Can testosterone replacement therapy prevent osteoporosis?

Testosterone is an important male sex hormone that has a wide range of impacts on men's health. However, as age increases, male testosterone levels tend to decline annually. Data shows that serum testosterone levels in elderly men decrease by an average of 1% per year. This hormonal change may eventually evolve into secondary hypogonadism and lead to various problems. Apart from emotional changes and decreased physiological functions, the most significant ones are the decrease in muscle strength, bone density, and the appearance of metabolic syndrome.hgh bodybuilding

In terms of bone health, although the incidence rate of osteoporosis in women is more common, osteoporosis in middle-aged and elderly men will also increase with age. For example, according to Japanese data, the prevalence of osteoporosis in men aged 40, 70-75, 75-80, and>80 years old is less than 10%, 13%, 18%, and 21% respectively , and the incidence of femoral neck fracture in men is four times that in women.

After androgen deprivation therapy (prostate disease treatment regimen), the serum testosterone levels of males receiving treatment will immediately decrease, corresponding to lower bone density and higher incidence of osteoporosis. Generally, after starting androgen deprivation therapy, bone density will decrease by 2-8% within one year, which is believed to be caused by a decrease in serum testosterone and estrogen (aromatase converts testosterone to estradiol) levels.

Based on the above information, it is not difficult to determine the correlation between testosterone deficiency and bone density loss. Can we deduce the following conclusion in reverse: supplementing with exogenous testosterone (testosterone replacement therapy, TRT) can reduce the risk of osteoporosis?

Positive view: TRT can reduce the risk of osteoporosis/fractures in men

Positive reasons:

Testosterone itself can affect bone metabolism by binding to androgens. In addition, testosterone can be converted to estradiol by aromatase, which can bind to estrogen receptors α Subtype (this subtype is related to bone metabolism). Testosterone can also have some indirect effects on bone metabolism through various cytokines and growth factors. And testosterone deficiency can promote nuclear factors κ- The activation of B promotes bone resorption and reduces bone density.

Positive evidence:

1. A study on 2447 elderly men showed that the incidence of low testosterone in men with osteoporosis and normal bone density was 6.9% and 3.2%, respectively. The incidence of osteoporosis in men with low testosterone was significantly higher than that in men with normal gonadal function (12.3% vs 6%)

2. A meta-analysis involving 29 randomized controlled studies and 1083 participants showed that compared to placebo, TRT can increase lumbar spine bone density by 3.7%

Negative view: TRT cannot reduce the risk of osteoporosis/fractures in men

Reason for opposition:

The serum testosterone level does not always reflect the local testosterone level and metabolism in bone tissue, which can lead to unclear effects of supplementing exogenous testosterone on bone metabolism. Studies have shown that estradiol levels can better predict the risk of fractures, and this predictability is not related to serum testosterone levels or total estrogen levels. In addition, the protective effect of testosterone on bones seems to be attributed to the maintenance of muscles and strength. (For more information on estrogen, please read: To successfully reduce fat, you must understand estrogen.)

Evidence to the contrary:

1. <Latest Evidence>A study published in the New England Journal of Medicine on January 18, 2024, showed that a median age of 3.19 years of testosterone replacement therapy (testosterone skin gel) was administered to over 5000 men aged 45-80. The results showed that compared to the control group, the fracture risk in the testosterone replacement group was not reduced, but slightly increased (3.8% vs 2.8%)

2. In a study on the effect of testosterone on weight loss in obese men, no differences in bone density between the lumbar spine and femur were found in the control group after oral administration of testosterone undecanoate for 10 weeks

Although testosterone plays an important role in maintaining male health, the evidence for its effect in promoting bone health is still unclear. TRT itself has various unhealthy side effects, especially in cardiovascular and prostate aspects, which may offset the potential benefits of TRT. The safety measures to improve the risk of osteoporosis in middle-aged and elderly men mainly include: 1. Supplementing with VD; 2. Regular resistance training