Risk factors for hypogonadism

Hypogonadism (testosterone deficiency) is a highly prevalent and under-diagnosed condition associated both with ageing and common medical comorbidities,1 as summarised in the table below. Although the prevalence of hypogonadism increases with advancing age, it can also occur in younger men.2 Hypogonadism has been associated with a higher risk of obesity and a high prevalence of stress.3-5

While the typical decline of serum T concentrations with ageing is considerable, there is evidence that specific changes in health and lifestyle such as increased BMI are accompanied by accelerated loss of serum T.6-14 In the current epidemic of obesity in all age groups,15,16 it is critical for health care professionals to recognise the association between body fatness and a reduction in plasma testosterone concentrations.14 Therefore, testosterone levels should be measured in men with excess body fat and/or large waist size, regardless of age.17

Although some risk factors for low testosterone are irreversible, improving lifestyle habits (such as making healthier food choices, regularly exercising, moderating alcohol consumption and reducing stress) may reduce the risk of hypogonadism.9,18,19

 

Table: Risk factors for hypogonadism.

Risk Factor Comment
Obesity Prevalence of hypogonadism in obese men has been shown to be around 29-45% however, one study with 33 men showed this to be up to 79%.20-23
Abdominal obesity Nearly 40% of men with a waist circumference of 94 cm or higher have low testosterone.24

1 of 4 men aged 20–59 have abdominal obesity and low testosterone.5

Younger men (age 20-39 years) with a large waist circumference (>102 cm or >40 inches) have a 6-fold increase risk of low testosterone.5

Among men with both abdominal obesity and erectile dysfunction, nearly 70% have low testosterone.25
Diabetes Prevalence of hypogonadism in type 2 diabetic men has been shown to be around 45-68.6% however, one study with 110 men showed this to be up to 79%.21,26-28
Metabolic syndrome Up to 35% of men with the metabolic syndrome have hypogonadism.29-31
Heart disease 1 in 4 (24%) men with coronary heart disease have hypogonadism.32

In men with heart disease, hypogonadism has been associated with a 2-fold increased risk of death.32
Stress Nearly half of men with erectile dysfunction who report having a high degree of life/work stress have low testosterone.4
Erectile dysfunction Among men with erectile dysfunction, over one third (36%) have low testosterone levels.4

Low testosterone can cause erectile dysfunction and/or non-responsiveness to treatment with PDE5i (phosphodiesterase 5 inhibitors).
Chronic diseases Chronic diseases such as liver disease, kidney disease and rheumatoid arthritis33 are associated with low testosterone.33
Normal ageing Testosterone levels decline with age in most men.
 

After the age of 40 years:

  • total testosterone decreases on average -4 ng/dL (-0.124 nmol/L) per year7 or 0.4% - 2% per year.18
  • bioavailable testosterone decreases on average -2 to -3% per year.8

In older men (over 60 years of age):

The average rate of decline in total testosterone levels is approximately 110 ng/dL per decade after the peak in young adulthood.12
Medications Certain medications, especially opioids,36 selective serotonin reuptake inhibitors (SSRIs),40 statins38-40 and glucocorticoid medications38 reduce testosterone levels.

5-alpha reductase inhibitors, which inhibit DHT synthesis, impair sexual function41-43 and also reduce testosterone levels44
Pituitary disorders Pituitary dysfunction can impair the release of LH and FSH, which are hormones that affect normal testosterone and sperm production, respectively.45,46
Cancer and cancer treatment Cancer of the testes or pituitary tumors can lead to low testosterone production.

Chemotherapy or radiation therapy can also interfere with testosterone production.45,46
Injury to the testes Damage to the testis can cause reduced testosterone production.45,46
Hemochromatosis A genetic disorder causing the body to absorb too much iron from the diet. Haemochromatosis can result in the deposition of iron in various body organs, including the hypothalamus, pituitary and testes, which impairs testosterone production.45,46

It is now recognised as a common disorder and 1 in 200 people of northern Europe may be at risk of developing iron overload.46
HIV/AIDS The HIV virus can cause low levels of testosterone by affecting the hypothalamus, pituitary and testes.45,46
Klinefelter’s syndrome A genetic chromosome disorder that can cause a deficiency in testosterone production.. Affects between 1 in 500 and 1 in 1000 men.45,46
Hypothalamic disorder Abnormal development of the hypothalamus and is a risk factor for low testosterone (a.k.a. Kallman syndrome).45,46
Mumps orchitis A mumps infection that involves the testes as well as the saliva glands may result in long-term damage affecting testosterone production if it occurs during adolescence or adulthood.45,46
Undescended testes Failure of one or both of the testes to descend at birth (which occurs in approximately 1 in 4 boys born prematurely and 1 in 20 boys born at term) may lead to a failure of the testes to develop properly if the condition does not correct itself naturally within the first year of life or if not corrected in early childhood.45,46

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References

  • Traish AM, Miner MM, Morgentaler A, Zitzmann M. Testosterone deficiency. Am J Med. 2011;124(7):578-587. Return to content
  • Khera M, Adaikan G, Buvat J, et al. Diagnosis and Treatment of Testosterone Deficiency: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). The journal of sexual medicine. 2016;13(12):1787-1804. Return to content
  • Gapstur SM, Gann PH, Kopp P, Colangelo L, Longcope C, Liu K. Serum androgen concentrations in young men: a longitudinal analysis of associations with age, obesity, and race. The CARDIA male hormone study. Cancer Epidemiol Biomarkers Prev. 2002;11(10 Pt 1):1041-1047. Return to content
  • Guay A, Seftel AD, Traish A. Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses. Int J Impot Res. 2010;22(1):9-19. Return to content
  • Gleicher S, Daugherty M, Ferry E, Byler T. Looking beyond hypogonadism: association between low testosterone and metabolic syndrome in men 20-59 years. Int Urol Nephrol. 2020. Return to content
  • Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice. The journal of sexual medicine. 2017;14(12):1504-1523. Return to content
  • Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of ageing on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Ageing. J Clin Endocrinol Metab. 2001;86(2):724-731. Return to content
  • 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 ageing study. J Clin Endocrinol Metab. 2002;87(2):589-598. Return to content
  • Travison TG, Araujo AB, Kupelian V, O'Donnell AB, McKinlay JB. The relative contributions of ageing, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metab. 2007;92(2):549-555. Return to content
  • Lapauw B, Goemaere S, Zmierczak H, et al. The decline of serum testosterone levels in community-dwelling men over 70 years of age: descriptive data and predictors of longitudinal changes. Eur J Endocrinol. 2008;159(4):459-468. Return to content
  • Mohr BA, Guay AT, O'Donnell AB, McKinlay JB. Normal, bound and nonbound testosterone levels in normally ageing men: results from the Massachusetts Male Ageing Study. Clin Endocrinol (Oxf). 2005;62(1):64-73. Return to content
  • Haring R, Ittermann T, Volzke H, et al. Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania. The ageing male : the official journal of the International Society for the Study of the Ageing Male. 2010;13(4):247-257. Return to content
  • Liu PY, Beilin J, Meier C, et al. Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. J Clin Endocrinol Metab. 2007;92(9):3599-3603. Return to content
  • Couillard C, Gagnon J, Bergeron J, et al. Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study. J Clin Endocrinol Metab. 2000;85(3):1026-1031. Return to content
  • Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of Obesity Among Adults and Youth: United States, 2015-2016. NCHS data brief. 2017(288):1-8. Return to content
  • Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. N Engl J Med. 2019;381(25):2440-2450. Return to content
  • Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Available at https://journals.aace.com/doi/pdf/10.4158/EP161365.GL (accessed 4 July, 2020) Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2016;22 Suppl 3:1-203. Return to content
  • 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 Ageing Study. J Clin Endocrinol Metab. 2008;93(7):2737-2745. Return to content
  • Camacho EM, Huhtaniemi IT, O'Neill TW, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol. 2013;168(3):445-455. Return to content
  • Pellitero S, Olaizola I, Alastrue A, et al. Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery. Obes Surg. 2012;22(12):1835-1842. Return to content
  • 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. Return to content
  • Calderón B, Gómez-Martín JM, Vega-Piñero B, et al. Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight. Andrology. 2016;4(1):62-67. Return to content
  • Dhindsa S, Miller MG, McWhirter CL, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010;33(6):1186-1192. Return to content
  • Fillo J, Levcikova M, Ondrusova M, Breza J, Labas P. Importance of Different Grades of Abdominal Obesity on Testosterone Level, Erectile Dysfunction, and Clinical Coincidence. American journal of men's health. 2017;11(2):240-245. Return to content
  • Fillo J, Breza J, Levčíkova M, et al. Occurrence of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome in patients with abdominal obesity. Where is a sufficient level of testosterone? Int Urol Nephrol. 2012;44(4):1113-1120. Return to content
  • Biswas M, Hampton D, Newcombe RG, Rees DA. Total and free testosterone concentrations are strongly influenced by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and diabetes-related quality of life. Clin Endocrinol (Oxf). 2012;76(5):665-673. Return to content
  • Rezvani MR, Saadatjou SA, Sorouri S, Hassanpour Fard M. Comparison of serum free testosterone, luteinizing hormone and follicle stimulating hormone levels in diabetics and non-diabetics men- a case-control study. J Res Health Sci. 2012;12(2):98-100. Return to content
  • Hackett GI, Cole NS, Deshpande AA, Popple MD, Kennedy D, Wilkinson P. Biochemical hypogonadism in men with type 2 diabetes in primary care practice. The British Journal of Diabetes & Vascular Disease. 2009;9(5):226-231. Return to content
  • Caldas AD, Porto AL, Motta LD, Casulari LA. Relationship between insulin and hypogonadism in men with metabolic syndrome. Arq Bras Endocrinol Metabol. 2009;53(8):1005-1011. Return to content
  • Laaksonen DE, Niskanen L, Punnonen K, et al. The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study. J Clin Endocrinol Metab. 2005;90(2):712-719. Return to content
  • Singh SK, Goyal R, Pratyush DD. Is hypoandrogenemia a component of metabolic syndrome in males? Exp Clin Endocrinol Diabetes. 2011;119(1):30-35. Return to content
  • Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010;96(22):1821-1825. Return to content
  • Mitra Pikwer,et al. Association between testosterone levels and risk of future rheumatoid arthritis in men: a population-based case–control study. Annals of the Rheumatic Diseases, 2013; DOI: 10.1136/annrheumdis-2012-202781z. Return to content
  • Rochira V. Hypogonadism in Systemic Diseases. In: Simoni M, Huhtaniemi I, eds. Endocrinology of the Testis and Male Reproduction. Cham: Springer International Publishing; 2017:1-51. Return to content
  • Morley JE, Kaiser FE, Perry HM, 3rd, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. 1997;46(4): 410-413. Return to content
  • Bawor M, Bami H, Dennis BB, et al. Testosterone suppression in opioid users: a systematic review and meta-analysis. Drug Alcohol Depend. 2015;149:1-9. Return to content
  • Corona G, Ricca V, Bandini E, et al. Selective serotonin reuptake inhibitor-induced sexual dysfunction. The journal of sexual medicine. 2009;6(5):1259-1269. Return to content
  • Corona G, Boddi V, Balercia G, et al. The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction. The journal of sexual medicine. 2010;7(4 Pt 1): 1547-1556. Return to content
  • Schooling CM, Au Yeung SL, Freeman G, Cowling BJ. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. BMC medicine. 2013;11:57. Return to content
  • Cohen PG. Statins and male hypogonadism. The journal of sexual medicine. 2011;8(6):1826. Return to content
  • Traish AM, Guay AT, Zitzmann M. 5alpha-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis. Hormone molecular biology and clinical investigation. 2014;20(3):73-80. Return to content
  • Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M. Adverse effects of 5alpha-reductase inhibitors: What do we know, don't know, and need to know? Reviews in endocrine & metabolic disorders. 2015. Return to content
  • Traish AM, Mulgaonkar A, Giordano N. The dark side of 5alpha-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression. Korean journal of urology. 2014;55(6):367-379. Return to content
  • Traish AM, Haider KS, Doros G, Haider A. Finasteride, not tamsulosin, increases severity of erectile dysfunction and decreases testosterone levels in men with benign prostatic hyperplasia. Hormone molecular biology and clinical investigation. 2015;23(3):85-96. Return to content
  • Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006;91(6):1995-2010. Return to content
  • Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S. 2018 European Association of Urology (EAU) Guidelines on Male Hypogonadism. Available at https://uroweb.org/guideline/ male-hypogonadism. Return to content

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