Can Testosterone Therapy Cause Gallstones? The Hidden Link Explained by Science

Introduction

Testosterone therapy, often called TT or hormone replacement therapy for men, has become one of the fastest-growing medical treatments in the world. It is used to help men who have low testosterone levels due to aging, medical conditions, or certain treatments. Testosterone is a natural hormone that plays a key role in muscle growth, energy levels, mood, and sexual function. Because of this, many men who experience fatigue, decreased libido, or loss of strength turn to testosterone therapy to feel better and regain vitality. However, as with many medical treatments that affect hormones, testosterone therapy can also influence other systems in the body — including the liver and gallbladder, two organs that play a vital role in digestion and metabolism.

At the same time, gallstones — small, pebble-like deposits that form inside the gallbladder — are becoming more common worldwide. They can cause pain, infection, and sometimes require surgery. Traditionally, gallstones have been thought of as a condition that affects women more than men, especially due to the effects of estrogen and pregnancy. Yet, in recent years, doctors have begun noticing changes in gallbladder health among men as well, especially those using hormone therapies or anabolic steroids. This trend has raised an important question: Can testosterone therapy increase the risk of gallstones?

Understanding this question matters for several reasons. First, testosterone therapy is now widely prescribed, not just for older men with low hormone levels but also for younger men seeking muscle enhancement or better physical performance. Second, gallstones can develop silently for months or even years before causing symptoms like abdominal pain, nausea, or indigestion. If testosterone therapy affects bile or cholesterol balance in the liver, it could lead to gallstone formation over time. Recognizing such a link early could help patients and healthcare providers take preventive steps to protect gallbladder health.

The connection between testosterone and gallstones may seem unexpected, but hormones have a powerful influence on how the gallbladder and liver work. The gallbladder stores bile — a fluid made by the liver that helps digest fats. Bile contains water, bile acids, cholesterol, and bilirubin. When these substances fall out of balance, cholesterol crystals can form and grow into stones. Hormones like estrogen and testosterone can change how bile is made, how cholesterol is processed, and how often the gallbladder empties. Even small hormonal changes can affect this delicate system.

Research has already shown that female hormones, especially estrogen, can increase the risk of gallstones by raising cholesterol levels in bile. On the other hand, testosterone may also play a role — but in a different way. Studies have suggested that testosterone can alter how the liver produces bile acids and how it breaks down fats. Some evidence also shows that high testosterone levels or the use of synthetic androgens (like anabolic steroids) can cause changes in liver function, which may indirectly influence the gallbladder. These findings have led scientists to take a closer look at whether men using testosterone therapy might also face a higher risk of gallbladder disease.

The goal of this article is to explore this possible link in a clear, scientific, and unbiased way. It will explain how testosterone therapy works, what gallstones are, and what current research says about their connection. The article will also look at biological mechanisms — how testosterone might affect bile composition or gallbladder movement — and review other risk factors that could make gallstones more likely in people receiving hormone therapy.

Importantly, this discussion is not meant to create fear about testosterone therapy. Many men benefit greatly from it under proper medical supervision. Instead, this article aims to give readers a balanced understanding based on current science. By learning how testosterone affects the liver and gallbladder, patients and healthcare professionals can make better decisions about monitoring, prevention, and treatment.

Finally, this topic highlights how complex and interconnected the human body truly is. Hormones influence not only reproductive health but also digestion, metabolism, and organ function. The liver and gallbladder are part of a finely tuned system that depends on hormonal balance to work properly. As testosterone therapy continues to rise in popularity, researchers are beginning to uncover both its benefits and its hidden effects. Exploring the relationship between testosterone and gallstones can help fill a critical gap in our understanding of hormone-related metabolic health.

In the sections that follow, we will break down what gallstones are, how testosterone therapy changes body chemistry, and what scientists currently know about the possible “hidden link” between these two conditions. Through this step-by-step explanation, readers will gain a clear view of how hormones, bile, and the gallbladder interact — and what it means for anyone using or considering testosterone therapy.

What Are Gallstones and How Do They Form?

Gallstones are small, stone-like substances that form inside the gallbladder — a small, pear-shaped organ located beneath the liver. The gallbladder’s job is to store and release bile, a digestive fluid that helps break down fats in food. When something disrupts the normal balance of substances in bile, such as cholesterol, bile salts, and bilirubin, tiny crystals can form. Over time, these crystals can grow and harden into gallstones.

Types of Gallstones

There are two main types of gallstones, based on what they are made of:

1. Cholesterol gallstones:
   • These are the most common type, especially in Western countries.

   • They form when bile contains too much cholesterol and not enough bile salts to keep it dissolved.

   • When the bile becomes “supersaturated,” cholesterol can crystallize and clump together, forming stones.

2. Pigment gallstones:
   • These stones are darker and smaller.

   • They are made mostly of bilirubin, a chemical that is produced when red blood cells break down.

   • People with liver disease, certain blood disorders (like sickle cell anemia), or infections in the bile ducts are more likely to develop pigment stones.

Some people can have a mix of both types.

How Gallstones Form

The process of gallstone formation, called cholelithiasis, usually develops slowly over many months or years. There are three major steps involved:

1. Bile composition changes:
   When the balance of bile components shifts — for example, when there’s too much cholesterol or bilirubin — crystals start forming.

2. Crystallization:
   The cholesterol or bilirubin particles clump together and form tiny solid particles, known as “sludge.”

3. Stone growth:
   Over time, these crystals can grow larger and stick together, becoming hard stones.

If these stones block the ducts that carry bile from the gallbladder to the small intestine, they can cause pain, inflammation, and infection.

The Role of Bile in Digestion

Bile is a yellow-green fluid made in the liver and stored in the gallbladder. It contains water, bile salts, cholesterol, bilirubin, and other substances. When you eat fatty foods, the gallbladder contracts and releases bile into the small intestine to help digest fats.

A healthy bile composition keeps cholesterol dissolved. But if there is too much cholesterol or not enough bile salts, the bile becomes thick and sluggish. This “stagnant” bile creates a perfect setting for gallstones to form.

Risk Factors for Gallstone Formation

Gallstones are influenced by several factors — some controllable and some not.

1. Diet and weight:
   • Diets high in fat, refined carbohydrates, or low in fiber can increase cholesterol in bile.

   • Being overweight or obese raises the risk because it increases cholesterol production by the liver.

   • Rapid weight loss or fasting can also trigger gallstone formation, as the gallbladder empties less often and bile becomes more concentrated.

2. Hormones:
   • Estrogen, the female hormone, can increase cholesterol in bile and slow gallbladder movement.

   • Pregnancy, birth control pills, or hormone replacement therapy can raise the risk in women.

   • Interestingly, testosterone — the male hormone — may also affect bile composition and liver metabolism, which is why researchers are exploring its connection to gallstones.

3. Genetics and family history:
   • Having close relatives with gallstones increases your risk.

   • Some ethnic groups, such as Native Americans and Hispanics, have higher rates due to genetic traits that affect bile processing.

4. Medical conditions:
   • Diabetes, metabolic syndrome, and liver disease can increase bile cholesterol levels.

   • People with blood disorders that cause rapid breakdown of red blood cells (like hemolytic anemia) often have pigment stones.

5. Age and gender:
   • Gallstones become more common with age, particularly after 40.

   • Women are more likely to develop them than men, though hormonal therapies in men can shift this balance.

Gallbladder Function and Gallstone Risk

The gallbladder is not just a storage pouch — it also plays a key role in bile movement. When the gallbladder fails to empty properly (a condition known as biliary stasis), bile becomes thick and concentrated. This allows cholesterol crystals to form more easily.

Certain medications, hormonal changes, and metabolic conditions can reduce gallbladder contractions. Over time, these sluggish movements promote gallstone growth.

Symptoms of Gallstones

Many people with gallstones do not have symptoms and may never know they have them. These are called “silent stones.” When symptoms do occur, they usually happen when a stone blocks a bile duct. Common symptoms include:

• Sharp pain in the upper right abdomen or under the right shoulder blade

• Nausea or vomiting after fatty meals

• Indigestion, bloating, or gas

• Fever or jaundice if infection develops

A severe blockage can lead to inflammation of the gallbladder (cholecystitis) or even infection of the bile ducts (cholangitis), both of which are medical emergencies.

Gallstones form when bile’s normal chemical balance is disrupted, often by high cholesterol or poor gallbladder movement. While diet, genetics, and hormones all play important roles, new research suggests that testosterone — a key hormone in men and in those receiving testosterone therapy — might also influence bile composition and gallbladder function.

Understanding how and why gallstones form sets the stage for exploring whether testosterone therapy could contribute to this process — a topic discussed in the following sections.

Understanding Testosterone Therapy

Testosterone therapy, often called testosterone replacement therapy (TRT), is a medical treatment that helps restore testosterone levels in people whose bodies do not produce enough of the hormone naturally. Testosterone is an essential male hormone that influences many body systems, including muscle growth, bone strength, mood, sexual health, and metabolism. Understanding what testosterone therapy is, how it works, and how it affects the body is important before exploring how it might be linked to gallstones.

What Testosterone Therapy Is and Why It’s Prescribed

Testosterone therapy is used to treat low testosterone levels, a condition known as hypogonadism. In men, this can happen because of testicular injury, aging, genetic conditions, or certain medications that affect hormone production. Symptoms of low testosterone include fatigue, reduced muscle mass, loss of libido, depression, and difficulty concentrating.

Doctors may also prescribe testosterone therapy to:

• Older men experiencing age-related declines in hormone levels (sometimes called “late-onset hypogonadism”).

• Transgender men as part of gender-affirming care to help develop male physical characteristics such as facial hair and a deeper voice.

• Certain medical conditions, including pituitary or hypothalamic disorders that affect hormone regulation.

The goal of therapy is to bring testosterone levels back to a healthy range and reduce the symptoms of deficiency.

Common Administration Routes

There are several ways to administer testosterone therapy. Each form has a different effect on the body, absorption rate, and potential for side effects.

1. Injectable Testosterone – Usually given as intramuscular injections every one to four weeks. This is one of the most common methods. Injections can cause fluctuations in hormone levels, leading to temporary highs and lows in energy and mood.

2. Transdermal Gels and Patches – These are applied daily to the skin, allowing testosterone to be absorbed steadily into the bloodstream. They maintain more stable hormone levels but can cause skin irritation and must be used carefully to avoid transferring the medication to others through skin contact.

3. Pellet Implants – Small pellets are inserted under the skin, typically in the hip area, and release testosterone gradually over several months. This method offers long-term control but requires a minor surgical procedure.

4. Oral and Buccal Forms – Pills and tablets are less commonly used because they can stress the liver when metabolized. Buccal systems (placed between the gum and cheek) deliver testosterone directly into the bloodstream, avoiding the liver.

Each method has its own advantages and disadvantages, and the choice often depends on medical condition, convenience, cost, and the patient’s response.

Effects of Testosterone on the Body

Testosterone has wide-ranging effects on almost every major organ system. It influences both anabolic (building) and metabolic processes.

• Muscle and Bone Health: Testosterone increases protein synthesis, which helps build muscle mass and maintain bone density.

• Fat Distribution: Low testosterone can lead to higher body fat, especially around the abdomen. Replacement therapy often helps reduce fat and increase lean mass.

• Mood and Energy: Adequate testosterone supports mood stability, mental focus, and motivation.

• Sexual Function: It enhances libido and supports erectile function.

• Red Blood Cell Production: Testosterone stimulates the bone marrow to make red blood cells, improving oxygen transport in the body.

However, these benefits come with physiological changes that can affect metabolism, liver function, and lipid balance — all of which may indirectly influence the gallbladder and bile composition.

Testosterone’s Effects on Metabolism and the Liver

The liver plays a central role in processing hormones and fats. Testosterone therapy can alter how the liver handles cholesterol, triglycerides, and bile acids.

• Some studies show that testosterone may lower HDL (“good”) cholesterol and slightly increase LDL (“bad”) cholesterol.

• These changes may increase the amount of cholesterol circulating in the bile, which is a known factor in gallstone formation.

• In oral testosterone, which is processed directly by the liver, there is also a small risk of liver enzyme elevation, which can signal hepatic stress.

Additionally, testosterone affects insulin sensitivity and fat metabolism, influencing how the body stores and breaks down fat. Since bile is made partly from cholesterol derived from fat metabolism, any hormonal changes that disrupt this balance may also affect bile composition.

Known Side Effects and Long-Term Effects

Although testosterone therapy is generally safe when prescribed correctly, it is not without side effects.
Common short-term side effects include:

• Acne or oily skin

• Hair loss or scalp thinning

• Fluid retention

• Breast tenderness or swelling (gynecomastia)

• Increased red blood cell count (polycythemia)

Possible long-term effects include:

• Cardiovascular concerns, such as an increased risk of blood clots or changes in cholesterol balance.

• Liver strain, especially with oral forms.

• Prostate changes, requiring regular monitoring in older men.

While the direct connection between testosterone therapy and gallstones is still under study, these metabolic and hepatic changes are biologically significant. The liver and gallbladder are closely linked — both handle cholesterol, bile, and fat digestion — meaning that alterations in one system can influence the other.

Testosterone therapy helps many individuals by restoring normal hormone levels and improving quality of life. However, the therapy also changes how the body handles cholesterol, fats, and liver metabolism — processes that are essential to bile production and gallbladder health. Because of these interactions, researchers are exploring whether testosterone therapy could indirectly increase the risk of gallstone formation. Understanding how testosterone acts on the body, especially the liver and bile systems, is key to uncovering this possible connection.

The Hormonal Link Between Testosterone and the Gallbladder

Hormones play a powerful role in how the gallbladder and liver work together to digest fats. While most people know that estrogen and progesterone influence gallbladder function—especially in women—testosterone also has important effects. Recent research has started to uncover how testosterone levels, both naturally occurring and through therapy, can change the way bile is produced and how the gallbladder functions. Understanding these effects helps explain why scientists are exploring a possible connection between testosterone therapy and gallstone formation.

Hormones and Gallbladder Physiology

The gallbladder’s main job is to store and release bile. Bile is a yellow-green fluid made by the liver that helps the body digest fats. It contains bile acids, cholesterol, and other substances. For bile to work properly, the ratio of these components must stay balanced. Hormones influence how bile is produced, stored, and released.

Estrogen, for example, increases cholesterol levels in bile. High cholesterol in bile can lead to stone formation if the cholesterol crystallizes. Progesterone, another female hormone, slows gallbladder emptying, which can cause bile to sit too long and become concentrated. Testosterone, on the other hand, has almost the opposite effect—it tends to speed up metabolism and affect bile acid production differently. However, when testosterone levels are very high, as in therapy or anabolic steroid use, the effects can become more complex and sometimes harmful.

How Testosterone Affects Bile and the Liver

Testosterone is processed in the liver, the same organ that makes bile. When a person takes testosterone therapy, the liver must handle the extra hormone, which can change the way it makes and secretes bile. Some studies show that high levels of testosterone can reduce the conversion of cholesterol into bile acids. When this happens, the bile becomes richer in cholesterol and more prone to forming crystals—an early step in gallstone development.

In addition, testosterone can change how the liver handles fats and cholesterol. It tends to increase the amount of “good” HDL cholesterol but may also affect how cholesterol is removed from the body. If the liver releases more cholesterol into bile than it can dissolve, bile becomes oversaturated. Over time, this can create the right conditions for gallstones to form, especially if bile flow slows down.

Impact on Gallbladder Motility and Bile Flow

Gallbladder motility means how well the gallbladder contracts to release bile after eating. Hormones regulate this process too. Estrogen and progesterone tend to relax gallbladder muscles, leading to slower emptying. Testosterone has different effects—it may increase muscle tone and contractility, helping the gallbladder release bile more efficiently under normal conditions.

However, with testosterone therapy or anabolic steroid use, muscle tissues—including those in the gallbladder—can respond differently. Too much testosterone can sometimes lead to abnormal muscle responses or even reduce the sensitivity of the gallbladder to hormones like cholecystokinin (CCK), which triggers bile release after eating. When bile is not emptied regularly, it becomes thick and concentrated, increasing the risk of crystal formation and, eventually, gallstones.

Interactions Between Hormones: Testosterone, Estrogen, and Progesterone

It’s important to remember that hormones do not work in isolation. Testosterone, estrogen, and progesterone all interact. In men, small amounts of estrogen are produced naturally when testosterone is converted by an enzyme called aromatase. In women, the balance between these three hormones shifts during life stages such as pregnancy and menopause, which can explain why gallstones are more common in women.

When testosterone therapy is used, especially at higher doses, it can lower the relative level of estrogen by reducing aromatase activity or through suppression of other hormones. This hormonal imbalance may indirectly influence how bile acids and cholesterol are produced and secreted. Some research suggests that low estrogen relative to testosterone can change bile composition and flow, although this area is still being studied.

In men undergoing testosterone replacement therapy (TRT), especially those with metabolic conditions, these hormonal shifts may add stress to the liver and biliary system. In transgender men receiving long-term testosterone for gender affirmation, similar metabolic changes have been observed, such as alterations in lipid profiles and liver enzyme levels, which could influence bile formation over time.

Evidence from Animal and Human Studies

Animal research provides additional clues. Studies in rats and mice show that high androgen levels can alter bile composition, increasing cholesterol concentration and changing bile acid profiles. These changes are similar to those seen in early gallstone development. While not all animal findings apply directly to humans, they help scientists understand possible biological mechanisms.

In humans, the data is more limited. Some studies on anabolic steroid users show changes in liver function tests and bile flow, but large-scale studies on testosterone therapy and gallstones are still lacking. However, the biological plausibility—the idea that a cause-and-effect link could exist based on how hormones act—is strong enough that researchers are continuing to investigate.

Testosterone affects the gallbladder and bile in several ways. It influences how cholesterol is processed in the liver, how bile acids are produced, and how the gallbladder contracts. When hormone levels are balanced, these systems work smoothly. But when testosterone levels rise significantly due to therapy or supplements, they can disrupt this balance. The result may be bile that contains too much cholesterol, poor gallbladder motility, or sluggish bile flow—all factors that can contribute to gallstone formation.

Testosterone is not the sole cause of gallstones, but it plays a role in the hormonal network that controls bile and gallbladder health. Understanding this connection helps both patients and healthcare providers recognize potential risks and monitor liver and gallbladder function during testosterone therapy.

Can Testosterone Therapy Increase the Risk of Gallstones?

The question of whether testosterone therapy can raise the risk of gallstones has become a topic of growing medical interest. Testosterone therapy (often called TT) is used to treat low testosterone levels in men, but its effects go beyond improving mood, energy, and muscle mass. Because testosterone affects how the liver processes fats and cholesterol, researchers have begun to explore if it could also change the way bile is made and stored — and possibly increase the chance of gallstones forming.

This section explores what scientists currently know about this possible link. We’ll look at clinical studies, biological explanations, and the limits of existing research to help you understand what the evidence really shows.

What Studies Show So Far

Right now, there are not many large clinical trials that directly study testosterone therapy and gallstones. Most of the information comes from smaller studies, case reports, and related research on anabolic steroid use. Some of these reports suggest that men who use high doses of anabolic steroids — which are synthetic forms of testosterone — can develop changes in liver function and bile composition. In rare cases, these changes may lead to gallstones or gallbladder inflammation.

For example, anabolic steroids have been shown to increase cholesterol levels in bile, which makes bile more likely to form stones. Although testosterone therapy given under medical supervision uses much lower doses than anabolic steroids, it still affects hormone balance, liver function, and cholesterol metabolism. This has led scientists to suspect that similar, though smaller, changes might occur in people receiving testosterone therapy over long periods.

Epidemiological data (large population-based studies) on this topic are limited. However, a few studies have looked at hormone replacement and liver metabolism in men and women. These studies show that hormones, including testosterone, can influence bile acid production, cholesterol breakdown, and the movement of bile through the gallbladder. Because gallstones form when bile contains too much cholesterol or does not flow properly, even small hormonal effects could increase the risk in some people.

How Testosterone Might Affect Gallstone Risk

To understand how testosterone could influence gallstone formation, it helps to know how the gallbladder and bile work. The liver produces bile to help digest fats. This bile is stored in the gallbladder and released into the intestine when needed. Bile is made up of water, bile acids, cholesterol, and other substances. Gallstones form when the balance between these components is disturbed — usually when cholesterol levels rise too high or the gallbladder does not empty completely.

Testosterone can change this balance in several ways:

• Cholesterol Metabolism: Testosterone therapy can raise total cholesterol production in the liver. When cholesterol in bile becomes too concentrated, it can crystallize and form stones.

• Bile Composition: Testosterone may reduce bile acid production or alter the ratio of bile acids to cholesterol. Lower bile acid levels mean that cholesterol is less soluble and more likely to clump together.

• Gallbladder Motility: Testosterone influences smooth muscle tone. It may reduce how strongly or how often the gallbladder contracts, which can cause bile to stagnate — another risk factor for stone formation.

• Liver Function: Long-term testosterone use can mildly affect liver enzymes. Even small changes in liver metabolism may alter the way bile is produced and released.

These mechanisms make biological sense, and animal studies have confirmed some of them. For example, rats given testosterone show thicker bile and higher cholesterol content in the gallbladder. Still, scientists caution that animal studies don’t always translate directly to humans.

Comparing Testosterone Therapy to Anabolic Steroid Use

It is important to separate medical testosterone therapy from anabolic steroid abuse. Medical therapy uses doses meant to restore normal hormone levels, while anabolic steroid use involves much higher amounts that can drastically affect the liver. In people who use anabolic steroids, gallstones and liver problems are more common and well documented. However, this does not automatically mean that standard testosterone therapy has the same risk.

That said, long-term therapy could lead to subtle liver or bile changes over time. The difference is likely one of degree rather than kind. Medical testosterone users may experience smaller changes that only become important when other risk factors — like obesity, rapid weight loss, or high-fat diets — are present.

Evidence Strength and Limitations

Even though there are good biological reasons to think testosterone therapy could influence gallstone risk, current evidence remains weak. The main challenges include:

• Small study sizes: Most studies involve few patients, making it hard to draw firm conclusions.

• Short duration: Many testosterone studies last only a few months, but gallstones often take years to form.

• Confounding factors: Men receiving testosterone therapy often have other risk factors such as obesity, diabetes, or liver disease. These make it difficult to tell whether gallstones are caused by the therapy or by the underlying conditions.

• Lack of direct data: No large randomized controlled trial has focused specifically on gallstone formation during testosterone therapy.

As a result, the link remains “biologically possible but not proven.” Researchers agree that more long-term studies are needed to clarify whether testosterone therapy directly increases gallstone risk or simply interacts with existing risk factors.

Current research does not conclusively show that testosterone therapy causes gallstones, but it may play a contributing role. Testosterone affects cholesterol metabolism, bile composition, and gallbladder movement — all factors known to influence stone formation. Evidence from steroid use and animal studies supports this biological connection, though human studies are still limited.

For now, doctors recommend regular liver function tests and monitoring of metabolic health in patients using testosterone therapy, especially those with other gallbladder risk factors. Understanding this link better will require more research, but awareness and preventive monitoring can already help reduce possible complications.

Mechanisms Proposed by Science

Researchers have not yet proven that testosterone therapy directly causes gallstones. However, several scientific studies show how testosterone may affect the liver, bile, and cholesterol in ways that could increase the risk of gallstone formation. Understanding these possible biological mechanisms helps explain why doctors are watching this link more closely.

Gallstones form when bile—the digestive fluid made by the liver—becomes unbalanced. Normally, bile contains water, bile salts, cholesterol, and waste products. When too much cholesterol or bilirubin is released, or when bile does not flow properly, solid crystals can form. Over time, these crystals grow into gallstones. Testosterone, being a powerful hormone that affects metabolism, may influence several steps in this process.

Altered Lipid Metabolism

One of testosterone’s main actions in the body is to change how fat and cholesterol are used. Testosterone helps build muscle and reduce fat, but it also affects how the liver handles lipids. Studies have shown that testosterone therapy can increase cholesterol turnover in the liver. In some people, it raises LDL (“bad”) cholesterol and lowers HDL (“good”) cholesterol, though results vary depending on the dose and form of therapy.

When the liver processes more cholesterol, it must also secrete more into bile. This extra cholesterol can make bile thicker and more “saturated.” Bile that is too rich in cholesterol is less stable and more likely to form crystals. Over time, these crystals may become gallstones.

In animal studies, high levels of testosterone and other androgens increased cholesterol levels in bile and reduced the ratio of bile acids that keep cholesterol dissolved. While animal data cannot always be applied directly to humans, these findings support the idea that testosterone could make bile more prone to gallstone formation by altering lipid metabolism.

Changes in Bile Composition

Bile is not just a waste product; it is a carefully balanced fluid that helps digest fats. Bile acids are chemicals made from cholesterol in the liver. They act like detergents, breaking down fats and keeping cholesterol dissolved in liquid form.

Testosterone may change the balance of bile acids and cholesterol in bile. Some studies suggest that higher testosterone levels reduce the activity of certain liver enzymes that produce bile acids. If fewer bile acids are made, the bile can become “cholesterol-heavy.” This imbalance increases the risk of cholesterol crystallizing.

Additionally, testosterone therapy can affect the proteins that transport bile acids and cholesterol through liver cells. These small shifts can change bile flow or its chemical structure. Over time, a small imbalance—too much cholesterol and too few bile acids—can lead to gallstone development, especially if other risk factors are present, such as obesity or rapid weight loss.

Gallbladder Motility

For the gallbladder to stay healthy, it must empty regularly after meals. This process keeps bile from sitting too long and forming crystals. Hormones play a big role in controlling gallbladder contractions.

Some studies suggest that testosterone may reduce gallbladder motility—that is, the strength and frequency of gallbladder contractions. If the gallbladder does not contract properly, bile can stagnate. When bile sits still, water is absorbed from it, making the bile thicker and increasing the chance of cholesterol crystals forming.

There is also evidence that androgens affect the smooth muscle cells of the gallbladder. These cells respond to hormones and nerve signals that tell the gallbladder to squeeze. If testosterone alters these signals, the gallbladder may not empty fully. Even small reductions in motility can lead to bile stasis, which is a known factor in gallstone formation.

This effect may also help explain why women—who have higher estrogen levels—tend to have more gallstones than men under normal circumstances. Estrogen increases cholesterol in bile, while testosterone may reduce gallbladder movement. In both cases, hormones play different roles that can affect the same outcome: bile imbalance.

Liver Metabolism and Bile Recycling

The liver is central to both hormone metabolism and bile production. When someone takes testosterone therapy, especially in oral or injectable forms, the liver must process the hormone. This extra work can alter liver enzyme activity.

Some oral testosterone forms, such as methyltestosterone, undergo what doctors call “first-pass metabolism” in the liver. This means the hormone is broken down in the liver before it reaches the bloodstream. During this process, certain liver pathways can become more active or strained. Changes in these pathways can affect how bile acids are made, recycled, or secreted.

Testosterone also interacts with bile salt transporters—proteins that move bile acids between liver cells and the bile ducts. If these transporters are affected, bile flow can slow down, causing bile buildup and higher pressure inside the liver and gallbladder system. Over time, reduced bile flow (cholestasis) can promote stone formation and even mild liver inflammation.

Integrating Findings from Multiple Fields

Endocrinologists, hepatologists, and metabolic researchers all look at the same question from different angles. Endocrinology studies show that testosterone changes cholesterol balance and enzyme activity. Hepatology research finds that these changes affect bile production and flow. Metabolic science connects the dots, showing how altered fat metabolism under hormone therapy might indirectly lead to gallstone risk.

So far, no single mechanism alone fully explains the link. Instead, researchers believe the process is multifactorial. Testosterone therapy might increase cholesterol load in bile, reduce bile acid production, slow gallbladder movement, and change liver metabolism—all working together to raise the chances of gallstone formation in certain people.

However, not everyone on testosterone therapy will develop gallstones. Genetics, diet, body weight, and overall liver health all play important roles. The key point is that testosterone therapy can influence several parts of the system involved in bile balance, which may explain why some patients are more prone to gallstones during long-term hormone use.

Scientific evidence suggests that testosterone therapy can affect cholesterol handling, bile composition, gallbladder movement, and liver function. Each of these mechanisms can contribute to gallstone formation under the right conditions. While more studies are needed to confirm the exact pathways in humans, the biological connection is plausible and supported by early research in both human and animal models.

Related Risk Factors That May Amplify Gallstone Formation

Gallstones rarely form because of one single cause. In most people, they happen when several small risk factors work together. When a person is taking testosterone therapy, these factors can combine to raise the chance of gallstones even more. This section explains how conditions like obesity, rapid weight changes, diet habits, and metabolic disorders can interact with testosterone therapy to affect the gallbladder.

Obesity and Body Weight

Obesity is one of the strongest known risk factors for gallstones. When a person has extra body fat, especially around the abdomen, their liver tends to produce more cholesterol. This cholesterol enters the bile, making it thicker and more likely to form stones.

Testosterone therapy can sometimes change body weight and fat distribution. Some men lose fat and gain muscle, while others may gain weight if diet and exercise are not balanced. In either case, body composition shifts can affect how the liver and gallbladder handle fats.

Obesity also slows down the emptying of the gallbladder after meals. When bile sits in the gallbladder for too long, cholesterol crystals can start to form. Over time, these crystals can grow into solid stones. For people using testosterone therapy, keeping a stable and healthy weight is an important step in reducing gallstone risk.

Rapid Weight Loss and Hormonal Shifts

Losing weight too quickly can also increase the risk of gallstones. This may seem surprising, since weight loss is often seen as healthy. However, during rapid weight loss, the body burns stored fat for energy, releasing a large amount of cholesterol into the bloodstream. The liver then passes some of this cholesterol into bile, which can become oversaturated.

Many people who start testosterone therapy also begin strict diets or intense workout programs. Rapid fat loss from these lifestyle changes can unintentionally raise the concentration of cholesterol in bile. If the gallbladder does not empty fully or regularly, gallstones may form.

Doctors often recommend gradual, steady weight loss — about one to two pounds per week — to prevent these complications. Maintaining proper hydration and eating regular meals can also help keep bile flow steady, reducing the chance of cholesterol buildup.

Diet and Nutrition Patterns

Diet plays a central role in both gallstone risk and how testosterone therapy affects metabolism. People on testosterone often follow high-protein, high-fat, or low-carbohydrate diets to build muscle or lose fat. While these diets may help achieve fitness goals, they can also strain the liver and gallbladder.

A diet very high in animal fats or cholesterol can cause bile to become thicker and less balanced. Low-fiber diets also reduce bile movement through the intestines, leading to sluggish digestion. When bile sits too long in the gallbladder, it can form stones.

In contrast, diets rich in fiber, whole grains, fruits, and vegetables help bile flow more smoothly. These foods support the liver in removing excess cholesterol and improving bile composition. Eating moderate amounts of healthy fats, such as olive oil or avocado, can also keep the gallbladder contracting normally.

It is not necessary for people on testosterone therapy to follow extreme diets. Instead, a balanced diet that includes lean protein, complex carbohydrates, and unsaturated fats can protect both the liver and gallbladder.

Metabolic Syndrome and Insulin Resistance

Metabolic syndrome is a cluster of conditions — including high blood pressure, high blood sugar, abnormal cholesterol, and excess abdominal fat — that increase the risk of heart disease and type 2 diabetes. It also plays a role in gallstone formation.

When someone has insulin resistance, their liver tends to produce more cholesterol while reducing the amount of bile acids that dissolve it. This imbalance leads to cholesterol-rich bile, which is the perfect environment for gallstones.

Testosterone therapy can influence metabolism in several ways. It can improve insulin sensitivity in some men, but in others, especially at higher doses or with anabolic steroid use, it may worsen lipid balance. If a person already has metabolic syndrome, testosterone therapy could magnify the effects on bile and cholesterol, making stones more likely.

Regular checkups that include fasting glucose and lipid panels can help monitor these risks. Managing blood sugar and cholesterol through diet, medication (if prescribed), and physical activity remains one of the best ways to protect the gallbladder.

Dehydration and Bile Concentration

Dehydration is another factor that can quietly raise gallstone risk. When the body lacks enough water, bile becomes more concentrated. Thick bile contains a higher proportion of cholesterol and bilirubin, which promotes stone formation.

Testosterone therapy can slightly increase metabolism and body temperature, leading to greater water loss through sweat. People who exercise intensely while on therapy may become dehydrated if they do not drink enough fluids. Ensuring proper hydration throughout the day helps maintain normal bile composition and flow.

For people on testosterone therapy, gallstone formation is rarely caused by testosterone alone. Instead, it develops from the combined effects of hormonal changes, body weight, diet, and metabolism. A healthy lifestyle — including gradual weight management, balanced nutrition, regular exercise, and adequate hydration — plays a vital role in preventing gallstones.

Doctors may recommend regular monitoring of liver function, lipid levels, and gallbladder symptoms during long-term testosterone therapy. Understanding how these related factors interact helps patients and clinicians take early steps to reduce risks before complications occur.

Do All Forms of Testosterone Therapy Carry the Same Risk?

When discussing testosterone therapy (TT) and gallstones, it is important to understand that not all forms of therapy affect the body in the same way. The type of testosterone, how it is delivered, and how it is processed by the liver can all change how the body reacts. Some forms of therapy may have stronger effects on liver metabolism and bile production, while others may bypass the liver almost entirely. These differences may influence how likely it is for a person to experience gallbladder or bile-related issues, including gallstones.

Oral Testosterone and the Liver’s First-Pass Effect

Oral testosterone tablets or capsules are the least commonly prescribed form of therapy because of how they interact with the liver. When taken by mouth, testosterone enters the digestive system and is absorbed into the bloodstream through the intestines. Before it can circulate through the rest of the body, it must pass through the liver — this is called the “first-pass effect.”

During this process, the liver must metabolize a large portion of the hormone before it becomes active in the bloodstream. This added workload can increase liver enzyme activity and alter the production of bile acids and cholesterol. When bile becomes thicker or overly concentrated with cholesterol, gallstones can form more easily.

In addition, oral testosterone can raise levels of low-density lipoprotein (LDL) cholesterol (the “bad” cholesterol) and lower high-density lipoprotein (HDL) cholesterol (the “good” cholesterol). These changes can affect how cholesterol is excreted through bile. Over time, such imbalances may increase the chance of gallstone formation, especially in people who already have liver or metabolic issues.

Because of these risks, oral testosterone is often replaced with other delivery forms that have less impact on the liver.

Injectable Testosterone: Higher Stability, Lower Liver Stress

Injectable testosterone, such as testosterone enanthate, cypionate, or undecanoate, is one of the most common types of therapy. Injections deliver testosterone directly into the muscle tissue, where it is slowly absorbed into the bloodstream over time. This route avoids the liver’s first-pass metabolism, which means the hormone does not need to be processed by the liver before it becomes active.

Since injectable forms do not overload the liver, they may carry a lower direct risk of bile imbalance or gallstone formation compared to oral forms. However, they can still influence metabolism indirectly. Testosterone injections can raise red blood cell counts, change lipid levels, and modify how fat is distributed in the body. These metabolic effects may, in turn, influence the composition of bile.

Another factor to consider is that injections often produce peaks and troughs in testosterone levels — very high levels shortly after injection and lower levels before the next dose. Rapid hormonal shifts may influence bile composition or gallbladder motility, but current studies have not confirmed a direct connection.

Transdermal Testosterone: Patches, Gels, and Creams

Transdermal testosterone is applied to the skin as a gel, patch, or cream. This method allows testosterone to be absorbed directly into the bloodstream through the skin. Because it avoids the digestive tract and liver metabolism, it usually causes fewer liver-related effects and does not significantly alter bile production.

Transdermal delivery produces more steady hormone levels than injections, reducing hormonal fluctuations that might affect gallbladder motility. For this reason, it is generally considered a safer option for liver and bile health. However, transdermal forms can still alter lipid metabolism over time, and some users may experience mild changes in cholesterol levels, which could indirectly influence gallstone risk.

Pellet Implants and Nasal Gels: Newer Delivery Systems

Testosterone pellets are small, slow-releasing implants placed under the skin, typically in the hip or buttock. They release testosterone steadily for several months. Like gels and injections, they bypass the liver, making them less likely to affect bile acid metabolism. Because hormone levels remain stable, these implants may have the least effect on gallbladder function, though data are still limited.

Nasal gels or sprays, a newer option, deliver testosterone through the nasal mucosa. Absorption is quick, and hormone levels remain relatively even. While convenient, they require multiple doses per day. Like other non-oral forms, nasal testosterone has little to no direct impact on the liver and bile system.

Synthetic vs. Bioidentical Testosterone

The type of testosterone molecule used also matters. Bioidentical testosterone has the same chemical structure as the hormone naturally produced by the human body. Synthetic testosterone or anabolic steroids may have slight chemical differences that make them act more strongly or last longer in the body.

Synthetic androgens can sometimes cause more pronounced changes in cholesterol metabolism and liver function. These effects can increase bile cholesterol concentration and potentially raise gallstone risk. Bioidentical forms are thought to cause fewer disturbances in bile composition because the body processes them in a more natural way, though evidence is still emerging.

Comparing Overall Risks Across Forms

While no single study definitively proves that testosterone therapy directly causes gallstones, researchers agree that the method of delivery can influence the degree of liver involvement and changes in bile metabolism.

• Highest theoretical risk: Oral testosterone, due to liver stress and bile changes.

• Moderate risk: Injectable testosterone, depending on dose and metabolic effects.

• Lower risk: Transdermal, pellet, and nasal formulations, which bypass the liver and produce stable hormone levels.

However, other factors such as diet, weight changes, hydration, and genetics also play key roles. Even with low-risk delivery methods, poor diet or rapid weight loss can still trigger gallstone formation.

Not all testosterone therapies affect the body equally. The form that passes through the liver (oral) has the greatest potential to disrupt bile composition and cholesterol metabolism. In contrast, injectable, transdermal, and pellet-based forms are less likely to affect bile and gallbladder function directly.

Choosing the right form of testosterone therapy should always involve a discussion between patient and healthcare provider, taking into account liver health, metabolic profile, and individual risk factors. Regular blood tests, including liver function and lipid levels, can help monitor for early signs of imbalance.

While all testosterone therapies can influence metabolism to some degree, oral testosterone appears most likely to contribute to bile-related changes, whereas non-oral forms pose a much lower risk for gallstone formation. Ongoing research continues to clarify these differences, but awareness of how each therapy type interacts with the liver and gallbladder is key to safe and effective treatment.

What Are the Warning Signs and How Are Gallstones Diagnosed?

Gallstones can form quietly in the gallbladder and go unnoticed for months or even years. Some people never develop symptoms, while others experience sudden and painful attacks. For those on testosterone therapy, being aware of these warning signs is important, especially because hormonal changes can subtly affect the liver and bile system. This section explains in clear terms how to recognize possible gallbladder problems, how doctors diagnose gallstones, and why monitoring is important during testosterone therapy.

Common Warning Signs of Gallstones

The gallbladder is a small organ located under the liver. Its job is to store bile, a digestive fluid that helps break down fats. When gallstones form, they can block the flow of bile and cause irritation or inflammation. Here are the main symptoms to look out for:

1. Upper Abdominal Pain (Biliary Colic):
   The most common symptom is sudden pain in the upper right side or middle of the abdomen, just below the ribs. The pain may last from 30 minutes to several hours. It can come after eating fatty or greasy food because bile is released more during digestion.

2. Pain Spreading to the Shoulder or Back:
   The pain sometimes travels to the right shoulder blade or back. This happens because nerves from the gallbladder connect to nearby muscles and tissues.

3. Nausea and Vomiting:
   Many people feel sick to their stomach or vomit during an attack. This is the body’s reaction to blocked bile flow and digestive stress.

4. Indigestion and Bloating:
   Some experience a feeling of fullness, gas, or burping after meals. While these symptoms are common in other digestive issues, persistent or severe cases may signal gallbladder problems.

5. Changes in Stool or Urine Color:
   If bile cannot flow properly into the intestines, stool may become pale or clay-colored. Urine may turn dark, similar to tea. These changes mean bile pigments are not being processed normally.

6. Jaundice (Yellowing of Skin or Eyes):
   In more serious cases, gallstones may block the main bile duct, causing a buildup of bilirubin. This leads to yellowing of the skin and eyes. Jaundice always requires medical attention.

7. Fever and Chills:
   If infection develops in the gallbladder (called cholecystitis), a person may develop a fever, chills, and more constant pain. This condition can be serious and needs immediate treatment.

Gallstone Symptoms vs. Other Conditions

Because gallstone symptoms overlap with other digestive or liver issues, people often mistake them for acid reflux, gastritis, or even heart problems. A healthcare provider can perform tests to confirm the true cause. It’s important not to self-diagnose, especially when on testosterone therapy, since hormones can also affect liver enzymes and digestion.

How Gallstones Are Diagnosed

Doctors use several tools and tests to detect gallstones and related complications. The goal is to confirm whether stones are present, where they are located, and whether they are causing inflammation or blockage.

1. Physical Examination and Medical History:
   A doctor will first ask about symptoms, eating habits, and any medications or hormone treatments. They may gently press on the abdomen to check for tenderness in the upper right area.

2. Abdominal Ultrasound:
   This is the most common and accurate test for gallstones. A technician uses sound waves to create images of the gallbladder and bile ducts. Ultrasound can detect even small stones and signs of inflammation.

3. CT (Computed Tomography) Scan:
   A CT scan provides a more detailed view of the liver, pancreas, and bile system. It helps identify complications like bile duct obstruction or infection that ultrasound may miss.

4. MRCP (Magnetic Resonance Cholangiopancreatography):
   This special type of MRI focuses on the bile ducts and pancreas. It helps doctors find stones lodged in the common bile duct without needing invasive procedures.

5. HIDA (Hepatobiliary Iminodiacetic Acid) Scan:
   In this test, a small amount of radioactive tracer is injected into the bloodstream. The scanner tracks how bile moves through the liver and gallbladder, showing if there’s blockage or sluggish bile flow.

6. Blood Tests:
   These check for signs of infection, inflammation, or liver problems. Elevated liver enzymes, bilirubin, or white blood cell counts can indicate gallbladder disease or bile obstruction.
   In testosterone therapy patients, liver function tests are often monitored routinely, so any sudden change may alert doctors to possible gallbladder involvement.

Monitoring for Those on Testosterone Therapy

For individuals undergoing testosterone treatment, regular check-ups are essential. Because testosterone can affect cholesterol metabolism and liver function, monitoring bile health indirectly becomes important. Doctors may suggest:

• Liver Function Tests (LFTs): to measure enzyme levels and bile pigments.

• Lipid Profile Tests: to track cholesterol, which can influence bile saturation.

• Ultrasound Scans (if symptoms occur): to rule out gallstones early.

• Reporting Symptoms Promptly: any unexplained abdominal pain, nausea, or yellowing should be discussed with a healthcare provider right away.

When to Seek Medical Attention

If pain lasts longer than a few hours, is severe, or is accompanied by fever, vomiting, or jaundice, medical evaluation should not be delayed. Untreated gallstones can lead to infections, pancreatitis, or bile duct obstruction—all of which can become emergencies.

Recognizing gallstone symptoms early can prevent serious complications. For people using testosterone therapy, understanding how hormonal changes interact with liver and bile systems helps in spotting potential problems faster. Regular monitoring, paying attention to body signals, and timely medical care are the best defenses against gallbladder disease. With awareness and proper follow-up, most gallstone-related issues can be managed safely and effectively.

What Does Current Research Recommend?

At this time, no major medical organization has issued official guidelines linking testosterone therapy directly to gallstone formation. However, experts in endocrinology and hepatology have emphasized the need for careful monitoring of metabolic and liver health in patients receiving testosterone therapy. The relationship between hormones and bile metabolism is complex, and researchers agree that more studies are needed to confirm how testosterone affects the gallbladder.

Most recommendations are based on evidence showing that testosterone therapy can change lipid levels, liver enzyme activity, and bile composition. These changes, while sometimes small, may increase gallstone risk in people who already have other risk factors such as obesity, insulin resistance, or rapid weight loss. The general expert view is that clinicians should monitor liver function and metabolic markers in all patients on long-term testosterone therapy.

Preventive Measures for Gallbladder Health

Maintaining gallbladder and liver health while on testosterone therapy involves paying close attention to diet, hydration, and lifestyle. Here are the most widely accepted preventive strategies supported by research and clinical experience:

Balanced Diet:

A diet rich in fiber, fruits, vegetables, and healthy fats supports proper bile flow and reduces cholesterol saturation in bile. Avoiding extreme high-fat diets, crash diets, or fasting for long periods can lower the risk of gallstones. While testosterone therapy can boost metabolism, combining it with a balanced eating plan prevents sudden metabolic shifts that may contribute to bile imbalance.

Maintain Healthy Body Weight:

Obesity and rapid weight loss are both major risk factors for gallstones. Testosterone therapy can help reduce body fat, but drastic calorie restriction or intense weight loss can cause the liver to release more cholesterol into bile. Steady weight management through moderate diet and exercise is key.

Regular Physical Activity:

Exercise helps regulate cholesterol levels and supports gallbladder motility—the muscle contractions that empty bile into the digestive system. Gentle, consistent activity such as walking or resistance training benefits both hormonal and metabolic balance.

Stay Hydrated:

Adequate water intake keeps bile fluid and reduces the concentration of cholesterol and bile salts. Dehydration can lead to thicker bile, which is more prone to crystallization and gallstone formation.

Limit Alcohol and Avoid Smoking:

Excessive alcohol intake and smoking both affect liver metabolism and increase oxidative stress, which can worsen bile imbalance. Avoiding these habits supports overall liver and gallbladder health.

Monitoring During Testosterone Therapy

Regular monitoring is essential to detect early changes that could signal gallbladder or liver stress. Medical professionals often recommend periodic tests, especially for patients on long-term or high-dose therapy. These may include:

• Liver Function Tests (LFTs): to assess enzyme levels such as ALT, AST, and alkaline phosphatase.

• Lipid Profile: to check cholesterol and triglyceride levels, since testosterone can alter lipid metabolism.

• Abdominal Ultrasound: to detect early signs of gallstones or gallbladder inflammation.

• Hormone Panels: to monitor testosterone and estrogen balance, as excess androgen or low estrogen can both influence bile composition.

Monitoring frequency can vary but is usually recommended every 6 to 12 months for stable patients and more often for those with pre-existing liver or metabolic conditions.

Personalized Medical Oversight

Because testosterone therapy affects each person differently, individualized care is crucial. Factors such as age, body composition, liver function, and metabolic health determine how a patient responds to therapy. Doctors should adjust testosterone dosage and treatment type based on laboratory results and symptom tracking.

Patients should always inform their healthcare providers about abdominal pain, nausea, bloating, or changes in digestion, as these may signal gallbladder issues. It’s also important to review all medications and supplements, since some can interact with testosterone metabolism or liver enzymes.

Areas Requiring Future Investigation

Current research leaves several unanswered questions. Studies have shown testosterone can affect bile cholesterol levels and gallbladder motility, but the degree of risk is still uncertain. Most available data come from animal research or small human studies, often involving athletes or bodybuilders using anabolic steroids rather than medically supervised therapy.

Future research priorities include:

• Large, long-term human studies examining gallstone rates in men on prescribed testosterone therapy.

• Investigation into differences between testosterone delivery forms (oral, injectable, transdermal) and their effects on bile metabolism.

• Understanding the interaction between testosterone, insulin resistance, and non-alcoholic fatty liver disease (NAFLD), which may increase gallstone risk.

• Genetic and molecular studies exploring how testosterone influences bile acid transporters and gallbladder muscle contraction.

These studies would help doctors identify which patients are most at risk and develop screening strategies to prevent gallstones during hormone therapy.

While science has not confirmed that testosterone therapy directly causes gallstones, the evidence points to a biologically plausible link. Testosterone can change cholesterol metabolism, bile composition, and gallbladder motility—all key factors in gallstone formation. Therefore, caution and regular medical follow-up are essential.

For most people using testosterone under medical supervision, the risk of gallstones appears low, but it increases when other factors—like obesity, poor diet, or liver disease—are present. The best protection comes from balanced nutrition, steady weight management, and consistent check-ups with healthcare professionals.

Testosterone therapy can be safe and effective when managed properly, but awareness of gallbladder health should be part of every long-term treatment plan.

Conclusion

The connection between testosterone therapy and gallstones is a growing topic of interest in medical research. Although scientists have not reached a final answer, current evidence suggests that testosterone can influence several body systems that may affect how gallstones form. Understanding this connection helps patients and healthcare providers monitor possible risks and make informed decisions about hormone therapy.

Testosterone therapy (TT) has become more common, especially among men experiencing age-related hormone decline and those receiving treatment for low testosterone. While it can improve energy, mood, muscle mass, and sexual health, testosterone also changes how the body handles fats and cholesterol. These changes can extend to the liver and gallbladder, two organs that work closely to process and store bile — a fluid that helps digest fats. Bile is made of cholesterol, bile salts, and waste products. If the balance among these components is disturbed, solid particles can form and eventually develop into gallstones.

Research has shown that sex hormones influence bile metabolism. Estrogen, for instance, is known to increase cholesterol in bile, which is one reason why women are more likely to develop gallstones. Testosterone, however, seems to have a different but still significant effect. Some animal studies suggest that androgens can alter bile acid production and affect how cholesterol is processed in the liver. When bile becomes saturated with cholesterol and is not emptied from the gallbladder efficiently, gallstones can begin to form. This process can be slow and may not show symptoms for a long time.

Another possible pathway involves gallbladder motility — how well the gallbladder contracts to release bile. Hormonal changes, including higher or fluctuating testosterone levels, can influence smooth muscle tone in the gallbladder. If bile is not released properly, it can sit and thicken, allowing stones to develop. While this mechanism is still being studied, it offers a logical explanation for how testosterone might contribute indirectly to gallstone risk.

However, not all studies show a clear link. Some research finds that testosterone therapy does not significantly increase gallstone cases, while others observe changes in liver enzymes or bile composition that could, over time, raise the risk. These mixed findings suggest that other factors likely play a major role. For example, many people receiving testosterone therapy also make lifestyle changes — they may eat more protein, consume more fat, or aim for rapid weight loss to build muscle. Sudden weight loss and high-fat diets are well-known triggers for gallstone formation. Thus, it can be hard to tell whether testosterone itself or related habits are responsible for increased gallstone risk.

Liver health is another important piece of the puzzle. The liver produces bile and also processes hormones. Testosterone therapy can affect liver enzyme activity, especially when taken orally. This may alter how bile is produced and recycled. Injectable or transdermal (skin-applied) forms of testosterone tend to bypass much of the liver’s direct processing and may therefore pose lower risks for gallbladder issues. Still, more research is needed to compare the effects of different delivery methods.

Current evidence does not justify avoiding testosterone therapy solely due to fear of gallstones. Instead, doctors recommend awareness and regular monitoring. Patients on long-term testosterone therapy should have periodic liver function tests and lipid panels to track cholesterol and bile-related markers. Maintaining a healthy diet, staying hydrated, and avoiding rapid weight loss can also help prevent gallstone formation. Since testosterone therapy can change metabolism, following medical guidance on nutrition and exercise is especially important.

At this stage, scientists agree that testosterone may play an indirect role in gallstone development through its effects on bile composition, cholesterol metabolism, and gallbladder movement. But a direct cause-and-effect link has not been proven. Large-scale clinical trials are still needed to understand how testosterone therapy interacts with the complex processes that lead to gallstones. These studies should also look at long-term users and different formulations to determine whether certain types of therapy pose greater risk.

In summary, testosterone therapy remains a valuable medical treatment for many people, but like all therapies, it should be used with caution and professional oversight. Gallstones are a potential but not certain risk. Awareness, healthy lifestyle habits, and regular medical monitoring can greatly reduce the chances of complications. Science continues to explore this “hidden link,” and future research will likely bring clearer answers. Until then, the safest approach is informed use — guided by evidence, personalized care, and open communication between patients and their healthcare providers.