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Talking testosterone
deficiency (TD)

Comorbidities

TD is related to a number of comorbidities in men which may result in increased mortality risk.1

TD appears to be closely linked to poor metabolic health, and obesity has a direct impact on the hypothalamic-pituitary-testicular (HPT) axis that regulates testosterone production.1,2 Moreover, low testosterone is further associated with visceral obesity and metabolic syndrome.3

52%

of men classified as obese (BMI >30 kg/m2) may suffer from TD4

The relationship between TD and T2DM appears to be bi-directional. Low testosterone levels are often observed in men with T2DM and insulin resistance, and men with TD are at an increased risk of developing T2DM.1 Furthermore, acute deprivation of testosterone induces insulin resistance in men.1

TD has been shown to predict an increased risk of mortality in men with T2DM vs. men with T2DM and normal testosterone levels. Normalisation of testosterone with testosterone therapy has been shown to reduce mortality risk in this population compared to that of eugonadal controls.5

Erectile dysfunction (ED) is a key presenting symptom of TD that is also common in men with T2DM.6

50% of men

of men with T2DM may suffer from TD4

Testicular cancer, as well as the surgical and medical treatments employed by oncologists, can have a significant effect on testosterone levels. A long-term study conducted by Steggink et al. demonstrated that 20% of patients who underwent orchidectomy, with or without chemotherapy, were diagnosed with primary TD.7

20%

of patients undergoing orchidectomy were diagnosed with TD7

Testosterone has a bi-directional relationship with lipid metabolism.1

Men with adverse lipid profiles (high density lipids [HDL] < 0.9 mmol/L and triglycerides [TG] > 1.8 mmol/L) are reported to have significantly lower levels of total testosterone.8

Haring et al. investigated a study population of 1468 men, aged 20–79 years, with a 5-year follow-up, concluding that low total testosterone is prospectively associated with an adverse lipid profile and increased risk of incident dyslipidaemia.9

Testosterone may have anti-inflammatory properties. Testosterone levels are frequently inversely correlated with markers of systemic inflammation and metabolic risk.

Several studies have shown an increase in pro-inflammatory cytokines in TD; where inflammation can be supressed when testosterone levels are normalised with testosterone therapy (TTh).10 It is important to note that more evidence is needed to confirm the relationship between TD and inflammation.1

The relationship between low testosterone and sexual dysfunction is well established. Typically, men with TD have low libido and erectile dysfunction (ED) which can be improved by TTh.1,11 Correction of testosterone levels <10.4 nmol/L may salvage non-responders to phosphodiesterase 5 inhibitors (PDE5i).12

TD not only impacts a man’s emotional and sexual health, it is also a predictive marker of vascular disease and mortality6

Cardiovascular health

Low testosterone in men is linked to hypertension, increased vascular stiffness and atherosclerosis.1 In men with congestive heart failure, low testosterone indicates poor prognosis, associated with increased hospital admissions and longer stays.13

The QRISK3 calculator has been updated to include ED, reflecting the new status of this common symptom of TD as a predictive marker of cardiovascular disease.14 Likewise, TD is also a marker of cardiovascular risk.15

Pharmaco-epidemiological studies suggest that men with untreated TD are at increased risk of mortality vs. eugonadal men, and vs. men with TD with normalised testosterone levels through treatment.1,15–17

The link between testosterone and erythropoiesis has been established for decades, with testosterone potentially playing a key role in the stimulation and regulation of the haematopoietic system.18,20

Therefore, low levels of testosterone could be detrimentally impacting red blood cell production, which may be the cause of unexplained anaemia in your male patients.18-20

Untreated TD is a mortality risk.14 TD is treatable.16 Learn more.

References

  1. Traish AM. Adverse health effects of testosterone deficiency (TD) in men. Steroids. 2014;88:106–116.
  2. Lee H-K, Lee JK, Cho B. The Role of Androgen in the Adipose Tissue of Males. World J Mens Health. 2013;31(2):136–140.
  3. Zarotsky V, Huang M-Y, Carman W, et al. Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men. Andrology. 2014;2(6):819–834.
  4. 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). J Sex Med. 2016;13(12):1787–1804.
  5. Muraleedharan V, Marsh H, Kapoor D, et al. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol. 2013;169(6):725–733.
  6. Hackett G, Heald AH, Sinclair A, et al. Serum testosterone, testosterone replacement therapy and all-cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins. Int J Clin Pract. 2016;70(3):244–253.
  7. Steggink LC, van Beek AP, Boer H, et al. Insulin-like factor 3, leuteinizing hormone and testosterone in testicular cancer patients: effects of ß-hCG and cancer treatment. Andrology. 2019;7(4):441–448.
  8. Agledahl I, Skjaerpe P-A, Hansen J-B, et al. Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: the Tromsø study. Nutr Metab Cardiovasc Dis NMCD. 2008;18(4):256–262.
  9. Haring R, Baumeister SE, Völzke H, et al. Prospective association of low total testosterone concentrations with an adverse lipid profile and increased incident dyslipidemia. Eur J Cardiovasc Prev Rehabil Off J Eur Soc Cardiol Work Groups Epidemiol Prev Card Rehabil Exerc Physiol. 2011;18(1):86–96.
  10. Mohamad N-V, Wong SK, Wan Hasan WN, et al. The relationship between circulating testosterone and inflammatory cytokines in men. Aging Male Off J Int Soc Study Aging Male. 2019;22(2):129–140.
  11. Saad F, Gooren L, Haider A, et al. Effects of testosterone gel followed by parenteral testosterone undecanoate on sexual dysfunction and on features of the metabolic syndrome. Andrologia. 2008;40(1):44–48.
  12. Hackett G, Kirby M, Wylie K, et al. British Society for Sexual Medicine –Guidelines on the management of erectile dysfunction in men – 2017. J Sex Med. 2018;15:430–457.
  13. dos Santos MR, Sayegh ALC, Groehs RVR, et al. Testosterone Deficiency Increases Hospital Readmission and Mortality Rates in Male Patients with Heart Failure. Arq Bras Cardiol. 2015;105(3):256–264.
  14. Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ. 2017;357.
  15. Corona G, Rastrelli G, Di Pasquale G, et al. Testosterone and Cardiovascular Risk: Meta-Analysis of Interventional Studies. J Sex Med. 2018;15(6):820–838.
  16. Yeap BB, Araujo AB, Wittert GA. Do low testosterone levels contribute to ill-health during male ageing? Crit Rev Clin Lab Sci. 2012;49(5-6):168–182.
  17. Testogel® 16.2 mg/g gel – Summary of Product Characteristics (SmPC) – https://www.medicines.org.uk/emc/product/8919/smpc. Accessed April 2021.
  18. Al-Sharefi A, Mohammed A, Abdalaziz A, et al. Androgens and anemia: current trends and future prospects. Front Endocrinol. 2019;10:754.
  19. Al-Sharefi A, Quinton R. Hiding in a plain sight: A high prevalence of androgen deficiency due to primary hypogonadism among acute medical inpatients with anaemia. Clin Endocrinol. 2018;89(4):527–529.
  20. Shahani S, Braga-Basaria M, Maggio M et al. Androgens and erythropoiesis: past and present. J Endocrinol Invest. 2009;32(8):704–716.

TES/2022/045. February 2023.

Adverse event reporting

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Besins Healthcare (UK) Ltd Drug Safety on 0203 862 0920 or Email: pharmacovigilance@besins-healthcare.com

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