Overview

Testosterone is an essential hormone which plays a key role in many bodily functions. While it’s important for both male and females, it is the major sex hormone in males. Testosterone is produced in the testicles in men and the ovaries in women (though in much smaller amounts).

The role of testosterone starts in the womb, playing a crucial part in sexual differentiation and going on to regulate sexual maturation and development. This includes a major influence on the development of primary and secondary sexual characteristics, such as forming genitalia and growth of facial hair, respectively. Though testosterone plays a continuous role in the body, its effects are most notable during puberty. These effects of testosterone include:

• Development of the penis and testes
• Deepened voice
• Appearance of facial and pubic hair
• Bone and muscle growth
• Increased libido
• Production of sperm

In adulthood, testosterone continues to have effects, not only maintaining muscle mass, bone density, and sexual function, but also impacting mood, cognition, and energy levels.

While produced in the testicles, the signals for testosterone production and release are sent from the pituitary gland in the brain. This pituitary gland is responsible for monitoring the amount of testosterone in the blood and “telling” the testicles to produce more or less to maintain the ideal amount of testosterone in the body. There are, however, sometimes issues with this system resulting in levels of testosterone that are too low. This is referred to as “hypogonadism” or “low testosterone”.

As men age, testosterone levels will naturally begin to drop as both the brain sends less signals and the testicles begin to produce less testosterone. This is only in very small amounts; as little as 1-2% per year. The exact drop in testosterone that is considered “too low” is relatively controversial as the “ideal” numbers vary from person to person. However, some men may experience symptoms from low testosterone and therefore may benefit from correcting these levels with testosterone replacement.

Statistics

It can be difficult to know how many men have low levels of testosterone since levels are not regularly checked in many individuals. Although it can occur at any age, it is particularly common among older men. Based on current data, it is suggested that about 2% of men may have reduced levels of testosterone, which equals to over 2 million men in the USA aged 40-70. As men age, this prevalence increases significantly, with up to 50% of men aged 80 and older having low testosterone levels. Factors such as elevated body mass index (BMI) and lifestyle choices contribute to this decline. Regular monitoring and awareness are essential for addressing this condition effectively.

Symptoms

Some men with reduced levels of testosterone experience unpleasant symptoms, including:

• Low libido
• Erectile dysfunction
• Decreased bone density
• Low energy
• Decreased muscle mass
• Worsened mood/poor concentration
• Weight gain
• Difficulty sleeping
• Reduced body/facial hair

Unfortunately, there are a number of different medical conditions that can cause similar symptoms. This is why it’s important to investigate all potential causes with a healthcare provider. Following a diagnosis, appropriate treatment may then be pursued.

Causes

There are two main classifications of conditions that result in low levels of testosterone: primary and secondary hypogonadism. Primary hypogonadism occurs due to a problem with the testicles’ production of testosterone, while secondary hypogonadism occurs as a result of an issue in the signalling process in the body but not from the testicles themselves. Either type of decreased testosterone can be genetic (you are born with it) or acquired (obtained later in life). Rarely, an individual can have both primary and secondary hypogonadism.

Causes of Primary hypogonadism

• Hemochromatosis (too much iron in the blood) can cause damage to the testicles which may result in reduced testosterone levels.
• Physical injury to the testicles can cause damage which may result in impaired ability to produce testosterone. This is of increased risk due to the position of the testicles descended outside of the protection of the abdomen.
• Klinefelter syndrome This is a genetic condition resulting in an extra X chromosome in males (typically males have one X and one Y chromosome). This often results in abnormal development of the testicles and a decreased production of testosterone.
• Certain medications, such as chemotherapy used to treat cancer, can interfere with the regular testosterone production of the testicles. Their effects may cause reversible or irreversible.
• Mumps infections in adolescence can result in damage to the testicles which may impact the production of testosterone.
• Undescended testicles Testicles develop in the abdomen and later descend into the scrotum. However, sometimes the testicles do not descend and, if not corrected, can result in reduced production of testosterone.

Causes of Secondary hypogonadism

• Certain inflammatory conditions, such as tuberculosis infection, can impact the parts of the brain involved in testosterone regulation.
• Kallmann’s syndrome This is a condition in which there was improper development of the part of the brain responsible for regulating testosterone production.
• Certain medications, such as steroids, can cause alterations to testosterone regulation.
• Certain medications, such as chemotherapy used to treat cancer, can interfere with the regular testosterone production of the testicles. Their effects may cause reversible or irreversible.
• Pituitary disorders Certain conditions or physical damage can impair function of the pituitary gland (which is involved in testosterone regulation) and therefore impair testosterone production.

Other conditions such as obesity, type 2 diabetes, and natural aging can also result in secondary hypogonadism.

Diagnosis

If you suspect you may have low levels of testosterone, it is crucial to consult with a healthcare provider for a thorough assessment. This evaluation typically includes a detailed health history, a physical examination, blood tests, and potentially imaging studies.

Initial Assessment

Health History: Your healthcare provider will ask about your medical history, including any symptoms you may be experiencing, such as fatigue, decreased libido, or mood changes. They will also inquire about any medications you are taking and any underlying health conditions.

Physical Examination: A physical exam will be conducted to look for signs of low testosterone, such as decreased muscle mass, body hair loss, or breast enlargement.

Blood Tests

Bloodwork is a critical component of the diagnosis and should include:

• Testosterone Levels: Two separate tests taken in the morning (between 8-10 AM) to account for the natural diurnal variation in testosterone levels.
• Hormone Levels: Measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) to evaluate overall endocrine function.
• Complete Blood Count (CBC): To rule out other potential causes of symptoms.
• Prostate-Specific Antigen (PSA): To exclude prostate-related issues.

Further Testing

If initial tests suggest low testosterone, additional tests may be required to identify secondary causes:

• Testicular Ultrasound or Biopsy: To check for testicular abnormalities.
• Brain MRI: To rule out pituitary gland disorders.
• Semen Analysis: To evaluate fertility, especially if low testosterone is suspected to be impacting reproductive health.

Diagnostic Criteria

The treatment goal varies depending on age:

• Adult Men: Aim to maintain testosterone levels between 600-900 ng/dL.
• Senior Men: 500-800 ng/dL

Testosterone deficiency is confirmed when two separate testosterone level tests fall below the normal range. Normal testosterone levels for adult men typically range from 300 to 1000 ng/dL. However, a diagnosis can still be made based on clinical judgment even if levels fall within this range but symptoms are present.

Treatment

Low levels of testosterone are typically treated with testosterone replacement medications. This works by giving the body the testosterone that it is lacking. The overall goal of testosterone therapy is to improve the symptoms and prevent permanent bodily changes from a lack of testosterone. Once the hormone reaches “normal” levels, symptoms including decreased mood, sex drive, and muscle mass should improve.

There are a number of different formulations to use for testosterone replacement. This includes testosterone injections, topical patches, topical gels, slow-release injectable pellets, and oral capsules.

Testosterone Injections

Testosterone injections are typically injected into the muscle once per week. There is also a longer-acting formulation which is dosed every 10 weeks.

Pros	Cons
Consistent doses Not applied daily	Painful administration
Medications: Aveed, Depo-Testosterone, Xyosted

Topical Patches

Testosterone patches are applied to the skin every day in the evening for best mimicking of the “natural” testosterone levels.

Pros	Cons
Easy to apply Painless	Daily application Visible on the skin
Medications: Androderm

Topical Gels

Testosterone gels are typically applied once per day to the skin of the shoulders, upper arm, or abdomen.

Pros	Cons
Easy to apply Painless	Daily application Can transfer from skin to partners/children Have to wait for it to dry
Medications: Androgel, Fortesta, Testim, Vogelxo

Slow-Release Pellets

Testosterone pellets are placed under the skin within the fat of the buttocks, thigh, or abdominal wall. These pellets slowly release testosterone into the body over the course of months.

Pros	Cons
Long-acting (up to 6 months)	Painful injection Can cause scarring
Medications: Testopel

Oral Capsules

Oral testosterone capsules are generally taken with food by mouth two times per day.

Pros	Cons
Consistent doses Easy to take Painless	Taken daily
Medications: Jatenzo, Kyzatrex, TLando