Testosterone Replacement Therapy

What Is Testosterone Therapy?

Testosterone therapy is a treatment that involves injections of replacement testosterone to treat conditions of a decline in testosterone levels in men.

What Is Testosterone?

Testosterone is a hormone that, in men, is produced in the testicles. It’s the hormone that controls sexual functions and development in men and also influences the following in men:

• Sex drive
• Production of sperm
• Facial hair
• Body hair
• Production of red blood cells
• Distribution of fat
• Muscle strength
• Muscle mass
• Bone density

Women also have small amounts of testosterone that are produced by the adrenal glands and the ovaries.

What Are the Side Effects of Testosterone?

Testosterone has a number of side effects that occur because it is a male hormone. Common side effects that are not dangerous to most and may be considered beneficial in some cases may include:

• Acne
• Aggressive behavior
• Oily skin
• Increased body hair growth
• Increased sex drive
• Gynecomastia
• Hypertension
• Headache
• Weight gain
• Hot flashes

What Does Testosterone Therapy Treat?

Testosterone therapy treats hypogonadism, also known as low testosterone. Typically, just having a low testosterone level isn’t enough to justify testosterone replacement therapy. However, those who experience negative symptoms may want to consider treatment.

What Is Hypogonadism?

Hypogonadism is a condition that occurs when someone has unusually low levels of testosterone. A certain amount of testosterone loss is normal with aging. Therefore, before attempting any treatment for low testosterone, it’s essential to determine just how low the testosterone levels really are. It’s normal for testosterone levels to decrease by 1% each year beginning around the age of 30 or 40, depending on the person. In hypogonadism, however, the testicles produce very little, if not no, testosterone because of an issue with either the testicles or with the pituitary gland, which controls the testicles.

What Are the Symptoms of Low Testosterone?

The symptoms of low testosterone can include:

• Fatigue
• Low energy
• Loss of muscle mass
• Loss of body hair
• Loss of facial hair
• Irritability
• Depression
• Poor sense of well-being
• Trouble concentrating
• Low libido
• Erectile dysfunction

Who Should Use Testosterone Replacement Therapy?

Although low levels of testosterone are normal for men as they age, it’s often not treated. In many cases, treatment isn’t necessary because no symptoms are experienced. However, with more severe cases of low testosterone, such as in those with hypogonadism, symptoms are present and therefore a doctor may recommend treatment for the condition.

What Testosterone Therapy Products Are There?

Testosterone therapy can be administered as a gel, a patch, or an injection. Products that treat low or inadequate testosterone levels include:

• AndroGel topical gel (AbbVie)
• Androderm transdermal patch (Actavis/Allergan)
• Axiron topical solution (Eli Lilly)
• Testim topical gel (Endo/Auxillium/GSK)
• Testopel topical solution (Endo/Auxillium)
• Bio T Gel topical gel (Teva)
• Delaestryl injection (Endo)
• Depo-Testosterone injection (Pharmacia Upjohn/Pfizer)
• Fortesta topical gel (Endo)
• Striant buccal tablet (Endo)

What Is Androgel?

AndroGel is a testosterone replacement therapy medication that is available in a topical gel form to be applied daily.  It is approved to treat low testosterone levels caused by a medical condition known as hypogonadism. Unfortunately, many men who have taken it were exposed to a higher than normal risk for life-threatening events, without ever having been tested for low hormones.

What Is Androderm?

Androderm patch is approved to treat low testosterone levels that occur due to hypogonadism, but thousands of men may have used the treatment for “Low-T” to combat normal signs of aging such as decreased libido, lack of energy, and muscle loss. Unfortunately, like other testosterone replacement treatments, Androderm has been shown to cause serious side effects.

What Is Axiron?

Axiron, a topical form of testosterone replacement therapy, is approved to treat the medical condition of hypogonadism however, it has been prescribed to thousands of men to combat the natural signs of aging such as loss of muscle mass, decreased libido, and fatigue. Testosterone manufacturers used compelling advertisements which promoted testosterone replacement therapy products for “Low-T”.

Low-T is not a diagnosis but a marketing message and many men who used testosterone products like Axiron were never tested for low testosterone levels and may have been experiencing normal symptoms related to aging.

What Is Testim?

Testim is a gel form of testosterone therapy medication approved for the treatment of low testosterone levels in those who have a medical condition known as hypogonadism. Like other testosterone replacement medications, Testim was marketed for a non-medical condition termed “Low-T” which listed symptoms that many now consider to be normal symptoms of aging. Hundreds of thousands of men used Testim and similar drugs for “Low-T” symptoms and were never tested for low testosterone levels which may have exposed them to unnecessary risk.

Men or loved ones of those who experienced severe side effects of Testim gel have filed lawsuits against the manufacturer, Endo, and co-marketer, Glaxo. The lawsuits claim that Endo and its subsidiaries misrepresented the risks of testosterone replacement therapy, particularly with regards to cardiovascular risks of heart attack and stroke, along with disorders caused by blood clotting.

What Is Testopel?

Testopel is an injectable pellet form of testosterone that is intended to be administered every 4 to 6 months for the treatment of low testosterone levels due to hypogonadism. Like many testosterone products, Testopel was inappropriately marketed for “Low-T”, a non-medical condition with symptoms that may have been caused by normal aging processes. Many men who used Testopel for Low-T never had their testosterone levels tested and may have been placed at high risk for serious side effects and complications.

Men who took Testopel injections and who experienced serious side effects or loved ones of those who died due to testosterone pellet injections have filed lawsuits against the manufacturer, Endo Pharmaceuticals. These lawsuits claim that Endo and its acquired company Auxilium misled the public about the use of testosterone replacement therapy and downplayed the risks of dangerous side effects.

How Was Testosterone Therapy Marketed?

Many men who used testosterone therapy may not have needed the medication but did so because of aggressive marketing tactics. Drug companies undertook massive advertising campaigns to promote testosterone use for symptoms of “Low-T”. These advertisements encouraged men to ask their health providers about testosterone products that would help them with fatigue, decreased sex drive, loss of muscle tone, and lack of energy.

Many of the men who received prescriptions for testosterone products, were never tested for low testosterone levels but were likely experiencing symptoms that only indicated normal aging. This may have placed them at a higher risk for serious side effects which were not adequately discussed.

Because of serious side effects caused by testosterone replacement therapy, a number of drug manufacturers are facing thousands of lawsuits filed by men or loved ones of those who were harmed or who died after using testosterone products.

How Was Androgel Marketed?

AndroGel was one of several medications which were marketed to treat symptoms of “Low-T” in television commercials, in print ads, and on the internet.  Low-T was not a diagnosis but a marketing term, coined to describe symptoms of low testosterone in male patients including lack of energy, loss of sex drive, and general fatigue.  

Many of the supposed symptoms of Low-T were actually normal signs of aging, not a medical condition, and did not warrant medical treatment.  Some evidence suggests that the majority of men who used AndroGel and other medications for “Low-T” were never tested for low testosterone levels and may have been given the prescription drug unnecessarily.  This may have exposed them to serious risks which were life-threatening with no clear medical reason.

AbbVie and other testosterone product manufacturers have been accused of improper marketing and of hiding or downplaying the risk of AndroGel and other drugs.

What Are the Side Effects of Testosterone Therapy Treatment?

Like most other medications, testosterone replacement has a number of side effects, most of which are mild to moderate but others may be severe or life-threatening. Testosterone may increase the risk of:

• Blood clots
• Deep vein thrombosis (DVT)
• Venous thromboembolism (VTE)
• Pulmonary embolism (PE)
• Myocardial infarction (MI) or heart attack
• Cerebrovascular accident (CVA) or stroke 

What Can Testosterone Therapy Increase the Risk for?

Testosterone increases the risk of conditions that may contribute to cardiac and vascular problems such as:

• Heart Attack
• Hypertension
• Difficulty breathing
• Sleep Apnea
• Edema
• Elevated hemoglobin and hematocrit
• Impaired cholesterol metabolism
• Blood clots

Can Testosterone Therapy Increase the Risk of Heart Attack?

Studies have shown that men over the age of 65 may have double the normal heart attack risk with testosterone therapy and this was seen within short-term use (under 90 days). Among younger men, those with a history of heart disease had a two to three-fold increase in the risk of heart attack within the first 90 days of treatment. In younger men without previous cardiac history, no increased risk was shown.

What Are the Symptoms of a Heart Attack?

The symptoms of a heart attack include:

• Pain or pressure in the:
• Chest
• Arm
• Shoulder
• Sense of impending doom
• Difficulty breathing
• Feeling cold
• Feeling clammy

Can Testosterone Therapy Increase the Risk of Coronary Heart Disease (CAD)?

Coronary artery disease (CAD) is caused by a narrowing of the arteries that supply blood and oxygen to the heart tissue. CAD is usually caused by the development of cholesterol-based deposits, known as plaques, along the inside of the arteries, also called atherosclerosis or arteriosclerosis. Testosterone is known to cause changes in the metabolism of lipids and cholesterol, making the development of CAD more likely.

Over time, narrowing of the arteries supplying blood and oxygen will cause weakening of the heart muscle. These blood vessels may eventually become completely blocked, requiring medical intervention. The vessels may be opened to restore blood supply by performing a balloon dilation procedure known as angioplasty. If angioplasty is not possible, a heart bypass procedure may be required to reroute blood vessels and restore arterial blood flow.

Myocardial infarction (MI) or heart attack is caused by a sudden blockage of the blood flow to the heart muscle. If the cardiac muscle does not have an adequate oxygen supply, the tissue will die. In some cases, CAD may lead to a heart attack but in other cases, a heart attack may be caused by a blood clot that has developed elsewhere in the body.

Can Testosterone Therapy Increase the Risk of Blood Clots?

Blood clots are formed in the body when a tissue is injured or when blood cells are traveling too slowly or are too close together. Testosterone increases blood clot formation in two ways, by restriction of blood vessels in the case of coronary artery disease or due to changes in blood clotting mechanisms.

Testosterone causes increases in hemoglobin and hematocrit levels, making the blood slightly “thicker” than normal. Testosterone also increases the production of a body chemical known as thromboxane which increases the blood pressure through vasoconstriction. CAD-related narrowing of blood vessels may cause the blood cells to “bump” into each other near plaque deposits leading to clot development. When the blood is thicker and under greater pressure, blood cells will more easily begin to clump together and develop a clot.

Clots can be formed anywhere in the body but often develop as deep vein thrombosis (DVT) in the legs. No matter where they are formed, they may break free and travel to the brain, heart, or lungs. Clots that travel to the heart may cause a heart attack.

Based on two studies that showed an increased risk of cardiovascular events including heart attack, in January of 2014, the Food and Drug Administration announced an investigation regarding testosterone use and heart attack. In 2015, the agency required changes to drug labeling which included a warning about heart attack risks. This was followed shortly by the addition of information about blood clot formation.

Men who have other conditions such as hypertension, diabetes, or poor cholesterol profiles may also be at an increased risk of both heart attack and stroke.

Can Testosterone Therapy Increase the Risk of Pulmonary Embolism?

Testosterone replacement therapy may increase the risk of blood clot formation and pulmonary embolism. A pulmonary embolism is the occurrence of a sudden blockage of the arteries that supply blood and oxygen to the lung tissue. If the blood supply is suddenly cut off, the lung tissue cannot survive and will die.

Pulmonary embolisms are most commonly caused by blood clots that develop in the legs but may be caused by other non-blood objects in the blood supply such as arterial plaques which have broken into pieces and flow through the arteries to lodge in the lungs.

What Are the Symptoms of a Pulmonary Embolism?

Some people with pulmonary embolism do not have symptoms but in others, symptoms may occur rapidly, worsen and quickly become fatal. Symptoms of pulmonary embolism should be treated as a medical emergency.

• Sudden shortness of breath
• Sharp chest pain that worsens with deep breaths or coughs
• Cough that produces bloody or pink mucous
• Fainting
• Sweating
• Anxiety
• Heart palpitations or rapid heart rate

Can Testosterone Therapy Increase the Risk of Stroke?

Taking testosterone replacement therapy may increase the risk of cerebrovascular accident (CVA) or stroke due to an increased chance of clotting. In addition, changes in the body’s cholesterol metabolism may also increase the risk of atherosclerosis which can lead to stroke.

A stroke or CVA is the occurrence of a sudden blockage of the arteries that supply blood and oxygen to the brain. When the supply of blood and oxygen to the brain is blocked, the brain tissue cannot survive. CVAs are most often caused by blood clots that have developed elsewhere in the body but may also be caused by arterial or venous plaques from atherosclerosis that have broken off, producing a piece that may lodge in an artery.

Strokes occur suddenly and are not always treatable. In some cases, a CVA will cause permanent damage to the brain, and physical disability and may even result in death.

What Are the Symptoms of a Stroke?

Symptoms of stroke include:

• Sudden numbness or weakness of the face or limbs (arm or leg), often on only one side of the body
• Sudden confusion or difficulty speaking
• Sudden dizziness, loss of balance or coordination
• Sudden headache

Symptoms of stroke should be treated as a medical emergency.  In some cases, though not always effective, immediate treatment will help to reverse some of the effects of a stroke.

The FDA announced an investigation in January of 2014 regarding severe adverse events caused by testosterone, particularly heart attack, and in June of 2014, the FDA began requiring a warning regarding the risk of clot formation on all testosterone products.  In 2015, a warning about heart attack risks was added to all testosterone product labeling.

What Prostate and Testicular Effects Can Testosterone Therapy Treatment Have?

Testosterone replacement has been shown to increase the risk of prostate disorder including:

• Prostate enlargement
• Difficulty urinating
• Elevated PSA levels
• Prostate cancer

Some men also see testicular atrophy (shrinking testicles), particularly with long-term use, oligospermia (slow sperm), and priapism (extremely prolonged erection which can cause penile damage).

Can Testosterone Therapy Treatment Damage the Liver?

Testosterone is metabolized in the liver and the use of testosterone and other hormones has been shown to increase liver enzyme levels. Those who use testosterone for a long period of time may be at an increased risk of liver cancer, hepatic encephalopathy, or liver failure. It is suspected that some well-known athletes may have developed liver cancer after years of steroid (testosterone) use.

Is Testosterone Treatment Dangerous to Others?

As testosterone is responsible for the male secondary sex characteristics, it should not be taken or used except under rare circumstances. Women and children who come into skin contact with testosterone gel or other forms of testosterone may absorb some of the medication which could result in adverse events. Testosterone can cause the development of male characteristics such as body hair, deepened voice, and reproductive anomalies in women and children and may cause the long bones (arms and legs) to stop growing prematurely in children.

What FDA Investigations Were There Into Testosterone Therapy Treatments?

In January of 2014, the U.S. Food and Drug Administration announced its investigation of AndroGel and other testosterone replacement treatments used for men. The investigation was prompted by the results of two studies. One of the studies showed a two-fold increase in heart attacks in those on testosterone who were over the age of 65. The second study showed a connection between testosterone and increased risk of both stroke and heart attack.

In July of 2014, separate from the heart attack investigation, the FDA required that manufacturers begin including warnings about an increased risk of clot disorders including deep vein thrombosis (DVT) and venous thromboembolism (VTE). Either of these conditions may result in life-threatening events including pulmonary embolism, heart attack, and stroke.

Based on the January 2014 investigation, the FDA concluded in mid-2015 that a warning label would be required regarding the increased heart attack risk. All labeling for testosterone replacement products now requires both warning statements.

What Androgel FDA Warnings Were There?

Androgel was included in the FDA’s 2014 investigation and was, per the FDA’s findings, required to update its warnings. The FDA required as of 2014 that Androgel’s prescription information include warnings regarding the increased risk of deep vein thrombosis and blood clotting. Later, in 2015, the FDA also required that Androgel’s labeling include warnings pertaining to the increased risk of heart attack, stroke, and other life-threatening cardiovascular events.

What Androderm FDA Warnings Were There?

Adroderm was also impacted by the FDA’s requirements that warnings be placed on the labeling and the prescription information. Like other testosterone replacement therapy medications, Androderm was also found to increase the risk of stroke, heart attack, blood clotting, and more.

What Axion FDA Warnings Were There?

The manufacturers of Axion were required by the FDA to include warning labels that alerted doctors and patients alike to the increased risk of stroke, heart attack, blood clotting, deep vein thrombosis, and other life-threatening health conditions.

What Testim FDA Warnings Have There Been?

Testim was introduced by Auxilium Pharmaceuticals as a competitor to the more popular AndroGel. Auxilium was acquired by Endo, who co-marketed Testim with pharmaceutical giant, Glaxo. In March 2015, the FDA ordered Testim and other testosterone manufacturers to update product labels with information about an increased risk of heart attack and stroke. In June of 2015, the labels were again updated to include a warning regarding a risk of venous thromboembolism (VTE), venous blood clots that include deep vein thrombosis (DVT), and pulmonary embolism (PE) which may be fatal.

What Testopel FDA Warnings Have There Been?

The FDA required that Testopel pellet injection and other testosterone medications have information about heart attack and other cardiovascular events be added to prescribing information. Separately, in June of 2014, the FDA had required that warnings about an increased risk of blood clots be added to Testopel and other testosterone product labels.

Allegations surround the companies deceiving marketing tactics which imply that the medication could be used to increase male sex drive, gain muscle and improve bone density for “Low-T”, a marketing term that is not an actual diagnosis. Many men who took Testopel and other products were never tested for low testosterone levels but were subject to serious risks, without an approved diagnosis.

What Testosterone Therapy Settlements Have There Been?

Thousands of lawsuits have been filed against testosterone manufacturers for injuries caused by their products. These lawsuits have accused the companies of:

• Misleading marketing tactics
• Understating risks
• Failure to warn of risks

Federal testosterone lawsuits have been consolidated into multidistrict litigation (MDL 2545) in the Northern District of Illinois. It is a highly complex litigation case involving a number of companies and products. A few of the cases, known as “bellwether” cases have already gone to trial, prompting some companies to offer settlements for testosterone cases against their products.

Though some cases have been dismissed and all of the manufacturers have denied fault, some companies may be in the process of settling many of their lawsuits for testosterone products. Notable testosterone settlements that have been offered or are under consideration include:

• AndroGel – Produced by AbbVie
• Androderm – Produced by Actavis, Inc. (formerly Watson Pharmaceuticals), a division of Allergan
• Axiron – Produced by Eli Lilly and Company
• Testim and Testopel – Produced by Auxillium/Endo Pharmaceuticals in cooperation with GlaxoSmithKline

What Androgel Settlements Have There Been?

Shortly after the FDA’s first announcement, men began filing AndroGel lawsuits for heart attack, stroke, and other life-threatening complications of testosterone treatment. Thousands of men followed suit and AbbVie has faced over 4,200 AndroGel lawsuits in federal court, along with others in state and local courts.

The first case to go to trial was decided in favor of AbbVie, against the plaintiff who had claimed that AndroGel caused a man’s pulmonary embolism but the jury decided that the death could have been a result of other medical conditions. Other early cases were decided against AbbVie and resulted in awards of a total of $290 million for two plaintiffs who suffered heart attacks while using AndroGel. Out of six early AndroGel lawsuits, AbbVie lost four of those cases.

Based on mixed results of AndroGel trials and similar trials of other testosterone replacement drugs, in September 2018, AbbVie announced plans to settle thousands of AndroGel lawsuits for undisclosed amounts. In the same time period, other manufacturers also settled thousands of testosterone lawsuits.

Though most AndroGel lawsuits have been settled, men or loved ones of those who suffered a heart attack, stroke, pulmonary embolism, or another debilitating event while using AndroGel, should seek legal advice. Past lawsuits have provided compensation for medical costs, lost wages, pain and suffering, and in some cases, punitive damages against companies who knew of the dangers of treatment but continued to market a product without adequate warnings.

What Androderm Settlements Have There Been?

Allergan and its subsidiary, Actavis, announced in July of 2018 that they had reached a tentative settlement agreement to resolve around 500 Androderm lawsuits. The cases to be settled were part of a larger group of around 8,000 federal testosterone lawsuits which had been consolidated into multidistrict litigation (MDL). The lawsuits had been filed against a number of manufacturers for improper marketing practices which promoted the products for “Low-T” and concealed the serious risks of testosterone replacement therapy.

Terms of the settlement offer were not been publicly disclosed and more lawsuits may be expected but men or loved ones of those who were harmed by Androderm should seek legal advice.

What Axion Settlements Have There Been?

Thousands of testosterone lawsuits have been filed against a number of testosterone product manufacturers. The majority of these cases were federal lawsuits that were consolidated into multidistrict litigation but in December of 2017, Eli Lilly settled about 400 Axiron lawsuits that had previously been part of the federal multidistrict litigation (MDL) case.

Based on the negotiations, pending trial dates for Axiron lawsuits were set aside and though an agreement was reached, no details were publicly announced. In addition to the federal lawsuits that may have been settled, Lilly may still be facing other lawsuits in state and local courts and more may be expected.

What Testim Settlements Have There Been?

In February of 2018, Endo Pharmaceuticals and GlaxoSmithKline agreed to settle lawsuits that accused the drug manufacturers of hiding risks of Testim, which was marketed toward middle-aged men. Endo had previously won a single case filed by the family of a man who died from a heart attack while using Testim. In that trial, the jury decided that the man had other health conditions which may have contributed to his death.

Despite that win, Endo and Glaxo were facing another round of testosterone lawsuits. Just before a bellwether case was slated to be tried in Philadelphia, the companies agreed to resolve more than 1,300 Testim lawsuits for an undisclosed amount. In June 2018, Endo announced they had set aside $200 million for these claims but more lawsuits may be expected.

What Testopel Settlements Have There Been?

In June 2018, Endo Pharmaceuticals announced they had set aside $200 million for claims related to another testosterone product, Testim. Though no announcements have been made public, this may indicate that Testopel settlements have been under consideration and similar testosterone lawsuits have resulted in settlements that have ranged from thousands to millions of dollars. Men or loved ones of those who experienced a stroke, heart attack, pulmonary embolism, or clotting disorders after receiving a Testopel (testosterone pellet) injection, should seek evaluation by a legal expert. 

What Testosterone Therapy Lawsuits Are There?

Thousands of Testosterone lawsuits have been filed against testosterone manufacturers for injuries and deaths related to the use of testosterone replacement therapy. Many of the lawsuits have been settled through agreements being offered by the manufacturers.

Notwithstanding claims relating to this product, the drug/medical device remains approved by the U.S. FDA.