The role of Testosterone in osteoarthritis and joint replacement

Take-home points

• Low testosterone levels in men increases the risk of bone fractures. 
• Men with chronically low testosterone and frailty are probably more likely to need hip and knee replacements in later life.
• Testosterone replacement therapy can improve markers of bone health in men with low testosterone levels and bone mineral density. 

Testosterone, hip and knee replacement

Scientists continue to uncover the role of testosterone in various aspects of men's health. One area of particular interest is the potential relationship between testosterone levels and hip and knee replacements, also known as total hip arthroplasty and total knee arthroplasty. Usually as a consequence of osteoarthritis, rheumatoid arthritis, or injury, these two surgical procedures replace damaged or worn-out hip or knee joints to improve strength, mobility, and reduce pain and stiffness. During surgery, the damaged joint surfaces are replaced with artificial components made of metal, plastic, or ceramic materials, restoring joint function and alleviating pain.

Prevalence of low testosterone and hip and knee replacement 

Testosterone levels decrease by approximately 1% per year in men starting at age 40 years.¹ As a consequence of this steady decline, the prevalence of clinically low testosterone levels increases with age: up to 20% of men over 60 years old have low testosterone, 30% of men over 70 years old, and 50% of men over 80 years old.²

Hip and knee replacements are among the most common elective surgical procedures performed worldwide. According to the World Health Organization, osteoarthritis, the leading cause of joint replacements, affects more than 250 million people globally. The prevalence of osteoarthritis increases with age, and as more people worldwide live longer, the demand for joint replacements continues to rise. The global economic impact of osteoarthritis will double by 2030, according to some predictions.³ Currently, 30% of adults will develop symptomatic knee osteoarthritis by the age of 65 years and nearly 50% by the age of 85 years, with the highest risk among those who are overweight for extended periods of life.⁴

Is testosterone linked with hip and knee replacement?

When men of any age develop severely low testosterone, the risk of bone fractures increases.⁵ Additionally, in the second half of life, women have a significantly higher prevalence of symptomatic knee osteoarthritis and greater disability from knee osteoarthritis than men.⁶ Taken together, these observations led to a hypothesis that hormonal differences or changes could affect bone health and the risk of hip and knee replacement surgeries, especially since the cartilage, bone, and muscle surrounding these joints all express testosterone receptors.⁷

In 2016, doctors at Monash University in Australia then reported in the medical journal Osteoarthritis Cartilage that circulating plasma sex steroids were indeed associated with both hip and knee arthroplasty for osteoarthritis.⁸ Using blood samples drawn from 2494 men in the years 1990–1994, links were made to the incidence of total knee and hip arthroplasty for osteoarthritis during 2001–2013 using national registry data. 104 of the men had knee and 80 of the men or hip arthroplasty during this time, and higher concentrations of androstenedione, a precursor of testosterone, were found to be associated with a 13–16% decreased risk of total knee and hip arthroplasty for osteoarthritis in overweight and obese men.  

Since then, a genetic analysis has provided even stronger support for the causal link between testosterone and joint replacement surgeries.⁹ From analysing nearly half a million European adults in two large datasets (UK Biobank and Arthritis Research UK Osteoarthritis Genetics), the study researchers found that testosterone levels are causally associated with the risk of hip osteoarthritis and hip replacement surgery risk. No significant association was found for knee replacement, however, suggesting testosterones effect may apply to certain joints only.  

But most currently available evidence does indicate that testosterone relates to osteoarthritis and associated symptoms within the knee joint. In one 18–month study of 309 overweight adults with knee osteoarthritis, higher testosterone levels were associated with less joint stiffness among men.¹⁰ Similarly, in a cross-sectional analysis of 273 seniors with severe knee osteoarthritis, higher testosterone levels were associated with less joint pain in the operated knee and less joint pain generally in normal-weight men.¹¹

How could testosterone reduce hip and knee replcaement risk?

The exact mechanisms underlying the relationship between testosterone and joint replacements remain unclear. One study in healthy middle-aged men with no symptoms of knee osteoarthritis or risk factors found that free testosterone levels were associated with the rate of tibial cartilage loss after two years, which typically leads to osteoarthritis development.¹² But it may be a two-way relationship; some experts suggest that chronic pain and physical limitations associated with joint problems could suppress testosterone production. In that case, low testosterone levels would contribute to and progress the development of osteoarthritis, leading to the need for joint replacements, with the consequences only further lowering testosterone. 

Does TRT help with hip and knee replacement?

It is well-known that hypogonadal men undergoing testosterone replacement therapy show improved health parameters, including bone mineral density, muscle mass, and physical strength.¹³ In this population, testosterone treatment also improves other markers of bone health such as trabecular architecture and mechanical properties.^14,15

Clinical trials have demonstrated that testosterone gel treatment in frail and hypogonadal older men can reduce chronic musculoskeletal pain, increase isometric knee extension peak torque, and improve overall power in stair-climbing and leg press activities.^16,17 Taken together, it is reasonable to hypothesise that such improvements would benefit the risk of knee and hip replacements and physical functioning post-surgery; however, direct research evaluating these outcomes remains scarce. 

The only direct evidence we found was a small study in 25 men, mean age 70, undergoing elective knee replacement surgery. Here, preoperative supraphysiologic testosterone administration (600 mg weekly intramuscular testosterone enanthate for 4 weeks) conferred early functional benefit shortly after the operation, including the mean hospital stay and ability to stand and walk.¹⁸ Similar benefits have been reported in pilot studies using anabolic steroids such as Nandrolone.¹⁹

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References

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19. Hohmann E et al. J Orthop Surg Res. 2010;5:93.