Free Testosterone

Testosterone, classically considered a male hormone, plays a multifaceted role beyond its association with masculinity. As a pivotal biomarker of health and wellness, testosterone influences various physiological processes in both men and women. 

Testosterone serves multiple essential functions in men and women, including regulating libido, building muscle mass and bone density, enhancing red blood cell production, stabilizing mood and promoting an overall sense of well-being. It also directs the development and maintenance of masculine secondary sexual characteristics including deepening of the voice, growth of facial and body hair, changes in fat distribution, leading to a more "masculine" body shape, and others.  

From its fundamental functions within the body to its intricate interplay with lifestyle factors and disease states, understanding testosterone’s effects in men and women is essential for optimizing health and vitality and addressing hormone-related pathology.

What is Testosterone?

Testosterone is an androgenic steroid hormone that is essential in the health and wellness of men and women.

Functions of Testosterone in the Body

• Primary sexual development in males: testicular descent, spermatogenesis, enlargement of the penis and testes, and increasing libido are all due to rising testosterone levels in males
• Secondary sex characteristics: it plays a crucial role in the development and maintenance of male secondary sexual characteristics in males including muscle mass,  enlargement of the Adam’s apple, voice deepening, and body hair growth
• Libido and sexual function: testosterone promotes healthy sexual function by  regulating libido and contributing to sexual desire and arousal in both men and women.  
• Spermatogenesis: testosterone is responsible for sperm production in men
• Increases in muscle mass: testosterone stimulates protein synthesis in muscles 
• Red blood cell production: through a process called erythropoiesis, testosterone stimulates red blood cell production, contributing to the oxygen-carrying capacity of the blood and overall cardiovascular health.  This is also why men have a higher hematocrit than women.  [1.]
• Mood: Testosterone may play a role in mood stability by enhancing the effects  affecting emotions and mental well-being and reducing depressed symptoms.  [11.]
• Bone Health in Females: In females, testosterone contributes to bone strength, helping to maintain skeletal health and reduce the risk of osteoporosis. [14.]

Production and Regulation of Testosterone: Where is Testosterone Produced?

Testosterone is a steroid hormone primarily produced in the testes of males and the ovaries of females, although smaller amounts are also synthesized in the adrenal glands.   Cholesterol is the precursor molecule for testosterone production. 

Testosterone production is regulated by a complex interplay of hormones, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secreted by the pituitary gland, which stimulate the testes to produce testosterone in men. 

In men, a small amount of circulating testosterone is converted to estrogen via the aromatase enzyme.

In women, testosterone production occurs predominantly in the ovaries under the influence of LH, although smaller amounts are also synthesized in the adrenal glands. 

Normal Testosterone Levels and Their Clinical Relevance

Normal testosterone levels vary depending on age, sex, and individual factors, but generally fall within a certain range that is considered optimal for health and well-being. 

It's important to note that testosterone levels can fluctuate throughout the day and may be influenced by various factors such as stress, illness, and medication use. 

Clinically, testosterone levels outside of the normal range may indicate underlying health conditions or hormonal imbalances, and monitoring testosterone levels can be useful in diagnosing and managing conditions such as hypogonadism, infertility, and certain endocrine disorders.  Testosterone levels also naturally decline with age in men and women.

What is Free Testosterone?  

The two main descriptors for testosterone levels in the blood are free and total testosterone.  

Free testosterone refers to the portion of testosterone in the bloodstream that is not bound to proteins and is readily available for use by the body's tissues, while total testosterone includes both free testosterone and testosterone bound to proteins such as albumin and sex hormone-binding globulin (SHBG). 

Free testosterone is considered the biologically active form, while total testosterone provides a broader measure of the hormone's overall concentration in the bloodstream.  

Clinicians concerned about a patient’s testosterone levels should consider testing levels of free testosterone, total testosterone, as well as albumin and sex hormone binding globulin.  

Testing and Monitoring Testosterone Levels

Overview of Testosterone Testing Methods

Testosterone levels can be assessed through blood, saliva, and urine tests. 

The most common method is a blood test, which measures total testosterone levels in the bloodstream. This test is often performed in the morning when testosterone levels are typically at their highest. 

Saliva tests are less common but can provide valuable information about free testosterone levels, which are not bound to proteins in the blood. 

Urine tests may also be used to assess testosterone levels, and hold value in illuminating an individual’s testosterone metabolism patterns. 

When and How to Test Testosterone Levels

Testosterone testing is typically recommended for individuals experiencing symptoms of low testosterone, such as decreased libido, fatigue, erectile dysfunction, or infertility. It may also be ordered for individuals with certain medical conditions or risk factors that may affect testosterone levels, such as diabetes, obesity, or pituitary gland disorders. 

Testosterone Blood Test:

With a blood test, testosterone levels are usually measured in the morning when they are at their peak, and fasting may be required before the test to obtain accurate results. The blood sample is typically drawn from a vein in the arm and sent to a laboratory for analysis.

Benefits: Considered the gold standard for testosterone assessment, blood tests are the most common and accurate method for assessing total testosterone levels. Provides valuable information for diagnosing and monitoring testosterone-related conditions, including hormone replacement therapy.  Blood tests provide accurate information regarding free and total testosterone levels in the blood.

Drawbacks: Requires venipuncture, which may be uncomfortable for some individuals. Testosterone levels can fluctuate throughout the day, so timing of the test may affect results.

Testosterone Saliva Test:

A saliva test measures the levels of free, bioavailable, testosterone in saliva samples.  Because salivary samples are unaffected by fluctuations in albumin and sex hormone binding globulin in serum, salivary testosterone accurately reflects tissue availability of the hormone.  [5., 7.]

Benefits: Non-invasive method that can be easily performed at home. Provides information about free testosterone levels, which may better reflect bioavailable testosterone available at receptor sites in tissues.

Drawbacks: Less commonly used and may not show total testosterone levels. Results may be affected by factors such as oral hygiene and time of day.

Testosterone Urine Test:

Testosterone urine testing offers insights into androgen metabolism pathways, particularly through assessing alpha vs. beta androgen metabolites. It aids in monitoring testosterone therapy, including transdermal, intramuscular injection, and pellet administration, as urine levels typically correlate with serum levels. [3., 4.]

Additionally, it provides information on androgen aromatization into estrogens and downstream estrogen metabolism patterns.

In men, the inclusion of epitestosterone measurements can assess endogenous testosterone production, offering insights into the efficacy of testosterone replacement therapy and potential testicular suppression.  [4.]

Benefits: Non-invasive method that can be easily collected. May provide additional information about testosterone metabolism.

Drawbacks: Less commonly used.  Testosterone levels in urine may be influenced by factors such as hydration status and kidney function.

Normal Reference Ranges

Reference ranges are set by labs.  Common reference ranges for serum include:

Men:

Serum: 300 to 1,000 nanograms per deciliter (ng/dL) or 10 to 35 nanomoles per liter (nmol/L)

Saliva: 44—148 pg/mL 

Urine: consult labs regarding reference ranges for testosterone and metabolites

Women:

Serum: 15 to 70 ng/dL or 0.5 to 2.4 nmol/L.

Saliva: 16—55 pg/mL 

Urine: consult labs regarding reference ranges for testosterone and metabolites

Interpretation of Testosterone Test Results

Testosterone test results are interpreted within the context of the individual's age, sex, and clinical presentation.  Abnormal testosterone levels may indicate underlying health conditions, such as hypogonadism, hypergonadism, or certain endocrine disorders, and further evaluation may be necessary to determine the cause and appropriate treatment.

Causes of Low Testosterone in Men

Age-related Decline 

One of the primary factors contributing to low testosterone levels in men is the natural decline in testosterone production that occurs with age, often referred to as andropause or late-onset hypogonadism. 

As men age, their testosterone levels gradually decrease, with levels declining by about 1% per year after the age of 30. This decline in testosterone production may lead to symptoms such as decreased libido, fatigue, decreased muscle mass, and erectile dysfunction.

Medical Conditions and Diseases

Various medical conditions and diseases can also contribute to low testosterone levels in men. These may include conditions affecting the testes, such as hypogonadism, testicular cancer, or injury to the testes. 

Additionally, conditions affecting the hypothalamus or pituitary gland, such as pituitary tumors or head trauma, can disrupt the production of hormones that stimulate testosterone production. 

Other medical conditions, such as obesity, diabetes, chronic illness, or HIV/AIDS, are also associated with lower testosterone levels.  [6.]

Medications and Lifestyle Factors

Certain medications and lifestyle factors can impact testosterone levels in men. Medications such as corticosteroids, opioid pain medications, and chemotherapy drugs can suppress testosterone production. Excessive alcohol consumption, smoking, and drug use can also negatively affect testosterone levels. 

Additionally, chronic stress, poor sleep quality, and a sedentary lifestyle may contribute to lower testosterone levels in men. Addressing these factors through lifestyle modifications and medication adjustments may help improve testosterone levels and overall health.  [6.]

Testosterone Replacement Therapy in Men

Testosterone replacement therapy (TRT) is a treatment option for men with clinically significant low testosterone levels, which can manifest with symptoms such as decreased libido, fatigue, and reduced muscle mass. 

TRT aims to restore testosterone levels to within the normal range, improving symptoms and overall well-being. It is typically initiated when laboratory tests indicate low testosterone levels, usually confirmed by measuring total testosterone levels in the blood. 

The decision to start TRT is based on clinical judgment and consideration of the severity of symptoms, as well as the potential risks and benefits of treatment.

Once TRT is initiated, regular monitoring of testosterone levels through laboratory tests is essential to ensure that levels remain within the target range. Testosterone levels may be measured periodically to assess treatment efficacy and adjust the dosage if necessary. 

Various methods of administering TRT include intramuscular injections, transdermal patches or gels, buccal patches, and subcutaneous pellets. The choice of method depends on factors such as patient preference, convenience, and individual response to treatment. 

In some cases, adjunctive therapy with medications like anastrozole, an aromatase inhibitor, may be considered to prevent the conversion of testosterone to estrogen and mitigate potential side effects such as gynecomastia. Clinical decisions regarding the use of anastrozole should be made on a case-by-case basis, considering the patient's symptoms, testosterone levels, and response to treatment.

Side Effects of Excessive Testosterone Replacement in Men

High testosterone levels, or hyperandrogenism, in men can lead to symptoms such as increased aggression, acne, and an increased risk of prostate enlargement or cancer.  It may also cause testicular atrophy.   

It's crucial for individuals undergoing TRT to be closely monitored by a healthcare provider to assess treatment response, manage potential side effects, and minimize risks associated with therapy.

Testosterone in Women

Role and Importance of Testosterone in Women 

While testosterone is often associated with male characteristics, it also plays a crucial role in women's health. Testosterone contributes to maintaining bone density, muscle mass, and strength in women, promoting overall physical well-being. 

Additionally, testosterone influences libido and sexual function in females, contributing to sexual arousal and satisfaction. 

Beyond its reproductive functions, testosterone also plays a role in mood regulation, muscle mass maintenance, cognitive function, and energy levels, highlighting its significance for women's health and quality of life.  [2., 9., 12.]

Signs and Symptoms of Low Testosterone in Women

Low testosterone levels in women can manifest with various signs and symptoms that may impact overall health and well-being. Common symptoms of low testosterone in women include decreased libido, reduced energy levels, fatigue, and diminished sense of well-being. 

Women with low testosterone may also experience mood changes, such as irritability, depression, or anxiety. [9.]

Additionally, low testosterone levels may contribute to changes in body composition, including loss of muscle mass and strength, increased body fat, and decreased bone density, putting women at risk for osteoporosis and fractures.  [9.]

Causes of low testosterone levels in women can be multifactorial and may stem from various physiological, hormonal, and lifestyle factors. One common cause is aging, as testosterone production naturally declines with age in both men and women. 

Other factors contributing to low testosterone in women include medical conditions such as hypothalamic or pituitary disorders, and primary ovarian insufficiency (premature ovarian failure). Additionally, certain medications such as oral contraceptives, glucocorticoids, and opioids may suppress testosterone production. 

Lifestyle factors like chronic stress, inadequate sleep, poor nutrition, and excessive alcohol consumption can also negatively impact testosterone levels in women. 

Identifying the underlying cause of low testosterone is crucial for appropriate management and may involve comprehensive evaluation by a healthcare provider.

Signs and Symptoms of High Testosterone in Women 

High testosterone levels in women, known as hyperandrogenism, can lead to a range of physical and psychological symptoms. 

Physically, women with high testosterone levels may experience acne, oily skin, and hirsutism (excessive hair growth in areas such as the face, chest, or back). They may also notice scalp hair thinning or male-pattern baldness.

 Additionally, high testosterone levels can disrupt menstrual cycles, leading to irregular periods or even amenorrhea (absence of menstruation). Psychologically, women with elevated testosterone may experience mood changes, such as irritability, aggression, or mood swings. These symptoms can significantly impact a woman's quality of life and may require medical evaluation and intervention.

Causes of High Testosterone in Women

High testosterone levels in women, known as hyperandrogenism, can result from various underlying causes, both physiological and pathological. 

One common physiological reason is polycystic ovary syndrome (PCOS), a hormonal disorder characterized by enlarged ovaries with small cysts and elevated androgen levels. PCOS disrupts the normal balance of hormones in the body, leading to symptoms such as hirsutism (excessive hair growth), acne, and irregular menstrual cycles. 

In some cases, excessive testosterone levels may also arise from adrenal gland disorders, such as congenital adrenal hyperplasia (CAH) or adrenal tumors. 

Additionally, excessive use of hormone replacement therapy (HRT), particularly with androgenic medications, can artificially elevate testosterone levels in women, leading to symptoms of hyperandrogenism. Identifying the underlying cause of high testosterone levels is essential for appropriate management and may involve comprehensive evaluation by a healthcare provider.

Testosterone Replacement Therapy in Women

Testosterone replacement therapy (TRT) in women is a treatment option for those with clinically significant low testosterone levels, also known as hypoandrogenism. Low testosterone levels in women can lead to symptoms such as reduced libido, fatigue, decreased muscle mass, and mood disturbances. 

TRT aims to restore testosterone levels to within the normal range, alleviating symptoms and improving overall well-being. The decision to initiate TRT in women is based on clinical judgment, taking into account the severity of symptoms, the impact on quality of life, and potential risks and benefits of treatment. 

Laboratory testing is crucial for monitoring testosterone levels before and during TRT to ensure that levels remain within the target range and to adjust treatment dosage accordingly.

There are various methods of administering TRT in women, including intramuscular injections, transdermal patches, creams or gels, and subcutaneous pellets. The choice of TRT method depends on factors such as patient preference, convenience, and individual response to treatment. 

Each method has its advantages and disadvantages; for example, injections may require less frequent dosing but can be associated with discomfort or injection site reactions, while transdermal patches or creams offer convenient application but may cause skin irritation in some individuals. 

Side Effects of Excessive Testosterone Replacement in Women

Clinical considerations for TRT in women include monitoring for potential side effects such as acne, hair growth, voice deepening, and changes in cholesterol levels, as well as assessing the risk of long-term effects on cardiovascular health and hormone-sensitive tissues like the breast and uterus. Regular follow-up visits with a healthcare provider are essential to evaluate treatment response, monitor for adverse effects, and adjust TRT as needed to optimize outcomes while minimizing risks.

Natural Ways to Increase Testosterone

Dietary Strategies

• Consume foods rich in nutrients that support testosterone production, such as zinc (found in oysters, red meat, poultry, and beans), vitamin D (obtained from sunlight exposure and fortified foods like fatty fish and fortified dairy products), and healthy fats (found in avocados, nuts, seeds, and olive oil).
• Include foods high in protein, such as lean meats, fish, eggs, and legumes, as protein is essential for testosterone synthesis.
• Limit consumption of processed foods, refined carbohydrates, and sugary snacks, as they may contribute to insulin resistance and lower testosterone levels.

Lifestyle Modifications

• Maintain a healthy weight, as excess body fat, especially visceral fat, can lead to lower testosterone levels.
• Manage stress through relaxation techniques such as meditation, deep breathing exercises, yoga, or spending time in nature.
• Get adequate sleep each night, aiming for 7-9 hours of quality sleep to support hormone balance and overall health.
• Avoid excessive alcohol consumption, as alcohol can impair testosterone production and metabolism.

Exercise and Physical Activity

• Engage in regular resistance training exercises, such as weightlifting or bodyweight exercises, to stimulate muscle growth and increase testosterone levels.
• Incorporate high-intensity interval training (HIIT) into your workout routine, as it has been shown to boost testosterone levels and improve overall fitness.
• Regular moderate-intensity aerobic exercise or vigorous-intensity aerobic exercise supports overall health and hormone balance and may increase testosterone levels [13.]
• Prioritize compound exercises that target multiple muscle groups, such as squats, deadlifts, and bench presses, to maximize testosterone-stimulating effects.

Targeted Nutrition for Testosterone Optimization

Foods That Increase Testosterone Levels

• Foods rich in zinc: oysters, red meat, poultry, beans, nuts, and seeds.
• Vitamin D sources: fatty fish (salmon, tuna, mackerel), fortified dairy products, egg yolks, and sunlight exposure.
• Healthy fats: avocados, olive oil, nuts (almonds, walnuts), seeds (flaxseeds, chia seeds), and fatty fish.
• Protein-rich foods: lean meats (chicken, turkey, lean beef), fish, eggs, dairy products, tofu, tempeh, and legumes.
• Cruciferous vegetables: broccoli, Brussels sprouts, cabbage, kale, and cauliflower, which contain compounds that may help regulate estrogen levels and indirectly support testosterone production.

Foods to Avoid for Testosterone Health

• Processed and refined carbohydrates: white bread, pastries, sugary snacks, and desserts, which can lead to insulin resistance and lower testosterone levels.
• Excessive alcohol consumption: heavy drinking can impair testosterone production and metabolism.
• High-sugar foods and beverages: soda, fruit juices, and other sugary drinks may contribute to insulin resistance and lower testosterone levels.
• Trans fats and unhealthy oils: fried foods, margarine, processed snacks, and baked goods made with hydrogenated oils, which can increase inflammation and interfere with hormone regulation.