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Testosterone is a hot topic. Every time I look up sports news on the internet, I see an advertisement for a TRT clinic. Driving around town, it seems like TRT clinics are as common as sandwich shops. All the guys at the gym want to talk about it. Testosterone is indeed important. The goal of this article is to provide a primer on the varied and important ways that testosterone impacts our body as men.
How Testosterone Changes As We Age
The majority of men’s testosterone is produced in the testes (about 90-95%, the other 5-10% is produced in the adrenal glands). The testes essentially have two jobs: 1) make sperm, and 2) produce testosterone. Specialized cells within the testes called Leydig cells do the job of producing testosterone. Males start to produce testosterone while in their mother’s womb, and it is the presence of testosterone that causes the development and growth of male genitalia in utero.
For most of childhood, testosterone levels are very low, almost negligible. Then at the start of puberty, a switch is turned on and the testes begin to secrete higher and higher levels of testosterone. This switch is initiated by a series of events in the brain which ultimately leads to the pituitary gland increasing its production of a hormone called luteinizing hormone (LH). LH then travels to the testes where it acts on Leydig cells and stimulates them to secrete testosterone.
The increase in testosterone levels at the start of puberty causes a number of changes that we associate with male pubertal development. Boys go through a pubertal growth spurt and continue to grow until their growth plates close. Their voice deepens. Muscles grow. Genitalia grows. Pubic and axillary hair and a beard develop. Libido arrives on the scene.
Testosterone levels reach full adult levels towards the end of puberty, and for most men they remain at optimal levels through their 20’s and 30’s. Then, somewhere around 40 years of age, an unfortunate thing happens. Testosterone levels begin to fall. In fact, testosterone levels decline on average about 1% per year starting at age 40-45 years old, and continue an inexorable decline for the rest of men’s lives. The decrease in testosterone production and the symptoms that go along with it is called andropause. Andropause does not get as much attention as the female equivalent, menopause. This is probably because menopause is a much more sudden change, with women experiencing a drastic decrease in their sex hormones (estrogen, progesterone, and testosterone) over 2-3 years, whereas the decline in testosterone for men is a more gradual event that occurs over at least 2-3 decades.
Historical Decline in Testosterone Levels
Not only do men’s testosterone levels decline as we age, but it turns out that there has been a historical decline in testosterone levels over time. Two recent population studies have shown that testosterone levels in age-matched populations of American men have declined rather sharply over the past generation. One study, published in 2007, measured average total testosterone levels of different groups of men, aged 45-80, across three time periods:
- 1987-1989: 501 ng/dl
- 1995-1997: 435 ng/dl
- 2002-2004: 392 ng/dl
That’s a 22% drop in less than 20 years, if you are keeping score at home. This change was highly statistically significant, even after controlling for age, BMI, and other potential confounding factors.
The second study was published in 2020 and showed a significant decrease in testosterone among American men with an average age of 26 from 1999-2016:
- 1999: 605 ng/dl
- 2016: 451 ng/dl
That’s a 25% decline in less than 20 years.
In this second study, the percentage of young men who had testosterone deficiency (defined as a level < 300 ng/dL) increased from 9% in 1999 to 20% in 2016. It’s unclear why testosterone levels have fallen so dramatically over the last generation, but there are many suspected culprits. Endocrine-disrupting chemicals (EDCs), including those found in ever-present plastics, exposure to blue light, exposure to cell phones and wi-fi, chronic stress, poor sleep, obesity, and other unknown factors all may be playing a role.
How to Evaluate Testosterone Levels
How do you know if your testosterone is low? The simple answer is to check your total testosterone level, which has historically been the gold-standard marker for evaluating testosterone. But it turns out it is not as simple as that. There are at least two reasons why it is more complicated.
The first reason is that the total testosterone level is only one aspect of a man’s testosterone status. Once secreted by the testes, testosterone is transported through our blood stream and carried to the tissues upon which it acts. The majority of testosterone is transported through the blood bound to a protein called sex hormone binding globulin (SHBG). This “bound” testosterone is not actually active, but is considered the storage form of the hormone. In order to become active, testosterone must be unbound from SHBG. This unbound testosterone, called “free testosterone,” accounts for only about 5% of the total testosterone in the blood, but it is this small minority that is the active form that actually acts on testosterone receptors (also called androgen receptors) in target cells. It turns out that the free testosterone level correlates more closely with symptoms of testosterone deficiency than the total testosterone level. Not only that, but the sensitivity of the androgen receptor also determines a man’s testosterone status, such that men who have a relative resistance to testosterone may experience symptoms of low testosterone at higher testosterone levels. Total and free testosterone levels can be measured with a simple blood test, but we have no way of assessing the sensitivity of the testosterone receptor.
The second reason that evaluating testosterone status is more complicated than it might seem is because of differences in perspective between the definition of “normal” and “optimal”. Most standard labs will report that the reference range for normal adult male testosterone levels falls somewhere between 250 ng/dL and 1000 ng/dL. If that seems like a very wide range, you are right. These normal ranges are not reported according to age, they are simply the published normal ranges for men from 18 years old all the way to 80 years old. But as we learned earlier, men’s testosterone levels consistently fall after the age of 40-45 years old. So it can be very misleading to evaluate a 65 year man’s testosterone level based on average levels from 20-80 year olds, but that is exactly what is typically done in conventional medicine. For example, it is not uncommon for a man to have testosterone level around 800-1000 ng/mL when he is in his 20s. By the time he is in his 50s and 60s, that level often falls somewhere in the 300 to 500 range (these levels are typical, but of course levels can vary widely). So a very common scenario is for a 60 year old man’s testosterone level to be half or even a third of the level he had when he was in his 20s. Is that level normal? Conventional medicine would say yes. But is the level optimal? That’s the million dollar question.
How Testosterone Impacts Our Bodies
Let’s be honest. When we think about testosterone physiology, the first thing we think about is sex. And for good reason. There is no question testosterone plays a major role in men’s (and women’s) sexual health. But optimal testosterone levels are associated with numerous other health benefits as well. Men with lower testosterone (and estradiol) levels die at a younger age. In fact, risk of death is nearly twice as high in men with low testosterone compared to men with higher levels. Testosterone improves bone health, increases muscle mass, and decreases visceral fat. Testosterone lowers cholesterol levels and is important for heart health. Testosterone can benefit cognition and decrease risk for Alzheimer’s. Testosterone boosts energy and mood as well. Let’s review these effects in more detail.
With the hormonal changes associated with andropause, men often experience a marked decline in abilities that once seemed second nature to them. Libido declines. Morning erections become less frequent, and sometime disappear altogether. Erectile dysfunction (ED) becomes prevalent. During this time men may find they have a hard time rising to the occasion. While different studies report different numbers, it is commonly quoted that 40% of men in their 40s, 50% of men in their 50s, and 60% of men in their 60s experience ED. Optimizing testosterone levels is the most effective treatment (or prevention) of the above symptoms that we have in medicine.
While sexual function is often the first thing on men’s minds, building muscle mass is probably a close second. Countless well-designed studies conducted over the past few decades demonstrate that testosterone therapy reliably increases muscle mass, while at the same time decreasing visceral fat (visceral fat is the type of fat that is found in the abdominal area and is highly linked with insulin resistance, inflammation, and heart disease). Conversely, when testosterone levels are reduced in various conditions (for example androgen deprivation therapy for prostate cancer), muscle mass consistently declines. How much muscle will you gain when your testosterone is optimized? The answer to that question is highly individual. Differences in testosterone dose, genetic potential, protein intake, and resistance training will all influence the outcome.
Moving on from muscle mass and body composition, bone strength is another important area that testosterone impacts. Most of us think of osteoporosis as a disease of elderly women, and it is true that women have a higher risk of frail bones and fractures than men. But with our increasing life span and with the Boomer generation entering into their silver years, the number of men suffering osteoporotic fractures is expected to increase significantly. Men with low testosterone levels have a much higher risk of brittle bones and fractures. While it has not been studied as extensively as in women, research demonstrates that testosterone, via its conversion to estrogen, effectively increases bone strength and reduces fracture risk in men.
It is a well-known fact that heart disease is the leading cause of death for men in the United States. Low testosterone levels are associated with higher risk of major cardiac events (e.g. hearts attacks) and mortality due to cardiovascular events. Optimal testosterone levels can positively impact heart health through multiple mechanisms. As we have learned, testosterone decreases visceral fat which in turn improves insulin resistance and metabolic health, which are major contributors to heart disease. Randomized controlled trials show that testosterone therapy improves insulin resistance and glucose levels compared to placebo in hypogonadal men with prediabetes or type 2 diabetes. Testosterone increases the production of nitric oxide which improves the health of the endothelium, the inner lining of our blood vessels. Testosterone lowers Apolipoprotein B and LDL cholesterol levels. Testosterone also reduces systemic inflammation, which is another important contributor to heart disease. Optimal testosterone levels are beneficial for strong, healthy hearts and help protect against cardiovascular disease.
Conclusion
Testosterone is a vital hormone for men’s health, impacting a wide range of systems including brain and heart health, bone strength, muscle mass, and sexual function. The fact that testosterone levels decline as men age, and the relative ease of optimizing testosterone levels if indicated, has created an ongoing controversy as to when to start testosterone replacement therapy. No one argues that men with frankly low testosterone, as defined by conventional standards, should be treated. But the question becomes more controversial when a man presents with clear-cut symptoms of low testosterone, has a testosterone level that is far lower than it was when he was younger, and yet his level remains in the normal range by conventional standards. Should such men be treated? Do the benefits outweigh the risks? As the medical world learns more about the benefits and importance of testosterone a more forward-leaning approach to this question is underway.cLearn more about the TRT services in Phoenix offered at Valley Healthspan by booking a consultation today.
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