Why testosterone replacement therapy (TRT) is not a good idea for anti-aging

Does testosterone slow down aging? Is testosterone replacement therapy a good longevity treatment?

When it comes to testosterone as it relates to longevity, our advice is simple: do nothing. 

This may come as a surprise to you if you think of the youthful associations with testosterone: muscles, sex drive, energy and masculine characteristics. And these associations are not unfounded. However, testosterone also comes at a cost: it accelerates aging, disease risk and reduces lifespan.

Despite this, testosterone therapies are being touted everywhere, from magazines, to TV,  online and by new startups with a financial incentive to downplay the long-term effects. There are even self-proclaimed longevity “experts” taking it themselves and incorrectly positing that younger biological measures of sexual health today are indicative of a longer healthspan and lifespan tomorrow. 

As we will explain in this article, although some people may feel younger from testosterone replacement therapy (TRT), they may be simultaneously burning the candle on both sides of the wick. Human longevity is about extending healthspan and lifespan, not about being 18 again.

When you follow a longevity lifestyle, your testosterone levels will adjust appropriately. Weight lifting and addressing nutrient deficiencies will raise testosterone levels, while fasting, reducing calories and decreasing protein intake will reduce them. Ultimately, your body will reach homeostasis, providing just the right dose of testosterone to maximize your lifespan, based on the well studied end results of these lifestyle tweaks – better health and lifespan. Supplementing with TRT will take you out of this homeostatic state and increase your risk for health issues, as this article will explore.

Testosterone For Anti-Aging: A Red Flag

One way to assess how knowledgeable a doctor or health expert is about longevity is by seeing what they recommend as anti-aging interventions, and whether they distinguish between feeling or looking younger and longevity (slowing down aging, extending healthspan and lifespan). The two are easy to confuse and do share common aspects, but they are ultimately different.

If someone is advocating taking testosterone, growth hormone and many of the common forms of antioxidants, they’re likely not an expert on the biology of aging and human longevity. After all, growth hormone accelerates aging and increases cancer risk (R,R,R,R), many antioxidants do not extend lifespan (R,R,R,R,R,R,R,R,R), and male hormones (“androgens”) like testosterone very likely shorten lifespan.

While there are some studies demonstrating some benefits of testosterone, like reduced fat mass, more muscle mass, more energy and greater sexual desire, these are only short-term aspects of health, not long-term.

To that point, many of the benefits of testosterone are based on short term studies and don’t look at how testosterone impacts aging and lifespan over extended periods of time. In the long run, testosterone very likely accelerates aging, even when given in small amounts to restore to youthful levels. Let’s dive in.

Testosterone and Aging: The Evolutionary Perspective

First, let’s zoom out and look at the big picture. There are various strong evolutionary reasons why male sex hormones like testosterone can accelerate aging.

In many species, there is an evolutionary tradeoff between sex and longevity. Typically, the more an organism is designed by nature to reproduce itself as quickly as possible, the shorter the lifespan. In other words, the more sex hormones circulating that drive reproduction, the shorter the lifespan. 

For example, mice have to reproduce very quickly and also have a very short lifespan. They need to reproduce as fast as possible before they are eaten or die of hunger or cold. Therefore, evolution has designed the bodies of mice to invest little in repairing and maintaining their tissues, while investing a lot in reproduction, so that the mice can quickly reproduce before they die. This involves greater activation of sex hormone pathways, especially male sex hormones.

These and many other studies show that higher levels of sex hormones are associated with faster aging and shorter lifespans. 

Conversely, an observation across species is that often the long-lived species reproduce much less or very late in life.

Sex Hormones At The Expense of Repair?

Professor Thomas Kirkwood has done extensive evolutionary biology research on the concept of the “disposable soma”: energy spent on reproduction (sex) is at the expense of energy spent at maintaining the tissues (slowing aging). In other words, the more an organism invests in reproduction the less it can invest resources to maintain its cells, which leads to faster wearing down of the cells (aging) (R). 

Health Outcomes of Very Low Testosterone Levels

We also see that castrating male animals extends their lifespan (R,R,R). With castration the gonads (testis) are removed, so the amount of male sex hormones such as testosterone declines precipitously.   

But what about humans? Similarly, castrated human males that have very low sex hormones like testosterone, live on average 14 years longer than their non-castrated counterparts (R,R,R,R). Eunuchs at courts are known for having significantly longer lifespans and less aging-related disease. In fact, a 2012 study found that 3.7% of Korean eunuchs studied lived to be centenarians, a frequency that is at least 130-times higher than the frequency in modern societies.

Men who have low testosterone throughout their lives as a result of Klinefelter’s syndrome have low rates of ischaemic heart disease, even though they have a high genetic vulnerability to diabetes (R).

What about comparing women, who have significantly less testosterone and more estrogen, to men? Women live on average seven years longer than men and one reason for this is believed to be that they have much less testosterone (R,R). This aligns with the 1969 theory of researchers Hamilton and Mestler, which is that testes markedly shorten lifespan, and is consistent with the idea that they are a determinant of the gender gap in human lifespan.

When we look at various interventions that extend lifespan, such as caloric restriction, fasting, eating less animal protein or consuming less essential amino acids, we find a common effect: a reduction in fertility and libido. This hints again at the body dialing back reproduction for the sake of better maintaining the body, and thus slowing down aging. (This is not to say that we recommend a reduction of fertility and libido – this is up to an individual’s lifestyle preferences and desires – we are just highlighting the connection.

The theory of antagonistic pleiotropy states that features that are “good” in young age could be bad in older age (or in the long term, accelerate aging). 

In the same vein, having lots of male sex hormones circulating when young (leading to increased reproduction) could later accelerate aging.

Puberty, Reproductive Age, and Lifespan

For humans, we start to age when puberty starts (characterized by sex hormones starting to rise dramatically). Before puberty, the risk of dying is very low (in children), while after puberty (starting from around age 11) the risk of dying doubles every eight years. Puberty is characterized by a massive production of sex hormones, such as testosterone, leading to adult male characteristics, like muscles, growth of facial and pubic hair, enlargement of the testicles, deepening of the voice and so on. 

In studies where scientists naturally extend lifespan, they often find that the organisms invest less energy in reproduction, or actually postpone reproduction, and invest more in maintaining their bodies, thereby slowing down aging.

Testosterone and Aging: Animal Studies

There are multiple studies that look into the effects of increasing or decreasing male hormones like testosterone on lifespan, as well as female hormones like estradiol on lifespan. Here are a few of the outcomes and studies:

• Giving testosterone to animals shortens their lifespan (R).
• Castrating male animals extends their lifespan (R,R,R).
• Giving male animals female hormones (like estradiol) extends their lifespan (R). 

Note that this is not a suggestion that males receive estradiol or be castrated! 🙂

Further, mouse studies suggest that androgens like testosterone are pro-inflammatory and may delay wound healing (R,R).

Testosterone, TRT, and Health Outcomes: Human Studies

Taking testosterone can improve some health biomarkers in humans, like increasing muscle mass, reducing fat mass, improving libido, and increasing energy. However, these are short term effects. In the long term, testosterone could accelerate aging.

Also, among the limited studies showing health benefits from TRT, they are often short term and disputed or have been refuted by other studies showing no long-term health benefits of testosterone (R).

On the other hand, people taking testosterone have an increased risk of prostate cancer, liver problems, clotting issues, dermatological and respiratory problems (R,R,R). 

One study found that men who get testosterone prescriptions were at an increased risk of non-fatal myocardial infarctions (R). Another study in which men were given testosterone was stopped prematurely due to much higher occurrence of cardiovascular adverse events (R). Other studies, especially when not funded by a pharmaceutical company, found an increased risk of cardiovascular disease and mortality in people who took testosterone, including people who had low testosterone levels (R). For example, a study published in JAMA found that giving TRT to elderly men with low testosterone increased their risk of a heart attack and mortality (R). 

Finally, it’s worth emphasizing that prostate cancer in men is primarily treated by giving patients drugs that block testosterone. 

Androgens and The Immune System

Androgens, or male hormones of which testosterone is the most well known, are generally known to suppress immune function, for example, by suppressing CD4 T-cell function (R,R,R,R). Oestrogen, on the other hand, is found to assist the immune system (R). Furthermore, androgen deprivation is associated with an enlargement of the thymus gland (a good thing), which produces the immune system’s white blood cells and atrophies with age, resulting in a weakened immune system in the elderly.

To that point, men tend to be more likely to get sick with an infection than females (R,R,R), but conversely, less likely to be afflicted by an autoimmune disorder.

Humans In The Wild

Often, anecdotal observations highlight that men with high levels of testosterone look strong (more muscle mass, deep voice, specific male facial features), but also often older for their age. Conversely, men with lower sex hormones and growth hormones have less muscle mass, but look younger, or more “boyish” for their age.

Anecdotal observations also show that bodybuilders or athletes who take male hormones often go bald at higher rates than the general population, as we explain in this article on preventing baldness. They also often look more aged.

Too much of the male sex hormone dihydrotestosterone is associated with baldness. Dihydrotestorone is a potent form of testosterone. Early baldness is a risk factor for various aging-related diseases, like heart disease and Alzheimer’s disease (R,R). Giving drugs that reduce the amount of the male hormone dihydrotestosterone reduces baldness. 

Government Warnings About Testosterone Therapy

In June 2014, the United States FDA added a warning about venous blood clots to testosterone product labels, and a month later in July 2014, Health Canada issued warnings about “serious and possible life-threatening heart and blood vessel problems such as heart attack, stroke, blood clot in the lungs or legs; and increased or irregular heart rate with the use of testosterone replacement products.” 

In March 2015, the US FDA extended its warning, declaring “the possible increased risk of heart attacks and strokes associated with testosterone use.” 

I’m a Male With Testosterone – What Should I Do For My Longevity?

As previously mentioned, multiple longevity lifestyle tweaks may result in lower testosterone levels, such as fasting, caloric restriction, reduction in protein intake, reduction in animal protein intake, etc. Some of the longevity benefits from these lifestyle changes are likely mediated by the reduction in testosterone (as well as a complex milieu of signaling pathways, like reduction in mTOR, increase in AMPK, etc.). 

At the same time, high-load weight-bearing exercises, especially those involving multiple muscle groups like squats, and correcting nutrient deficiencies will increase testosterone levels.

Ultimately, we urge you to not be concerned about your testosterone levels when following a longevity lifestyle, because the longevity interventions we share are shown to increase health span and lifespan, regardless of their effect on testosterone. This is because the testosterone levels are where the body needs them to be and are not being artificially increased.

Despite this, there are longevity “experts” who take TRT and testosterone patches in an effort to raise their levels back to a youthful state, likely reversing many of the longevity benefits of the lifestyle tweaks.

Using testosterone patches to make up for reduced levels caused from fasting or caloric restriction is quite unreasonable and is a simplistic view of biology, because endogenous testosterone production being abrogated impacts many more aspects of biology (e.g., signaling pathways).

We urge you to be very skeptical of these supposed experts, as they seem to have an overly simplistic comprehension of longevity science.

Instead, focus on getting the other aspects of your longevity lifestyle right: your diet, meal timing, longevity supplements, general health supplements, exercise and activity, recovery and reducing stress, etc., and don’t focus on altering your testosterone levels.

But What About My Libido, Energy Levels, and Muscle Loss?

There’s a common argument that having too little testosterone could lead to complaints like fatigue, loss of muscle mass, loss of libido, erectile dysfunction, and so on. However, a decline in testosterone is not the leading cause of each of these maladies. In fact, many other health problems, nutrient deficiencies, and fundamental aging processes predominantly lead to these issues. As it relates to sexual health and longevity, we cover the topic in this post.

Additionally, as many studies demonstrate, exercise and weight lifting are more than adequate to offset sarcopenia (muscle weakness and loss of muscle mass with age) for the vast majority of people, without the added risks that arise from meddling with testosterone levels.

Conclusion

Testosterone, like many other male hormones, can accelerate aging. One big red thread through biology is that there is a tradeoff between reproduction and aging. 

Unfortunately, it’s a common, though understandable misinterpretation that feeling young – for example, having the libido and sexual capacity of an 18 year old – is conducive to longevity, when it’s actually quite the opposite. It’s for this reason that we see consumers, amateur longevity public figures or founders, and even some MDs being proponents for testosterone replacement and incorrectly claiming that a youthful sex drive is an indicator of longevity.

Long-lived species invest more effort (on the cellular level) into maintaining their tissues than in reproduction. 

Conversely, short-lived species often invest a lot into reproduction, neglecting to maintain and repair their tissues, making them age comparatively faster.

As always, it’s a delicate balance. Taking extra testosterone is not something we at NOVOS recommend for longevity purposes, even if it’s just to restore testosterone to more youthful levels.

If you choose to pursue TRT to feel younger you can do so with your doctor’s approval and supervision, just realize that it may come at a cost later in life and is not pro-longevity. 

For clarity on ways to extend healthspan and lifespan, trust in NOVOS to provide science-backed longevity guidance, and to distinguish between popularized short-term “anti-aging” approaches that may come at a cost later in (a shortened!) life.

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Common Questions: 

What do you suggest regarding testosterone and longevity?

We suggest that you don’t do anything to modify your testosterone.

We don’t advise taking extra testosterone, nor do we suggest that you try to replenish your testosterone to more youthful levels. Similarly, we don’t recommend attempting to reduce your testosterone levels, unless it’s a natural result of a pro-longevity lifestyle change, such as a change in diet or caloric intake.

However, given everyone is different and has a unique medical history, we recommend always consulting with your doctor.

What about exercise and testosterone?

Acute rises in testosterone that may result from weightlifting, especially from exercises like squats, is unlikely to have a negative effect on longevity. Meanwhile, the benefits of weightlifting on longevity are significant. For this reason, we suggest you continue to weight lift without concern about its impact on your testosterone levels.

What about female hormones, like estrogen?

Contrary to testosterone, female hormones like estrogen can have longevity effects. Not only in females, but also even when given to males (R,R,R,R). 

Female hormones like estrogen could also be one of the reasons why women live on average seven years longer than men. 

Therefore, we are proponents of natural hormone treatment in postmenopausal women, as long as it is done with bioidentical hormones and given via the skin (via transdermal administration) and not orally (as some studies showing that hormone treatment was associated with an increased risk of blood clotting or heart disease used non-bio-identical hormones that were given orally). 

We will explain more about bioidentical hormone replacement therapy for menopausal women in a future blog article.

Should I have less sex to slow my aging?

At this point, you might be curious about the impact that having sex may have on your testosterone levels and by extension your lifespan, and whether having less sex would extend your lifespan. Fortunately, having sex is not going to have a notable impact on your testosterone levels.

Whether you have sex or not, sex hormones, including testosterone, keep circulating. The only significant way of reducing the levels of male sex hormones is by castration, which means removing the testis in men. Only then do testosterone levels go down enough to enable life-extending effects (do not do this, unless your doctor is advising you to for a medical condition).

Having less sex will have very little effect on lifespan. In fact, the opposite is likely true: more sex equates to a longer lifespan.

Although there is no indication whether the effect is causal or merely a correlation, some studies have found that sexually active people have lower levels of stress and improved cardiovascular health, both of which have been linked to a longer lifespan.
For example, one study published in the British Medical Journal in 1997 found that men who had frequent sexual intercourse (at least twice a week) had a 50% lower risk of fatal heart attack compared to men who had sex less often. Another study published in the Journal of Sexual Medicine in 2020 found that sexually active adults had a lower risk of mortality from all cause and cancer mortality for middle aged adults compared to those who were sexually inactive (R).