Risk Factors

What are risk factors for low testosterone?

Many systemic diseases (e.g. diabetes mellitus, metabolic syndrome, coronary artery disease, liver disease, chronic obstructive pulmonary disease, rheumatoid arthritis, other inflammatory conditions and generalized infections) correlate with low testosterone levels.1-3,5-9 Therefore, signs or symptoms of hypogonadism can be an early indication leading to diagnosis of an underlying condition. In addition, obesity, injury to the testes, genetic factors and normal aging can contribute to hypogonadism.1,6 A summary of the risk factors can be found in the table below. Although many risk factors for low testosterone are not modifiable, improving diet, moderating alcohol consumption, losing weight and reducing stress can be helpful to men wanting to reduce the risk of hypogonadism.


Risk factor Comment
Obesity Up to 79% of obese men have hypogonadism.1
Diabetes Up to 81% of men with type 2 diabetes have hypogonadism.2-5
Metabolic syndrome Up to 35% of men with the metabolic syndrome have hypogonadism.6-8
Chronic diseases Chronic diseases such as cardiovascular diseases, liver or kidney disease, and rheumatoid arthritis may be risk factors for low testosterone.

In some cases, it is not clear whether the chronic illness is a cause or a consequence of low testosterone. It is likely that the causal relationship is bi-directional.
Normal aging 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 year9 or 0.4% - 2% per year.10
  • bioavailable testosterone decreases on average -2 to -3% per year.11
* In older men (over 60 years of age):

The average rate of decrement in total testosterone levels has been found to be 110 ng/dL every decade.12
Medications Statins13-15 (which are widely prescribed for dyslipidemia), glucocorticoid medications16,17 and opioid treatment18-20 for chronic pain are well known medications that reduce testosterone levels and may precipitate hypogonadism.

5-alpha reductase inhibitors, which inhibit DHT synthesis, impair sexual function21-23 and reduce testosterone levels.24
Pituitary disorders Pituitary dysfunction can impair the release of LH and FSH, which are hormones that affect normal testosterone and sperm production, respectively.25,26
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.25,26
Injury to the testes Testicular damage can cause reduced testosterone production.25,26
Hemochromatosis A genetic disorder causing the body to absorb too much iron from the diet. Hemochromatosis can result in the deposition of iron in various body organs, including the hypothalamus, pituitary and testes, which impairs testosterone production.25,26

It is now recognized as a common disorder and 1 in 200 people of northern Europe may be at risk of developing iron overload.26
HIV/AIDS The HIV virus can cause low levels of testosterone by affecting the hypothalamus, pituitary and testes.25,26
Klinefelter’s syndrome A genetic deficiency in testosterone production. Affects between 1 in 500 and 1 in 1000 men.25,26
Hypothalamic disorder Abnormal development of the hypothalamus and is a risk factor for low testosterone (a.k.a. Kallmann's syndrome).25,26
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.25,26
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.25,26

References

1 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.

2 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.

3 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.

4 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.

5 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.

6 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.

7 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.

8 Singh SK, Goyal R, Pratyush DD. Is hypoandrogenemia a component of metabolic syndrome in males? Exp Clin Endocrinol Diabetes. 2011;119(1):30-35.

9 Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86(2):724-731.

10 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.

11 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.

12 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.

13 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.

14 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.

15 Cohen PG. Statins and male hypogonadism. The journal of sexual medicine. 2011;8(6):1826.

16 Reid IR, Wattie DJ, Evans MC, Stapleton JP. Testosterone therapy in glucocorticoid-treated men. Arch Intern Med. 1996;156(11):1173-1177.

17 Crawford BA, Liu PY, Kean MT, Bleasel JF, Handelsman DJ. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. J Clin Endocrinol Metab. 2003;88(7):3167-3176.

18 Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3 Suppl 1):S12-18.

19 Aloisi AM, Aurilio C, Bachiocco V, et al. Endocrine consequences of opioid therapy. Psychoneuroendocrinology. 2009;34 Suppl 1:S162-168.

20 Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. The journal of pain : official journal of the American Pain Society. 2002;3(5):377-384.

21 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.

22 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.

23 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.

24 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.

25 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.

26 Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S. 2017 EAU Guidelines on Male Hypogonadism. Available at http://uroweb.org/wp-content/uploads/18-Male-Hypogonadism_2017_web.pdf (accessed April 1st, 2018).

Last updated: 2018
G.MKT.GM.MH.01.2018.0500