Why and how to screen for hypogonadism in men with diabetes/pre-diabetes and obesity

Description

Professor Hackett summarizes the BSSM (British Society for Sexual Medicine),1 AUA (American Urological Association)2 and EAU (European Association of Urology)3 guidelines on testosterone deficiency (also known as hypogonadism), which recommend screening for hypogonadism in men with obesity (BMI ≥30 kg/m² or waist circumference ≥102 cm), erectile dysfunction, metabolic syndrome and type 2 diabetes.

The BSSM guidelines also recommend screening for testosterone deficiency in men on long-term opiate, antipsychotic or anticonvulsant medication. The ADA (American Diabetes Association) and AACE (American Association of Clinical Endocrinologists) / ACE (American College of Endocrinology) also recommend screening for testosterone deficiency in men with obesity or type 2 diabetes.

Regarding diagnosis of testosterone deficiency, the BSSM guidelines recommend a trial of testosterone therapy for at least 6 months in symptomatic men even if they have testosterone levels in the low-normal range. Men with a total testosterone level lower than 8 nmol/L or free testosterone level lower than 180 pmol/L (<0.180 nmol/L) usually require testosterone therapy.

The BSSM guidelines also state:

  • A free testosterone level lower than 225 pmol/L (0.225 nmol/L) provides supportive evidence for testosterone therapy in the presence of symptoms, regardless of total testosterone levels.
  • Increased LH levels in the presence of testosterone levels below normal or in the low-normal range indicate testicular failure, which warrants testosterone therapy.
  • Symptomatic men with normal testosterone levels but increased LH levels should be considered as having testosterone deficiency.
  • Symptoms are more closely related to calculated free testosterone levels than total testosterone levels.

The BSSM guidelines includes a practical guide/algorithm for the hypogonadism diagnostic process.

Professor Hackett points out the AUA guideline recommendation that clinicians should inform patients with testosterone deficiency that low testosterone is a risk factor for heart disease. Many men with low testosterone also have erectile dysfunction, which is another independent risk factor for heart disease. Unfortunately, low testosterone and erectile dysfunction are commonly not taken into consideration by clinicians when evaluating men for heart disease risk.

Obesity and type 2 diabetes are major risk factors for testosterone deficiency.

  • Up to 75% of men with type 2 diabetes have erectile dysfunction.
  • 16% of men with type 2 diabetes have testosterone levels below the normal range with a further 24% in the low normal/borderline range associated with symptoms of hypogonadism.
  • An average clinical practice with 9,000 patients will have 29 men with diabetes and definite low testosterone and a further 42 in the borderline range.
  • 7 million UK adults have pre-diabetes (35.3%), which is also associated with testosterone deficiency.

The European Male Aging Study (EMAS) showed that low testosterone is more strongly correlated with obesity (BMI) than age, and that weight loss can increase testosterone levels to a small degree. However, in order to significantly increase testosterone levels, a large amount of weight loss (15%) and weight loss maintenance are required, which is notoriously difficult to achieve.

In contrast to the BSSM, AUA and EAU guidelines, the European Academy of Andrology (EAA) guidelines provides contradictory recommendations. Where does this leave general practitioners? Professor Hackett notes that contradictory guidelines are a hindrance for the provision of effective and safe medical care for men with hypogonadism, and that accurate up-to-date guidelines for clinical practice, such as those provided by the BSSM, are needed.

For more information about clinical guidelines on hypogonadism and testosterone therapy, see:

Clinical guidelines for treatment of hypogonadism with testosterone therapy

Clinical practice guidelines on diagnosis and treatment of hypogonadism – important issues

The BSSM guidelines also recommend screening for hypogonadism in men receiving long-term opiate, antipsychotic or anticonvulsant medications.1 The ADA (American Diabetes Association)4 and AACE (American Association of Clinical Endocrinologists) / ACE (American College of Endocrinology)5 also recommend screening for hypogonadism in men with obesity or type 2 diabetes.

Regarding diagnosis of hypogonadism, the BSSM guidelines recommend a trial of testosterone therapy for at least 6 months in symptomatic men even if they have testosterone levels in the low-normal range.1 Men with a total testosterone level lower than 8 nmol/L or free testosterone level lower than 180 pmol/L (<0.180 nmol/L) usually require testosterone therapy.

The BSSM guidelines further state:1

  • Free testosterone levels below 225 pmol/L (0.225 nmol/L) provides supportive evidence for testosterone therapy in the presence of symptoms, regardless of total testosterone levels.
  • Increased LH levels in the presence of testosterone levels below normal or in the low-normal range indicate testicular failure, which warrants testosterone therapy.
  • Symptomatic men with normal testosterone levels but increased LH levels should be considered as having hypogonadism.
  • Symptoms are more closely related to calculated free testosterone levels than total testosterone levels.

NOTE:
Calculated free testosterone can easily be obtained by inputting measured values for total testosterone and SHBG into an online calculator

Professor Hackett points out the AUA guideline recommendation that clinicians should inform patients with testosterone deficiency that low testosterone is a risk factor for heart disease. Many men with low testosterone also have erectile dysfunction, which is another independent risk factor for heart disease. Unfortunately, low testosterone and erectile dysfunction are commonly not taken into consideration by clinicians when evaluating men for heart disease risk.

Obesity and type 2 diabetes are major risk factors for hypogonadism:6

  • Up to 75% of men with type 2 diabetes have erectile dysfunction.
  • 16% of men with type 2 diabetes have testosterone levels below the normal range with a further 24% in the low normal/borderline range associated with symptoms of hypogonadism.
  • 7 million UK adults have pre-diabetes (35.3%), which is also associated with testosterone deficiency.

The European Male Aging Study (EMAS) showed that low testosterone is more strongly correlated with obesity (BMI) than age, and that weight loss can increase testosterone levels to a small degree.7 However, in order to significantly increase testosterone levels, a large amount of weight loss (15%) and weight loss maintenance are required, which is notoriously difficult to achieve.

In contrast to the BSSM,1 AUA2 and EAU3 guidelines, the European Academy of Andrology (EAA) guidelines8 provides contradictory recommendations. Where does this leave general practitioners? Professor Hackett notes that contradictory guidelines are a hindrance for the provision of effective and safe medical care for men with hypogonadism, and that accurate up-to-date guidelines for clinical practice, such as those provided by the BSSM, are needed.

For more information about clinical guidelines on hypogonadism and testosterone therapy, see:

"Clinical guidelines for treatment of hypogonadism with testosterone therapy"

"Clinical practice guidelines on diagnosis and treatment of hypogonadism – important issues"


 

Speakers

Dr. Geoffrey Hackett

Professor Geoff Hackett
Aston University & University Hospitals Birmingham NHS Foundation Trust

References

  • 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. Dec 2017;14(12):1504-1523. Return to content
  • Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urol. Aug 2018;200(2):423-432. Return to content
  • Salonia A, Bettocchi C, Carvalho J, et al. 2020 EAU Guidelines on Sexual and Reproductive Health (available at https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-Sexual-and-Reproductive-Health-2020.pdf accessed April 9th, 2021). Return to content
  • American Diabetes Association. Summary of Revisions: Standards of Medical Care in Diabetes 2018. Diabetes Care. Jan 2018;41(Suppl 1):S4-S6. 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://www.endocrinepractice.org/article/S1530-891X(20)44630-0/fulltext (accessed April 9, 2021) Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. Jul 2016;22 Suppl 3:1-203. Return to content
  • Salonia A, Rastrelli G, Hackett G, et al. Paediatric and adult-onset male hypogonadism. Nat Rev Dis Primers. May 30 2019;5(1):38. 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 Aging Study. J Clin Endocrinol Metab. Jul 2008;93(7):2737-45. Return to content
  • Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: Endorsing organization: European Society of Endocrinology. Andrology. Sep 2020;8(5):970-987. Return to content