Drug companies that manufacture testosterone replacement drugs like AndroGel heavily market their products promising men increased vitality, strength, sex drive and an overall better quality of life.
The reality, however, is that testosterone therapy can cause a number of health complications that, some doctors say, might not be worth the benefits.
Studies and clinical trials have linked the drugs to heart attacks, blood clot injuries, stroke and an increased risk for prostate cancer, among other health reactions. Sadly, men using the drugs aren’t the only ones affected by them. If exposed to testosterone products, women, children and even pets can suffer serious side effects, too.
Evidence from published studies and expert input from an advisory committee prompted the U.S. Food and Drug Administration (FDA) to require labeling changes to reflect some risks associated with use of testosterone products. Still, critics say even more warnings about side effects are needed.
Timeline of FDA Testosterone Warnings and Announcements
April 22, 2009
The FDA sent a letter to Solvay Pharmaceuticals Inc. informing the company that new safety information regarding secondary exposure should be included in the labeling for AndroGel.
April 22, 2009
The FDA sent a letter to Auxilium Pharmaceuticals Inc. informing the company that new safety information regarding secondary exposure should be included in the labeling for Testim.
May 7, 2009
The FDA announced it is requiring manufacturers of two prescription topical testosterone gel products, AndroGel 1% and Testim 1%, to include on the products’ labels a boxed warning — the agency’s strongest warning — for secondary exposure in children.
January 31, 2014
The FDA announced its plan to investigate the risk of stroke, heart attack and death in men taking FDA-approved testosterone products.
June 19, 2014
The FDA announced it is requiring manufacturers to include a general warning in the drug labeling of all approved testosterone products about the risk of blood clots in the veins.
March 3, 2015
The FDA announced required labeling changes for all prescription testosterone products to reflect the possible increased risk of heart attacks and strokes associated with testosterone use.
Testosterone Associated Heart Attacks
Testosterone treatment of older men was associated with a significant increase of coronary artery plaque, a waxy substance that can build up, harden and reduce the flow of oxygen to the heart. That was the finding in a recent clinical trial of 138 men over the age of 64.
“… testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months.”
- According to a recent JAMA clinical trail of 138 men over 64
The results were published in February 2017 in the Journal of the American Medical Association. Researchers for a year studied the effect of testosterone on cardiovascular health in men who had low testosterone levels that couldn’t be explained by anything other than age. Of the 138 men studied, 73 received testosterone treatment and 65 received a placebo.
Risk Doubled in Some Younger Men
A different testosterone study published in January 2014 found increased heart attack risk in men who used testosterone. The risk was not limited to older men. Men younger than 65 with preexisting heart disease had “a twofold increase in risk of nonfatal heart attack shortly after initiation of testosterone therapy,” according to the study.
The study’s author, epidemiologist William Finkle, told NPR “the risk of heart attack should be added to the discussion between patients and physicians.”
Finkle’s study involved the records of 55,000 men prescribed testosterone in the U.S. It found that in the first 90 days of beginning hormone therapy, 1 in 167 men aged 65 or older could suffer a heart attack, while 1 in 100 men under 65 with preexisting heart disease could have one.
Man Dies During Study; Separate Study Canceled
A smaller study in 2010 published in the New England Journal of Medicine (NEJM) involved men who were frail or elderly and found that these men were more likely to suffer from several cardiac events, including heart attacks.
In fact, during the NEJM study, one man died and investigators said it was likely a heart attack brought on by testosterone use.
That same year, Boston University School of Medicine researchers stopped a study of testosterone therapy use in older men because of the potentially high cardiovascular risk to subjects. Compared with subjects taking a placebo, men taking the testosterone drugs were five times as likely to experience severe heart problems such as congestive heart failure.
Another study from November 2013 found an increase in the rate of heart attacks and other cardiovascular issues in veterans who took the hormone replacement drugs versus those who did not.
Calls for Black-Box Warning
The risk of cardiovascular problems has led consumer advocacy groups to call for a black-box warning on all testosterone drug packaging. Dr. Sidney Wolfe of Public Citizen said that the organization petitioned the FDA to require manufacturers to add warnings to the packages of several hormone replacement products already on the market.
“[Previous studies] showed that there was a 50 percent increase in cardiovascular risk . . . 14 studies that weren’t funded by the drug industry [showed] over a doubling of risks.”
–Dr. Sidney Wolfe, of Public Citizen
“The FDA is part of the public health service. It is doing the public no health service to make conclusions like that, and de facto encourages more of this massive use – we would argue misuse for most people – of testosterone products.”
Finkle echoed Wolfe’s sentiments in an interview with NPR.
“We have a 2010 study that was canceled because of unexpected cardiovascular risk,” Finkle told NPR. “I think that was sufficient to justify a warning. Why withhold that from the patient?”
Blood Clots Linked to Testosterone Use
Blood clotting is a normal function of the body and helps prevent excessive bleeding after an injury. Normally, these clots are dissolved by the body. Some blood clots, however, form inside veins and don’t dissolve naturally. Taking testosterone can increase the likelihood of developing blood clots.
When blood cells clump together in veins and arteries, the thick masses of blood may restrict blood flow. When the clot forms in a major vein, it is called deep-vein thrombosis (DVT). DVTs can travel to the lungs, causing a pulmonary embolism, or the brain, causing a stroke. These types of blockages are very dangerous and can be fatal.
Another side effect of testosterone therapy is polycythemia, a condition characterized by increased levels of red blood cells. When too many red blood cells are produced by the bone marrow, it causes the blood to thicken and increases the risk of blood clots.
Testosterone also increases production of thromboxane, a lipid that promotes blood vessel constriction, which further slows blood flow. Slower-moving blood is more likely to form clots.
Blood Clots May Form After One Month
A study published in the August 2013 issue of Clinical and Applied Thrombosis/Hemostasis found that blood clots may develop as quickly as one month after beginning hormone therapy drugs.
“Our research found that 1.2 percent of men who landed in the hospital with dangerous and potentially lethal blood clots in the deep veins of the legs or in the lungs developed these clots within three months of starting testosterone therapy,” study author Dr. Charles Glueck of the Jewish Hospital Cholesterol and Metabolism Center told the Cincinnati Business Courier.
According to Glueck, an inherited clotting disorder can make the risk worse. Many people are unaware they should be tested for these genetic mutations as well as hormone levels before beginning Low T therapy.
FDA Requires Testosterone Blood Clot Warning
The FDA is requiring manufacturers of testosterone replacement drugs to include warnings about the increased risk of blood clots that may develop and cause conditions such as deep vein thrombosis and pulmonary embolism.
The FDA told NBC News, “We are evaluating the potential risk of these cardiovascular events, which are related to blood clots in the arteries.”
Testosterone Induced Strokes and Mini-Strokes
Blood clots caused by testosterone replacement drugs can lead to a stroke if they block blood flow to the brain. Stroke is the fifth leading cause of death in the U.S. and a leading cause of serious long-term disability in adults, according to the Centers for Disease Control and Prevention.
Studies found testosterone gels raised the risk for stroke – also called a cerebrovascular accident or CVA. Men who took testosterone drugs were 30 percent more likely to suffer from strokes. Some men who participated in a testosterone study had to undergo “emergency artery-clearing” procedures, the Los Angeles Times reported.
One of the reasons why men using testosterone therapy drugs have stokes and mini-strokes may be the fact that testosterone therapy drugs cause blood cells to increase in size. This causes the blood to thicken and increases the risk for blood clots, which can lead to a stroke.
When Strokes Occur
A stroke occurs when blood vessels that supply the brain with oxygen and nutrients become blocked by clots (ischemic stroke) or rupture (hemorrhagic stroke), causing brain cells in the affected area to die. Depending on the area of the brain affected and the amount of damage done, the effects of stroke can range from mild impairments in vision, speech, memory and movement, to major long-term disabilities in these areas.
- Chest pain
- Shortness of breath or trouble breathing
- Weakness in one part or one side of the body
- Slurred speech
A man named Edward Downes filed a lawsuit against Abbott Laboratories and AbbVie after he took AndroGel and suffered a stroke. Other men also filed lawsuits after using testosterone products and experiencing heart attacks or blood clot injuries.
“I was in a lot of pain. Dizziness. Confusion,” Downes told CBS Chicago. Downs continues to struggle to recover and said that he would never have taken the drug if he had known the risks.
The FDA advises patients using testosterone to seek medical attention immediately if symptoms of a heart attack or stroke are present.
Testosterone Linked to Prostate Cancer
Testosterone therapy drugs are also linked to a possible increase in prostate cancer risk. One of the reasons for this is a spike in testosterone levels.
One study led by Dr. Terrence Shaneyfelt involving men who received testosterone replacement therapy found there was a two-fold increase in the risk of prostate cancer among men whose testosterone levels were above normal. Beth Israel Deaconess Medical Center and Harvard conducted the study.
Another study reviewed the medical records of six urology practices. Men involved underwent testosterone replacement therapy for sexual dysfunction or “rejuvenation.” In this study, a number of men were diagnosed with prostate cancer after they began testosterone therapy, some within two years of beginning therapy.
Many researchers agree that more study is needed on the relationship between testosterone therapy and prostate cancer. Men who undergo testosterone replacement therapy should be monitored by doctors to make sure that prostate cancer does not develop. Men who have a history of prostate problems should not use testosterone products.
A 2014 study led by professor Maarten Bosland of the University of Illinois at Chicago’s College of Medicine found that rats that were exposed to a carcinogen did not develop cancer but that 10 to 18 percent of ones that were exposed to testosterone did.
In addition, 50 to 71 percent of the rats exposed to both the carcinogen and testosterone developed prostate cancer — and usually more than one tumor.
The findings led researchers to believe that not only can testosterone cause cancer on its own, but it also can accelerate tumor growth in the presence of other carcinogens. Even low doses of the hormone replacement drug were enough to create tumors, according to the study.
Prior to this study, about five studies using rats also showed a link between testosterone therapy and prostate cancer, Bosland said.
Sleep Apnea Exacerbated by Testosterone
Studies show that testosterone therapy may exacerbate obstructive sleep apnea (OSA). OSA is a condition where the flow of air stops or decreases during sleep because of a blocked or narrowed airway. It can cause stroke, atrial fibrillation and cardiac ischemia, a condition where not enough blood is flowing to the heart.
A common and serious sleep disorder, sleep apnea causes an individual’s breathing to be interrupted repeatedly during sleep. Pauses in breathing can last anywhere from a few seconds to more than a minute and may occur as frequently as 30 times or more per hour in severe sleep apnea cases. This leads to low oxygen levels, which rouses the individual from deep sleep. When this happens, breathing starts again, often with a loud snore, gasp or choking sound. According to the American Sleep Apnea Association, sleep apnea affects more than 18 million Americans.
Because it causes fragmented, poor-quality sleep, untreated sleep apnea results in excessive daytime sleepiness.
Over time, a lack of restful sleep can over time take a harsh toll on overall health, increasing a person’s risk of developing:
- High blood pressure
- Heart attack
- Heart failure
- Cardiac arrhythmia
Sufferers are often unaware of their condition because they are generally not awakened fully by sleep interruptions. The vast majority of people affected by the disorder remain undiagnosed and untreated.
Sleep Habits Affect Testosterone Levels
Sleep quality and quantity both affect testosterone levels. Levels of sex hormones, including testosterone, rise as we sleep and decrease when we’re awake, with the most marked increase occurring during periods of deep, restorative sleep, called REM sleep. Sleep disorders like sleep apnea reduce the amount of REM sleep a person gets.
Given the association between sleep and testosterone levels, it is no surprise that studies show that men affected by sleep apnea are more likely to have sexual problems such as low libido and erectile dysfunction, issues in which low testosterone levels may be a contributing factor.
This interaction between testosterone levels and sleep apnea can become a viscous cycle for some men. Low testosterone can lead to more sleep-quality issues.
Low T and Sleep Studies
According to a study published in the Journal of Clinical Endocrinology, men with low testosterone have reduced sleep efficiency, increased nighttime awakenings, less REM sleep and more severe symptoms related to sleep apnea and other forms of sleep-disordered breathing.
Testosterone therapy, however, may induce sleep apnea. Researchers studied five hypogonadal (testosterone deficient) men to determine whether testosterone therapy may play a role in sleep apnea. After six weeks of treatment, obstructive sleep apnea developed in one man and markedly worsened in another in association with testosterone administration. Both also had significantly decreased oxygen levels and developed cardiac arrhythmias during sleep.
Treating sleep apnea — as opposed to treating the Low-T condition — often causes a rebound in testosterone levels once restful sleep is restored.
Other Possible Side Effects of Testosterone Products
Labels on testosterone products identify additional side effects and risks associated with the drugs. These range from enlargement of male breasts to harm to unborn babies.
Testosterone therapy can upset the balance of hormones in the body. The testicles may also shrink, and there is a risk of infertility that is irreversible.
This can cause:
- Enlargement of male breasts
- Skin irritations
- Oily skin
- Changes in hair patterns and growth
Dangers to Women, Children and Pets
Testosterone therapy for men can be dangerous to women and children if they come in contact with the drug by touching the patient’s skin. This usually occurs when men use testosterone gel and the application site is exposed. Anyone who comes in contact with the application site is at risk of developing side effects.
Women can experience acne or hair growth, and if they are pregnant, the unborn baby may be harmed.
In 2009, the FDA issued a warning about adverse effects in children exposed to testosterone gels through contact with application sites. Symptoms included abnormally large genitalia (penis and clitoris), advanced bone age, early puberty and aggressive behavior. Young boys may even develop enlarged breasts. A doctor should be contacted right away if these symptoms occur.
Pets exposed to testosterone can become violent and aggressive and develop enlarged genitals.
Emily Miller holds five Health Literacy certificates from the Centers for Disease Control and Prevention as well as a Bachelor of Science in Journalism from the University of Florida. She is a member of The Alliance of Professional Health Advocates, the American Association for the Advancement of Science and the Society for Technical Communication. Emily was diagnosed with a chronic illness as a child and has firsthand experience with many of the topics she writes about as a member of the Drugwatch team. She is an award-winning journalist who has reported on health and legal news for reputable organizations, including the South Florida Sun Sentinel, San Antonio Express-News, UF Health News and Reporters Committee for Freedom of the Press. She draws on her background as both a patient and a journalist to help readers understand complex health and legal topics.