Data strongly suggests a relationship between testosterone deficiency and frailty in elderly men

March 2012

The relationship between testosterone deficiency and frailty in elderly men. Saad F. Horm Mol Biol Clin Invest 2010;4(1):529-538.

This review aimed to discuss the relationship between low testosterone level and frailty in elderly men and to evaluate the data which show that treatment of frail hypogonadal men with testosterone therapy improves physical functioning and reduces some common risk factors for cardiovascular disease.1


In elderly men:

  • Testosterone is important as a regulator of body composition and for maintaining bone mineral density
    1. Increases fat-free mass and decreases fat mass
    2. Increases muscle mass and improves lean body mass
    3. Increases physical strength and reduces fatigue
  • Low testosterone is associated with frailty
    1. As an anabolic hormone, testosterone is involved in regulating protein, carbohydrate and lipid metabolism and may regulate pluripotential cell differentiation (enhanced myogenesis and inhibition of adipogenesis)
    2. The probability of frailty increases with reduced total testosterone level
    3. Low testosterone appears to be associated with an increased risk of falls and bone fracture
    4. Various measures of frailty (incident or worsening mobility limitation, fatigue, difficulty climbing stairs and/or walking any distance, multiple illnesses and weight loss) are associated with low testosterone level in community-dwelling older men
  • Low testosterone is associated with higher mortality
    1. Low testosterone level is associated with increased: insulin resistance, type 2 diabetes, metabolic syndrome, abdominal obesity, risk of cardiovascular disease (CVD), thrombosis, inflammatory markers, chronic obstructive pulmonary disease, depression, chronic renal disease, and a higher incidence of mortality
    2. There is evidence that low testosterone is an independent risk factor for mortality, rather than just a marker of an underlying condition
  • Low testosterone is common in men with heart failure
    1. Between 24% and 43% of patients with cardiac dysfunction have testosterone deficiency
    2. Low testosterone and dehydroepiandrosterone (DHEA) levels appear to be independent predictors of death in men with heart failure

Testosterone therapy has been shown to be beneficial in elderly frail men with low testosterone, including those with cardiac dysfunction and/or heart failure

  • Improves lean body mass and reduces fat mass
  • Improves hip and spine bone mineral density
  • Improves strength, physical and metabolic function
  • Reduces CVD risk factors, including waist circumference, cholesterol and proinflammatory cytokines and insulin sensitivity
  • However, it should be noted that frailty is a composite syndrome and not all aspects of frailty will be ameliorated by testosterone therapy

What is known

Frailty in aging men is the vulnerable health condition characterized by a cumulative decline in body composition and function, including decreased reserve, weight loss, diminished activity and mobility, sensitivity to change and a deterioration in nutritional status, cognition and endurance.1-3 Often a forerunner to the onset of overt disability, aspects of frailty are related to the neurological system, metabolism, joints, bones and muscles. Frailty in older adults is associated with increased morbidity and mortality; in one study in over 5000 subjects aged 65 years or over, frail individuals had a death rate almost double that of those classified as intermediate frail, and over three times that of non-frail individuals.2 Sarcopenia (the age-related loss of skeletal muscle mass, strength and function) and diminished bone mineral density are major determinants of frailty.3 As testosterone has a profound effect on body composition and is a key hormone necessary for the maintenance of bone mineral density, testosterone therapy may have a role in the management of frail older men with confirmed low testosterone levels.

What this study adds

This review demonstrated that, although frailty is a complex condition, the evidence suggests that testosterone therapy in frail elderly men with low testosterone level improves body composition and axial bone mineral density and physical function while ameliorating a number of risk factors for CVD. Although frailty is a composite syndrome and not all aspects of frailty will be ameliorated by testosterone therapy, available data strongly suggest a relationship between testosterone deficiency and frailty and warrant further investigation to determine those frail elderly men most likely to benefit from testosterone therapy and to define the role of testosterone therapy in the management of elderly men with frailty.


  • Saad F. The relationship between testosterone deficiency and frailty in elderly men. Horm Mol Biol Clin Invest 2010;4(1):529-538. Return to content
  • Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56(3):M146-156. Return to content
  • Pel-Littel RE, Schuurmans MJ, Emmelot-Vonk MH, et al. Frailty: defining and measuring of a concept. J Nutr Health Aging 2009;13(4):390-394. Return to content

For additional detail and supporting references for the statements summarised in this Research News article please click here to access the original review article.