All About Testosterone

All About Testosterone

Anil Kumar, PhD
Created On
Nov 19 2017
Last Updated
Jan 17 2022

You will learn about: testosterone as a male hormone; low testosterone; low-T blood test; hypogonadism; history & properties of T; symptoms of low-T; testosterone in women; different forms of T; natural ways to boost testosterone levels; muscle strength and aging


Summary:

As the male hormone, testosterone—often abbreviated as T—is responsible for building muscles, increasing bone density, and maintaining sexual health in both men and women.

Testosterone levels start rising in puberty until they peak in the mid-twenties. Then they slowly decline about one-percent every year. This natural decline shows up in common signs of getting old: weight gain, weak muscles, hair loss, decreased libido, mental & behavioral changes, and low energy.

Chronic conditions such as obesity and diabetes can abnormally lower T levels, causing a cascade of other health problems. Hypogonadism is the term used to describe unusually low levels.

It is relatively easy to monitor and correct for low testosterone levels. An at-home testosterone test can measure free testosterone levels with a simple saliva sample. Checking other hormones, especially estrogen levels, with a men’s health test might also be useful.

This article discusses the history and science related to testosterone, the natural decline with age, and how to naturally maintain healthy levels.



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T for Testosterone

We commonly associate testosterone with men's sexual health. In reality, both men and women produce it. Since T is responsible for building strong muscles and bone, it's important regardless of gender. It is a key player in storing fat—especially around the waist.

Testosterone levels peak in youth, around the age of 25 years. Then start declining, about 1% per year in men.

This property of tissue growth is especially desirable: Athletes often use testosterone supplements for building muscles and to recover from the intense physical demands of sports. The supplements also help in delaying the drop in muscle mass, that naturally occurs with age. In general, the role of testosterone in athletic performance is hotly debated, especially in female athletes.

Despite controversy, supplements are especially useful for cancer patients & victims of starvation for much needed recovery and strength.

The medical term for unusually low T levels is hypogonadism. For healthy adults, low T levels, can cause weight gain, weak muscles, anxiety, and fatigue. The resulting health conditions such as diabetes and obesity can negatively affect T levels, further compounding these problems.

Among the elderly, low levels appear as being ‘cranky’, disinterested, and less sociable.

An at-home saliva test kit is relatively inexpensive method to check for low-T levels, with the added benefits of convenience and confidentiality. The biggest advantage is the ease of saliva sample collection, which eliminates any blood draw. However, results might be difficult to interpret if instructions are not carefully followed. Testosterone levels fluctuate throughout the day and it's best to collect the saliva early morning, after 30 mins of waking up.

With a doctor's help, it's easy to correct for low-T as hundreds of product are available as gels, patches, and sprays.

Over 2.3 million Americans regularly use testosterone products, based on the data available from 2013.

However, testosterone supplements have known side effects and the FDA warns they may increase the risk of heart attack and stroke.


History

History is full of rich stories about discovering the 'fountain of youth'. The sketch below highlights some of the key milestones, from early days of quackery to modern day ubiquity of supplements.


History-of-testosterone

Figure: Timeline and key events in the history of testosterone. From Nature magazine review: Testosterone: An Unauthorized Biography, by Rebecca Jordan-Young, Katrina Karkazis (Harvard University Press, 2019).


Properties

Testosterone belongs to the family of male hormones known as Androgens (e.g., DHEA, Androstenedione). It is one of the anabolic hormones—a class of hormones that help in building muscles, by switching on the genes responsible for tissue growth. (Cortisol, on the other hand, is a catabolic hormone that helps break down muscles into fat).

T uses a 4-ring “steroid” nucleus as backbone, due to its origin from cholesterol, which makes it a steroid hormone. Other steroid hormones include estrogen, progesterone, cortisol, Vitamin D, androstenediones, aldosterone, DHEA-S, and pregnenolone.

Because it coverts to estrogen many test panels check both hormones for optimal health.

The Leydig cells in testicles produce testosterone in men. Ovaries produce it in women.


Testosterone-levels-by-age

Figure: Testosterone at different phases of life. From Anna Gray and others, Age, Disease, and Changing Sex Hormone Levels in Middle-Aged Men: Results of the Massachusetts Male Aging Study, JECM, 1991.


Important roles

Both physical and mental health are heavily influenced by testosterone levels. For instance, low male hormone levels may help explain the decrease in sexual drive over age. Similarly, low T results in reduced muscle size and strength, increased body fat, and fatigue and chronic tiredness.

Lower levels can cause thinning of bones, cholesterol problems, and high risk of heart disease—conditions that tend to rise with age.

Testosterone is the ‘crankiness hormone’: low levels can affect the mood, causing anxiety and depression, a low zest for life, and reduced tendency to socialize.

In contrast, higher levels might cause aggressive behavior.

Various studies suggest testosterone is an important player in family dynamics, divorce rates, crimes, and social unrest.


Popularity among athletes

Androgens (i.e., anabolic steroids) are popular among athletes to build muscles, and to maintain muscle strength that comes with age.

Body builders often use male hormone in order to build strong muscles.

Recent studies suggest it can provide surprising boost in performance to female athletes. In fact, its role as a marker for defining genders in global sports has been highly controversial.


Hypogonadism: low-T problem

Testosterone levels starts to drop around the age of 25-30, a natural part of aging. But any abrupt drop, or abnormally low levels for a given age, can cause deficiency, defined as hypogonadism (gonads is a biological term for testicles and ovaries, therefore hypogonadism is a deficiency related to these organs).

There is no cure, but a lab test and diagnosis can help understand the root cause, and a doctor might prescribe supplements to help maintain healthy levels.


Symptoms of hypogonadism

The most common symptom of low testosterone levels in men is low sexual performance (or erectile dysfunction).

Although normal erection continues, it may result in low quality of sex, less frequency or inability to maintain it for long. Poor response to medications such as Viagra or Cialis may often appear as a symptom.

Such a deficiency can result in decreased libido, mainly due to its impact on the brain, which regulates the sex drive.

Low T results in weight gain (especially around the middle) due to increase in fat & reduction in muscle mass. It also causes slower metabolism and less desire to exercise.

Muscle weakness, loss of endurance and lower tendency to play sports also correlate with low levels.

Other symptoms include fatigue, low energy, frequently falling asleep after dinner. This fatigue can be due by low muscle strength, poor sleep, depression, and anemia—as testosterone affects all these conditions.

Depression or anxiety, changes in mood, nervousness, and low sense of well being, higher irritability, anger, or negative thinking, poor response to anti-depressant medications, feeling terrible & no interest in life are all stereotypical characteristics of aging that match with low T symptoms in men.

Decrease in quality of life and sense of well-being often correlate with lower levels. Insomnia, which can add to fatigue, is often observed.

Poor memory and lack of concentration—that is beyond normal age related decline—may impact work performance as a consequence of low-t.

Premature aging, with a look and feel of being older than actual age, often appears.


Less Commonly Known Symptoms of Low-T

  • Male breast growth in men, especially in obese men.

  • Bone problems—due to thinning of bones. This can result in hip, wrist or spine fracture and a strong reason for medical practitioners to recommend therapy. Since T converts to estrogen, this process needs to slow down to help bone strength.

  • Joint problems which result in aches and pains in joints.

  • High blood pressure.

  • Sensation of warmth, flashes, and excessive sweating in the night—somewhat similar to menopause.

  • Anemia due to low red blood cell production from reduction in levels.

  • Decreased frequency of shaving as male hormone correlates to hair growth.

  • Loss of body hair including chest, pubic, and armpit hair.

  • Dry, flaky, and thinner skin as male hormone regulates the amount of oil produced by skin.

  • Male fertility problems, e.g., low ejaculate volume, poor sperm count as T, LH, FSH hormones are needed for normal sperm production.

  • Softening or shrinking of testicles.

  • Softening of voice with more feminine sound.


Causes of low testosterone

Most common cause of low T is the natural age related decline. However, trauma or injury to testicles where the hormone is produced, may have serious affect.

Similarly, head injury—that might affect pituitary glands or complications of vasectomy might cause low-T. Urological conditions that block blood supply to cells Leydig cells might also cause problems.

Diabetes—which can affect male hormone production, and can be affected by it, is known issue for low-T. Type 1 diabetes patients generally tend to have a high rate of deficiency.

Combination of age-related androgen decline, excess weight, chronic illness, high blood pressure, and insulin resistance can cause a vicious cycle of low T and high blood sugar. Diabetes patients tend to have more SHBG (sex hormone-bounding globulin) that increases the bound, inactive form making the total T level normal but the free, active form may be low.

Obesity increases testosterone controlling hormones (leptin, cortisol, inflammatory cytokines or adipokines) that signal the brain for lower T production and thus lower muscle mass and more fat. This creates a vicious cycle of further reducing levels in the body. Gain in weight increases aromatase—the enzyme converting testosterone into estrogen—thus making less of the it available for muscle mass & fat control.


Less commonly known causes of Low-T:

  • Infections of testicles (Orchitis), mumps, and HIV.

  • Immune system problems, such as Type 1 diabetes and autoimmune thyroid diseases attack body.

  • Hereditary Hemochromatosis (HH) is a genetic disorder that causes too much iron which can block pancreas and pituitary glands.

  • Sarcoidosis, which are granulomas formed in the body, and when formed in brain, they can affect hypothalamus and pituitary gland (it is mostly a genetic condition that tends to be more prevalent in African American population).

  • Alcohol is one of the most common cause of damage to testicles; tobacco, marijuana, cocaine, heroine, and narcotic medications can affect hypothalamus and pituitary gland.

  • Excess cortisol can lower the levels.

  • Fluid retention in the body can cut-off blood supply to testicles, and can result in kidney, liver, or heart problems.

  • Chronic pain increases cortisol levels and insulin resistance resulting in lower testosterone.

  • Radiation and chemotherapy can impact hypothalamus & pituitary glands.

  • Liver diseases can result in higher estrogen and lower T levels.

  • Exposure to female hormones, e.g., estrogen creams from spouse.

  • Any other problem related to the brain & pituitary glands.


Testosterone levels in women

Testosterone is equally important for women to maintain muscle mass, bone density, and weight gain.

Women have about 10 times lower testosterone levels than men.

High levels occur more often deficiency. But unusually high T levels in women can cause:

  • too much facial hair.

  • increased muscle mass and low body fat content.

  • deepening of voice and smaller breasts.

  • irregular or absent menstrual cycle.

  • fertility problems, especially polycystic ovary syndrome (PCOS) that makes it difficult to get pregnant.

  • in some case, high testosterone can result in acne in women.


Different forms of testosterone measured in a test

Testosterone is measured in three different forms, depending on how it is available in the blood, as shown in the sketch below.


total-free-bioavailable-testosterone-optimal

The two common measurements a lab test shows are:

  • Total Testosterone: includes all the available male hormone in the body. It has three component:
    i. free testosterone (about 2%)
    ii. testosterone bound to SHBG protein (60-80%)
    iii. testosterone bound to albumin (20-40%).

    Whatever is bound to SHBG is not active. Therefore, total testosterone is not the best indicator of healthy levels.

  • Free Testosterone: not bound to protein & is the better indicator of testosterone levels. It is the dialyzable portion and can either be from measurement or calculation. Free Testosterone is not bound and therefore not affected by SHBG.

Normally, there are two blood tests available:

  • Equilibrium dialysis – a more accurate method for free & total T, but tends to be expensive.

  • Analog method – cheap, easy but not as reliable.

Calculated free T is calculated from the total T, SHBG & albumin values and is sometimes more accurate than measured free T, as it combines best of both worlds.

It is also important to understand the values of SHBG (Sex hormone-binding globulin) in certain cases:

i. if normal SHBG – total will be normal.

ii. Is abnormal, especially low SHBG – surely there is a problem.

iii. If high SHBG – total T may appear normal but can be low, this will need further analysis.

For more details, the Harvard Men’s Health Watch provides an excellent description of total and free testosterone.


How to get tested for low testosterone?

A blood or saliva sample can measure testosterone levels.

A saliva test is simple and more convenient than a blood test. Nonetheless, it provides equivalent or sometimes superior results.

Saliva testing is relatively new technique and not as widely popular as blood test.

A saliva test measures free testosterone, the most active form, thus providing reliable results.

The challenge with blood test is that a venipuncture blood draw can cause adrenal stress in children and those afraid of needles.

The main concern with saliva test is variations in results. However, an at-home health test from CLIA-certified labs that regularly compare their results with others can provide highly reproducible and reliable results.

Several scientific studies have shown that saliva can often deliver superior results. One scientific review from the journal of Clinical Chemistry confirmed this observation in 1500 males aged 20 to 90 years.

It is highly recommended to provide samples in the morning, around 7-10 am. They should be collected within 30 minutes of waking up when the T levels are highest.

Testosterone is age dependent and therefore should be compared against a reference of same age group for better interpretation.


Saliva based testosterone test

With saliva samples, only free-testosterone is tested. Therefore, SHBG & albumin proteins do not affect these results.

Such a test is not susceptible to temporary fluctuations that might arise due to stress induced by the fear of needles.

However, one should ensure the lab has a history of reliable testing with clearly defined ranges.

As an example, for a 40 year male, the testosterone levels–which are highly dependent on age–will be low, normal or high if the values are:

  • 50 pg/ml or below: low levels requiring further attention (likely hypogonadism, low-t problems).

  • 50 – 185 pg/ml: normal range.

  • 185 pg/ml or above: high levels that also need attention (due to higher aggression and other concerns).


Blood based testosterone test

This is traditional method of testosterone testing which requires blood draw. Although reliable, it might show spike from stress of needles.

Ranges for a T blood test are:

  • Normal range: 260 – 1000 ng/dL

  • if < 500 ng/dL – low and may need attention

  • < 300 ng/dL – needs treatment


Challenges in testosterone testing

Few challenges in testing include:

  • Test reliability – it easier to measure high T than low T, although most people want to know if they have low levels.

  • Lab imperfections – assay variability & different reference ranges from lab-to-lab might cause variations. That’s why it is recommended to use labs that are
    i. CLIA certified.
    ii. Have a history of testing thousands of samples with well defined ranges.
    iii. Regularly compare their data with other labs across the country.
    Our at-home testosterone test meets all the three conditions.

  • Hormone flexes – T is highest in the morning (one reason why men tend to get erection in the morning). If morning values are low, there is a very high chance of low T. Sometimes it's best to measure 3 or 4 samples from the same day at different times for confidence.

  • Blood proteins – 98% of T is attached to proteins & only about 2% is free T, therefore any variations in these proteins might affect the results. 60-80% T is attached to SHBG and is biologically inactive. 20-40% is bound to a protein called albumin where it can become free & biologically active.

  • Variation may appear in specific individuals and due to age.

  • The blood test results may have an impact from sudden stress—from the fear of needles.


What else might affect testosterone results?

It is important to know few other parameters that might affect your results:

SHBG:

  • It tightly binds with T (60 – 80%, which is significant).

  • Cases of normal SHBG values are reliable for total T measurement.

  • Low or high values, means it can’t predict T accurately.

  • SHBG also increases with aging, complicating the results.

Albumin:

  • 20 – 40% of T binds weekly with Albumin and is called bioavailable T.

  • It’s relatively less important for measurements.

  • Abnormal levels are rare.

  • It is often part of a standard blood test for metabolism.

DHT (di-hydro-testosterone):

  • Testosterone converts to DHT (by an enzyme called 5-alpha-reductase) – both might impact the results.

  • It is used for high T issue diagnosis, and can result in hair loss and prostate enlargement.

Estrogen:

  • High levels of Estrogen (and, estrone and estriol) often result in low T.

  • High levels can be due to liver problems, obesity, or accidental exposure from women’s prescriptions.


Diagnosis for low levels

Medical professionals prescribe Testosterone Replacement Test (TRT) to those with low T to achieve normal levels

However, there is no pill to cure deficiency – because TRT pills cause liver toxicity,

The most common prescriptions include gels, injections, or chewable prescriptions.

Low T can cause low red blood count resulting in anemia. However, TRT may sometimes cause too much blood & needs to be monitored for blood count and prostate growth.


testosterone-levels-over-life-span

Figure: Testosterone Levels With Age - each line is an independent clinical study showing number of people in each study.


Natural ways of increasing Testosterone

Exercise makes muscles physically and metabolically stronger. It is one of the best ways to increase testosterone levels and balance other hormones.

Weight training increases muscle mass and metabolism. That's why it is the best natural way to increase levels. Medical professionals recommend 30 minutes of weight training at least twice a week.

Other methods include:

  • Stress relief – stress lowers testosterone and other androgens. Low T slows down metabolism resulting in low muscle mass and high body fat.

  • Vitamin D – although critical for bone health, it is equally important for muscles. Low Vitamin D might result in feeling tired, flabby, and cause weak muscles. Vitamin D deficiency increases with age. Data suggest more than half of US elders might be below recommended Vitamin D levels.

  • Sleep time – our body secretes key hormones during sleep, without enough sleep the body can’t produce enough of them.

  • Growth hormone (GH) – since GH is important for muscle growth, any deficiency will result in low testosterone symptoms.

  • Insufficient proteins – since proteins are the building blocks of healthy muscles, low protein levels in diet will impact testosterone levels.


Source: Hormone Balance by Scott Isaacs, MD.


References:

  • Learn from the experts at Mayo Clinic about Male Hypogonadism: Symptoms & causes | Diagnosis & treatment.

  • Also see the Mayo Clinic’s page on Testosterone therapy: Potential benefits and risks as you age.

  • From Harvard Men’s Health Watch, read about the complexity of symptoms of low T, details on different ‘kinds’ of testosterones, what are normal testosterone levels, and how even experienced physicians have differing opinions on getting tested for low T: Testing your testosterone: It’s tricky.

  • In our review of key literature on testosterone, please also read: Testosterone vs parenting: Men’s relationship status, fatherhood, and how invested they are in paternal care significantly impact their testosterone levels.

  • After testing, please see your physician for next steps. The FDA Drug Safety Communication says there may be an increase in the risk of heart attack and stroke from using testosterone.