlag, “Long-term effect of testosterone therapy on bone mineral density in hypogonadal men,” J. Clin. Endocrinol. Metab., vol. 82, no. 8, pp. 2386–2390, 1997.
S. Bhasin et al., “Testosterone Therapy in Men with Hypogonadism: An Endocrine Society,” Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 5. Oxford University Press, pp. 1715–1744, 01-May-2018.
N. B. Watts et al., “Osteoporosis in men: An Endocrine Society clinical practice guideline,” Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 6. J Clin Endocrinol Metab, pp. 1802–1822, Jun-2012.
M. R. Smith, J. Eastham, D. M. Gleason, D. Shasha, S. Tchekmedyian, and N. Zinner, “Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer,” J. Urol., vol. 169, no. 6, pp. 2008–2012, Jun. 2003.
G. Corona, G. Rastrelli, G. Di Pasquale, A. Sforza, E. Mannucci, and M. Maggi, “Endogenous Testosterone Levels and Cardiovascular Risk: Meta-Analysis of Observational Studies,” Journal of Sexual Medicine, vol. 15, no. 9. Elsevier B.V., pp. 1260–1271, 01-Sep-2018.
R. Pasquali et al., “Effect of obesity and body fat distribution on sex hormones and insulin in men,” Metabolism, vol. 40, no. 1, pp. 101–104, 1991.
N. Lima, H. Cavaliere, M. Knobel, A. Halpern, and G. Medeiros-Neto, “Decreased androgen levels in massively obese men may be associated with impaired function of the gonadostat,” Int. J. Obes., vol. 24, no. 11, pp. 1433–1437, Nov. 2000.
F. C. W. Wu et al., “Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men,” N. Engl. J. Med., vol. 363, no. 2, pp. 123–135, Jul. 2010.
T. G. Travison, A. B. Araujo, V. Kupelian, A. B. O’Donnell, and J. B. McKinlay, “The Relative Contributions of Aging, Health, and Lifestyle Factors to Serum Testosterone Decline in Men,” J. Clin. Endocrinol. Metab., vol. 92, no. 2, pp. 549–555, Feb. 2007.
C. H. Gravholt, S. Chang, M. Wallentin, J. Fedder, P. Moore, and A. Skakkebæk, “Klinefelter syndrome: Integrating genetics, neuropsychology, and endocrinology,” Endocr. Rev., vol. 39, no. 4, pp. 389–423, 2018.
R. Vigen et al., “Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels,” JAMA - J. Am. Med. Assoc., vol. 310, no. 17, pp. 1829–1836, 2013.
L. Xu, G. Freeman, B. J. Cowling, and C. M. Schooling, “Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled randomized trials,” BMC Med., vol. 11, no. 1, Apr. 2013.
G. Corona, G. Rastrelli, Y. Reisman, A. Sforza, and M. Maggi, “The safety of available treatments of male hypogonadism in organic and functional hypogonadism,” Expert Opinion on Drug Safety, vol. 17, no. 3. Taylor and Francis Ltd, pp. 277–292, 04-Mar-2018.
M. Etminan, S. C. Skeldon, S. L. Goldenberg, B. Carleton, and J. M. Brophy, “Testosterone therapy and risk of myocardial infarction: A pharmacoepidemiologic study,” Pharmacotherapy, vol. 35, no. 1, pp. 72–78, 2015.
“Testosterone and Cardiovascular Risk in Men: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials- ClinicalKey.” [Online]. Available: https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0025619611609646?scrollTo=%23hl0000841. [Accessed: 10-Apr-2020].
G. Corona et al., “Cardiovascular risk associated with testosterone-boosting medications: A systematic review and meta-Analysis,” Expert Opinion on Drug Safety, vol. 13, no. 10. Informa Healthcare, pp. 1327–1351, 01-Oct-2014.
K. M. Pantalone et al., “Testosterone replacement therapy and the risk of adverse cardiovascular outcomes and mortality,” Basic Clin. Androl., vol. 29, no. 1, Mar. 2019.
O. M. Calof et al., “Adverse Events Associated With Testosterone Replacement in Middle-Aged and Older Men: A Meta-Analysis of Randomized, Placebo-Controlled Trials,” 2005.
V. De Sanctis et al., “Gonadal dysfunction in adult male patients with thalassemia major: an update for clinicians caring for thalassemia,” Expert Review of Hematology, vol. 10, no. 12. Taylor and Francis Ltd, pp. 1095–1106, 02-Dec-2017.
C. VULLO et al., “Endocrine Abnormalities in Thalassemia,” Ann. N. Y. Acad. Sci., vol. 612, no. 1 Sixth Cooley', pp. 293–310, Dec. 1990.
A. Petryk et al., “Endocrine disorders in Fanconi anemia: Recommendations for screening and treatment,” Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 3. Endocrine Society, pp. 803–811, 01-Mar-2015.
A. W. Huang and O. Muneyyirci-Delale, “Reproductive endocrine issues in men with sickle cell anemia,” Andrology, vol. 5, no. 4, pp. 679–690, Jul. 2017.
V. Mandese et al., “Endocrine and metabolic complications in children and adolescents with Sickle Cell Disease: An Italian cohort study,” BMC Pediatr., vol. 19, no. 1, Feb. 2019.
A. Al-Sharefi, A. Mohammed, A. Abdalaziz, and C. N. Jayasena, “Androgens and Anemia: Current Trends and Future Prospects,” Front. Endocrinol. (Lausanne)., vol. 10, Nov. 2019.
R. Stauder, P. Valent, and I. Theurl, “Anemia at older age: etiologies, clinical implications, and management,” Blood, vol. 131, no. 5. American Society of Hematology, pp. 505–514, 01-Feb-2018.
. C. E. Higham, G. Johannsson, and S. M. Shalet, “Hypopituitarism,” The Lancet, vol. 388, no. 10058, pp. 2403–2415, 2016.
. N. Mauras, “Testosterone Deficiency in Young Men: Marked Alterations in Whole Body Protein Kinetics, Strength, and Adiposity,” Journal of Clinical Endocrinology & Metabolism, vol. 83, no. 6, pp. 1886–1892, Jan. 1998.
. G.-M. Wang, P. J. O’Shaughnessy, C. Chubb, B. Robaire, and M. P. Hardy, “Effects of Insulin-Like Growth Factor I on Steroidogenic Enzyme Expression Levels in Mouse Leydig Cells,” Endocrinology, vol. 144, no. 11, pp. 5058–5064, 2003.
. F. Chuzel, A. M. Clark, O. Avallet, and J. M. Saez, “Transcriptional Regulation of the Lutropin/Human Choriogonadotropin Receptor and Three Enzymes of Steroidogenesis by Growth Factors in Cultured Pig Leydig Cells,” European Journal of Biochemistry, vol. 239, no. 1, pp. 8–16, 1996.
. C. T. Parker, D. Taylor, and G. M. Garrity, “Exemplar Abstract for Butyricicoccus desmolans (Morris et al. 1986) Takada et al. 2016, Eubacterium desmolans Morris et al. 1986 and Agathobaculum desmolans (Morris et al. 1986) Ahn et al. 2016 pro synon. Butyricicoccus desmolans (Morris et al. 1986) Takada et al. 2016.,” The NamesforLife Abstracts, Jan. 2003.
. N. T. Shahidi, “Androgens and Erythropoiesis,” New England Journal of Medicine, vol. 289, no. 2, pp. 72–80, Dec. 1973.
. Pivonello, Rosario, et al. “Metabolic Disorders and Male Hypogonadotropic Hypogonadism.” Frontiers in Endocrinology, vol. 10, 2019, doi:10.3389/fendo.2019.00345.
.J.-Y. Oh, E. Barrett-Connor, N. M. Wedick, and D. L. Wingard, “Endogenous Sex Hormones and the Development of Type 2 Diabetes in Older Men and Women: the Rancho Bernardo Study,” Diabetes Care, vol. 25, no. 1, pp. 55–60, Jan. 2002.
J.-Y. Oh, E. Barrett-Connor, N. M. Wedick, and D. L. Wingard, “Endogenous Sex Hormones and the Development of Type 2 Diabetes in Older Men and Women: the Rancho Bernardo Study,” Diabetes Care, vol. 25, no. 1, pp. 55–60, Jan. 2002.
. E. M. Lo, K. M. Rodriguez, A. W. Pastuszak, and M. Khera, “Alternatives to Testosterone Therapy: A Review,” Sexual Medicine Reviews, vol. 6, no. 1, pp. 106–113, 2018.
. G. Morgante, C. Tosti, R. Orvieto, M. C. Musacchio, P. Piomboni, and V. D. Leo, “Metformin improves semen characteristics of oligo-terato-asthenozoospermic men with metabolic syndrome,” Fertility and Sterility, vol. 95, no. 6, pp. 2150–2152, 2011.
. D. Kapoor, H. Aldred, S. Clark, K. S. Channer, and T. H. Jones, “Clinical and Biochemical Assessment of Hypogonadism in Men With Type 2 Diabetes: Correlations with bioavailable testosterone and visceral adiposity,” Diabetes Care, vol. 30, no. 4, pp. 911–917, 2007.
. M. E. Ramirez, M. P. Mcmurry, G. A. Wiebke, K. J. Felten, K. Ren, A. Meikle, and P.-H. Iverius, “Evidence for sex steroid inhibition of lipoprotein lipase in men: Comparison of abdominal and femoral adipose tissue,” Metabolism, vol. 46, no. 2, pp. 179–185, 1997.
. A. M. Isidori, M. Caprio, F. Strollo, C. Moretti, G. Frajese, A. Isidori, and A. Fabbri, “Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels1,” The Journal of Clinical Endocrinology & Metabolism, vol. 84, no. 10, pp. 3673–3680, 1999.
. A. R. Glass, R. S. Swerdloff, G. A. Bray, W. T. Dahms, and R. L. Atkinson, “Low Serum Testosterone and Sex-Hormone-Binding-Globulin in Massively Obese Men,” The Journal of Clinical Endocrinology & Metabolism, vol. 45, no. 6, pp. 1211–1219, 1977.
. B. Andersson, P. Marin, L. Lissner, A. Vermeulen, and P. Bjorntorp, “Testosterone Concentrations in Women and Men With NIDDM,” Diabetes Care, vol. 17, no. 5, pp. 405–411, Jan. 1994.
. P. Gyawali, S. A. Martin, L. K. Heilbronn, A. D. Vincent, A. J. Jenkins, A. S. Januszewski, A. W. Taylor, R. J. T. Adams, P. D. O’Loughlin, and G. A. Wittert, “Cross-sectional and longitudinal determinants of serum sex hormone binding globulin (SHBG) in a cohort of community-dwelling men,” Plos One, vol. 13, no. 7, Nov. 2018.
. S. A. S. Aftab, S. Kumar, and T. M. Barber, “The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism,” Clinical Endocrinology, vol. 78, no. 3, pp. 330–337, 2013.
. M. A. Yialamas, A. A. Dwyer, E. Hanley, H. Lee, N. Pitteloud, and F. J. Hayes, “Acute Sex Steroid Withdrawal Reduces Insulin Sensitivity in Healthy Men with Idiopathic Hypogonadotropic Hypogonadism,” The Journal of Clinical Endocrinology & Metabolism, vol. 92, no. 11, pp. 4254–4259, Jan. 2007.
. J. C. Smith, S. Bennett, L. M. Evans, H. G. Kynaston, M. Parmar, M. D. Mason, J. R. Cockcroft, M. F. Scanlon, and J. S. Davies, “The Effects of Induced Hypogonadism on Arterial Stiffness, Body Composition, and Metabolic Parameters in Males with Prostate Cancer,” The Journal of Clinical Endocrinology & Metabolism, vol. 86, no. 9, pp. 4261–4267, 2001.
. M. Smith, “Treament-related diabetes and cardiovascular disease in prostate cancer survivors,” Annals of Oncology, vol. 19, pp. vii86–vii90, 2008.
. P. C. Walsh, “Changes in Body Composition During Androgen Deprivation Therapy for Prostate Cancer,” The Journal of Urology, pp. 378–379, 2002.
. M. R. Smith, H. Lee, and D. M. Nathan, “Insulin Sensitivity during Combined Androgen Blockade for Prostate Cancer,” The Journal of Clinical Endocrinology & Metabolism, vol. 91, no. 4, pp. 1305–1308, 2006.
. C. Bosco, D. Crawley, J. Adolfsson, S. Rudman, and M. V. Hemelrijck, “Quantifying the Evidence for the Risk of Metabolic Syndrome and Its Components following Androgen Deprivation Therapy for Prostate Cancer: A Meta-Analysis,” Plos One, vol. 10, no. 3, 2015.
. N. L. Keating, A. J. Omalley, S. J. Freedland, and M. R. Smith, “Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy: Observational Study of Veterans With Prostate Cancer,” JNCI Journal of the National Cancer Institute, vol. 102, no. 1, pp. 39–46, Jul. 2009.
F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, ‘Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries’, CA. Cancer J. Clin., vol. 68, no. 6, pp. 394–424, 2018, doi: 10.3322/caac.21492.
‘Cancer Statistics Review, 1975-2015 - Previous Version - SEER Cancer Statistics Review’, SEER. https://seer.cancer.gov/archive/csr/1975_2015/index.html.
F. team, ‘Epidemiology of prostate cancer in Europe’, EU Science Hub - European Commission, 08-Mar-2017. https://ec.europa.eu/jrc/en/publication/epidemiology-prostate-cancer-europe).
C. Huggins and C. V. Hodges, ‘Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941’, J. Urol., vol. 167, no. 2 Pt 2, pp. 948–951; discussion 952, Feb. 2002.
J. E. Fowler and W. F. Whitmore, ‘The response of metastatic adenocarcinoma of the prostate to exogenous testosterone’, J. Urol., vol. 126, no. 3, pp. 372–375, Sep. 1981, doi: 10.1016/s0022-5347(17)54531-0.
G. R. Prout and W. R. Brewer, ‘Response of men with advanced prostatic carcinoma to exogenous administration of testosterone’, Cancer, vol. 20, no. 11, pp. 1871–1878, Nov. 1967, doi: 10.1002/1097-0142(196711)20:11<1871::aid-cncr2820201112>3.0.co;2-d.
S. Bhasin et al., ‘Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline’, J. Clin. Endocrinol. Metab., vol. 103, no. 5, pp. 1715–1744, 01 2018, doi: 10.1210/jc.2018-00229.
A. Morgentaler, C. O. Bruning, and W. C. DeWolf, ‘Occult prostate cancer in men with low serum testosterone levels’, JAMA, vol. 276, no. 23, pp. 1904–1906, Dec. 1996.
Y. Zhou et al., ‘Low Testosterone Alters the Activity of Mouse Prostate Stem Cells’, The Prostate, vol. 77, no. 5, pp. 530–541, 2017, doi: 10.1002/pros.23290.
B. S. Shin et al., ‘Is a decreased serum testosterone level a risk factor for prostate cancer? A cohort study of korean men’, Korean J. Urol., vol. 51, no. 12, pp. 819–823, Dec. 2010, doi: 10.4111/kju.2010.51.12.819.
L. Mearini, A. Zucchi, E. Nunzi, T. Villirillo, V. Bini, and M. Porena, ‘Low serum testosterone levels are predictive of prostate cancer’, World J. Urol., vol. 31, no. 2, pp. 247–252, Apr. 2013, doi: 10.1007/s00345-011-0793-x.
J. Park, S. Y. Cho, S.-H. Jeong, S. B. Lee, H. Son, and H. Jeong, ‘Low testosterone level is an independent risk factor for high-grade prostate cancer detection at biopsy’, BJU Int., vol. 118, no. 2, pp. 230–235, 2016, doi: 10.1111/bju.13206.
X. Xu et al., ‘Dynamic Patterns of Testosterone Levels in Individuals and Risk of Prostate Cancer among Hypogonadal Men: A Longitudinal Study’, J. Urol., vol. 199, no. 2, pp. 465–473, 2018, doi: 10.1016/j.juro.2017.08.117.
P. Léon 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., vol. 33, no. 9, pp. 384.e21–27, Sep. 2015, doi: 10.1016/j.urolonc.2014.11.010.
Y. Neuzillet et al., ‘Obesity and hypogonadism are associated with an increased risk of predominant Gleason 4 pattern on radical prostatectomy specimen’, Horm. Mol. Biol. Clin. Investig., vol. 22, no. 3, pp. 101–109, Jun. 2015, doi: 10.1515/hmbci-2015-0005.
M. Shiota et al., ‘Low Serum Testosterone But Not Obesity Predicts High Gleason Score at Biopsy Diagnosed as Prostate Cancer in Patients with Serum PSA Lower than 20 ng/ml’, Anticancer Res., vol. 35, no. 11, pp. 6137–6145, Nov. 2015.
J. Fuentes-Pastor et al., ‘Association between late-onset hypogonadism syndrome plus metabolic syndrome and prostate cancer and its aggressiveness’, Actas Urol. Esp., vol. 40, no. 7, pp. 440–445, Sep. 2016, doi: 10.1016/j.acuro.2016.02.001.
M. Ferro et al., ‘Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance’, Oncotarget, vol. 8, no. 11, pp. 18424–18434, Mar. 2017, doi: 10.18632/oncotarget.12906.
E. Llukani et al., ‘Low levels of serum testosterone in middle-aged men impact pathological features of prostate cancer’, Prostate Int., vol. 5, no. 1, pp. 17–23, Mar. 2017, doi: 10.1016/j.prnil.2016.12.003.
H. Tu et al., ‘Low serum testosterone is associated with tumor aggressiveness and poor prognosis in prostate cancer’, Oncol. Lett., vol. 13, no. 3, pp. 1949–1957, Mar. 2017, doi: 10.3892/ol.2017.5616.
G. A. M. L. de Albuquerque et al., ‘Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer’, Rev. Assoc. Medica Bras. 1992, vol. 63, no. 8, pp. 704–710, Aug. 2017, doi: 10.1590/1806-9282.63.08.704.
K. M. Atkins et al., ‘Low testosterone at first prostate-specific antigen failure and assessment of risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials’, Cancer, vol. 124, no. 7, pp. 1383–1390, 01 2018, doi: 10.1002/cncr.31204.
Y. Neuzillet et al., ‘Aggressiveness of Localized Prostate Cancer: the Key Value of Testosterone Deficiency Evaluated by Both Total and Bioavailable Testosterone: AndroCan Study Results’, Horm. Cancer, vol. 10, no. 1, pp. 36–44, 2019, doi: 10.1007/s12672-018-0351-8.
L. Izzo et al., ‘Low-serum testosterone and high-chromogranin A rare case associated with high-grade prostate cancer and higher pathological stages of the disease’, Ann. Ital. Chir., vol. 90, pp. 451–456, 2019.
M. B. Cook et al., ‘Testosterone Therapy in Relation to Prostate Cancer in a U.S. Commercial Insurance Claims Database’, Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol., vol. 29, no. 1, pp. 236–245, Jan. 2020, doi: 10.1158/1055-9965.EPI-19-0619.
M. Kardoust Parizi et al., ‘Oncological safety of testosterone replacement therapy in prostate cancer survivors after definitive local therapy: A systematic literature review and meta-analysis’, Urol. Oncol., vol. 37, no. 10, pp. 637–646, Oct. 2019, doi: 10.1016/j.urolonc.2019.06.007.
J. P. Mulhall et al., ‘Evaluation and Management of Testosterone Deficiency: AUA Guideline’, J. Urol., vol. 200, no. 2, pp. 423–432, 2018, doi: 10.1016/j.juro.2018.03.115.
G. Hackett et al., ‘British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice’, J. Sex. Med., vol. 14, no. 12, pp. 1504–1523, 2017, doi: 10.1016/j.jsxm.2017.10.067.
M. Khera et al., ‘Diagnosis and Treatment of Testosterone Deficiency: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)’, J. Sex. Med., vol. 13, no. 12, pp. 1787–1804, 2016, doi: 10.1016/j.jsxm.2016.10.009.
B. Lunenfeld et al., ‘Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men’, Aging Male Off. J. Int. Soc. Study Aging Male, vol. 18, no. 1, pp. 5–15, Mar. 2015, doi: 10.3109/13685538.2015.1004049.
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