LOW TESTOSTERONE

Testosterone is a naturally occurring sex hormone found in all humans. Hormones act as the body’s messengers, travelling from one region of the body to another to produce a response. Wrongful labelling of testosterone as a ‘male’ hormone obscures the fact that it’s also produced by women and plays a role in various functions.

In men, testosterone is produced by the testes and in women, smaller amounts are produced by the ovaries. The process of making testosterone is controlled by a system that involves the brain and the pituitary gland at the base of the brain. This gland sends messages to the gonads (testes in men and ovaries in women), telling them to produce testosterone. There's a built-in "feedback loop" that keeps an eye on hormone levels in the blood. If testosterone levels get too high, the brain tells the pituitary gland to slow down production.

A smaller contribution comes from the adrenal glands—specifically, the zona reticularis—which produce dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S). These are among the most abundant androgenic steroids in humans and act as precursors, or building blocks, for more powerful androgens like testosterone and dihydrotestosterone (DHT).

Research has shown that DHEA and DHEA-S can influence gene activity by binding to androgen receptors, though their primary role is to be transformed into stronger androgens through conversion processes in the body. Part of this testosterone is further converted into DHT, a stronger version of the hormone, by an enzyme called 5α-reductase found in tissues sensitive to androgens, such as the prostate, hair follicles, and testes.

Once formed, free testosterone and DHT bind to specific receptors inside cells, enabling them to interact with DNA and trigger the effects typically associated with male sex hormones, such as growth and reproductive functions.

The human body increasingly produces testosterone up until the age of 30, after which levels then begin to dip. It is at this point that some men may experience below ‘normal’ testosterone levels, which translate into a myriad of symptoms ranging from low mood and loss of libido to fatigue and infertility.

Testosterone plays a crucial role in both primary and secondary male sexual development. It's essential for testicular descent, sperm production, and the enlargement of the penis and testes, not to mention a boost in libido. Typically, the testes start to descend into the scrotum around the seventh month of gestation (the period where the foetus develops in the womb), driven by significant testosterone production. Sometimes male children can be born with undescended testes. If this remains to be the case by the age of 4 to 6 months, testosterone therapy can aid their descent through the inguinal canals.

Bulging muscles, a healthy sex drive, and strong bones are also a few of the key secondary male traits testosterone is linked to. Other characteristics which testosterone is responsible for also include male-pattern hair growth, vocal changes, and the deepening of the voice. It supports intense growth spurts and enhances muscle growth. Testosterone also boosts erythropoiesis, leading to higher red blood cell counts in males compared to females.

However, as men age, testosterone levels naturally decline, resulting in reduced testicular size, decreased libido, lower bone density, and loss of muscle mass, alongside increased fat accumulation and a drop in red blood cell production, potentially leading to anaemia.

Testosterone is a jack-of-all-trades hormone, proving crucial in stabilising a complex psychological network that influences mood, behaviour, self-perception, and the overall quality of life in men of all ages. 

It has a profound impact on physical health, particularly bone health. By converting into estradiol (a potent oestrogen), testosterone activates bone oestrogen receptors, which helps to reduce bone deterioration and increase bone mineral density. Also vital for regulating bone calcium levels and, inadvertently, bone health, is vitamin D, to which testosterone is linked. Studies have established a robust link between vitamin D levels and free testosterone, even after adjusting for factors like age and body weight.

Beyond its role in bone health, testosterone significantly influences muscle mass and body fat composition. While testosterone alone does not significantly enhance muscle function or mass, it does so effectively when combined with strength training. Older men engaging in strength training experience notable improvements in muscle function and, with the addition of testosterone therapy, gains in muscle mass as well.

Working locally to the gonads, testosterone exerts beneficial effects for men with benign prostatic hypertrophy – a condition whereby the prostate gland becomes enlarged – by helping to manage urinary symptoms. 

Some research has found that testosterone can provide short-term cognitive benefits, such as improved memory. Testosterone's impact on mental health is significant and complex, affecting mood and potentially overlapping with symptoms of mood disorders. It has been shown that high levels of testosterone can lead to depression and even hypomania, whereas low levels are often linked to depression in specific groups of people, therefore spotlighting the importance of using testosterone treatments conservatively within the right clinical parameters.

Testosterone is a relatively powerful hormone that controls various essential human functions, from sperm production to muscle gain. As men age, their testosterone levels naturally decline, typically by about 1% per year from the age of 30 or 40. This gradual decrease can raise questions about whether lower levels of testosterone are simply a part of the ageing process or a sign of an underlying condition such as hypogonadism.

Defining "normal" testosterone levels in the bloodstream can be complex, as these levels can vary significantly due to factors like thyroid function and protein status. Traditionally, the diagnosis of testosterone deficiency hasn't varied by age; however, it's becoming clear that what is considered a normal testosterone level for young men differs from that of older men. This has led to calls for age-specific values to be used when assessing young men for testosterone deficiency.

Typically, testosterone levels peak at around ages 18 or 19, then gradually decrease throughout the rest of a man's life. Recent guidelines from the British Society for Sexual Medicine (BSSM) suggest that a total testosterone level of at least 12 nmol/l is considered normal for men. One study found that the average total testosterone levels for those aged 19 is 15, and 13 for those aged 40. Those with levels below 12 nmol/l should undergo further testing to explore the reasons behind their low testosterone.

Maintaining healthy testosterone levels offers a host of benefits that contribute significantly to men's physical and mental health across various stages of life. Testosterone is vital for heart health as it helps to pump blood efficiently around the body, ensuring that muscles and organs receive the oxygen needed for peak performance. It supports the production of red blood cells in the bone marrow – and it’s these red blood cells which carry oxygen to all the right places. 

Low levels of testosterone are associated with increased cardiovascular risks, including coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Studies have shown that testosterone replacement therapy can improve certain cardiovascular conditions in men with CAD and enhance exercise capacity in those with congestive heart failure. It also improves insulin resistance and glucose levels in men with diabetes and prediabetes. 

While the cardioprotective benefits of testosterone are supported by some studies, the relationship between testosterone levels and heart health remains complex, with ongoing research needed to fully understand its impact.

Testosterone is also responsible for increased muscle mass – and leaner body mass helps control weight and boosts energy levels. For men with low testosterone, treatment has been shown to decrease fat mass and increase lean mass, especially when testosterone therapy is combined with strength training and exercise.

As well as increasing muscle mass, testosterone significantly affects bone mineral density, which naturally diminishes over time. Lower testosterone levels raise the risk of osteoporosis and fractures. Research indicates that testosterone treatment can increase bone density, particularly in the spine and hip, which helps support muscles and internal organs, potentially enhancing athletic performance.

Higher ratios of total testosterone have been linked with a reduced incidence of Alzheimer’s disease. Some studies suggest that testosterone supplementation can modestly improve cognitive functions such as processing speed and executive function. Although testosterone may have a protective effect on cognition, especially in men with Alzheimer's, further large-scale studies are necessary to fully explore the benefits of testosterone on cognitive health.

Testosterone plays a pivotal role in sexual function, influencing libido and erectile function significantly. In humans, sexual stimuli can increase testosterone levels, enhancing sexual arousal and responsiveness. Men experiencing erectile dysfunction or reduced libido, particularly when linked to documented testosterone deficiency, can often find relief through testosterone therapy. This treatment has been shown to address venous leakage in the corpus cavernosum—a common cause of (erectile dysfunction) in older men—thus improving erectile function.

Research suggests testosterone therapy can have beneficial effects on sexual health, though more investigation is needed, especially with older men who aren’t diagnosed with low testosterone. Long-term studies have highlighted that men receiving testosterone replacement report a notable increase in libido, more energy for sex-related activities, and sleep-related erections. However, it's important to note that erectile dysfunction is often caused by other conditions or medications, and not solely by low testosterone levels.

Lower testosterone levels can affect a person’s quality of life, contributing to symptoms such as depression, fatigue, and irritability. Testosterone replacement therapy has been reported to improve mood, wellbeing, and energy levels in men with hypogonadism.

Low testosterone can manifest through a variety of signs and symptoms that considerably impact men's health and quality of life. These include a loss of libido, erectile dysfunction, diminished cognitive function, depression, lethargy, osteoporosis, and a noticeable decline in muscle mass and strength.

Further studies have shed light on the severe health risks associated with untreated hypogonadism (low testosterone), including a heightened risk of death, coronary artery disease, and stroke.  However, testosterone replacement therapy (TRT) itself carries potential risks. Notably, TRT has been associated with polycythemia (higher concentration of red blood cells), and a reduction in HDL (good) cholesterol levels. Prostate and lower urinary tract-related events, such as prostate enlargement, elevated PSA levels, and prostate cancer, are also increased with TRT, although no definitive link has been established between TRT and risk of prostate cancer or changes in Gleason (a type of grading used for prostate cancer) scores. On the contrary, older studies have found that men with lower testosterone levels have a 23% reduced risk of developing prostate cancer.

Low testosterone levels can have a profound and multifaceted impact on men's health, affecting their physical, mental, and emotional wellbeing. The symptoms of low testosterone are varied and significant, and can severely dampen quality of life, leaving men feeling less interested in activities they once enjoyed and struggling with lower overall engagement in life.

The psychological toll of low testosterone is particularly notable, with many experiencing symptoms of depression and a general sense of lethargy. This can spiral into a reduced desire to engage in social activities or pursue personal interests, further isolating individuals and bringing on stronger feelings of sadness or hopelessness.

Physically, low testosterone contributes to decreased muscle mass and strength, which can impair a man's ability to perform everyday tasks and reduce his overall physical fitness. When coupled with osteoporosis, another consequence of low testosterone, the risk of fractures becomes greater, which can lead to a further decrease in activity levels.

The health implications of low testosterone extend beyond quality of life. Studies have highlighted serious health risks associated with untreated hypogonadism, such as an increased likelihood of coronary artery disease and stroke. These conditions can have life-altering, if not fatal, consequences, emphasising the need for men to keep on top of their testosterone count.

Low testosterone does not inherently lead to infertility, as the ability to produce healthy sperm primarily hinges on other hormones. Nonetheless, testosterone plays a supporting role in the reproductive system, and its deficiency can indirectly affect sperm production. Inside the testicles—where sperm is produced—the concentration of testosterone is significantly higher than in the bloodstream, indicating its importance in optimal sperm production.

There are also some indirect impacts of low testosterone on fertility. It often leads to a diminished sex drive, compounded by its role in causing erectile dysfunction, where a man may experience fewer and weaker erections. Such changes can make it challenging not only to achieve climax but also to engage in sexual activity frequently enough to facilitate conception.

While testosterone therapy can improve certain aspects of sexual function, it can adversely affect fertility. Exogenous testosterone (testosterone used as treatment) can disrupt certain physiological processes such as the hypothalamic-pituitary-gonadal axis which are crucial for reproductive hormone production. It also inhibits the secretion of follicle-stimulating hormone and luteinising hormone, both of which are essential for the production of sperm. Testosterone used as a form of contraceptive has been shown to suppress sperm production in a significant percentage of men within a few months of use.

The effects of testosterone therapy on fertility are reversible for many men with the majority of men experiencing a return to normal sperm production when treatment is stopped. However, the recovery time can vary, with some taking up to two years to return to baseline levels.

Hypogonadism is a condition where the body is unable to produce normal amounts of testosterone due to issues with the testicles or the pituitary gland, which regulates them. The BSSM has introduced new guidelines that make a clear distinction between general testosterone deficiency and hypogonadism. According to these guidelines, testosterone deficiency is defined as a syndrome resulting from lower testosterone levels, while hypogonadism is a specific disorder that may be either congenital or acquired, leading to the same syndrome.

This distinction underscores the different causes behind each condition which can help men and their doctors better understand the cause of their symptoms. Despite the BSSM's efforts to differentiate these terms, there is an argument to be made that they represent variations of the same underlying issue rather than completely separate conditions.

Hypogonadism manifests in two primary forms—each stemming from different origins within the body.

Primary hypogonadism: This form is also known as primary testicular failure, and it arises directly from problems within the testicles. The causes of primary hypogonadism can be diverse, ranging from genetic disorders like Klinefelter's Syndrome to physical issues such as undescended testicles, testicular injury, or the effects of cancer treatment. Ageing can also play a significant role in its development. In these cases, the testicles themselves are impaired and fail to produce sufficient levels of testosterone.

Secondary hypogonadism: In contrast, secondary hypogonadism points to difficulties in the brain regions that regulate the testicles—the hypothalamus or the pituitary gland. The hypothalamus produces gonadotropin-releasing hormone which causes the pituitary to release follicle-stimulating hormone (FSH) and luteinising hormone (LH). LH then signals the testes to produce testosterone. If there's a disruption in this chain of communication, such as from Kallmann syndrome (a genetic condition), inflammatory diseases, HIV/AIDS, certain medications, or even obesity, the testicles may be healthy but underutilised due to insufficient hormonal signals.

Both types of hypogonadism can be congenital, meaning they are present from birth, or acquired due to factors like injury or infection later in life. While primary hypogonadism targets the testicles' ability to produce hormones, secondary hypogonadism involves enhancing the hormonal signals they receive, addressing the root of the signalling problem.

Although low testosterone levels can naturally decline over time, they can be exacerbated by a number of underlying health conditions, each compounding the other in a cycle of detriment to overall wellbeing.

Type 2 diabetes is commonly associated with low testosterone. Research shows that a significant proportion of men with type 2 diabetes also suffer from low levels of testosterone. This relationship may be influenced by insulin resistance, where the body fails to use insulin effectively, impacting hormone levels including testosterone.

Obesity also plays a critical role in testosterone deficiency. Excessive body fat can increase the activity of an enzyme called aromatase, which converts testosterone into oestrogen, reducing available testosterone. 

Non-alcoholic fatty liver disease (NAFLD), predominantly seen in overweight individuals, can lead to lowered testosterone levels through reduced insulin sensitivity and increased visceral fat, both of which are linked to low testosterone.

Traumatic brain injuries affecting the hypothalamus or pituitary gland can disrupt the hormonal signals essential for testosterone production, leading to decreased levels.

Sleep apnoea takes a heavy toll on sleep quality, drastically cutting into REM and deep sleep phases. Men who struggle with sleep apnea often experience frequent nighttime awakenings and poor sleep efficiency, leading to significantly lowered testosterone levels, and consequently, diminished overall health.

Kidney failure is associated with lower levels of luteinising hormone production, which in turn causes low testosterone levels.

Other conditions such as testicular injury, AIDS, iron overload, and various infections can all lead to decreased testosterone production. Conditions like Kallmann syndrome and Klinefelter’s syndrome, genetic disorders affecting hormonal development, directly impair the body's ability to produce adequate testosterone levels.

Testosterone deficiency is more widespread than many might assume, affecting an estimated 10–40% of men globally. However, this statistic is subject to debate due to the varying diagnostic thresholds different countries employ. Specifically, in the UK, around 9% of the male population is estimated to suffer from this condition – meaning that nearly 1 in 10 men have low testosterone.

Testosterone deficiency (TD) manifests through a variety of symptoms that can significantly impact daily life. The key symptoms (those directly linked to low testosterone levels) include a reduced sex drive, diminished erectile function, loss of body hair, decreased beard growth, loss of lean muscle mass, persistent fatigue, obesity, and symptoms of depression. These specific indicators provide clear signals of potential TD.

However, there are also non-specific symptoms that may or may not be associated with testosterone deficiency. These include a lower level of energy, endurance, physical strength, poor memory, difficulty finding words, lack of focus, and underperformance at work. While experiencing any one of these symptoms alone may not necessarily mean a man has TD, the presence of a combination of symptoms—such as persistent tiredness coupled with reduced sexual desire and depressive feelings—should prompt consideration of TD.

Men who have a mix of both specific and non-specific symptoms, particularly changes that affect their emotional and physical wellbeing over time, are advised to consult with a healthcare professional to explore the possibility of testosterone deficiency.

Erectile dysfunction (ED) is the inability to achieve or sustain an erection during sex. It can be an awkward subject that many men fear or have difficulty discussing. Due to personal and/or societal expectations, many men feel that their penises should work on cue. However, they may face tremendous pressure when things don't go as planned, which can have a significant impact on their self-esteem. 

ED is very common. In the UK alone, 4.3 million men struggle with ED each year, presenting with any of the following symptoms:

• Trouble getting an erection

• Trouble maintaining an erection throughout sexual activity

• Decreased libido

Low testosterone is a key factor behind ED, affecting erections both physiologically and psychologically. Testosterone plays a crucial role in maintaining libido and facilitating the bodily processes necessary for achieving an erection. Low levels of testosterone can dampen sexual desire and reduce the efficiency of these physiological processes.

Research indicates that between 20% and 40% of men with erectile dysfunction have low free testosterone levels. It's important to note, however, that while both ED and hypogonadism (low testosterone) commonly occur as men age, they may not always be directly linked.

Testosterone influences erectile function on two primary levels. Firstly, in the central nervous system, it stimulates the release of neurotransmitters like dopamine, nitric oxide, and oxytocin, which are crucial for initiating an erection. Secondly, testosterone acts at the spinal level, influencing nerves that regulate the blood flow necessary for maintaining an erection.

Low testosterone significantly impacts libido. Physiologically, hormonal disruptions in the brain can dampen sexual drive. Psychological issues like depression, along with environmental stressors such as marital discord or anxiety, also play critical roles. However, sexual desire itself is governed by sophisticated neural circuits within the brain, where testosterone and its derivatives bind to androgen receptors. Hence, exactly how common low libido is in men varies depending on the symptoms they’re exhibiting that may or may not be attributed to low testosterone.

Various studies underscore that libido naturally declines with age in men, which correlates with decreasing testosterone levels. This decline in hormone levels reduces the activation of androgen receptors in the brain, leading to a lowered sexual drive. Understanding this connection highlights the critical role testosterone plays in maintaining sexual desire and how its deficiency can profoundly affect personal wellbeing, but researchers have yet to pinpoint exactly how low testosterone levels reduce sex drive.

When testosterone levels are low, individuals may experience muscle wasting, where muscles lose bulk and strength. This can manifest not just in reduced muscle size, but also as a decrease in energy, stamina, and physical performance—perhaps affecting how much weight a person can bench press or how far they can run.

Muscle mass reaches its peak when a man reaches their late twenties, but begins a steady decline thereafter, diminishing by roughly 1% to 2% per year. This decline in muscle mass is attributed to changes in both the type and size of muscle fibres. Alongside the reduction in mass, muscle strength also wanes, falling approximately 2% to 3% each year. 

Testosterone interacts with androgen receptors in muscle cells to maintain muscle fibre integrity. A deficiency in testosterone leads to insufficient activation of these receptors, which in turn, causes the muscle fibres to degrade and weaken over time. While the precise mechanisms through which testosterone influences muscle are still being explored, several hypotheses suggest that testosterone promotes muscle growth by enhancing protein synthesis. 

Testosterone is believed to enhance muscle growth not only through traditional genetic pathways but also via more rapid, non-genomic routes. It activates certain receptors in muscle cells that lead to increased calcium levels inside the cells, and thereby stimulate cellular growth. Testosterone can also promote muscle enlargement by elevating the levels of IGF-1, a potent growth factor that operates through specific biochemical pathways to enhance muscle hypertrophy. 

Evidence from one of the largest non-injectable testosterone trials, the Testosterone's Effects on Atherosclerosis Progression in Aging Men (TEAAM) trial, suggests that long-term testosterone replacement can lead to modest improvements in upper body strength, muscle power, and lean body mass, though the effects on lower body strength can be inconsistent.

The link between obesity and low testosterone has been well-documented for over three decades. A drop in testosterone levels below normal can lead to a decrease in muscle mass, which in turn, slows down your metabolism. This domino effect sets the stage for weight gain and persistent fat that resists even the most diligent efforts at diet and exercise. This weight gain can become a stubborn issue, particularly as the body's metabolic rate declines with less muscle mass to fuel it.

Fat cells function much like other organs, secreting chemicals, sending signals, and impacting bodily functions. One key activity of fat cells is the production of an enzyme called aromatase, which converts testosterone into oestrogen. This conversion can disrupt the balance between testosterone and oestrogen levels, leading to an increase in body fat. Low testosterone levels are specifically linked to an increase in abdominal fat, which is not only cosmetically undesirable but also elevates the risk of heart disease.

Recent studies, including a comprehensive analysis from the European Male Aging Study (EMAS), have consistently shown a strong correlation between increased body fat and lower levels of both total and free testosterone. In this study, obesity was associated with a significantly higher risk of secondary hypogonadism (see question 10), and even men who were merely overweight showed a noticeable reduction in testosterone levels.

Testosterone is essential for maintaining vitality and vigour, significantly boosting metabolism and enhancing physical performance. When testosterone levels drop, men often notice a significant drain on their energy, feeling unusually tired and less driven. It’s important to remember, though, that fatigue isn’t always due to low testosterone; factors like ageing and depression can also sap energy.

As testosterone declines, it becomes harder for the body to replace muscle, and instead, more body fat accumulates. This shift in body composition — more fat and less muscle — can make anyone feel less motivated to exercise. Moreover, low testosterone often disrupts sleep, leading to insomnia. This means men might wake up feeling groggy and unfocused, struggling to shake off that feeling of sleepiness. Together, these changes can create a frustrating cycle of low energy that impacts daily activities and overall wellbeing.

The overlap in symptoms between low testosterone and depression often complicates diagnosis, especially since issues such as difficulty thinking and anxiety are also common in ageing. As men grow older, the likelihood of both depression and hypogonadism (low testosterone) increases, prompting questions about whether the gradual decline in testosterone levels contributes to increased depression rates in older men.

Symptoms common to both conditions include irritability, anxiety, sadness, low sex drive, memory problems, trouble concentrating, and sleep disturbances. However, the physical manifestations of low testosterone and depression can significantly differ. While individuals with depression typically do not show physical signs such as breast swelling or decreased muscle mass—symptoms often associated with low testosterone—they may experience headaches and back pain.

Research into the link between testosterone levels and depression has yet to find a consistent relationship, but many studies confirm that lower testosterone levels are often associated with depressive symptoms. These studies have found that TRT shows promising results in alleviating depressive symptoms in men with low testosterone, the reasons for which may stem from testosterone’s role as a modulator of GABAA receptors and an inhibitor of 5-HT3 receptors in the brain.

Interestingly, men with specific types of depression respond particularly well to testosterone replacement therapy (TRT), including those with HIV/AIDS, mild depression, severe testosterone deficiency, or those using transdermal (on the skin) rather than intramuscular (injected) testosterone. It has been found that even patients who do not respond to standard antidepressants like SSRIs often see significant improvement in their depressive symptoms after starting TRT.

Although primarily associated with reproductive functions, testosterone has a significant impact on the brain: it not only signals the brain to regulate its release but also has multiple positive effects on brain health, such as delaying nerve cell death, promoting nerve cell regrowth after damage, and reducing the effects of nerve damage.

Testosterone can also cross the blood-brain barrier—a protective mechanism designed to shield the brain from potentially harmful substances while allowing essential ones like certain medications to pass through. This means that testosterone has the ability to play a direct role in brain functions, including cognitive processes. 

Cognitive decline is a common aspect of ageing, affecting functions such as verbal and visual memory, executive function, and spatial abilities. This decline in cognitive abilities in men correlates with a reduction in testosterone levels, hinting that lower testosterone may be a contributing factor to age-related cognitive decline or brain fog.

Clinical research, particularly among postmenopausal women and men experiencing andropause, has consistently shown that testosterone supplementation can significantly improve both learning and memory capabilities. Notably, even a short-term testosterone treatment lasting just six weeks has been observed to enhance spatial and verbal memory in older men.

This improvement is believed to be due to better brain perfusion, the process of delivering blood to the brain, which is rich in oxygen and nutrients. Studies, including one using positron emission tomography (PET) scans, have shown that testosterone treatment can lead to improved visuospatial performance. This is likely because testosterone interacts with androgen receptors in the brain, which play a crucial role in how neurons function and respond to hormones.

Sleep is fundamentally categorised into two types: non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM encompasses four phases, with the first two being lighter and the latter two, known as slow-wave sleep (SWS), being deeper. REM sleep, characterised by eye movements, becomes longer and more frequent as the night progresses. The pattern of how we cycle through these phases evolves with age, meaning that we unfortunately get less deep sleep and more frequent awakenings as we get older.

From a hormonal perspective, testosterone levels are closely tied to our sleep patterns. Testosterone levels naturally rise during sleep and reach peak levels during the first REM episode. However, sleep deprivation can significantly reduce testosterone production, leading to a cyclic problem where poor sleep decreases testosterone, which in turn can lead to even poorer sleep quality.

This relationship becomes particularly concerning around middle age onwards, when natural declines in testosterone begin to occur. Men in this age group who experience sleep disturbances may see an even more pronounced drop in testosterone levels. Furthermore, as testosterone decreases, the body compensates by increasing levels of cortisol – the primary stress hormone known for its role in heightening alertness – which can disrupt sleep further, leading to shorter and shallower sleep cycles.

The best way to check your testosterone levels is by taking a blood test. A venous blood test (drawn from the vein) is the most reliable way to assess your testosterone levels. If possible, it’s worth getting a test that also looks into possible causes of low testosterone.

For example, testing luteinising hormone and follicle-stimulating hormone levels could indicate whether you have primary or secondary hypogonadism. High levels could mean primary testicular failure due to conditions like Klinefelter syndrome or certain infections. On the other hand, low levels could point to secondary hypogonadism, indicating potential problems with your hypothalamus or pituitary gland.

Don't forget about sleep—its quality has a major impact on your testosterone levels. Aiming for about 7 to 9 hours of sleep per night is ideal. Interestingly, both too little and too much sleep can negatively affect testosterone, so finding that sweet spot is key to keeping your levels balanced.

It’s crucial that you don’t let the symptoms of low testosterone slide, as it can negatively affect your quality of life.

Low testosterone can often be reversed, but managing it typically involves long-term treatment. When low testosterone stems from a secondary condition like obesity, addressing that underlying issue may restore hormone levels to normal. For instance, losing weight and improving fitness can sometimes naturally boost testosterone levels back to a healthy range.

However, for men diagnosed with hypogonadism (testosterone deficiency), the scenario is different. These men often require lifelong testosterone replacement therapy (TRT). TRT has been shown to improve body weight and metabolic factors in men with hypogonadism, enhancing overall health and quality of life. However, if TRT is stopped, these benefits typically reverse, and symptoms can worsen. Restarting treatment usually brings back the positive effects.

Yes, testosterone deficiency, clinically known as hypogonadism, is a recognised medical condition that results in low testosterone, often due to a decreased function of the testes (in men). Hypogonadism is a common condition in the male population, but it’s more likely to occur in men who are older, have obesity, or have type 2 diabetes. It’s estimated that approximately 35% of men older than 45 years of age and 30-50% of men with obesity or type 2 diabetes have hypogonadism.  

Testosterone is essential for both general and sexual health in men and to a lesser extent in women. The causes of testosterone deficiency can vary from person to person and to that extent, low testosterone may be part of another condition associated with low testosterone, for example, Kallmann syndrome or Klinefelter syndrome. Symptoms may also be caused by comorbidities such as obesity and depression rather than low testosterone itself – but it’s important to highlight that these symptoms can also be a result of low testosterone.

Testosterone deficiency, no matter the cause, is characterised by various symptoms such as decreased libido, erectile dysfunction, fatigue, reduced strength and endurance, and mood changes. For men, erectile dysfunction tends to be the principal concern, and often what prompts the investigation that leads to a diagnosis.

The first step in any diagnosis is the patient presenting to a clinician with any number of symptoms that may otherwise fail to improve on their own, including decreased libido, erectile dysfunction, fatigue, reduced strength and endurance, and mood changes. Other pre-existing medical issues such as obesity, type 2 diabetes, and cardiovascular disease, especially in older men, increase the likelihood of TD.

The physician may then order one or more tests to confirm low testosterone and explore potential causes, these may include:

• Serum total testosterone

• Free testosterone

• Prolactin

• Luteinising hormone (LH) 

• Follicle-stimulating hormone (FSH)

• Full blood count (FBC)

An accurate diagnosis ideally requires serum total testosterone levels to be measured in a fasted state (before you eat or drink) and within the first few hours of waking as testosterone levels vary throughout the day. Testosterone levels are generally highest in the morning and are influenced by blood glucose, meaning that non-fasted levels may be up to 30% lower.

Testosterone levels that fall below the reference range (< 12mmol/L) on at least two different occasions support a diagnosis of hypogonadism. Additional investigations include the measurement of other hormones such as gonadotrophins and prolactin, as well as calculating free testosterone levels if total testosterone levels are borderline.

Issues relating to testosterone, be it having too much or too little of it, should be addressed by either an endocrinologist, urologist, or doctor with a specialist interest in testosterone deficiency. 

These specialists are qualified to order the necessary blood tests to measure total testosterone, free testosterone, and other relevant hormones like luteinizing hormone (LH) and follicle-stimulating hormone (FSH). They can also perform physical examinations, review your medical history, and recommend additional tests (e.g.imaging) if needed to determine the underlying cause of low testosterone.

While general practitioners (GPs) can also order testosterone tests, they may not have the specialised expertise to fully evaluate and manage testosterone deficiency. Therefore, it is often recommended to consult a specialist, especially if your GP is unable to identify the cause or provide effective treatment for your low testosterone symptoms.

Endocrinologist

An endocrinologist is a doctor who specialises in diagnosing and treating hormonal imbalances and disorders related to the endocrine system, which includes the testicles (responsible for testosterone production). Endocrinologists are well-versed in evaluating testosterone levels, interpreting test results, and identifying the underlying causes of low testosterone.

Urologist 

A urologist is a doctor who specialises in diagnosing and treating conditions related to the male reproductive system and urinary tract, including the testicles. Urologists are knowledgeable about testosterone deficiency and its impact on male sexual and reproductive health

Testosterone deficiency specialist

As the causes, symptoms, and treatments for testosterone deficiency are complex and unique to each individual, specialist care is recommended when exploring optimising your levels.

As testosterone levels vary throughout the day and are affected by factors such as blood glucose, it’s recommended to take blood samples early to ensure testosterone is measured at its highest point in the daily cycle, providing an accurate representation of the body's maximum production capability.

Typically, two separate blood tests are needed to diagnose testosterone deficiency, preferably 4 weeks apart. Both samples are to be taken in the morning on an empty stomach. There are two main reasons as to why two levels are needed:

• To establish a baseline

• To confirm consistently low levels 

A single testosterone reading can fluctuate based on multiple factors so having two separate tests helps confirm if low levels are persistent rather than just a one-time occurrence.

The first blood test establishes a baseline testosterone level. The second test, taken on a different day, allows the doctor to compare the results and ensure the low levels are consistent and not just an anomaly.

For comprehensive testosterone testing, multiple biomarkers are evaluated to provide a complete picture of testosterone levels and function in the body. 

Total Testosterone

This measures the total amount of testosterone in the blood, both bound and unbound forms. It gives an overall assessment of testosterone production.

Free Testosterone

This test measures the fraction of testosterone that is not bound to proteins like sex hormone-binding globulin (SHBG) and albumin. Free testosterone is the biologically active form that can interact with tissues to elicit certain responses.

Sex Hormone-Binding Globulin (SHBG)

SHBG binds to testosterone and regulates how much can ‘work’ in your body at any given time.  Measuring SHBG levels helps determine how much testosterone is bound and unavailable. High SHBG levels can effectively reduce free testosterone levels, even if total testosterone is normal. 

Albumin

Albumin works as a carrier protein and binds to testosterone but with a weaker affinity than SHBG. Measuring albumin levels helps account for the testosterone bound to this protein, which is less bioavailable than free testosterone.

Prolactin

Prolactin is a hormone typically found in women and is responsible for the production of breast milk. In men, it enhances the effect of LH, which in turn increases testosterone secretion. Too much prolactin can suppress testosterone production and cause symptoms like erectile dysfunction and low libido, even with normal testosterone levels. Testing prolactin helps identify if high prolactin could be contributing to symptoms.

ALT and AST

These liver enzymes can indicate liver health. Since the liver plays a role in testosterone metabolism, and decreased testosterone levels are common in patients with severe liver disease, abnormal ALT and AST levels may suggest an underlying liver condition affecting testosterone levels.

Gonadotropins: Luteinising hormone (LH) and follicle-stimulating hormone (FSH) 

The levels of LH and FSH help determine if the cause of low testosterone is due to a problem in the testes (primary hypogonadism) or in the hypothalamus/pituitary gland (secondary hypogonadism), guiding the appropriate treatment.

• In primary hypogonadism, the testes are not functioning properly, leading to low testosterone levels. As a compensatory mechanism, LH and FSH levels will be elevated as the pituitary tries to stimulate the underperforming testes.

• In secondary hypogonadism, the problem lies in the hypothalamus or pituitary gland, resulting in inadequate LH and FSH production. This, in turn, leads to low testosterone levels from lack of stimulation of the testes.

Growth Hormone (GH), Thyroid-Stimulating Hormone (TSH), Adrenocorticotropic Hormone (ACTH)

Sometimes these tests may be requested if it is suspected that there may be other pituitary hormone deficiencies. Consequently, these tests are often ordered to rule out other endocrine disorders that may coexist with or contribute to testosterone deficiency.

Total testosterone refers to the overall amount of testosterone in the bloodstream, including both the testosterone bound to proteins and the unbound or "free" testosterone. 

Free testosterone, on the other hand, is the small fraction (around 2-5%) of testosterone that is not bound to proteins like sex SHBG and albumin, and is therefore ready and able to interact with cells and exert its effects. In other words, free testosterone is considered the biologically active form, whereas bound testosterone is not immediately available for use by the body's tissues.

While total testosterone provides an overall picture of testosterone production, free testosterone levels are often considered a better indicator of the body's potential for strength, virility, and overall testosterone activity. It is possible to have normal total testosterone levels but still experience symptoms of low testosterone if the free testosterone levels are low.

Oestrogen is a hormone that plays a crucial role in female reproductive and sexual development. However, it also plays a key role in regulating testosterone production and maintaining a healthy balance between the two hormones in both sexes.

Effects of oestrogen on testosterone levels in women

• Oestrogen helps regulate testosterone production in the ovaries. A balance between oestrogen and testosterone is important for normal ovarian function and fertility.

• Conditions like polycystic ovary syndrome (PCOS) can lead to high testosterone and low oestrogen levels, causing irregular periods, excess hair growth, and other symptoms.

• During menopause, oestrogen levels decline sharply, which can lead to a relative increase in testosterone levels compared to oestrogen. This hormonal imbalance contributes to some menopausal symptoms.

Effects of oestrogen on testosterone levels in men

• Men produce small amounts of oestrogen, which is important for modulating libido, erectile function, and spermatogenesis (sperm production).

• As men age, their testosterone levels gradually decrease, while oestrogen levels remain unchanged. An excessive oestrogen-to-testosterone ratio can cause symptoms like gynecomastia (male breast enlargement) and erectile dysfunction.

Obesity can increase aromatase activity, which converts testosterone to oestrogen, leading to higher oestrogen and lower testosterone levels in men.

Venous blood tests are generally considered gold-standard blood tests as they’re more accurate and reliable, and can give a clearer view of all biomarkers and cells that are being tested. Capillary blood tests, on the other hand, can sometimes give erroneous high or low results due to factors like hemolysis (rupturing of blood cells), interference from proteins/antibodies, and dilution with extracellular fluid when milking the finger.

While capillary blood tests are easier and more convenient to do at home, and though they can be used for many tests, venous blood is better suited for tests that require larger sample volumes or where multiple tests need to be run in a lab. A 2016 study comparing venous and capillary blood samples for complete blood count testing suggests that capillary samples may be used as a substitute for venous samples for general parameters, however, their reliability diminishes for platelet counts higher than 150,000 μL.

Venous blood testing is often preferred because it provides more accurate and reliable results, makes it easier to collect a high-quality sample, is suitable for a wider range of tests, and avoids potential complications associated with capillary sampling. However, capillary testing can still be useful when only a small volume is needed, venous access is difficult, or for specific applications where it has been validated.

Developed in Germany in 1999, the Aging Males' Symptoms (AMS) scale is a concise tool designed to assess the quality of life in ageing men, particularly identifying potential andropause—a decline in testosterone akin to menopause in women. The questionnaire evaluates 17 different symptoms across psychological, physical, and sexual health, with each symptom rated on a severity scale from 1 to 5. These scores are compiled into three subscales which are then summed to produce a composite score reflecting overall health.

The AMS questionnaire takes only a few minutes to complete. It assists in diagnosing symptoms of andropause and distinguishing between causes of erectile dysfunction, such as hormonal issues versus vascular problems. The comprehensive output from the AMS questionnaire is invaluable in helping form medical decisions and improving treatment strategies.

First and foremost, any diagnosis relating to testosterone levels should be made by an appropriate healthcare professional. During the consultation, the doctor will ask you about the intricacies of your symptoms, including what they are, how long they’ve been going on, and how they’ve been affecting your professional and personal life. You will also be asked questions about your past medical history, medications you take or have taken in the past, and whether you have any family history of low testosterone.

It would be helpful if you could list the specific symptoms you’re experiencing, such as decreased libido, erectile dysfunction, fatigue, and muscle loss (to name a few) during your consultation, while identifying how long they’ve been interfering with your life.

Please also prepare to discuss your lifestyle in detail, and hone on factors like your diet, how often you exercise, whether or not you feel stressed, and the quality of your sleep, as all of these are linked to fluctuating testosterone levels.

Finally, your doctor may suggest that you need to perform a physical examination in addition to laboratory testing. During the physical exam, they will be looking for signs of hormonal imbalances such as the presence of gynecomastia (male breast enlargement), or abnormal testicular size. Laboratory testing and possibly imaging may then be ordered to confirm a diagnosis.

With a comprehensive understanding of your medical history, symptoms, physical findings, laboratory results, and other relevant factors, a healthcare provider can better determine the underlying cause of your testosterone deficiency.

If your total testosterone levels are within the normal range, but you’re still experiencing symptoms commonly associated with low testosterone, there could be a few potential explanations.

It’s important to stress that if you’re experiencing persistent symptoms despite normal testosterone levels, it’s important to have a comprehensive evaluation by a healthcare provider. They may recommend additional testing and imaging to reach a diagnosis. 

Low free testosterone levels:

While your total testosterone may be normal, you could have a lower-than-normal level of free (bioavailable) testosterone. Free testosterone is the testosterone that is not bound to proteins and can readily interact with cells and receptors to exert its effect. Even with normal total levels, having low free testosterone can cause symptoms.

Androgen insensitivity: 

In some cases, the body's tissues may be resistant or insensitive to the effects of testosterone, despite having adequate levels. This condition, known as androgen insensitivity syndrome, can lead to symptoms mimicking low testosterone.

Other hormonal imbalances:

An imbalance or deficiency in other hormones like oestrogen, prolactin, thyroid hormones, or growth hormone can sometimes cause symptoms similar to those of low testosterone, even when testosterone levels are normal.

Medical conditions:

Certain medical conditions, such as obesity, diabetes, sleep apnea, chronic stress, or depression, can contribute to symptoms like low libido, fatigue, and erectile dysfunction, even if testosterone levels are not the primary cause.

Medication side effects:

Some medications, such as opioid painkillers, oral glucocorticoids, or certain antipsychotic drugs, can potentially interfere with testosterone production or function, leading to symptoms despite normal levels.

Testosterone is involved in regulating multiple biological processes and therefore if left untreated, low levels can lead to several potential risks and complications.

It's important to note that while low testosterone can contribute to these risks, the severity and individual impact may vary. Early diagnosis and appropriate treatment, such as testosterone replacement therapy (TRT), can help mitigate these potential complications and improve overall health and quality of life.

Osteoporosis and increased fracture risk

Testosterone plays a crucial role in maintaining bone density. Chronic low levels can accelerate bone loss, leading to osteoporosis and an increased risk of fractures, especially in older men.

Metabolic syndrome and cardiovascular disease

Untreated low testosterone is associated with an increased risk of developing metabolic syndrome, which includes obesity, insulin resistance, dyslipidemia, and hypertension. These factors can contribute to the development of cardiovascular diseases, such as heart attacks and strokes.

Erectile dysfunction and decreased libido

One of the most common symptoms of low testosterone is a reduced sex drive and erectile dysfunction. If left unaddressed, this can lead to relationship issues and decreased quality of life.

Decreased muscle mass and strength

Testosterone is essential for maintaining muscle mass and strength. Chronic low levels can result in muscle wasting, decreased physical performance, and an increased risk of falls and frailty, especially in older men.

Anaemia

Low testosterone can lead to a decrease in red blood cell production, causing anaemia, which can result in fatigue, weakness, and shortness of breath.

Cognitive and emotional changes

Testosterone deficiency has been linked to cognitive impairment, memory problems, and an increased risk of depression and mood disturbances.

Infertility

In men, low testosterone can impair sperm production and lead to infertility or reduced fertility.

Increased risk of mortality

Some studies have suggested that untreated low testosterone may be associated with an increased risk of all-cause mortality, particularly in older men.

Most people stay on TRT for at least 12 months, but the expected length of treatment depends on individual factors such as age, health, the underlying cause of testosterone deficiency, and the response to treatment. If low testosterone is due to testicular failure or an irreversible cause, it’s unlikely that physiological testosterone levels will ever be sustained without continued use of TRT. In these cases, TRT is intended to be a lifelong treatment. However, this does not apply to people with low testosterone due to a potentially reversible cause (e.g. obesity or type 2 diabetes). These individuals may eventually be able to maintain physiological testosterone levels without using TRT, once the underlying aetiology has been treated. There may also be rare circumstances when TRT must be stopped prematurely due to unwanted side effects or adverse events.

TRT is legal when prescribed by a licensed healthcare provider and used for medical purposes. However, as TRT is the same chemical substance as an anabolic steroid, just in a much lower dose, then it’s illegal to possess, import or export TRT if not for personal use. Anabolic steroids are Class C drugs that are illegal to supply or sell outside of medical approval.

As testosterone supplementation is performance enhancing, TRT is banned in most professional sports. Detectable levels of TRT or its metabolites in the urine or blood can result in an athlete being banned from competition for a number of years, if not indefinitely. Only in rare cases will an anti-doping organisation grant an athlete a Therapeutic Use Exemption to use TRT due to a genuine medical condition (such as hypogonadism).

The main users of TRT are men with clinically diagnosed hypogonadism (testosterone deficiency), who aim to restore physiological levels of testosterone. Approximately 20% of hypogonadal men are actively treated with TRT, with a continually increasing number of annual prescriptions. There has also been an increase in the use of men using TRT without hypogonadism. An estimated 25–50% of new TRT users have not had a pre-treatment test for blood testosterone.

The goal of TRT is to induce and maintain primary and secondary sex characteristics while correcting symptoms of testosterone deficiency. Primary sexual characteristics include testicular descent, sperm production, libido, and the size of the penis and testicles. Secondary male characteristics include muscle mass, bone mineral density, red blood cell production, hair growth, and deepening of the voice. The specific goals of treatment for each individual will differ depending on their personal circumstances. As suggested by some clinical guidelines, a key objective of TRT may simply be to maintain general wellbeing and promote a better quality of life.

The four most common ways to administer TRT are injections (intramuscular or subcutaneous), oral tablets, topical gels, and transdermal patches. TRT can be administered with implantable pellets beneath the skin (via surgical procedure) but is rarely used. All options have different dosing regimens, pharmacokinetic profiles, and monitoring requirements. 

Injections are typically given no more than once per week, with an initial peak in blood testosterone levels after the injection followed by a gradual decline before the next injection. People can administer their own injection but it’s usually performed by a healthcare professional in a clinical setting. In contrast, oral tablets, topical gels, and transdermal patches are typically self-administered every day. They gradually release testosterone into the blood and cause more stable elevations in blood testosterone, without the large spikes in levels.

There is no gold-standard method for administering TRT—all have nearly equal efficacy in restoring testosterone to normal levels. The method of choice depends on individual preference, convenience, cost, adherence, and individual medical considerations. People starting TRT should discuss the available options with a healthcare professional to determine the most suitable method for their needs.

One of the main aims of TRT is to restore blood testosterone to normal levels, which it can achieve very quickly. In most studies of TRT, at least half of the participants normalise their testosterone levels when checked up after 10 days to 6 months of treatment. But the effects may be even more immediate. In one study that measured testosterone levels after just one day of TRT, 53% of men had already achieved normal blood testosterone levels. 

The duration it takes for TRT to correct signs and symptoms of low testosterone is highly variable depending on the specific individual symptom that needs to be addressed. Improvements in sexual function tend to be more immediate upon achieving normal testosterone levels, with many studies no longer than 8 weeks reporting significant benefits in erectile dysfunction and libido. Psychological benefits, such as improved mood and quality of life, have also been reported within this time period. However, it may be longer for people using TRT to improve physical function to notice results, such as increased muscle mass and bone mineral density, or improved physical performance. Small benefits to body composition have been reported within 6 months of using TRT but longer-term studies suggest that improvements progress and become more noticeable when continued for more than a year.

In addition, at least in terms of sexual symptoms, the most obvious responses to TRT are seen when baseline testosterone levels are lowest (below 8 nmol/L) and when changes in blood testosterone responses are greatest. Men without low testosterone before TRT do not notice significant improvements in sexual function; whereas, in men with hypogonadism (testosterone deficiency), the magnitude of improvement in sexual function is proportional to the increase in blood testosterone levels. It’s therefore likely that men with severe testosterone deficiency will notice symptomatic improvements faster than men with mild testosterone deficiency.

Generally speaking, approximately two-thirds of men with hypogonadism who begin TRT will experience symptomatic benefit (erections, libido, energy and/or mood) and will complete at least 12 months of treatment.

As with all medications, TRT has potential side effects that all users should be made aware of before use. These side effects include:

• Reduced sperm production

• Elevated hematocrit levels

• Gynecomastia

• Mood changes

• Sleep apnea

• Lipid abnormalities (e.g. reduced HDL-C)

• Fluid retention

• Prostate issues

• Acne

• Male pattern balding

• Skin reactions (not applicable to oral administration)

TRT is often accompanied by several prevention therapies aimed at reducing the prevalence of these side effects. Your healthcare provider should monitor individual risk of side effects before and during treatment, and respond appropriately to reports of side effects by either changing the dose, method of administration, introducing cotherapies, or ceasing use of TRT.

TRT can offer several positive long-term effects for individuals experiencing symptoms of low testosterone. Over time, TRT may contribute to improved bone density, and enhanced muscle mass and physical performance, which can have long-lasting benefits for overall health and mobility. Maintaining sexual function is another potential positive outcome of TRT, as it can help sustain libido, erectile function, and sexual satisfaction. All of these improvements can also accumulate to significantly enhance quality of life, promoting overall wellbeing and vitality for people using TRT as they age.

However, there are also potential risks associated with long-term use of TRT. One concern is the increased risk of cardiovascular events, including heart attacks and strokes, particularly in older men or those with pre-existing cardiovascular risk factors. Another risk is the impact of TRT on prostate health, as testosterone can stimulate prostate growth and potentially exacerbate symptoms of benign prostatic hyperplasia (BPH) or contribute to the development of prostate cancer. Additionally, TRT can suppress natural testosterone production, leading to a reduction in sperm production and potential infertility. 

It's crucial for individuals considering TRT to carefully weigh the potential benefits against these risks and undergo regular monitoring by a healthcare provider to optimise treatment outcomes and minimise complications.

TRT does not increase the risk of cardiovascular disease; however, the FDA requires that TRT is labelled with a warning it may cause venous thromboembolism (blood clots in the veins). Current guidelines specify that TRT is not recommended to people with a haematocrit 48-50%, a family history of venous thromboembolism, or a diagnosis of thrombophilia. 

Although these recommendations are based mostly on clinical observations rather than scientific investigations, the common increase in haemoglobin concentrations when using TRT warrants a safety-first approach for these vulnerable individuals. At least in animals, ​increased haemoglobin can lead to erythrocyte aggregation and increase blood viscosity, which might cause a blood clotting effect. Whether the same effect occurs in humans is more uncertain.

To prevent the potential risks of blood clotting while using TRT, it’s recommended to monitor for changes in haematocrit levels. Haematocrit levels above 54% require either TRT withdrawal or a change in the dose or formulation used. Other signs or symptoms, as observed by your healthcare provider, may also lead to changing in your TRT protocol.

The increased incidence of prostate cancer has been reported in users of TRT. However, it’s not clear whether TRT increases the risk of prostate cancer or if the increased screening for prostate cancer while using TRT leads to more diagnoses (that would otherwise have been missed). Because of the high prevalence of subclinical prostate cancer in older men, more prostate biopsies in men receiving TRT would lead to the detection of a greater number of subclinical prostate cancers.

Currently, there’s no strong evidence for the association between prostate cancer risk and testosterone concentrations or polymorphisms in genes that encode for proteins involved in androgen metabolism. Summaries of observational studies have found no significant association between testosterone levels and the risk of prostate cancer, with some inconsistencies among studies. Plus, reviews of TRT interventions have not found clear evidence that the therapy is safe or problematic for hypogonadal (testosterone deficient) patients with previous or active localised prostate cancer.

Despite the need for more evidence, the general advice for TRT states is that people with prostate cancer shouldn’t have this type of treatment. People with previous or ongoing prostate issues that are interested in using TRT should consult with their healthcare provider to weigh up the risks and rewards of TRT and alternative therapies. If TRT is initiated in people at high risk of prostate cancer, monitoring should include PSA and DRE 3 to 12 months after treatment initiation. If PSA concentrations increase by >1.4ng/mL or exceed 4.0ng/mL in the first 12 months of using TRT, a urological consultation may be recommended. Digital rectal examinations may be performed to check for prostate abnormalities, when required.

TRT reduces the production of sperm within the testicles. Approximately 40% of people on TRT have no sperm in their ejaculation (azoospermia). Although fertility tends to return to normal after stopping treatment, some people may need lifelong TRT, and if not, the recovery period is highly variable with no guarantee that normal sperm production will return. Currently, TRT isn’t prescribed to men with an active desire to father children. 

Hypogonadal (testosterone deficient) men wanting to preserve their fertility and benefit from TRT can be prescribed selective oestrogen receptor modulators (SERMs) such as clomiphene or low-dose human chorionic gonadotropin (hCG). Both of these medications have been found to increase sperm concentration and total sperm count in infertile patients, including those with low testosterone levels.

Sperm banking (also known as sperm cryopreservation) is another option for men who are concerned about their fertility while on TRT. This involves collecting and freezing sperm for future use in assisted reproductive techniques, such as in vitro fertilisation (IVF) or intrauterine insemination (IUI). Sperm banking allows individuals to preserve their fertility before starting TRT or during treatment.

TRT is not safe for everyone. TRT should not be prescribed to people with prostate or breast cancer, an active desire to father children, haematocrit >54% or severe chronic heart failure (NYHA class IV). Healthcare professionals may also deem the risks of TRT to outweigh the benefits for certain individuals, depending on health status, treatment goals, medical history, and other ongoing therapies.

Under the appropriate circumstances, TRT can be safely used by younger and older adults. TRT is currently MHRA-approved and recommended for men with hypogonadism (testosterone deficiency) at all stages of life, including from birth for people with congenital conditions that inhibit testosterone production. Regular monitoring of health status while using TRT is strongly recommended, particularly for individuals at high risk of cardiovascular disease or with prostate issues.

TRT is likely to improve your body composition. Most notably, TRT increases muscle protein synthesis and causes small to moderate increases in fat-free mass (including muscle mass), even without exercising. Men with low testosterone can expect higher than average muscle growth from TRT, with the greatest effects when TRT is combined with consistent resistance exercise for prolonged periods (1+ years). Larger amounts of muscle gain are expected from intramuscular versus transdermal TRT, as intramuscular injections lead to larger, temporary spikes in blood testosterone that are more anabolic than gradual, steady increases.

In addition, TRT has been associated with reduced body fat and waist circumference, such that total body weight—when accounting for increases in muscle mass—tends to fall only slightly (roughly 3kg after 2 years). One hypothesis is that the fat loss is a knock-on effect of the increased muscle mass, energy levels, and motivation that often improve with TRT. People starting TRT due to increases in body fat levels or obesity may experience larger reductions in body fat than people who are already a healthy body weight. 

Some sources suggest that TRT may cause other physical changes to your appearance, such as widening of the jaw or increasing shoulder girth and penis size, but these are based mainly on self-reports, not scientific investigation. If true, these changes will likely apply to adolescents using TRT due to a congenital condition or delayed puberty, as opposed to adults who are already fully developed.

TRT can greatly improve the way that you feel, depending on individual factors such as baseline testosterone levels, health status, and the specific goals of the therapy. Potential benefits include improved mood and potentially less symptoms of depression or anxiety. TRT may also indirectly help you to feel better about yourself by providing you with more energy and improving your body composition and overall sexual function. Treatment responses can vary considerably, though, and are extremely difficult to predict before treatment has started.

Two-thirds of men with low testosterone who begin TRT will experience symptomatic benefit and will complete at least 12 months of treatment. The key benefits of TRT for people with low testosterone levels are:

• Improved libido and sexual function

• Improved quality of life

• Improved mood

• Improved body composition

• Improved physical function

Not everyone starting TRT will experience the same benefits as it’s largely dependent on the initial symptoms experienced before using TRT. For example, if a person already has high libido and good mood before starting TRT, they will be far less likely to experience a change in these outcomes compared to a person with low libido and mood. In addition, many studies have found the best responses to treatment are reported in individuals with the lowest baseline testosterone levels and the greatest increases in blood testosterone level from TRT use.

The most specific signs of low testosterone (hypogonadism) are sexual symptoms; specifically, incomplete or delayed sexual development, very small testes, reduced libido, and erectile dysfunction. The presence of these symptoms, especially in combination, is highly suggestive of low testosterone, warranting the use of TRT.

A number of high-quality clinical trials have reported significantly greater improvements in

libido, erectile function, and sexual activity with TRT versus placebo in hypogonadal men

with low libido or sexual problems. Other markers of sexual health may also improve. One of the largest TRT trials, The Sexual Function Trial of the Testosterone Trials (TTrials), documented consistent improvements in 10 of 12 measures of sexual activities in older (≥ 65 years) hypogonadal men, particularly in frequency of intercourse, masturbation, and

nocturnal erections.

The strongest evidence of benefit in sexual function applies to treating erectile dysfunction. A summary of clinical trials showed that TRT significantly improves erectile function (as measured by International Index of Erectile Function), with clinical significance in patients with mild erectile dysfunction. Similar results have also been confirmed in an update analysis and a Cochrane review. Phosphodiesterase 5 Inhibitors (PDE5Is) are the commonplace treatment for erectile dysfunction; however, a summary of relevant clinical trials found that combination therapy of testosterone plus PDE5Is was superior to PDE5Is alone in improving erectile function.

TRT increases muscle protein synthesis and causes small to moderate increases in fat-free mass (including muscle mass), even without exercising. Men with low testosterone can expect higher than average muscle growth from TRT, with the greatest effects when TRT is combined with consistent resistance exercise for prolonged periods (1+ years). Larger amounts of muscle gain are expected from intramuscular versus transdermal TRT, as intramuscular injections lead to larger, temporary spikes in blood testosterone that are more anabolic than gradual, steady increases.

One of the most common symptoms of low testosterone is decreased energy or loss of vitality. In fact, one study found that a “lack of energy” was the strongest predictor of low testosterone in men under 40 years. Some researchers suggest that testosterone has a direct and important role in energy metabolism, which explains the association, whereas others argue that low testosterone is just a marker of poor health status that inevitably causes fatigue issues.

The evidence for TRT improving energy levels is highly conflicting. Results from the Testosterone Trial, the largest controlled study of TRT to date, provided mixed results. Following a 1 year of TRT, a statistical benefit was reported with TRT versus placebo based on a vitality survey; however, the same investigators did not observe a clinically meaningful difference on a fatigue survey. Similarly, some scientific reviews have concluded that TRT does not impact vitality, whereas others on health-related quality of life, which generally include questionnaires on energy and vitality, tend to report a benefit. 

If TRT is to benefit energy levels, it’s more likely to do so in people with low testosterone levels at baseline and experiencing symptoms of fatigue. Not everyone will experience this potential benefit and the effects of TRT on energy levels will likely vary from person to person, depending on an individual's overall health, lifestyle, and adherence to treatment.

Testosterone plays a pivotal role in maintaining balance within the psychological network of mood, behaviour, self-perception, and perceived quality of life. Testosterone levels are typically reduced In major depressive disorder and bipolar disorder, and, in agreement, people undergoing androgen-deprivation therapy for prostate cancer exhibit mood disturbances such as anxiety, fatigue, and lack of vitality. The reason for these differences is unclear, with no clear indication if low testosterone causes these mood/disease states, or if these mood/disease states cause testosterone levels to lower. 

Based on current available data, TRT has a small, positive effect on quality of life and

mood in older men with hypogonadism (testosterone deficiency). This effect seems to apply to men with late-onset, low-grade, persistent depressive disorder, but not in men with clinical depression. In line with this, the largest summary of available studies, including 1,890 hypogonadal men from 27 clinical trials, documented that the positive effect of TRT on depressive symptoms was particularly evident in patients with milder symptoms. There is, however, considerable disagreement between studies, probably due to the various methods in which mood is measured from one study to another.

Impaired sleep has been associated with low testosterone levels but the details of this relationship are not clear. On the one hand, sleep deprivation (24–48 hours) considerably reduces testosterone levels, even if just temporarily. On the other, testosterone affects the organisation of circadian rhythms and the timing (though not the duration) of sleep. Recent studies speculate that the association between low testosterone and less healthy sleep is largely explained by excess body fat (as low testosterone is closely linked with obesity).

There remains a lack of studies investigating TRT and sleep quality and duration. Those which are available seem to report a slight benefit, based on a subset of questions in the Aging Males Symptom Questionnaire, but more research is needed for definitive conclusions. It’s important to note, however, that TRT may play a small role in inducing or worsening changes in obstructive sleep apnea, a condition of a collapsed upper airway that decreases oxygen availability when sleeping. Clinicians may choose to exercise caution in prescribing TRT to individuals suffering from severe obstructive sleep apnea.

Testosterone has been implicated in improved memory due to some evidence that it improves energy production in nerve cells and reduces beta-amyloid deposits (sticky plaques) in the brain. Impaired memory remains one of the nonspecific signs of hypogonadism (testosterone deficiency), when testosterone levels are biochemically low. However, whether the impaired memory is the result of a lack of testosterone or other health complications associated with low testosterone (i.e. chronic disease) is not clear.

The evidence for TRT improving memory is highly conflicting. One summary of high quality trials concluded that TRT does not significantly improve cognition in memory-impaired older men with low testosterone, which included many tests for visual, verbal and working memory. In contrast, another review of the evidence found that TRT may improve short-term (3 months) verbal memory as measured by story recall but not necessarily other types of memory. The low number of relevant studies in this area prompts the need for more evidence to draw more certain conclusions.

As low testosterone levels often stem from poor overall health, then lifestyle changes that improve health status may naturally increase testosterone levels in certain individuals. For example, one large analysis in people with obesity-associated hypogonadism found that a low-calorie diet intervention was associated with significant increases in blood testosterone levels; plus, the degree of weight loss was the best determinant of how much testosterone increased, with particularly large effects in people with more severe obesity. Generally healthy lifestyle changes are, therefore, recommended. This includes eating lots of fruits and vegetables, reducing consumption of highly processed and calorie dense foods, and exercising frequently.

Some evidence suggests that correcting a deficiency in zinc, magnesium, and vitamin D may lead to small increases in blood testosterone levels, but this is based on only a few small studies and often paired with exercise. Reviews of lifestyle changes and testosterone also recommend avoiding low-fat diets, high intakes of alcohol, and, in people who are already a healthy body weight, very low energy diets. The potential for these lifestyle interventions (or avoidance of) to raise testosterone levels is largely unknown and may be highly individual, so monitoring your testosterone levels is recommended.

It should be highlighted that lifestyle changes are not necessarily a substitute for TRT in people with hypogonadism (testosterone deficiency). Studies have found that biochemical reversal of secondary hypogonadism with lifestyle intervention are not always associated with symptomatic improvement. Plus, in men with obesity and hypogonadism, treated with severe weight reduction and either TRT or placebo for 12 months, only the TRT group achieved symptomatic benefit. For this reason, some clinical guidelines state that patients with distressing symptoms of low testosterone should be offered the most effective relief of those symptoms, which includes lifestyle modification in conjunction with TRT.

The effects of TRT can interact with the effects of other medications. The primary medications of concern, are insulin, oral anticoagulants, and corticosteroids. Abstaining from these drugs may not be necessary but a healthcare professional may need to monitor individual responses more frequently and/or modify the dosage to maintain efficacy and reduce the risk of adverse events. It’s crucial for individuals undergoing TRT to inform their healthcare provider about all medications they’re taking to minimise the risk of interactions and ensure the safe and effective use of TRT. There’s no strong evidence that food supplements and herbal products interact with TRT, though it’s worth patients mentioning these to their healthcare provider for an additional safety measure.

In hypogonadal (testosterone deficient) men who have started TRT, the Endocrine Society and European Society of Endocrinology recommend monitoring whether the patient has responded to treatment, is suffering any adverse effects, and is complying with the treatment regimen. In subsequent clinical visits after the initiation of TRT, the clinician should monitor for blood testosterone and hematocrit levels in the physiological range at 3–6 months and again at 12 months. In addition, clinicians should evaluate symptoms and signs of testosterone deficiency and formulation-specific adverse events at each in-person visit.

In people at high risk of prostate cancer and who agree to prostate monitoring, it should include PSA and DRE 3 to 12 months after treatment initiation. If PSA concentrations increase by >1.4ng/mL or exceed 4.0ng/mL in the first 12 months of using TRT, a urological consultation may be recommended. Digital rectal examinations may be performed to check for prostate abnormalities, when required.

Specific clinical practices may include their own monitoring practices that deviate from or add to clinical guidelines. In addition, the frequency and extent of monitoring may vary depending on individual factors such as age, overall health, treatment response, and the presence of any underlying medical conditions. Individuals with severely low testosterone levels and experiencing many symptoms of testosterone deficiency may require more frequent monitoring. Individuals taking medications that may interact with TRT may also be subject to individual monitoring practices based on the clinician’s best judgement.

The benefits of TRT depend on maintaining blood testosterone within the physiological range, which requires adhering to the dosing protocol. Missing a dose of TRT medication may risk your testosterone temporarily dropping to low levels until the next dose is administered. 

If you’re taking TRT daily, in the form of oral tablets, patches, or gels, the duration of low testosterone is likely no more than 24 hours when a dose is missed, and should not lead to any serious problems. However, if you’re taking TRT in the form of injections on a weekly to monthly basis, you may experience symptoms of low testosterone for a prolonged period, similar to what you experienced before starting treatment.

If you have any concerns about missed doses or if you frequently forget to take your medication, it’s important to contact your healthcare provider. They can provide guidance on how to manage missed doses and may offer strategies to help you remember to take your medication regularly. Additionally, they can assess your treatment response and adjust your treatment plan as needed to ensure the best possible outcome.

Determining whether TRT is working for you involves assessing changes in blood testosterone levels and relevant symptoms. Ideally, you will know that testosterone is working for you based on achieving testosterone levels within the physiological range and self-reporting the improvement or resolution of symptoms that you were experiencing before using TRT. Improvements to physical (e.g. increased muscle mass) and metabolic health (e.g. lower fasting blood sugar) may also be reported with TRT usage, but they’re rarely the primary goal of treatment.

If you’re unsure if TRT is working for you, it’s recommended to contact your healthcare provider to get more clarity on the goals of your treatment plan and expected timeframes for benefit. Although blood testosterone levels should normalise quickly upon starting TRT, it may take time to notice improvements in symptoms, particularly if there are issues with adherence or the dose and administration method needs to be adjusted.

The impact of TRT on cardiovascular risk is debated among experts. Conflicting evidence from the highest quality studies initially raised concerns about the safety of TRT, particularly in individuals with a high risk of cardiovascular disease. While some studies reported no effect or even improvements in cardiovascular health, others found arterial plaque progression and cardiovascular events that stopped the trials early.

However, in 2023, the TRAVERSE clinical trial was published, which is the largest intervention of TRT assessing cardiovascular risks. It involved over 5,000 men with hypogonadism (testosterone deficiency) and cardiovascular disease (or high risk) assigned to receive either TRT (65 mg per day) or placebo. After nearly 2 years of treatment and 3 years of follow-up, the main finding was that there were no significant differences in any primary cardiovascular outcomes between TRT and placebo groups. In fact, the group taking TRT had a non-significant 16% lower incidence of death due to cardiovascular causes, providing strong evidence against the hypothesis that TRT increases the risk of cardiovascular disease.

There remain some concerns for specific populations, however. In TRAVERSE, although TRT did not significantly change the primary endpoint, it was associated with a 46% increased risk of venous thromboembolic events and a statistical increase in the risk of non-fatal arrhythmias and atrial fibrillation. It's important for individuals considering TRT to undergo a thorough cardiovascular evaluation before starting treatment, and healthcare providers should carefully weigh the potential risks and benefits of TRT for each individual.

There are no specific dietary considerations when starting TRT that are not otherwise advised to the average person. However, many clinical guidelines stress the importance of lifestyle modification (including a healthy dietary pattern) in conjunction with TRT as a first-line approach for treating hypogonadism (testosterone deficiency). This is particularly important for people with low testosterone due to a chronic disease (e.g. obesity or type 2 diabetes), as it may be possible to maintain physiological levels of testosterone without TRT once the underlying aetiology has been successfully reversed.

People starting TRT with the goal to increase muscle mass, bone health, and physical performance may also want to be mindful of their protein intake. Current recommendations for optimising these factors include a daily protein intake of 1.6 grams per kilogram of bodyweight, which is slightly more than the average person consumes. So an individual who weighs 70 kg should aim for a protein intake of at least 110 grams per day.

If you experience adverse effects while on TRT, it's crucial to contact your healthcare provider and address them promptly. All symptoms should be communicated in detail, alongside other relevant information about your treatment, such as whether you have been following the treatment plan or recently made any other medical or lifestyle changes.

Depending on the assessment of your healthcare provider, you may need to undergo medical evaluation. There may also be a need for your healthcare provider to adjust your treatment plan, such as lowering the dose of TRT, exploring an alternative formulation, or addressing lifestyle factors that may contribute to your symptoms.

For adverse effects that require immediate attention (e.g. chest pain, breathlessness, severe bleeding), then you should visit an A&E department or urgent care centre as soon as possible. Notifying friends or family of any adverse effects is also helpful to ensure you get the support you need.

Most people stay on TRT for at least 12 months, but the expected length of treatment depends on individual factors such as age, health, the underlying cause of testosterone deficiency, and the response to treatment. If low testosterone is due to testicular failure or an irreversible cause, it‘ unlikely that physiological testosterone levels will ever be sustained without continued use of TRT. In these cases, TRT is intended to be a lifelong treatment. However, this does not apply to people with low testosterone due to a potentially reversible cause (e.g. obesity or type 2 diabetes). These individuals may eventually be able to maintain physiological testosterone levels without using TRT, once the underlying aetiology has been treated. There may also be rare circumstances when TRT must be stopped prematurely due to unwanted side effects or adverse events.