Alt tag

Research news

Testosterone deficiency - prevalence and treatment rates

Bayer logo Bayer logo Bayer logo Bayer logo

Testosterone deficiency - prevalence and treatment rates

March 2015

Systematic Literature Review of the Epidemiology of Non-Genetic Forms of Hypogonadism in Adult Males. Victoria Zarotsky, Ming-Yi Huang, Wendy Carman, Abraham Morgentaler, Puneet Singhal, Donna Coffin, and T. H. Jones, Journal of Hormones 2014

Testosterone deficiency, also known as hypogonadism, is gaining recognition among both clinicians and the general population. This editorial summarizes the findings from a review on the prevalence of testosterone deficiency, as well as the proportion of hypogonadal men who are receiving testosterone treatment.

KEY POINTS

Abbreviations: TT = total testosterone, FT = free testosterone, BMI = body mass index (a proxy for obesity)

  • In community-based studies, cut-offs of TT ranging from <200 to <400 ng/dL, with and without low FT, and with and without symptoms, the prevalence of hypogonadism in men aged 54-76 years ranges from 9.5% to 31.2%.1-3
  • In primary care/screening-based studies, the prevalence of hypogonadism in men aged 53-62 years ranges up to 38.7%.4
  • Clinical condition-based studies assessed prevalence of hypogonadism among patients with specific medical conditions. The prevalence of hypogonadism in men aged 53-62 years with morbidities ranges up to 78.8% and varies considerably by medical condition. 
    • Hypogonadism occurs commonly among patients with obesity, type 2 diabetes, and/or the metabolic syndrome.
    • The prevalence of hypogonadism in obese patients was found to be 57.7% and 35.6%, using the cut-offs TT <317 ng/dL and FT <78 pg/ml, respectively.5 Another study using the cut-offs TT < 300 ng/dl or FT < 65 pg/ml found the prevalence in obese patients to be 78.8% and 51.5%, respectively.6
    • The prevalence of hypogonadism in patients with type 2 diabetes ranges from 24.5% to 43% using the cut-off TT <10.4mmol/L (300 ng/dL).7-10 With the cut-off TT <12nmol/L (346 ng/dL), the prevalence is 45%.11
    • The prevalence of hypogonadism in patients with the metabolic syndrome ranges from 30 to 35%.12-14
    • The prevalence of hypogonadism in patients with type 2 diabetes who are also obese or have the metabolic syndrome is 51%15 and 47%16, respectively.
  • The prevalence of hypogonadism in men with erectile dysfunction is 7%, 23%, 33%, and 47% for testosterone levels of less than 200, less than 300, less than 346, and less than 400 ng/dL, respectively.17
  • Prevalence of hypogonadism increases with age.
    An abrupt increase in hypogonadism prevalence occurred in men aged 45 to 50 yr.17 Using the cut-off < 300 ng/dL, hypogonadism prevalence in primary care patients has been reported to be 34% in men aged 45–54 yr, 40.2% in men aged 55–64 yr, 39.9% in men aged 65–74 yr, 45.5% in men aged 75–84 yr, and 50% in men aged 85 yr and older.4 Every 10-year increase in age confers a 17% increase in risk of hypogonadism.4
  • Population-based (BACH, Boston Area Community Health)18 and clinical-based (HIM, Health In Men)4 studies report that only 10% to 12% of hypogonadal patients were receiving treatment for hypogonadism.

What is known

Diagnosis of hypogonadism is typically based on the signs and symptoms associated with a deficiency of testosterone levels or its actions, followed by biochemical confirmation of low testosterone levels.19-21 It is well-documented that testosterone levels decline with age in men. After the age of 40 years, total testosterone decreases on average -4 ng/dL ( -0.124 nmol/L) per year22 or 1.6% per year23, and bioavailable testosterone by -2 to -3% per year.23 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.24 The aging demography will thus cause a large increase in the burden of testosterone deficiency.25

Besides aging alone, lifestyle and different co-morbidities are associated with testosterone deficiency, suggesting that the age-related testosterone decline may be at least partly prevented through the management of potentially modifiable risk factors and health related behaviour.26

What this study adds

The prevalence of hypogonadism and suboptimal testosterone levels is high. It should be noted that most the prevalence numbers listed above are based on the cut-off of 300 ng/dL. Even conservative investigators find a TT cut-off of 12.1 nmol/L (348.3 ng/dl), as opposed to the 300 ng/dl (that some clinicians already think is too high), as the defining lower limit of the testosterone reference range.27 Using this higher cut-off, the prevalence of testosterone deficiency is likely much greater.

Notable is the lack of a standardized definition for hypogonadism diagnosis. As outlined here, the hypogonadism literature reports wide-ranging prevalence based not only on the different populations or subpopulations studied, but also on the use of diverse biochemical cut points or varied choices of symptoms.

Co-morbidities

Besides age per se, obesity, metabolic syndrome, diabetes and dyslipidaemia are risk factors of incident testosterone deficiency.26 This is underscored by a head-to-head comparison of the prevalence of subnormal free testosterone levels in lean, overweight, and obese non-diabetic men, which was found to be 26%, 29% and 40%, respectively.15 In lean, overweight, and obese diabetic men, the prevalence of subnormal free testosterone levels is even higher; 44% , 44% and 50%, respectively.15

The analysis reported here also brings to the attention that in every BMI category, the prevalence of subnormal total testosterone levels is consistently higher than that of free testosterone levels.5 In type 2 diabetics, the reverse is true, i.e. the prevalence of subnormal free testosterone levels is consistently higher than that of total testosterone levels.10,11 One study found that 43% of men with type 2 diabetes had a reduced total testosterone level, while 57% had a reduced free testosterone levels.10 The corresponding numbers in a more recent study are 45% and 61%, respectively.11

Another important finding is the greatly increased prevalence of hypogonadism among men with obesity, type 2 diabetes and/or the metabolic syndrome. The prevalence of obesity and the metabolic syndrome among men aged 20 yr and older is 35.5%28 and 36.1%, respectively.29 26.9% of adults aged 65 years or older have diabetes.30 Because these clinical conditions have become more and more prevalent in all age groups29,31 and have reached epidemic proportions, an alarming increase of non-aging related prevalence of hypogonadism may be expected. It is therefore imperative that clinicians are aware of the impact of co-morbidities on testosterone, and screen their patients for hypogonadism.

Testosterone Prescribing

Testosterone prescribing has increased over the past decade.32-34 From 2001 through 2011, testosterone supplementation among men 40 years or older increased more than 3-fold, from 0.81% in 2001 to 2.91% in 2011. The increase was seen in all age groups. By 2011, 2.29% of men in their 40s and 3.75% of men in their 60s were taking some form of testosterone therapy.32 However, despite an increased use of testosterone therapy, population-based (BACH, Boston Area Community Health) and clinical-based studies (HIM) report that only 10%18 and 12%4 of patients were receiving treatment for hypogonadism, respectively.

It is notable that in the BACH study 40% of men met the Endocrine Society definition for testosterone deficiency (symptoms and/or signs coupled with total testosterone < 300 ng/dL or free testosterone < 5 ng/dL), but only 10% received testosterone therapy.18 In the HIM study, the prevalence of testosterone deficiency (defined by TT <300 ng/dl) was 38.7%. Based on free testosterone (<52 pg/ml) and bioavailable testosterone levels (<95 ng/dl for men <70 years of age and <60 ng/dl for men 70 and older), approximately 40% and 45% of men were hypogonadal, respectively. In this study, a similarly low proportion of men were receiving testosterone therapy (12%). Reasons for this low frequency of hypogonadism treatment may include inadequate knowledge among physicians regarding hypogonadism and uncertainty about diagnostic criteria. Also, patients may not be able to afford therapy in countries that do not provide coverage for testosterone prescriptions.

Another reason is safety concerns. Two world-wide surveys found that concerns about potential side effects of testosterone therapy among doctors is increasing, and that concerns were predominantly related to prostate cancer and cardiovascular disease.35,36 This is not congruent with the growing body of research showing that testosterone therapy is safe for prostate and cardiovascular outcomes.37-39 We have covered prostate and cardiovascular safety issues in previous editorials, see "Testosterone and Prostate Cancer - a paradigm shift" and "Testosterone Treatment and Heart Attack Risk". An assessment of beliefs, knowledge and practice patterns of general practitioners and cardiologists found that testosterone deficiency is not well-understood by general practitioners and cardiologists, and that these key clinicians lack knowledge on its deleterious cardiovascular effects.40

Thus, it is critical to look at both sides of the prescribing - need equation; citing increases in testosterone prescribing without looking at hypogonadism prevalence and men's health status will give a misleading picture. The review reported here indicates that the reported increase in testosterone prescribing still does not offer treatment for the vast majority of men who need it for their health and wellbeing.

Recommendations

Do you have symptoms of low testosterone?

Do you have symptoms of low testosterone?
Testosterone deficiency FAQs

Testosterone deficiency FAQs

Related topics

Check your symptoms Testosterone deficiency Diagnosis and treatment

References

  • Khoo EM, Tan HM, Low WY. Erectile dysfunction and comorbidities in aging men: an urban cross-sectional study in Malaysia. The journal of sexual medicine. 2008;5(12):2925−2934. Return to content
  • Ponholzer A, Madersbacher S, Rauchenwald M, et al. Vascular risk factors and their association to serum androgen levels in a population-based cohort of 75-year-old men over 5 years: results of the VITA study. World journal of urology. 2010;28(2):209-214. Return to content
  • Wong SY, Chan DC, Hong A, et al. Prevalence of and risk factors for androgen deficiency in middle-aged men in Hong Kong. Metabolism: clinical and experimental. 2006;55(11):1488-1494. Return to content
  • Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. International journal of clinical practice. 2006;60(7):762−769. Return to content
  • Hofstra J, Loves S, van Wageningen B, et al. High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment. The Netherlands journal of medicine. 2008;66(3):103−109. Return to content
  • Pellitero S, Olaizola I, Alastrue A, et al. Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery. Obesity surgery. 2012;22(12):1835−1842. Return to content
  • Corona G, Mannucci E, Petrone L, et al. Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. International journal of impotence research. 2006;18(2):190-197. Return to content
  • Dhindsa S, Prabhakar S, Sethi M, et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. The Journal of clinical endocrinology and metabolism. 2004;89(11):5462−5468. Return to content
  • Grossmann M, Panagiotopolous S, Sharpe K, et al. Low testosterone and anaemia in men with type 2 diabetes. Clinical endocrinology. 2009;70(4):547-553. Return to content
  • Grossmann M, Thomas MC, Panagiotopoulos S, et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. The Journal of clinical endocrinology and metabolism. 2008;93(5):1834-1840. Return to content
  • Biswas M, Hampton D, Newcombe RG, et al. 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. Clinical endocrinology. 2012;76(5):665-673. Return to content
  • Caldas AD, Porto AL, Motta LD, et al. Relationship between insulin and hypogonadism in men with metabolic syndrome. Arquivos brasileiros de endocrinologia e metabologia. 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. The Journal of clinical endocrinology and metabolism. 2005;90(2):712−719. Return to content
  • Singh SK, Goyal R, Pratyush DD. Is hypoandrogenemia a component of metabolic syndrome in males? Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2011;119(1):30-35. 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
  • Ogbera AO. Relationship between serum testosterone levels and features of the metabolic syndrome defining criteria in patients with type 2 diabetes mellitus. West African journal of medicine. 2011;30(4):277-281. Return to content
  • Kohler TS, Kim J, Feia K, et al. Prevalence of androgen deficiency in men with erectile dysfunction. Urology. 2008;71(4):693-697. Return to content
  • Hall SA, Araujo AB, Esche GR, et al. Treatment of symptomatic androgen deficiency: results from the Boston Area Community Health Survey. Archives of internal medicine. 2008;168(10):1070-1076. Return to content
  • Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2010;95(6):2536−2559. Return to content
  • 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. Journal of andrology. 2009;30(1):1-9. Return to content
  • Wu FC, Tajar A, Beynon JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. The New England journal of medicine. 2010;363(2):123-135. Return to content
  • Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. The Journal of clinical endocrinology and metabolism. 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 aging study. The Journal of clinical endocrinology and metabolism. 2002;87(2):589-598. 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: clinical and experimental. 1997;46(4):410-413. Return to content
  • Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. The Journal of clinical endocrinology and metabolism. 2007;92(11):4241−4247. 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 aging male : the official journal of the International Society for the Study of the Aging Male. 2010;13(4):247-257. Return to content
  • 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. The Journal of clinical endocrinology and metabolism. 2011;96(8):2430-2439. Return to content
  • Flegal KM, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA : the journal of the American Medical Association. 2012;307(5):491-497. Return to content
  • Ford ES, Li C, Zhao G. Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US. Journal of diabetes. 2010;2(3):180−193. Return to content
  • American Diabetes Association. Statistics About Diabetes: Data from the National Diabetes Statistics Report, 2014 (released June 10, 2014), avaliable at http://www.diabetes.org/diabetes-basics/statistics (accessed July 21, 2014). Return to content
  • Svartberg J, von Muhlen D, Sundsfjord J, et al. Waist circumference and testosterone levels in community dwelling men. The Tromso study. European journal of epidemiology. 2004;19(7):657−663. Return to content
  • Baillargeon J, Urban RJ, Ottenbacher KJ, et al. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA internal medicine. 2013;173(15):1465-1466. Return to content
  • Gan EH, Pattman S, S HSP, et al. A UK epidemic of testosterone prescribing, 2001-2010. Clinical endocrinology. 2013;79(4):564-570. Return to content
  • Layton JB, Li D, Meier CR, et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000 to 2011. The Journal of clinical endocrinology and metabolism. 2014;99(3):835-842. Return to content
  • Gooren LJ, Behre HM, Saad F, et al. Diagnosing and treating testosterone deficiency in different parts of the world. Results from global market research. The aging male : the official journal of the International Society for the Study of the Aging Male. 2007;10(4):173-181. Return to content
  • Gooren LJ, Behre HM. Diagnosing and treating testosterone deficiency in different parts of the world: changes between 2006 and 2010. The aging male : the official journal of the International Society for the Study of the Aging Male. 2012;15(1):22-27. Return to content
  • Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. The journals of gerontology Series A, Biological sciences and medical sciences. 2005;60(11):1451-1457. Return to content
  • Fernandez-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. The Journal of clinical endocrinology and metabolism. 2010;95(6):2560−2575. Return to content
  • Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clinic proceedings Mayo Clinic. 2007;82(1):29-39. Return to content
  • Wallis CJ, Brotherhood H, Pommerville PJ. Testosterone deficiency syndrome and cardiovascular health: An assessment of beliefs, knowledge and practice patterns of general practitioners and cardiologists in Victoria, BC. Canadian Urological Association journal = Journal de l'Association des urologues du Canada. 2014;8(1-2):30-33. Return to content

Copyright © 2021, Bayer AG

This website contains information on Nebido (testosterone undecanoate) which is based on the Summary of Product Characteristics (SPC) as approved by the European Commission.

 

This website is intended to provide information to an international audience outside Austria, France, Germany, Hungary, Ireland, the Middle East, the Philippines, Thailand, the UK, and the USA.

Page last modified 01/04/2021

PP-NEB-ALL-0223-1 April 2021

BayerBayer