Does Ageing Reduce Testosterone Levels?

Take-home points

• Testosterone seems to decline beyond the age of approximately 40 years old, although more evidence is needed.
• Staying in great health and avoiding chronic disease will minimise the risk of low testosterone with advancing age. 
• If you have symptoms of low testosterone, contact a health professional as soon as possible.

The role of testosterone in men

Testosterone is central to men's health. Without enough of this androgenic hormone, men risk impairing reproductive health, sexual function, bone health, fat metabolism, muscle mass and strength, among other key functions. It is therefore unsurprising that males are concerned with low testosterone levels as they age. ‘I want to feel like I did in my 20s’ is a common goal of older male patients, with an interest in the potential treatments that might bring their levels back to normal. 

Does ageing lower testosterone levels?

The question of whether ageing reduces testosterone brings with it many interesting sub-questions that we will soon cover, but the question itself is fairly straight forward to answer: most likely, yes. The bulk of high-quality evidence suggests that, on average, testosterone levels decrease by 0.4–2% each year after the age of 30.^1,2,3 This is not as drastic a decline as some people might assume, but a decline nonetheless. As a consequence of this steady decline, the prevalence of clinically low testosterone levels also 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

Only a few studies in the last 10 years provide evidence against ageing reducing testosterone in men. One analysis of 13 studies (including over 10,000 males) found that the average male testosterone level peaks at age 19, falls only slightly until 40 years, and then remains relatively stable until death.⁴ Similarly, another study of 60,000 males found minimal decline in testosterone beyond 35 years old, until 80.⁵ What these studies then supported was a slightly different hypothesis: not that aging reduces testosterone, but rather that it increases testosterone variance; in other words, that ageing increases the proportion of males with considerably higher and lower testosterone levels than the average.

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To be clear, however, this alternate hypothesis is still in its infancy and should be interpreted with caution. The data is at odds with the totality of evidence (we never expect all evidence to favour a truthful claim) and the studies tended to measure testosterone with less accurate and more variable tools (non-extraction immunoassays) compared to ‘gold-standard’ methods (mass spectrometry).^6,7 If we also use mere intuition, it is simply unlikely that unknown factors increase testosterone in ageing men as much as known factors (such as chronic disease) decrease it. Possible, but unlikely.

Ageing and testosterone: The impact of chronic diseases on testosterone

A range of chronic diseases wreck havoc on the endocrine system, and low testosterone is often the end result. Whether it is the systemic inflammation induced by certain cancers⁸, the oxidative stress from high blood sugars levels in type 2 diabetes⁹, the conversion of testosterone to estrogen from excess abdominal fat in obesity¹⁰, or even some of the medications used to treat chronic disease, there are many different mechanisms by which chronic disease (and its treatment) can lower circulating testosterone levels. Experts agree that chronic diseases, which are more common with advancing age, are a main driver of low testosterone.

The question then becomes, how much of the age-related decline in testosterone is a product of chronic diseases? Or in more relatable terms, if a man were to remain in great health, will his testosterone levels still drop as a function of age alone? 

These are thought-provoking questions and the answer is not clear-cut. Indeed there is evidence that testosterone levels do not significantly differ in men above and below 40 years old if they are deemed in very good to excellent health.¹¹ However, a large number of well-designed observational studies have shown that testosterone still decreases in ageing men without chronic disease.^2,12,13  Perhaps the largest trial (the Massachusetts Male Ageing Study) of all also supports this conclusion too.¹⁴

We also note that even if testosterone remains stable when you account for chronic diseases, it is important to remember that age and chronic diseases are closely tied. Cardiovascular disease, for instance, is the consequence of sufficient lifetime exposure to certain lipids (specifically, ApoB-containing lipoproteins). You are more likely to have cardiovascular disease with each year of life. Therefore, estimating the testosterone-reducing effect of age independent of chronic disease is inherently problematic. Likewise, trying to put a percentage on how much the changes in testosterone with age is due to chronic disease is probably a fools errand. 

What is widely agreed on, though, is that chronic diseases accelerate the rate of testosterone decline, and some medications used to treat the chronic disease may further exacerbate this effect. Quite simply, it is more likely that a man above 40 years old will have low testosterone if he has at least one chronic disease (versus a man with none), and it may be considered a prerequisite for men to remain in good health if they want to minimise their chances of low testosterone. 

How does age itself reduce testosterone?

If age itself reduces testosterone levels–which it probably does–it would be explained mostly by the degeneration of testosterone-producing leydig cells in the testes.¹⁵ This is a fairly consistent observation in older men with low testosterone¹⁶, and has been seen experimentally in many animal studies, too. In rodents, the capacity of leydig cells to produce testosterone is reduced by approximately 50% with ageing. Aged leydig cells appear to become less responsive and sensitive to the leutinising hormone which stimulates the testes to produce testosterone.¹⁷

The greatest decrease with age is also not testosterone per se, but actually bioavailable testosterone. Even in studies reporting that testosterone levels remain stable with age, bioavailable testosterone (if measured) still tends to decline linearly over the life span.¹⁸ Some reports find that bioavailable testosterone can reduce by 50% by age 75.¹⁹ This is explained by a rise in sex-hormone binding globulin (SHBG) with age, as only testosterone unbound from SHBG is considered “free” or “bioavailable”. 

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References

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14. Gray A, et al. J Clin Endocrinol Metab 1991;73(5):1016-25.
15. Cohen J, et al. Front Endrocrinol (Lausanne) 2019;10:916.
16. Zirkin BR, Tenover JL. J Androl 2012;33(6)1111-1118.
17. Chen H, et al. Mol Cell Endrocrinol 2009;306(1-2):9-16.
18. Fabbri E, et al. J Gerontol A Biol Sci Med Sci 2016;71(9):1202–1209.
19. Vermeulen A, et al. J Clin Endrocrinol Metab 1996;81(5):1821-6.

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