Testosterone Therapy and Depression: The Surprising Link You Need to Know

Introduction: Understanding the Testosterone–Depression Connection

For many years, testosterone has been known mainly as the “male hormone.” It helps with muscle growth, sex drive, and energy levels. But scientists now know that testosterone does much more than that—it also plays an important role in mood, mental health, and emotional balance. In both men and women, testosterone affects how the brain processes emotions, handles stress, and maintains motivation. Because of this, when testosterone levels are too low or too high, it can sometimes affect how a person feels and behaves.

In recent years, testosterone therapy—often called TRT, or testosterone replacement therapy—has become a popular treatment for people with low testosterone levels. Doctors prescribe it to men whose hormone levels drop due to age or medical conditions, and in some cases, to women or transgender individuals as part of gender-affirming care. Testosterone therapy can come in many forms, such as injections, gels, patches, or small pellets inserted under the skin. The goal is simple: to bring hormone levels back to a normal range and improve overall quality of life.

However, along with the rise in testosterone therapy use has come an increase in public curiosity and confusion. Many people search online with questions like “Can testosterone therapy cause depression?” or “Does testosterone help with mood?” These questions show that there is still uncertainty about how testosterone truly affects mental health. Some people report feeling more energetic, confident, and focused when they start therapy, while others say they experience mood swings, anxiety, or even depression. Understanding why this happens—and who is most at risk—is one of the most important questions in modern hormone medicine.

To understand this connection, it helps to know how testosterone interacts with the brain. Testosterone is not just a “physical” hormone—it also acts as a chemical messenger in the brain. It influences neurotransmitters like serotonin and dopamine, which play a big part in how we feel pleasure, motivation, and emotional stability. When testosterone levels are balanced, these brain chemicals work smoothly, supporting a stable and positive mood. But when levels are too low or change too quickly, it can disrupt this balance, sometimes leading to symptoms that look like depression.

The relationship between testosterone and mood is also complicated because many of the signs of low testosterone overlap with the signs of depression. For example, both can cause low energy, poor sleep, loss of interest in activities, irritability, and trouble concentrating. This overlap makes it difficult to know which problem came first—does low testosterone cause depression, or does depression lower testosterone levels? Research shows that both may influence each other. People with chronic depression often have lower testosterone levels, and those with low testosterone are more likely to experience depressive symptoms.

Another factor that adds to the confusion is the way testosterone therapy affects people differently. Not everyone responds to treatment in the same way. For some, restoring testosterone levels brings back mental clarity, motivation, and emotional balance. For others, especially if the therapy is not properly managed, hormone levels may fluctuate too quickly, leading to mood swings or emotional lows. In rare cases, too much testosterone can also create irritability, impulsive behavior, or anxiety. Because of these differences, medical supervision is essential for anyone considering testosterone therapy.

The growing popularity of testosterone therapy has also been fueled by marketing and social media, where it is often promoted as a way to “feel younger” or “boost energy.” While some people do see real benefits, these promises can sometimes oversimplify what testosterone therapy really does. It is not a magic fix for depression or fatigue, and it can have side effects if not carefully monitored. Understanding both the benefits and the risks is key to making informed decisions.

As researchers continue to study testosterone’s effect on mood, new insights are emerging. Studies suggest that testosterone may help improve depression in people who have low hormone levels, especially older men. But in people who already have normal levels, adding extra testosterone does not always help—and in some cases, it might make mood symptoms worse. This shows how complex the relationship is between hormones and mental health.

The purpose of this article is to bring clarity to this topic. It will explore what testosterone therapy is, how it affects the brain, and what current science says about its link to depression. It will also explain why some people feel better on therapy while others may feel worse, and what steps can be taken to ensure treatment is safe and effective. The goal is not to promote or discourage testosterone therapy, but to give readers clear, evidence-based information so they can have informed discussions with their healthcare providers.

By the end of this article, readers will have a better understanding of how testosterone and depression are connected, what the science shows about hormone therapy’s benefits and risks, and why careful medical guidance is so important. Hormones are powerful, and while they can influence our mood and mental health in major ways, they are only one piece of a much larger puzzle. Recognizing this balance is the first step toward understanding the surprising link between testosterone therapy and depression.

What Is Testosterone Therapy?

Testosterone therapy, often called TRT (testosterone replacement therapy), is a medical treatment that helps restore healthy levels of the hormone testosterone in the body. Testosterone is often thought of as the “male hormone,” but it is present in both men and women and plays an important role in overall health. It affects mood, energy, muscle mass, bone strength, and even the way we think and feel.

When testosterone levels drop too low, people may experience a range of symptoms such as fatigue, low sex drive, sadness, irritability, and loss of focus. Testosterone therapy is used to correct these imbalances by replacing or supplementing what the body is no longer making in sufficient amounts.

Understanding Testosterone and Its Role in the Body

Testosterone is a hormone produced mainly in the testes in men and the ovaries and adrenal glands in women. It is responsible for developing male characteristics during puberty, such as deeper voice, facial hair, and increased muscle mass. In adults, testosterone helps maintain bone density, muscle strength, red blood cell production, and sexual function.

Beyond physical effects, testosterone also influences the brain and mood. Healthy levels of this hormone can support motivation, confidence, and emotional stability. When levels fall too low—a condition known as hypogonadism—it can lead to symptoms that mimic or worsen depression.

When Testosterone Therapy Is Used

Doctors may recommend testosterone therapy when blood tests confirm that a person has clinically low testosterone levels along with related symptoms. Common causes of low testosterone include:

• Aging – Natural decline begins around age 30 and continues slowly over time.

• Medical conditions – Problems with the pituitary gland, testicular injury, or certain chronic illnesses.

• Medications – Long-term use of steroids or opioids can suppress testosterone production.

• Obesity or metabolic disorders – High body fat levels can interfere with hormone balance.

Testosterone therapy is approved for men diagnosed with primary or secondary hypogonadism, meaning their bodies cannot make enough testosterone naturally. In some cases, doctors also use it as part of gender-affirming hormone therapy for transgender men.

However, many people seek testosterone therapy for non-medical reasons, such as to increase energy, improve mood, or slow aging. While these goals are popular, the scientific evidence for “anti-aging” or “lifestyle” testosterone use remains limited. Medical experts emphasize that therapy should only be used when a clear hormonal deficiency is proven by lab testing.

Forms of Testosterone Therapy

Testosterone can be given in several ways, depending on personal preference, cost, and medical need. Each method delivers the hormone into the bloodstream differently and has unique benefits and drawbacks:

1. Injections (Intramuscular or Subcutaneous):
   These are one of the most common methods. Injections can be given every one to four weeks, depending on the dose and formulation. They raise testosterone levels quickly, but some people experience “peaks and crashes,” meaning mood and energy may fluctuate between doses.

2. Topical Gels and Creams:
   Applied daily to the skin, usually on the shoulders, arms, or abdomen. These provide a steady level of testosterone and are easy to use. However, there’s a risk of transferring the hormone to others through skin contact, so users must take care to wash their hands and cover the application site.

3. Patches:
   Worn on the skin and replaced daily, these deliver a consistent dose but may cause mild skin irritation.

4. Pellets (Implants):
   Small pellets are inserted under the skin every few months. They release testosterone slowly over time. The procedure must be done by a healthcare provider, but it avoids the need for frequent applications or injections.

5. Oral and Buccal Tablets:
   These forms are less common because some oral versions can affect the liver. Buccal tablets, placed between the gum and cheek, release testosterone gradually without passing through the digestive system.

Each method requires medical supervision and periodic blood tests to ensure testosterone levels stay within a healthy range. The right form depends on the patient’s lifestyle, hormone levels, and how their body responds to treatment.

Goals of Testosterone Therapy

The main goal of TRT is to restore normal physiological levels of testosterone—not to boost it beyond what the body naturally maintains. Keeping testosterone within the normal range helps relieve symptoms of deficiency, such as:

• Low energy or fatigue

• Depressed mood or lack of motivation

• Decreased muscle strength

• Reduced sex drive

• Difficulty concentrating

Restoring balance can improve quality of life and emotional health. However, too much testosterone can cause problems, such as mood swings, irritability, or aggression, which is why therapy must always be medically guided.

Medical Supervision and Safety

Before starting TRT, a doctor performs a full evaluation, including:

• Blood tests for total and free testosterone levels (usually done in the morning).

• Assessment of symptoms and overall health.

• Checking for underlying causes of hormone imbalance.

Once therapy begins, regular follow-up visits are essential. The doctor will monitor testosterone levels, check for side effects, and adjust the dosage if needed. Proper management reduces risks such as increased red blood cell count, acne, or sleep apnea.

Testosterone therapy is not one-size-fits-all. What works for one person may not be suitable for another. Safe and effective treatment depends on a personalized plan developed with a qualified healthcare professional.

Testosterone therapy is a carefully controlled medical treatment used to restore hormone balance in people with low testosterone levels. It can improve energy, mood, and overall well-being when used correctly under medical supervision. However, because hormones affect nearly every system in the body, it’s crucial that treatment be guided by blood tests, professional care, and ongoing monitoring. Understanding how TRT works helps patients make informed decisions and recognize that the goal is balance—not excess.

How Testosterone Affects the Brain and Mood

Testosterone is often called the “male hormone,” but in reality, it plays an important role in both men and women. While it is best known for controlling physical traits like muscle mass, hair growth, and reproductive health, testosterone also affects the brain. It can influence how we think, feel, and react to stress. Scientists now know that testosterone interacts with key areas of the brain that control emotion, motivation, and mood. Understanding how testosterone affects these systems helps explain why hormone changes can sometimes lead to depression or emotional changes.

Testosterone and the Brain’s Chemistry

The brain uses chemical messengers called neurotransmitters to send signals between nerve cells. These chemicals help control mood, energy, and behavior. Testosterone affects several of the most important ones, including serotonin, dopamine, and GABA.

• Serotonin helps regulate mood, anxiety, and sleep. Low serotonin is often linked to depression and irritability. Research shows that testosterone can increase serotonin activity in certain parts of the brain, which may help stabilize mood and promote a sense of well-being.

• Dopamine is the brain’s “motivation” and “reward” chemical. It plays a big role in pleasure, focus, and drive. Testosterone can increase dopamine signaling, especially in regions linked to motivation and satisfaction. This is one reason why low testosterone levels are sometimes linked to fatigue, apathy, and lack of motivation.

• GABA (gamma-aminobutyric acid) is a calming neurotransmitter that reduces anxiety and helps control stress. Testosterone may support GABA function, helping people feel more relaxed and balanced.

When testosterone levels are too low or too high, these systems can become unbalanced. This imbalance can lead to mood swings, irritability, or depression. The brain relies on steady hormone levels to maintain emotional stability.

How Testosterone Acts in the Brain

Testosterone affects the brain in two main ways:

1. Direct action on brain cells. Testosterone can cross the blood–brain barrier and attach to special receptors in nerve cells. These receptors are found in many brain regions linked to emotion and behavior. When testosterone binds to these receptors, it changes how genes are expressed and how nerve cells communicate.

2. Conversion to other hormones. In the brain, testosterone can also be converted into estradiol, a type of estrogen. Estradiol plays an important role in protecting brain cells and regulating mood. This conversion may explain why both men and women need a balance of testosterone and estrogen for emotional health.

Key Brain Regions Involved

Testosterone influences several major parts of the brain that are responsible for emotional and cognitive function:

• Amygdala: This area helps process emotions like fear and anger. Testosterone can increase activity in the amygdala, which may heighten emotional intensity or reactions to stress. When balanced, this can make a person more confident or assertive. When unbalanced, it can lead to irritability or aggression.

• Prefrontal cortex: This part of the brain helps with decision-making, impulse control, and emotional regulation. Healthy testosterone levels support prefrontal function, helping individuals think clearly and manage emotions. Low testosterone, on the other hand, may weaken this control, making people more prone to mood swings or poor concentration.

• Hippocampus: This region is involved in memory and mood regulation. Studies show that testosterone helps protect the hippocampus from stress and supports the growth of new brain cells. Low levels of testosterone may be linked to memory problems and depressive symptoms.

These brain regions work together to balance emotion, motivation, and cognition. Testosterone helps them communicate efficiently, which is why changes in hormone levels can quickly influence how a person feels or behaves.

The Role of Hormone Balance

It’s important to understand that both too little and too much testosterone can cause problems. The brain functions best when hormone levels are within a healthy range.

• Low testosterone can lead to low motivation, sadness, irritability, and fatigue. These symptoms often overlap with depression.

• Excess testosterone, such as from misuse or unregulated therapy, can lead to aggression, anxiety, and mood instability.

Hormonal balance is especially important because the body’s endocrine system is connected—when one hormone changes, others may also shift. For example, testosterone interacts with cortisol, the main stress hormone. High cortisol levels can suppress testosterone, while low testosterone can increase cortisol’s negative effects on mood and energy.

Why Steady Levels Matter

The brain is sensitive to sudden hormonal changes. People who start, stop, or change testosterone therapy too quickly may experience mood swings because their brain and body have not yet adjusted. This is similar to how people may feel mood changes when starting or stopping antidepressants. Maintaining consistent testosterone levels under medical supervision helps reduce these risks.

Testosterone plays a powerful role in how the brain regulates mood, motivation, and emotional well-being. It supports healthy levels of key neurotransmitters like serotonin and dopamine, helps protect brain cells from stress, and keeps important regions like the amygdala and hippocampus functioning properly. However, both too little and too much testosterone can disrupt this balance. That is why testosterone therapy must be carefully managed by healthcare professionals. When properly balanced, testosterone supports not just physical strength, but also mental resilience and emotional health.

Can Testosterone Therapy Cause Depression?

Testosterone therapy (often called TRT) is designed to help people who have low testosterone levels feel better—physically, mentally, and emotionally. Many people report improvements in mood, energy, and focus after starting therapy. However, there are also reports from patients and doctors that some individuals feel worse, anxious, or even depressed while taking testosterone. This may seem confusing since testosterone is often linked to better mood and vitality. But the truth is more complex. Testosterone therapy affects many systems in the body, including the brain, hormones, and emotions. When these systems are thrown off balance, mood changes can happen.

How Testosterone Therapy Can Affect Mood

Testosterone plays a powerful role in how the brain works. It affects brain chemicals like serotonin, dopamine, and GABA, which control mood, motivation, and calmness. When testosterone levels rise or fall too quickly, these brain chemicals can also shift. This change can lead to feelings of sadness, irritability, or anxiety in some people.

Testosterone therapy is meant to keep hormone levels steady within a normal range. But sometimes, the dose or delivery method can cause levels to go too high or drop too low between doses. For example:

• Injections may cause high spikes right after the shot and then low levels before the next dose.

• Gels or patches may be more stable but can still vary depending on how well the skin absorbs the medication.

When these hormone levels swing up and down, a person’s mood may follow. Some people describe this as an “emotional roller coaster,” where they feel great for a few days and then suddenly tired, irritable, or down.

Biological Mechanisms Behind Mood Changes

There are several biological reasons testosterone therapy might cause or worsen depression in some cases:

1. Hormonal Imbalance – If testosterone levels become too high, the body may convert extra testosterone into estradiol (a form of estrogen). High estrogen levels can sometimes cause emotional sensitivity, fatigue, and mood swings, especially in men.

2. Suppressed Natural Production – When someone takes external testosterone, their body may reduce or stop its own natural production. If therapy is stopped suddenly, testosterone levels can crash, leading to low mood and fatigue.

3. Changes in Brain Chemistry – Sudden increases or decreases in testosterone can affect neurotransmitters. For example, low serotonin is linked with depression and anxiety, while fluctuating dopamine can cause motivation or energy changes.

4. Sleep and Energy Effects – Testosterone also affects sleep patterns and energy metabolism. Poor sleep or fatigue from hormonal shifts can easily contribute to feeling depressed or mentally foggy.

These biological effects show that testosterone therapy is not simply “mood-boosting.” It works differently for each person, depending on their body chemistry and mental health background.

When Depression May Appear During Testosterone Therapy

Depressive symptoms are more likely to appear in certain situations:

• During the adjustment phase: When starting therapy, it can take several weeks or months for hormones to stabilize. Some people feel worse before they feel better.

• After dosage changes: Increasing or decreasing the dose too quickly can upset hormonal balance.

• With unmonitored use: Taking testosterone without medical supervision or using doses that are too high can cause side effects, including irritability, anxiety, or sadness.

• After stopping therapy: Abruptly stopping testosterone can lead to withdrawal symptoms, including low mood, low energy, and loss of motivation. This is because the body’s natural testosterone production may take time to restart.

Doctors who specialize in hormone therapy often stress that consistency and careful monitoring are key to avoiding these emotional ups and downs.

Psychological Factors That Can Influence Depression on TRT

Besides biology, emotional and psychological factors can also play a role. For example, some men and women begin testosterone therapy with high expectations—they hope it will solve problems like fatigue, loss of interest, or sadness right away. When results are slower or less dramatic than expected, disappointment can trigger depressive feelings.

In some cases, changes in body image or identity can also affect mood. A person may look or feel different on TRT—more muscular, more energetic, or sometimes more irritable or restless. If these changes cause stress or conflict in relationships or self-image, they can contribute to emotional distress.

It’s also important to consider underlying mental health conditions. People with a history of depression or anxiety might be more sensitive to hormonal changes. Testosterone therapy does not cure mental health disorders, but it can interact with them in ways that either help or worsen symptoms.

What the Research Says

Scientific studies show mixed results. Most research finds that testosterone therapy improves mood in men with low testosterone. For example, clinical trials show reduced symptoms of fatigue, sadness, and irritability when testosterone levels return to normal. However, a small number of studies and case reports show that too much testosterone or improper dosing can have the opposite effect.

For instance, high testosterone levels have been linked with impulsivity, aggression, or restlessness in some individuals. On the other hand, sudden drops in testosterone can cause apathy or depression. These findings suggest that balance—not simply “more” or “less”—is what matters most for emotional health.

The Importance of Medical Supervision

Because testosterone therapy influences both the body and the mind, medical supervision is essential. A healthcare provider can:

• Check hormone levels regularly with blood tests.

• Adjust the dose carefully to avoid large fluctuations.

• Monitor for mood changes or signs of depression.

• Work with mental health professionals if emotional symptoms appear.

Patients are encouraged to report any mood changes, sleep problems, or energy shifts early. Addressing these signs quickly helps prevent deeper depressive episodes.

Testosterone therapy can help many people feel more energetic, focused, and emotionally stable—but in some, it can cause or worsen depression, especially if hormone levels swing too much or treatment is poorly managed. Biological changes, brain chemistry shifts, unrealistic expectations, or underlying mental health issues can all contribute. The key to avoiding these problems is balance, close monitoring, and open communication with healthcare providers. Testosterone can support well-being when used correctly—but when misused or unmanaged, it can disrupt mood and emotional health.

Does Low Testosterone Cause Depression?

Low testosterone, sometimes called “low T” or male hypogonadism, can affect much more than physical health. It can also change how a person feels emotionally. Over the past two decades, researchers have found a strong connection between low testosterone levels and symptoms of depression, especially in men. Understanding this link can help patients and doctors make better choices about when testosterone therapy may be useful — and when other factors might be causing low mood.

What Is Low Testosterone?

Testosterone is a hormone made mostly in the testicles in men and, in smaller amounts, in the ovaries and adrenal glands in women. It supports many important body functions, such as:

• Building muscle and bone strength

• Regulating energy and metabolism

• Supporting sexual health and fertility

• Helping control mood, confidence, and motivation

When testosterone levels drop below normal — usually under 300 ng/dL for adult men — the body and brain can both feel the effects. This condition can develop gradually with age or suddenly due to medical problems that affect hormone production.

Shared Symptoms: Low Testosterone vs. Depression

Low testosterone and depression can look very similar. Many men with low T report symptoms that overlap with those seen in clinical depression, such as:

• Fatigue and low energy

• Loss of interest in favorite activities (anhedonia)

• Sadness or feelings of emptiness

• Irritability or short temper

• Trouble focusing or making decisions

• Low self-esteem or loss of confidence

• Problems with sleep and appetite

Because of this overlap, low testosterone can sometimes go unnoticed — especially if mood changes are blamed only on stress or aging. In reality, both physical and hormonal factors might be contributing to how a person feels.

Biological Reasons for the Connection

Scientists believe that testosterone affects several brain systems that regulate emotions and motivation. For example:

• Serotonin and dopamine, two major brain chemicals, help control feelings of pleasure, motivation, and well-being. Testosterone appears to influence how these chemicals are made and used in the brain.

• Testosterone also affects the amygdala and prefrontal cortex, areas that help manage stress, mood, and decision-making.

• Low testosterone may increase inflammatory markers in the body, which are linked to depressive symptoms in many studies.

• In addition, low testosterone can increase cortisol, a stress hormone. High cortisol levels for long periods can worsen anxiety, fatigue, and emotional instability.

When testosterone levels fall too low, these combined effects can create a biological environment that increases the risk of depression.

What the Research Says

Many studies have explored this link. Large clinical and population-based research shows that men with low testosterone are more likely to report symptoms of depression compared to those with normal hormone levels.

For example:

• A study published in Archives of General Psychiatry found that men with the lowest testosterone levels were four times more likely to experience depressive symptoms.

• Research from the Journal of Clinical Endocrinology & Metabolism showed that testosterone replacement therapy (TRT) can improve mood, energy, and sense of well-being in men with hypogonadism.

• Another review from JAMA Psychiatry analyzed multiple trials and concluded that TRT may reduce depressive symptoms, especially in men with confirmed low testosterone and mild to moderate depression.

However, researchers also note that not everyone with depression has low testosterone, and not every person with low testosterone becomes depressed. This means testosterone is one factor among many — including genetics, life stress, sleep, and other medical conditions — that can affect mood.

How Testosterone Therapy May Improve Mood

When testosterone levels are restored to normal, many patients notice changes within a few weeks to months:

• Increased energy and motivation

• Better concentration

• Improved self-confidence and mood stability

• Reduced irritability and fatigue

These improvements seem strongest in people whose depression is linked to a clear hormonal deficiency. But testosterone therapy is not a replacement for antidepressant treatment when depression has other causes. Doctors often recommend a combined approach, balancing hormone therapy with lifestyle changes, counseling, or antidepressant medication if needed.

Caution and Individual Differences

It is important to remember that hormone therapy is not one-size-fits-all. Giving testosterone to someone with normal hormone levels will not necessarily improve mood and can sometimes make anxiety or irritability worse. Also, if depression is caused by another medical condition or psychological stress, testosterone alone may not help.

That’s why testing, careful diagnosis, and medical supervision are essential. Before starting TRT, doctors check hormone levels through blood tests and evaluate mood using standardized questionnaires. This helps ensure that both physical and emotional health are addressed safely.

Low testosterone can play a real and measurable role in depression. The link comes from the hormone’s impact on brain chemistry, stress response, and overall energy balance. For men with genuine hormone deficiency, testosterone therapy can improve mood and vitality. Still, not all depression stems from low testosterone, and proper medical guidance is vital before beginning treatment.

What Happens When Testosterone Therapy Is Stopped or Misused?

Testosterone therapy (TRT) is meant to restore balance to the body’s natural hormone levels. When prescribed and monitored by a doctor, it can improve energy, mood, and overall well-being in people who have low testosterone. However, when testosterone therapy is stopped suddenly or used incorrectly, the body and mind can react strongly. Understanding what happens during withdrawal or misuse is important for anyone thinking about starting or stopping therapy.

How the Body Adjusts to Testosterone Therapy

When someone begins TRT, the brain and glands that control hormone production start to adapt. Normally, the brain releases hormones from the hypothalamus and pituitary gland to tell the testes (in men) or ovaries (in women) how much testosterone to make.

When external testosterone is introduced—through injections, gels, or pellets—the body senses that it already has enough hormone. As a result, the brain slows or even stops sending signals to produce more testosterone naturally. Over time, the body can become dependent on the external source to maintain normal hormone levels.

This process is reversible, but it takes time. If testosterone therapy is stopped suddenly, the brain and glands do not immediately resume normal function. This can lead to a temporary period of hormonal imbalance, often called testosterone withdrawal.

The Effects of Stopping Testosterone Therapy

When TRT is stopped without medical supervision, testosterone levels can drop sharply. This sudden decline can affect the body and the brain in several ways:

1. Hormonal Rebound and Imbalance

After stopping therapy, the body needs time to restart its natural testosterone production. For some people, this happens slowly. During this adjustment period, testosterone levels may stay very low for weeks or even months. Low testosterone can cause:

• Fatigue or low energy

• Decreased muscle strength

• Weight gain or increased body fat

• Low sex drive

• Difficulty concentrating

• Depressed mood or irritability

These symptoms can feel similar to those that led to starting testosterone therapy in the first place. The key difference is that now the body must relearn how to produce testosterone naturally.

2. Emotional and Psychological Changes

Because testosterone affects brain chemistry, stopping therapy can also cause noticeable mood changes. Some people experience:

• Feelings of sadness or hopelessness

• Anxiety or nervousness

• Irritability or anger

• A lack of motivation or interest in activities

These symptoms do not mean that testosterone therapy causes depression, but rather that hormonal withdrawal can temporarily disturb mood-regulating brain chemicals such as serotonin and dopamine. For people who already have depression or anxiety, this effect can be more severe.

3. Physical Symptoms

Physical withdrawal symptoms can also occur. These may include:

• Muscle weakness or soreness

• Headaches

• Hot flashes or night sweats

• Changes in sleep patterns

• A general sense of “slowing down”

In men, long-term or heavy testosterone use can also shrink the testes, since they stop producing their own testosterone. After discontinuation, this can take time to recover.

The Dangers of Misuse or Cycling

Some people misuse testosterone by taking higher doses than prescribed, often to enhance muscle growth or athletic performance. Others “cycle” testosterone—using it for a few months, then stopping, and later starting again. Both practices can cause severe hormonal swings, which increase the risk of mood disorders, including depression and irritability.

High doses can also lead to side effects such as acne, hair loss, increased aggression, and in some cases, heart or liver strain. When these individuals stop suddenly, their natural testosterone levels can crash far below normal. This rebound effect can make withdrawal symptoms worse and longer-lasting.

Misuse of testosterone is especially risky without medical supervision because the body’s recovery process is unpredictable. Some people may develop long-term suppression of natural testosterone, requiring months or even years to return to normal.

How to Stop Testosterone Therapy Safely

If testosterone therapy needs to be stopped—for example, due to side effects, changes in medical condition, or treatment goals—it should always be done under the guidance of a qualified healthcare provider. Doctors can help taper the dose slowly or prescribe medications to help the body restart its natural hormone production. Blood tests can monitor progress and ensure hormone levels return to a healthy range.

Some physicians may recommend post-therapy medications such as clomiphene citrate or hCG (human chorionic gonadotropin) to stimulate natural testosterone production. These treatments help minimize symptoms and reduce the emotional crash that can occur after stopping TRT.

The Role of Support and Monitoring

Psychological support is also valuable during this period. Talking with a healthcare professional about mood changes, fatigue, or anxiety can help prevent worsening depression. Regular monitoring—both hormonal and psychological—is essential to ensure a safe recovery.

People who misuse testosterone or obtain it without prescription should seek medical help if they plan to stop. Doctors can assess liver and heart function, evaluate hormone levels, and guide recovery safely.

Stopping testosterone therapy or misusing it can lead to major changes in mood, energy, and overall health. The body may take time to restart natural hormone production, and emotional side effects like sadness or irritability can occur. Safe discontinuation requires medical supervision, regular blood tests, and often additional medication support. The best approach is always a gradual, supervised plan that allows the body to rebalance hormones at its own pace.

Can Testosterone Therapy Help Treat Depression?

For many years, doctors have known that testosterone affects more than just muscles, energy, or sex drive. It also plays an important role in how the brain works and how people feel emotionally. Because of this, scientists have started to study whether testosterone therapy (TRT) might help people with depression—especially those who do not respond well to standard antidepressant medications. The results so far are interesting, but they are also complex.

Testosterone and Mood: Why It Matters

Testosterone is not only a sex hormone; it is also a neuroactive steroid, meaning it affects brain function. It helps regulate several neurotransmitters—chemicals that send signals in the brain. Two of the most important are serotonin and dopamine, which play a large role in feelings of happiness, motivation, and emotional balance. Low levels of testosterone can lead to less activity in these systems, which may result in fatigue, lack of motivation, or a “flat” mood.

When testosterone levels return to normal through therapy, the brain often becomes more responsive to these mood-regulating chemicals. As a result, people may experience more energy, better focus, and a more positive outlook.

Research on Testosterone Therapy and Depression

Several studies have explored whether testosterone therapy can relieve symptoms of depression. Results vary depending on who was studied and how the therapy was used.

• Men with Low Testosterone (Hypogonadism):
  Research shows that men who have low testosterone and also experience depression often improve after starting TRT. For example, clinical studies have found that after several months of treatment, these men report higher mood scores, greater energy, and better quality of life.
  One study published in the American Journal of Psychiatry showed that men with low testosterone who received testosterone injections experienced a clear decrease in depressive symptoms compared to those who received a placebo.

• Older Men:
  As men age, their testosterone levels naturally drop. This decline can cause fatigue, reduced motivation, and low mood. Studies in older men have found that testosterone therapy can improve feelings of well-being and vitality. However, not all studies show a major change in depression scores, suggesting that the benefit may depend on how low testosterone levels were before treatment began.

• Men with Treatment-Resistant Depression:
  Some people with depression do not respond well to antidepressant drugs. In these cases, doctors have tried adding testosterone therapy as an adjunctive (supportive) treatment.
  Research suggests that for some men, especially those with borderline or low testosterone levels, adding TRT to antidepressants may lead to improved mood and energy. For example, a study in Biological Psychiatry found that men with persistent depression saw greater improvement when testosterone was added to their treatment plan.

Who Might Benefit Most

Not everyone who feels depressed will benefit from testosterone therapy. The people most likely to see positive effects are those who have:

• Clinically low testosterone confirmed by blood tests.

• Symptoms of low mood, fatigue, and reduced motivation linked to hormonal deficiency.

• No untreated medical or psychiatric conditions that could explain their symptoms.

Men with normal testosterone levels usually do not benefit from TRT for depression. Giving testosterone to people with normal hormone levels can upset the body’s balance and may even cause irritability, anxiety, or mood swings.

How Testosterone May Help Improve Mood

There are several ways testosterone might help relieve depression:

1. Boosting energy and reducing fatigue – Testosterone increases muscle mass and red blood cell production, which can improve energy and stamina.

2. Enhancing motivation and drive – By influencing dopamine pathways, testosterone can improve motivation and reward processing.

3. Reducing anxiety and stress – Some studies show testosterone helps reduce overactivity in the amygdala, the part of the brain linked to fear and anxiety.

4. Improving sleep – Better sleep from balanced hormones can also improve mood stability.

5. Increasing self-confidence – Positive changes in energy and physical well-being may lead to improved self-image and outlook.

Limitations and Controversies

Despite encouraging evidence, scientists still have mixed opinions about how effective testosterone therapy truly is for depression. Some studies show clear improvement, while others show little to no effect. Reasons for these differences include:

• Differences in study design (type of testosterone, dosage, and duration).

• Small sample sizes or short follow-up times.

• Failure to separate men with low testosterone from those with normal levels.

There are also concerns about long-term safety. Testosterone therapy can affect cholesterol levels, blood pressure, and the prostate. Therefore, doctors must monitor patients closely and adjust treatment when necessary. The therapy should always be medically supervised and never started based on symptoms alone.

The Importance of Individualized Treatment

The decision to use testosterone therapy as part of depression treatment should be made with a healthcare professional who can perform the right tests and rule out other causes of mood problems. Before starting therapy, doctors usually measure morning testosterone levels, check thyroid and cortisol function, and evaluate mental health history.

For the right patient—someone with true testosterone deficiency—TRT can be life-changing. But for others, especially those with normal hormone levels, it may offer little benefit and carry unnecessary risks. Every case must be carefully reviewed and followed up with regular blood tests and mental health assessments.

Testosterone therapy has the potential to help treat depression in certain men, especially those with low testosterone levels or those whose depression has not improved with standard treatment. It can boost energy, mood, and motivation by improving brain chemistry and hormone balance. However, it is not a universal solution. TRT should always be guided by medical testing, professional supervision, and ongoing monitoring to ensure both safety and effectiveness.

Risk Factors: Who Is More Likely to Experience Mood Changes on TRT

Testosterone therapy can have a powerful impact on both the body and the brain. While many people report improvements in energy, motivation, and mood, others may notice emotional ups and downs. These differences are not random. Several biological, psychological, and lifestyle factors can influence how a person reacts to testosterone replacement therapy (TRT). Understanding these risk factors helps doctors and patients work together to make treatment safer and more effective.

Genetic and Biological Differences

Each person’s body processes testosterone in its own way. The way testosterone affects mood is influenced by genetics — specifically by variations in the androgen receptor (AR) gene. These receptors are proteins in the body that respond to testosterone. Some people have receptors that are more sensitive to the hormone, while others have receptors that respond more weakly.
If someone has highly sensitive receptors, even a small dose of testosterone might cause strong emotional or physical effects, such as irritability, anxiety, or sudden energy surges. On the other hand, if receptors are less sensitive, a person might not experience any emotional changes, even with higher doses.

Liver and enzyme activity also play a role. The body must convert testosterone into other hormones like estradiol (a form of estrogen) and dihydrotestosterone (DHT). If conversion happens too quickly or too slowly, hormone balance can shift. High levels of estradiol, for example, can cause mood swings or low motivation. This is one reason why regular blood tests are essential during TRT—to make sure all hormone levels stay within healthy ranges.

Age and Hormonal Baseline

Age affects how testosterone interacts with the brain and other hormones. Younger men who use testosterone for non-medical reasons—such as bodybuilding—often experience stronger mood changes than older men who receive therapy for medical hypogonadism.
In older adults, testosterone therapy usually restores hormone levels to a normal range, which can improve well-being and focus. However, in younger men with normal testosterone levels, taking extra hormones can disrupt the body’s natural production. This imbalance may cause emotional instability, irritability, and depressive symptoms once the therapy is stopped.

Baseline hormone levels also matter. People who start TRT with very low testosterone are more likely to feel an improvement in mood. In contrast, those whose levels were already in the normal range might experience overstimulation or anxiety when additional testosterone is introduced.

Pre-existing Mental Health Conditions

A person’s mental health before starting therapy is one of the strongest predictors of how they will react emotionally. If someone already has depression, anxiety, bipolar disorder, or a history of mood swings, testosterone therapy can sometimes worsen those conditions—especially during the first few weeks when the body is adjusting.
This happens because testosterone affects brain chemicals such as dopamine and serotonin, which are also involved in depression and anxiety. When these systems are suddenly altered, emotional reactions can become stronger or less predictable.

That does not mean people with depression or anxiety cannot benefit from TRT. In fact, many experience mood improvement when low testosterone was part of the problem. However, it does mean that mental health should be carefully monitored. Regular check-ins with both an endocrinologist and a mental health professional are important to ensure that changes in mood are managed early.

Lifestyle, Stress, and Sleep Patterns

Lifestyle factors can also change how testosterone therapy affects mood. Chronic stress, poor sleep, heavy alcohol use, and lack of exercise can all interfere with the way hormones work in the body.
For example, poor sleep reduces the natural rhythm of hormone production. Even with TRT, people who sleep fewer than six hours a night may continue to feel tired or emotionally flat.
Stress hormones such as cortisol can also block some of testosterone’s positive effects. When cortisol levels remain high for a long time, mood problems such as irritability or sadness may become worse. Managing stress through relaxation, counseling, or physical activity often improves results from TRT.

Diet plays a smaller but still important role. A balanced diet rich in protein, healthy fats, and micronutrients like zinc and vitamin D helps stabilize hormones. Poor nutrition, especially crash dieting or extreme calorie restriction, can increase fatigue and mood instability during therapy.

Dose, Duration, and Delivery Method

Not all testosterone therapies are the same. Injections, gels, patches, and pellets each release testosterone at different rates. Injections tend to cause sharper spikes and drops in hormone levels, which can lead to emotional highs and lows.
Gels and patches provide more stable levels, but absorption can vary depending on skin type or daily habits.
People who are sensitive to hormonal shifts may feel more stable with slow-release methods, while others tolerate injections well. The best method is usually determined through medical supervision and regular monitoring.

Taking doses that are too high or extending therapy without medical oversight increases the risk of side effects, including mood swings, irritability, and aggression. Using testosterone with anabolic steroids or other hormones (sometimes done in fitness settings) makes these risks even greater.

The Importance of Individualized Care

Because each person’s response to testosterone therapy is unique, a “one-size-fits-all” approach does not work. A thorough evaluation before treatment—including hormone testing, medical history, and mental health screening—helps identify who may be more likely to experience mood changes.
Throughout therapy, regular follow-up visits allow doctors to adjust doses, check lab values, and assess emotional well-being. Patients should report any feelings of sadness, anxiety, irritability, or loss of interest early, rather than waiting for them to pass.

Testosterone therapy can improve quality of life when used correctly, but it must be personalized. Knowing the risk factors—and addressing them with professional guidance—can prevent unnecessary distress and make treatment both safer and more effective.

Monitoring, Safety, and Clinical Best Practices

Starting testosterone therapy (TRT) is not just about restoring hormone levels. It also involves close and careful medical supervision. Testosterone affects many body systems — the brain, heart, liver, and reproductive organs — so monitoring is essential to make sure treatment stays safe and effective. Proper monitoring can also reduce the risk of side effects such as mood swings, fatigue, or depression. This section explains how doctors track therapy progress, what tests are needed, and what signs patients should look out for during treatment.

Pre-Treatment Evaluation

Before starting testosterone therapy, a full medical evaluation is necessary. This helps confirm that low testosterone is truly the cause of a person’s symptoms.

A doctor will usually begin with a comprehensive history and physical examination. They will ask about energy levels, mood, sleep, sexual function, and general health. They also check for other conditions that can cause similar symptoms, such as thyroid disease, sleep apnea, or chronic stress.

Blood tests are a major part of the evaluation. These tests measure total and free testosterone levels, ideally taken in the morning when testosterone is highest. Doctors often order additional tests, including:

• Complete blood count (CBC) – to check red blood cell levels.

• Liver and kidney function tests – to ensure the body can safely process hormones.

• Lipid profile – to measure cholesterol and triglycerides.

• Prostate-specific antigen (PSA) – for men over 40, to screen for prostate health.

• Thyroid and cortisol levels – since imbalances in these can affect mood.

If a patient has a history of depression, anxiety, or bipolar disorder, a mental health assessment is also valuable. This helps the healthcare provider understand a patient’s baseline emotional state before beginning TRT.

Ongoing Monitoring During Therapy

Once therapy begins, consistent follow-up visits are crucial. Monitoring helps the provider see whether the treatment is working and whether adjustments are needed.

Blood tests are usually repeated every 3 to 6 months during the first year, then once or twice a year after that. These tests measure:

• Testosterone levels: to ensure they are within the normal range — not too low and not too high.

• Hematocrit and hemoglobin: to detect if blood becomes too thick, which can raise the risk of clots.

• Liver function tests: to monitor for stress on the liver.

• Lipid profile: since testosterone can alter cholesterol levels.

• PSA levels (for men): to check for changes in prostate health.

Mood and mental health monitoring should be part of every follow-up. Some patients experience mood swings, irritability, or even depressive symptoms if testosterone levels rise or fall too sharply. Regular check-ins with the doctor — and sometimes with a mental health professional — can help manage these changes early.

Patients are encouraged to track how they feel throughout therapy. Writing down energy levels, sleep quality, motivation, and emotional state each week helps both the patient and doctor understand how the body is responding.

When to Adjust or Reconsider Therapy

Not every person responds to testosterone therapy in the same way. Some notice improvements in mood and energy within weeks, while others need several months. If there are no improvements after consistent therapy, or if side effects occur, the doctor may:

• Adjust the dosage to keep testosterone within a safe range.

• Change the form of delivery (for example, from injections to gel) if absorption seems uneven.

• Evaluate for underlying conditions, such as thyroid problems or vitamin deficiencies.

• Refer to a mental health specialist if mood symptoms worsen or persist.

In rare cases, a patient may need to stop therapy if serious side effects occur — such as very high hematocrit, worsening sleep apnea, or persistent depression or aggression. Stopping therapy should always be done gradually and under medical supervision, since hormone levels drop slowly, and sudden withdrawal can cause emotional or physical discomfort.

The Role of Collaborative Care

Managing testosterone therapy safely often requires teamwork between specialists. An endocrinologist monitors hormone levels and metabolic health. A primary care provider tracks general health, blood pressure, and organ function. A psychiatrist or psychologist may help monitor and treat any changes in mood, anxiety, or self-image.

This team approach ensures that both physical and mental health are supported during therapy. For example, if a patient feels more irritable or anxious, coordination between the endocrinologist and mental health provider can lead to timely adjustments before symptoms worsen.

Patient Education and Self-Awareness

Patients should be informed about what to expect from testosterone therapy before starting. It is important to understand that TRT is not an instant cure for fatigue, weight gain, or mood issues. It may take several months for hormone levels and symptoms to stabilize.

Doctors should explain possible side effects in clear language, including:

• Acne or oily skin

• Fluid retention

• Mood changes

• Increased red blood cell count

• Fertility reduction in men

Patients should also be told what warning signs to report right away, such as chest pain, shortness of breath, swelling in the legs, or sudden mood swings.

Education empowers patients to take an active role in their care. When people understand the purpose and possible risks of TRT, they are more likely to follow medical advice and report concerns early.

The safety of testosterone therapy depends on responsible monitoring, teamwork, and communication. Proper blood testing, mental health follow-up, and patient education all help reduce risks. With careful management, most people can use testosterone therapy safely and experience improvements in mood, energy, and quality of life.

Testosterone can be powerful medicine — and like any treatment that affects hormones, it works best when guided by science, regular testing, and honest conversations between patient and healthcare team.

Conclusion: What We Know—and What We Still Need to Learn

The connection between testosterone therapy and depression is complex, but understanding it is essential for both patients and healthcare providers. Over the years, research has shown that testosterone plays an important role in regulating mood, motivation, energy, and emotional well-being. When testosterone levels drop too low—whether due to age, medical conditions, or other factors—many people experience symptoms that look a lot like depression. These can include fatigue, irritability, sadness, poor focus, and loss of interest in daily activities. For some individuals, restoring testosterone levels through therapy can improve these symptoms and help them feel more balanced and energetic again.

However, testosterone therapy is not a simple fix for depression. It can help some people, but it is not meant to replace antidepressants or psychotherapy in those who have major depressive disorder. Testosterone therapy works best when it is used for a clear medical reason—such as low testosterone confirmed by blood tests—and under the supervision of a trained healthcare provider. Without proper monitoring, hormone therapy can lead to side effects or mood changes that may make a person feel worse instead of better.

The research so far suggests that testosterone therapy can improve mood in men who truly have low testosterone, especially when their symptoms include fatigue, lack of motivation, and mild depressive feelings. Several studies have found that men with hypogonadism (a medical term for low testosterone production) often report improvement in mood and energy after beginning therapy. For older men, testosterone treatment may also help improve mental clarity and vitality. However, when testosterone is given to people who already have normal hormone levels, the effects are much less clear. In some cases, using more testosterone than the body needs can lead to irritability, anxiety, or emotional ups and downs.

Another important finding is that stopping testosterone therapy suddenly can cause mood problems. When the body gets used to an external source of testosterone, it slows down its own production. If therapy is stopped too quickly, hormone levels can drop sharply. This sudden change can trigger fatigue, low mood, or even depressive symptoms. That is why it is so important for anyone considering ending therapy to do so gradually and with medical supervision. Doctors can adjust the dosage slowly or add supportive treatments to help the body return to its natural balance.

While testosterone therapy can be helpful, it is not suitable for everyone. People with certain health conditions, such as prostate cancer or serious heart disease, may not be good candidates. Likewise, people who have a history of severe depression or bipolar disorder should be closely monitored, since hormone shifts can sometimes affect mood stability. For these individuals, working with both an endocrinologist and a mental health professional is often the safest approach.

It is also important to recognize that depression is a multi-layered condition. Hormones like testosterone are only one piece of the puzzle. Psychological, social, and environmental factors—such as stress, trauma, sleep quality, and physical activity—also play a major role. A person may need therapy, medication, or lifestyle changes in addition to testosterone therapy to achieve full emotional recovery. The best results often come from a comprehensive treatment plan that addresses both the body and the mind.

Looking ahead, researchers continue to study how testosterone affects the brain and emotions. There is growing interest in whether testosterone might help certain groups—such as men with treatment-resistant depression or older adults with mild cognitive decline—but larger and longer-term studies are still needed. Scientists also want to understand how testosterone interacts with other hormones, such as cortisol and estrogen, and how these combined effects influence mood. Future studies may help doctors tailor hormone therapy more precisely, reducing risks and improving benefits.

In summary, testosterone therapy and depression are linked in several important ways, but the relationship is not one-size-fits-all. Low testosterone can contribute to feelings of depression, and restoring hormone levels can bring relief to some people. Yet in others, therapy may cause mood swings or even worsen emotional symptoms if not carefully managed. The key is balance—using therapy only when medically needed, under close supervision, and as part of a larger plan that considers mental health as well as physical health.

The best way forward is through informed decision-making. Anyone thinking about testosterone therapy should discuss the risks, benefits, and possible mood effects openly with their healthcare provider. Regular check-ups, honest communication, and ongoing lab tests can help ensure that therapy remains safe and effective. More research will continue to refine our understanding, but what we already know is clear: when used correctly and responsibly, testosterone therapy can be a helpful tool—but it should never replace a full, thoughtful approach to mental well-being.