Testosterone Therapy for Idiopathic Hypogonadotrophic Hypogonadism has Beneficial and Deleterious Effects on Cardiovascular Risk Factors
Curator: Aviva Lev-Ari, PhD, RN
UPDATED on 5/20/2014
New Studies Highlight Benefits, Risks of Testosterone Therapy
New data also indicate who may benefit most from treatment
PR Newswire
ORLANDO, Fla., May 18, 2014 /PRNewswire-USNewswire/ —
Three new studies examining the predictors, effects and durability of testosterone therapy on men will be presented to reporters at the 109th Annual Scientific Meeting of the American Urological Association (AUA) during a special press conference in the Orange County Convention Center,Orlando, FL on Sunday, May 18 at 2:00 p.m. ET.
Testosterone, a hormone produced primarily in the testicles, helps maintain a man’s:
- Bone density
- Fat distribution
- Muscle strength and mass
- Red blood cell production
- Sex drive
- Sperm production
Testosterone therapy is used to treat men with clinically diagnosed testosterone deficiency, also known as hypogonadism. While hypogonadism can be associated with fatigue, erectile dysfunction, decreased muscle mass and even infertility, these symptoms may not always be related to low levels of this hormone. Men with these symptoms should consult with their physicians and undergo blood tests prior to starting testosterone replacement therapy.
Study Details
Exercise Improves the Effect of Testosterone Replacement Therapy and the Durability of Response After Cessation of Treatment (#MP48-02): Exercise may help sustain the positive effects of testosterone therapy even after treatment ends, according to a new study from Ansan Hospital and Seoul Paik Hospital in Korea. Fifty patients with late-onset hypogonadism and similarly sedentary lifestyles were enrolled and placed into one of two random groups prior to starting the 20-week study, which included 12 weeks of Testosterone Replacement Therapy (TRT) and eight weeks of follow-up without therapy. One group was offered a supervised physical activity program concurrent with TRT therapy for the duration of the study while the other received TRT alone. Throughout the study, improvements were seen in both groups, with total serum testosterone levels significantly increased at 12 weeks; however, greater increases were seen in the exercise group. This group also showed more sustained improvements in symptoms following the cessation of TRT. In particular, 72.2 percent of patients in the exercise group reported improvements in erectile function at the conclusion of the study, compared to 45.5 percent of the non-exercise group, leading researchers to conclude, the combination of exercise and TRT offers significant improvements in testosterone levels and late-onset hypogonadism symptoms, which can be well sustained with continuous exercise even after the cessation of TRT.
Long-term Testosterone Treatment Leads to Progressive Weight Loss and Waist Size Reduction in Hypogonadal Men (#MP48-01): Obesity and other metabolic disorders may be related to low levels of testosterone and restoring hormone levels may improve these conditions in some men, according to a new study from researchers in Germany and the United States. Using data from a prospective registry of 261 men (ages 32 to 84) with low testosterone (<12nmol/L), researchers examined 164 men for five years of testosterone therapy. After five years of follow up, the men had experienced statistically significant weight loss (mean weight decrease from 104.23 kg to 92.49 kg), decreases in body mass index (average 33.17 to 29.44) and waist circumference (average 108.61 to 99.03) as well as changes in total cholesterol, glucose and blood pressure levels.
Predictors of Poor Response to Transdermal Testosterone Therapy in Men with Metabolic Syndrome (#MP48-04): A new study from Weill Cornell Medical College in New York indicates men with diabetes and obesity may have less success with TRT than men without these conditions. Researchers reviewed 58 patients, with 32 having a BMI of less than 30 (non-obese) and 26 with a BMI greater than 30 (obese). All 58 patients were of similar age, with similar baseline hormone levels. At the end of the study period, 81 percent of non-obese men had achieved normal testosterone levels, compared to 52 percent of obese men (P=0.03). Total testosterone levels were 81 percent and 54 percent, respectively, suggesting that metabolic conditions may impact the efficacy of TRT.
“In the right patients, TRT can significantly improve symptoms,” said Tobias S. Köhler, MD, MPH, FACS; session moderator and associate professor & residency program director with Southern Illinois University School of Medicine. “However, as these studies show, not all men may be good candidates for this therapy. It”s extremely important for men to talk with their doctors about the benefits and risks of this therapy.”
About the American Urological Association: The 109th Annual Meeting of the American Urological Association takes place May 16 – 21 at the Orange County Convection Center in Orlando, FL.
Founded in 1902 and headquartered near Baltimore, Maryland, the American Urological Association is a leading advocate for the specialty of urology, and has more than 20,000 members throughout the world. The AUA is a premier urologic association, providing invaluable support to the urologic community as it pursues its mission of fostering the highest standards of urologic care through education, research and the formulation of health policy.
Contact:
Christine Frey, AUA
410-999-7091, cfrey@AUAnet.org
SOURCE American Urological Association
UPDATED on 4/16/2014
The Risks of Taking Testosterone – How Men’s Hormone Supplements Threaten Heart Health
It’s not uncommon for middle-aged men to become concerned about low testosterone levels as they age, 
and advertisements that play on this fear to market hormone products are commonplace. The ads may be effective, however, since prescriptions for testosterone therapy more than tripled among men age 40 and up from 2001 to 2011.
As the trend to turn to testosterone supplements continues to grow, the medical community has begun to raise concerns about risks that have emerged in connection with taking the hormones.
For example, the risk of having a nonfatal heart attack more than doubled for men age 65 or older during the three months after starting a testosterone prescription, according to a recent study published in the January 2014 journal PLOS One (Public Library of Science). The same study found that men younger than 65 who took testosterone for the same time period only experienced a higher risk for heart attack if they had a prior history of heart disease. The research reviewed data from 55,593 men who filled their first prescription for testosterone, comparing the 90 days after the prescription was filled with data from the prior year, in which they were not taking the hormone at all.
“This study found that risk levels dropped down to normal levels for men who stopped taking the hormone after 90 days,” says Michael C. Gavin, MD (right), a cardiologist in the CardioVascular Institute at BIDMC. “The same study found no association with increased heart risk among men taking drugs like Viagra, which do not contain any testosterone.”
A second study found that taking testosterone caused a 30 percent increase in the risk for heart attack, stroke and death among a group of veterans with a history of heart disease. This clinical trial, published in the Journal of the American Medical Association in 2013, was halted prematurely to the emerging concerns about testosterone safety.
What Causes a Decrease in Testosterone?
“Testosterone levels naturally begin to drop after the age of 30,” says Gavin. “The symptoms are what many men begin to feel when they reach their 40s, 50s or older, which may include a drop in muscle mass, energy, and interest or performance in sex. The trouble is that these symptoms may also be connected to metabolic syndrome, which involves a number of conditions — excess body weight around the waist, high blood pressure or blood sugar, and abnormal cholesterol levels — that also increase risk of heart disease.”
The connection between loss of testosterone and abdominal girth is no accident.
“Fat cells are hormonally active and release or metabolize compounds, including estrogen-like hormones,” says Gavin. “That’s why we often see a connection with abdominal fat and breast tissue, which can then lower the brain’s ability to produce natural testosterone. Physiology is very complex, and the associations between excess weight and hormonal issues are clear, and seen over and over again in patients.”
The Need for Testing and Weighing the Risks
About one-quarter of men who receive testosterone prescriptions are not tested for low testosterone, according to Gavin, who stresses that a lab test must confirm that the patient’s hormone level has slumped to an abnormal number before a prescription is considered.
“While there is certainly a connection between aging and low testosterone, and some men with low-T could benefit from hormone therapy, the risks need to be carefully considered first,” he says.
Gavin explains that research has found that the use of synthetic testosterone in a lab setting decreases HDL, or healthy, cholesterol levels, and increases red blood cell counts, which leads to an increased risk for blood clots — often the cause for heart attacks and stroke.
The Final Analysis
As a cardiologist, Gavin recommends lifestyle interventions as the first action to combat low testosterone.
“There’s no doubt about beneficial effects of exercise and weight loss on risk factors for low testosterone,” he says. “Men can begin lifting light weights to increase muscle mass and follow a healthy diet to promote weight loss.
“For those people who still feel unwell and show low testosterone in lab tests along with no signs for cardiovascular disease, it’s reasonable to consider hormone therapy. But biochemical evidence is needed, and I still recommend trying lifestyle changes first,” Gavin adds. “And, for older men or those with cardiovascular risk factors, I would exercise extreme caution in balancing risks with benefits. The numbers in the studies are alarming and should not be taken lightly.”
Above content provided by the CardioVascular Institute at Beth Israel Deaconess Medical Center. For advice about your medical care, consult your doctor.
Posted April 2014
more information:
REFERENCES
Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0085805
Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels
http://jama.jamanetwork.com/article.aspx?articleid=1764051
SOURCE
Several Research Findings are presented for the exposition of the Beneficial and the Deleterious Effects of Testosterone Therapy on Cardiovascular Risk Factors
Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels
Rebecca Vigen, MD, MSCS1; Colin I. O’Donnell, MS2,3; Anna E. Barón, PhD2,3; Gary K. Grunwald, PhD2,3; Thomas M. Maddox, MD, MSc2,3,4; Steven M. Bradley, MD, MPH2,3,4; Al Barqawi, MD3; Glenn Woning, MD3; Margaret E. Wierman, MD2,3; Mary E. Plomondon, PhD2,3,4; John S. Rumsfeld, MD, PhD2,3,4; P. Michael Ho, MD, PhD2,3,4
Importance Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.
Objectives To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease.
Design, Setting, and Patients A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011.
Main Outcomes and Measures Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke.
Results Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. At 3 years after coronary angiography, the Kaplan-Meier estimated cumulative percentages with events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%). In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41).
Conclusions and Relevance Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
SOURCE
Testosterone therapy doubles heart risk in older men
Taking testosterone therapy doubled the risk of heart attack among men over age 65 and nearly tripled the risk in younger men with a history of heart disease, a new study shows.
The report, which involved 56,000 men, is the latest in a series of studies raising concerns about the heart attack risk from testosterone therapy, whose popularity has ballooned in recent years. The study was published Wednesday in PLOS One.
Francisco Lopez-Jimenez, a cardiologist at the Mayo Clinic in Minnesota not involved in the new study, describes the heart risks posed by testosterone therapy as substantial.
“That’s equivalent to smoking one or two packs of cigarettes a day, or having sky-high cholesterol,” Lopez-Jimenez says.
Authors of the study, led by researchers at the University of California-Los Angeles and others, say doctors should discuss these risks with patients. Testosterone is often called the “male hormone” because it causes development of male sex organs, facial hair and other masculine features.
Doctors recommend testosterone therapy to treat hypogonadism, which causes abnormally low testosterone levels. Studies show that testosterone can improve sexual function, bone density, lean muscle mass and strength while lowering cholesterol and insulin resistance, a condition that increases the risk of diabetes.
Drug companies also have marketed testosterone directly to consumers, however, urging men to consider hormones to treat the symptoms of “low T,” which are said to include energy loss, mood changes and reduced sex drive.
Those ads appear to have been hugely successful.
Doctors wrote more than 5.3 million prescriptions for testosterone therapy in 2011, five times as many as in 2000, according to a November report in the Journal of the American Medical Association. The number of men taking testosterone tripled from 2001 to 2011, with the drugs now used by nearly 4% of men in their 60s, according to a separate study last year in JAMA Internal Medicine.
Yet only about half of men taking testosterone therapy had been diagnosed with hypogonadism, and 25% hadn’t even had their testosterone levels tested, according to the JAMA Internal Medicine study. The rest of patients had been diagnosed with other problems such as fatigue or sexual dysfunction.
A spokesman for AbbVie, which makes AndroGel, one of the most popular testosterone therapies, notes that studies also have found health benefits from the medications. A 2012 study linked testosterone with a lower risk of death. A 2013 study in the Journal of Clinical Practice found that men taking the therapy long-term had healthier cholesterol levels, blood sugar levels and blood pressure.
“We encourage discussion between physicians and patients that leads to proper diagnosis based on symptoms, lab tests and a patient’s other health needs,” says David Freundel, a spokesman for AbbVie.
Abraham Morgentaler, an associate clinical professor of urology at Harvard Medical School, says it’s possible that the men’s heart attacks in this study were caused by their underlying medical problems, not by testosterone. He notes that most heart attacks occurred in the first 90 days after a prescription was written. It’s unlikely that heart attacks could develop in such a short period of time, he says.
Cardiologist Steven Nissen says the Food and Drug Administration should require companies that sell testosterone therapy to conduct rigorous clinical trials examining the medication’s heart risks.
Nissen, chair of cardiovascular medicine at the Cleveland Clinic, notes that hormones have powerful and sometimes surprising effects throughout the body, not just on sexual organs. He cited hormone replacement therapy, which was once touted as a way to prevent heart disease in women but was later found to cause heart attacks, strokes and breast cancer. Prescribing testosterone therapy to thousands of men who may not really need it, he says, is “a “gigantic experiment, and I’m extremely concerned.”
SOURCE
http://www.usatoday.com/story/news/nation/2014/01/29/testosterone-heart-risks/4967795/
Testosterone Therapy May Raise Cardiovascular Risk
Testosterone therapy was associated with adverse cardiovascular (CV) outcomes in a large observational study. The findings raise questions about the potential safety of testosterone use in men, wrote Rebecca Vigen MD, and her colleagues in the Journal of the American Medical Association (2013;310:1829-1836).
VIEW VIDEO
Testosterone and the heart
Testosterone is responsible for men’s deep voices, increased muscle mass, and strong bones. It also has crucial effects on male behavior, contributing to aggressiveness, and it is essential for the sex drive and normal sexual performance.
Although testosterone acts directly on many tissues, some of its least desirable effects don’t occur until it is converted into another male hormone, dihydrotestosterone (DHT). DHT acts on the skin, sometimes producing acne, and putting hair on the chest but often taking it off the scalp. DHT also stimulates the growth of prostate cells, producing normal growth in adolescence but contributing to benign prostatic hyperplasia (BPH).
But while testosterone’s effects on many organs are well established, research is challenging old assumptions about how the hormone affects a man’s heart, circulation, and metabolism.
Early worries
A direct association between testosterone and heart disease has never been established, but for many years, doctors have suspected that a link exists. The reasoning goes like this: men have much more testosterone than women, and they develop heart disease about 10 years before their female counterparts. Like other muscle cells, cardiac muscle cells have receptors that bind male hormones. Animals that are given testosterone develop enlarged hearts. Athletes who abuse testosterone and other androgenic steroids have a sharply increased risk of high blood pressure, heart attack, and stroke. And in high doses, testosterone can have a negative effect on cardiac risk factors, including HDL (“good”) cholesterol levels.
The fact that large amounts of testosterone harm the heart and metabolism doesn’t necessarily mean that physiological amounts are also harmful. In fact, research is challenging these old dogmas.
Complex relationships
It’s hard for scientists to study possible new risk factors for heart disease. One reason is that there are so many cardiac risk factors, including family history, age, gender, blood pressure, cholesterol, blood sugar, obesity, smoking, exercise, and personality.
It’s also hard for scientists to study testosterone. There is an exceptionally wide range of normal values. Healthy men can have testosterone levels between 270 and 1,070 nanograms per deciliter (ng/dL).
Heart disease and testosterone are mighty complex on their own, and studies that evaluate the two together are more complex still. Scientists who undertake these daunting investigations must account for all the things that influence heart disease and all the variables that affect testosterone.
With all these pitfalls, it’s not surprising that more research is needed to fill in all the blanks. Still, even if current information can’t tell us if testosterone can protect a man’s heart, it can dispel fear that physiologic levels of the hormone are toxic.
Testosterone and cardiac risk factors
In high doses, androgens tend to raise LDL (“bad”) cholesterol levels and lower HDL cholesterol levels. That’s one of the things that gave testosterone its bad reputation. But in other circumstances, the situation is very different. Men who receive androgen-deprivation therapy for prostate cancer drop their testosterone levels nearly to zero, and when that happens, their cholesterol levels rise. Even within the normal range, men with the lowest testosterone levels tend to have the highest cholesterol levels.
Diabetes is another important cardiac risk factor. Prostate cancer treatments that lower levels of testosterone produce insulin resistance and increase the risk of diabetes. Obesity increases the risk of both diabetes and heart disease. Men with low testosterone have more body fat and more of the abdominal fat that’s most harmful than men with higher hormone levels, but since obesity itself reduces testosterone, it’s not clear which is the cause and which the effect.
Peripheral artery disease (PAD) is an important form of atherosclerosis in its own right, and it also signals an increased risk for heart disease. A Swedish study of over 3,000 men with an average age of 75 linked low testosterone levels to an increased risk of PAD. At present, the hormone does not appear linked to hypertension or inflammatory markers.
Testosterone therapy and cardiovascular function
Low testosterone levels have been linked to various cardiac risk factors, but that doesn’t prove that low levels actually cause heart disease. Still, if testosterone therapy could help men with heart disease, it would bolster the argument that testosterone may be safe for the heart. Only a few small, short-term studies have been published to date, and the results offer mixed support for this theory.
Testosterone tinkering
As men age, it’s not just heart disease they need to worry about. They also begin to lose muscle mass and bone density; red blood cell counts sag; sexual ardor declines; mood, energy, and memory drift down; and body fat increases. In theory, at least, testosterone therapy might blunt or reverse each of these woes. But the theoretical benefits should be balanced against the theoretical risks.
The most serious long-term complications of testosterone therapy include an increased risk of benign prostate disease (BPH). Although some doctors worry that testosterone treatments might increase the risk of prostate cancer, the evidence for this is small. Indeed, there is evidence that men with low testosterone levels (who therefore might benefit from testosterone treatment) have a higher risk of developing prostate cancer.
Do the potential gains of testosterone treatment outweigh the possible pains? Nobody knows. To date, only small, short-term studies have been completed. More research is needed to learn how testosterone affects the heart and the rest of a man’s body and mind.
The best advice is to protect your heart and your body by taking care of known risk factors, such as cholesterol, blood pressure, diabetes, obesity, and tobacco exposure. And don’t forget that diet and exercise remain the keys to reducing the risk of heart disease.
April 2010 update
SOURCE
http://www.health.harvard.edu/fhg/updates/testosterone-and-the-heart.shtml
Testosterone Treatments Linked with Risk of Heart Problems, Deaths
|
 Credit: Doctor’s visit via Shutterstock
|
Men with signs of heart problems who take injections of testosterone or use gel containing the hormone may have an increased risk of heart attack or stroke, a new study finds. The findings call for more cautious prescribing of testosterone, doctors say.
In 2011, 5.3 million prescriptions for testosterone were written in the United States. Testosterone therapy is often prescribed to men in order to counteract the age-related decline in the hormone and improve sex drive, bone density and muscle mass. But the benefits and risks of the long-term use of testosterone therapy are not well known.
In the new study, Dr. Rebecca Vigen, a researcher at the University of Texas, and her colleagues looked at 9,000 male veterans who had undergone coronary angiography between 2005 and 2011, a procedure for testing the arteries when people have symptoms such as chest pain or are at high risk for heart problems. The men, whose average age was 60, were also found to have low testosterone levels during their exam, and 1,200 of them started testosterone therapy after their tests.
The researchers followed up with the men after an average of 2.4 years after their angiography. During the study, 26 percent of men who were receiving testosterone therapy had either a heart attack or a stroke, or died from any cause, while 20 percent of men who did not receive testosterone therapy had experienced such events or died. [5 Myths About the Male Body]
In other words, the men who used testosterone therapy had a 30 percent increased risk of heart attack, stroke or dying, compared with men who didn’t use the hormone, and the results held after being adjusted for several other factors that could have affected the outcomes, according to the study, published today (Nov. 5) in the Journal of the American Medical Association (JAMA).
The results “make us take a pause, and make sure that everyone taking testosterone is taking it for the right reasons and is experiencing benefits,” said Dr. Anne Cappola, an associate professor of medicine at the University of Pennsylvania who wasn’t involved in the study.
Doctors and patients should be wary of the aggressive marketing used by testosterone manufacturers, Cappola said.
“There’s a lot of marketing out there of testosterone and low-T syndrome, and a lot of men who want to feel better,” she said. “So that marketing appeals to them, but they are not hearing any of the risks side, which is often harder to quantify.”
In the United States, rates of testosterone prescription tripled between 2000 and 2011, reaching sales of $1.6 billion in 2011, according to a previous study.
The researchers said the new study was prompted by a recent clinical trial of testosterone therapy in men who were at high risk for heart disease. That study was stopped early, due to higher rates of heart problems in the group receiving the hormone.
All of the men in the new study generally had higher rates of medical conditions — including coronary artery disease, diabetes and previous heart attacks — than men in the general population.
Cappola said the study participants represented a “real-world” population of men who have more health problems than the men enrolled in most randomized clinical trials do.
The researchers noted that they couldn’t verify whether the men in the study had been prescribed testosterone according to doctors’ guidelines, which require doctors to draw blood in the morning on two different days and look for medical problems that could be related to testosterone deficiency. Cappola said there’s evidence that sometimes patients are prescribed testosterone without having their hormone levels properly checked.
It is still unclear whether the results extend to other populations of men — for example, men of the same age group who are taking testosterone for low-T syndrome or for anti-aging purposes, or younger men taking it for physical enhancement.
“Although physicians should continue to discuss the benefits of testosterone therapy with patients, it is also important to inform patients that long-term risks are unknown and there is a possibility that testosterone therapy might be harmful,” the researchers said.
Email Bahar Gholipour or follow her @alterwired. Follow LiveScience @livescience, Facebook & Google+. Original article on LiveScience.
Editor’s Recommendations
- 8 Tips for Healthy Aging
- 5 Myths About the Male Body
- Beyond Vegetables and Exercise: 5 Surprising Ways to Be Heart Healthy
SOURCE
Popular Testosterone Therapy May Raise Risk Of Heart Attack
by RICHARD KNOX
Some men take testosterone hoping to boost energy and libido, or to build strength. But at what risk?
iStockphoto
There’s new evidence that widely prescribed testosterone drugs — touted for men with flagging libidos and general listlessness — might increase the risk of heart attacks.
A study of more than 55,000 men found a doubling of heart attack risk among testosterone users older than 65, compared with men who didn’t take the drug.
The research was inspired by a smaller study published in 2010 that hinted at an elevated risk among frail, older men who were on testosterone replacement therapy. The earlier study was halted ahead of schedule because of a higher rate of heart attacks, strokes and other cardiovascular problems.
What’s new, says William Finkle, lead author of a study published Wednesday by PLOS ONE, is that in men younger than 65 with known heart disease, “we also found a twofold increase in risk of nonfatal heart attack shortly after initiation of testosterone therapy.”
Nonusers had a risk of heart attack of 5 per 1,000 men followed for 1 year, while testosterone users older than 65, and those under 65 with known heart disease, had an absolute risk of 10 per 1,000 patient years. These numbers were adjusted to account for other health issues, including high blood pressure, diabetes and smoking.
As men age, their production of testosterone falls. For some, testosterone drops so low that it becomes a medical problem. But millions of U.S. men use testosterone drugs as lifestyle drugs, resorting to replacements to reverse a natural decline. In a sign of the drugs’ popularity, sales of AbbVie’s Androgel, the leading testosterone replacement, surpassed Viagra’s in 2012.
In one frequently aired TV ad, a youthful-looking 50-something man owns up to having “low T,” which his doctor discovered after he complained of sagging energy and irritability. After taking Androgel, he’s back in the swing of things, the ad suggests, riding around in a convertible with a younger-looking woman.
With such inducements (and common symptoms), some specialists worry that many men are being prescribed testosterone drugs even if they have normal levels of the male sex hormone. The drugs cost around $300 to $400 a month, but companies are offering to cover patients’ insurance copayments or are giving away the first month’s supply.
In addition to the new study and the one in 2010, a Veterans Affairs study last November found a higher rate of heart attacks, strokes and deaths among 1,223 men taking testosterone therapy, compared with 7,486 who didn’t get the hormone treatment.
Finkle, who’s with a California firm called Consolidated Research, tells Shots that “the risk of heart attack should be added to the discussion between patients and physicians” before anyone starts testosterone treatment.
He also says the Food and Drug Administration should require a warning on the labels of testosterone drugs such as Androgel and Axiron. “We have a 2010 study that was canceled because of unexpected cardiovascular risk,” he tells Shots. “I think that was sufficient to justify a warning. Why withhold that from the patient?”
Dr. Sidney Wolfe, of the Health Research Group, tells Shots that his consumer advocacy organization plans to petition the FDA, asking for a strong warning on the instructions for testosterone drugs. The group also intends to ask the FDA to hold off on a long-acting, injectable form of testosterone called Aveed. The agency is expected to make a decision on the drug in February.
But at least one advocate of testosterone therapy says the evidence of risks is overblown and poorly founded. “It feels almost like it’s open season on testosterone,” Boston urologist Abraham Morgentaler tells Shots. “None of the studies is very impressive.”
Morgentaler, author of Testosterone for Life, published by Harvard Health Books, says authors of the latest study “have made the classic mistake of confusing treatment for a condition with the condition. There’s a rich literature spanning more than 20 years that shows low testosterone itself is a risk factor for cardiovascular events.”
He also criticizes the new study for not following patients long enough, and notes that the rate of heart attacks among testosterone users was low.
It’s “high time” for a study of testosterone therapy involving a large number of men who are followed for years, Morgentaler says, similar to the Women’s Health Initiative study on postmenopausal estrogen supplements.
“There is potential for testosterone to be important for general health and longevity,” Morgentaler says. “There’s strong evidence it increases muscle strength and decreases fat — things we would associate with improved health.”
But large, lengthy studies cost hundreds of millions of dollars. And in the case of estrogen replacement, that sort of research ultimately discredited the long-held belief that taking hormone supplements lowers the risk of heart attacks.
SOURCE
Cardiovascular Issues in Hypogonadism and Testosterone Therapy
Ridwan Shabsigh, MD,* Mark Katz, MD, Grace Yan, BA, and Nawras Makhsida, MD
A systematic literature search was conducted to investigate the cardiovascular issues related to hypogonadism and testosterone therapy. Vascular cells contain sex steroid hormone receptors. Testosterone can exert effects on the vascular wall, either by itself or through aromatization as estrogen. Hypogonadism is associated with central obesity; insulin resistance; low levels of high-density lipoprotein (HDL); high cholesterol levels; and high levels of low-density lipoprotein (LDL), triglycerides, fibrinogen, and plasminogen activator–1.
Some observational studies show a correlation between low testosterone and cardiovascular disease (CVD), and others show no correlation.
Interventional studies do not reveal a direct long-term relation between testosterone therapy and CVD. Short-term data suggest cardiovascular benefits of testosterone. Testosterone therapy has beneficial and deleterious effects on cardiovascular risk factors. It improves insulin sensitivity, central obesity, and lowers total cholesterol and LDL. In some studies, testosterone therapy has an HDL-lowering effect, and in other studies this effect is insignificant. This should not be assumed to be atherogenic because it might be related to reverse cholesterol transport and effects on the HDL3 subfraction.
The cardiovascular effects of testosterone therapy may be neutral to beneficial. There is no contraindication for testosterone therapy in men with CVD and diagnosed hypogonadism with or without erectile dysfunction. Caution should be exercised regarding occasional increases in hematocrit levels, especially in patients with congestive heart failure. Conversely, evidence does not support testosterone therapy in aging men for the purpose of cardiovascular benefit, despite claims to this effect. Further research on the cardiovascular benefits and risks of testosterone is strongly recommended. © 2005 Elsevier Inc. All rights reserved.
SOURCE
Am J Cardiol 20052005;96[suppl]:67M–72M
Testosterone treatment in hypogonadal men may reduce cardiovascular disease risk
Published on October 24, 2013 at 1:06 AM · No Comments
Research from Boston University School of Medicine (BUSM) suggests that testosteronetreatment in hypogonadal (testosterone deficient) men restores normal lipid profiles and may reduce the risk of cardiovascular disease. These finding currently appear online in the International Journal of Clinical Practice.
Metabolic syndrome (MetS) is associated with increased risk for cardiovascular disease and diabetes mellitus. There is a strong association between MetS and testosterone deficiency.
Hypogonadal men are more likely to suffer from metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes and hypertension. Additionally, obese and overweight men also may exhibit testosterone deficiency.
In this observational study, BUSM researchers investigated the effects of testosterone treatment in 255 hypogonadal men between the ages of 33-69 and followed them for a period of five years. They found that men treated with testosterone therapy experienced a gradual reduction of their total cholesterol, low density lipoproteincholesterol (LDL/bad cholesterol), triglycerides and increased high density lipoprotein (HDL/(good cholesterol). “In addition to improving their cholesterol levels, we found that the testosterone treatment resulted in marked reductions in systolic and diastolic blood pressure as well, suggesting amelioration of hypertension,” explained lead author Abdulmaged M. Traish, MBA, PhD, professor of biochemistry and urology as well as Research Director of the Institute of Sexual Medicine at BUSM.
Traish found this treatment also reduced fasting blood glucose and hemoglobin A1c, a surrogate marker of hyperglycemia, suggesting that testosterone treatment may improve insulin sensitivity and hyperglycemic control. It also reduced the levels of inflammatory biomarkers such as C-reactive protein (CRP) and markers of liver dysfunction such as alanine aminotransferase and aspartate aminotransferase, suggesting reduction in the inflammation responses.
“These data are congruent with our previous work in which we reported that long-term testosterone resulted in a gradual decline in weight and waist circumference and strongly suggests that testosterone therapy in hypogonadal men may prove useful in reducing the risk of cardiometabolic diseases,” he added.
Source: Boston University Medical Center
1. Shabsigh R, Kimoto Y, Amar E, Hackett G, Jarow JP, Mirone V,
Richter S, Schmidt A, Yaffe L. Economical aspects in sexual dysfunctions.
In: Lue TF, Basson R, Rosen R, Giuliano F, Khoury S, Montorsi
F, eds. Sexual Medicine, Sexual Dysfunctions in Men and Women.
Paris: Health Publications, 2004:139 –160.
2. Zimmerman GA, McIntyre TM, Prescott SM. Adhesion and signaling
in vascular cell– cell interactions. J Clin Invest 1996;98:1699 –1670.
3. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med
1999;340:115–126.
4. Wu FC, von Eckardstein A. Androgens and coronary artery disease.
Endocr Rev 2003;24:183–217.
5. Levy D, Kannel WB. Search for answers to ethnic disparities in
cardiovascular risk. Lancet 2000;356:266 –267.
6. Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer KS. Testosterone
as a protective factor against atherosclerosis: immunomodulation and
influence upon plaque development and stability. J Endocrinol 2003;
178:373–380.
7. Larsen BA, Nordestgaard BG, Stender S, Kjeldsen K. Effect of testosterone
on atherogenesis in cholesterol-fed rabbits with similar
plasma cholesterol levels. Atherosclerosis 1993;99:79–86.
8. Smith JC, Bennett S, Evans LM, Kynaston HG, Parmar M, Mason
MD, Cockcroft JR, Scanlon MF, Davies JS. The effects of induced
hypogonadism on arterial stiffness, body composition, and metabolic
parameters in males with prostate cancer. J Clin Endocrinol Metab
2001;86:4261– 4267.
9. Rockhold RW. Cardiovascular toxicity of anabolic steroids. Annu Rev
Pharmacol Toxicol 1993;33:497–520.
10. Sullivan ML, Martinez CM, Gennis P, Gallagher EJ. The cardiac
toxicity of anabolic steroids. Prog Cardiovasc Dis 1998;41:1–15.
11. Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P. Effects
of testosterone on coronary vasomotor regulation in men with coronary
heart disease. Circulation 1999;100:1690 –1696.
12. English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Low-dose
transdermal testosterone therapy improves angina threshold in men
with chronic stable angina: a randomized, double-blind, placebo-controlled
study. Circulation 2000;102:1906 –1911.
13. Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia
with coronary artery disease in men. Arterioscler Thromb
1994;14:701–706.
Shabsigh/Cardiovascular Issues in Hypogonadism and Testosterone Therapy 71M
14. Marckmann P, Sandstrom B, Jespersen J. Favorable long-term effect
of a low-fat/high-fiber diet on human blood coagulation and fibrinolysis.
Arterioscler Thromb 1993;13:505–511.
15. Yang XC, Jing TY, Resnick LM, Phillips GB. Relation of hemostatic
risk factors to other risk factors for coronary heart disease and to sex
hormones in men. Arterioscler Thromb 1993;13:467– 471.
16. Freedman DS, O’Brien TR, Flanders WD, DeStefano F, Barboriak JJ.
Relation of serum testosterone levels to high density lipoprotein cholesterol
and other characteristics in men. Arterioscler Thromb 1991;
11:307–315.
17. Caron P, Bennet A, Camare R, Louvet JP, Boneu B, Sie P. Plasminogen
activator inhibitor in plasma is related to testosterone in men.
Metabolism 1989;38:1010 –1015.
18. Hamalainen E, Adlercreutz H, Ehnholm C, Puska P. Relationships of
serum lipoproteins and apoproteins to sex hormones and to the binding
capacity of sex hormone binding globulin in healthy Finnish men.
Metabolism 1986;35:535–541.
19. De Pergola G. The adipose tissue metabolism: role of testosterone and
dehydroepiandrosterone. Int J Obes Relat Metab Disord 2000;
24(suppl):S59 –S63.
20. Kiel DP, Baron JA, Plymate SR, Chute CG. Sex hormones and lipoproteins
in men. Am J Med 1989;87:35–39.
21. Glueck CJ, Glueck HI, Stroop D, Speirs J, Hamer T, Tracy T. Endogenous
testosterone, fibrinolysis, and coronary heart disease risk in
hyperlipidemic men. J Lab Clin Med 1993;122:412– 420.
22. Tsai EC, Boyko EG, Leonetti DL, Fujimoto WY. Low serum testosterone
level as a predictor of increased visceral fat in Japanese-
American men. Int J Obes Relat Metab Disord 2000;24:485– 491.
23. Hergenc G, Schulte H, Assmann G, von Eckardstein A. Associations
of obesity markers, insulin, and sex hormones with HDL-cholesterol
levels in Turkish and German individuals. Atherosclerosis 1999;145:
147–156.
24. Tchernof A, Labrie F, Belanger A, Despres JP. Obesity and metabolic
complications: contribution of dehydroepiandrosterone and other steroid
hormones. J Endocrinol 1996;150(suppl):S155–S164.
25. Simon D, Charles MA, Nahoul K, Orssaud G, Kremski J, Hully V,
Joubert E, Papoz L, Eschwege E. Association between plasma total
testosterone and cardiovascular risk factors in healthy adult men: the
Telecom Study. J Clin Endocrinol Metab 1997;82:682– 685.
26. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuornainen
TP, Valkonen VP, Salonen R, Salonen JT. Testosterone and sex
hormone-binding globulin predict the metabolic syndrome and diabetes
in middle-aged men. Diabetes Care 2004;27:1036 –1041.
27. Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia
in men with non–insulin-dependent diabetes mellitus. Ann Intern
Med 1992;117:807– 811.
28. Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB.
Testosterone, sex hormone-binding globulin, and the development of
type 2 diabetes in middle-aged men: prospective results from the
Massachusetts male aging study. Diabetes Care 2000;23:490–494.
29. Makhsida N, Shah J, Yan G, Fisch H, Shabsigh R. Hypogonadism and
the metabolic syndrome: implications for testosterone therapy. J Urol
2005;174:827– 834.
30. Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation
in men with type 2 diabetes, visceral obesity and partial androgen
deficiency. Aging Male 2003;6:1–7.
31. Li JY, Zhu JC, Dou JT, Bai WJ, Deng SM, Li M, Huang W, Jin H.
Effects of androgen supplementation therapy on partial androgen deficiency
in the aging male: a preliminary study. Aging Male 2002;5:
47–51.
32. Dockery F, Bulpitt CJ, Agarwal S, Donaldson M, Rajkumar C. Testosterone
suppression in men with prostate cancer leads to an increase
in arterial stiffness and hyperinsulinaemia. Clin Sci 2003;104:195–
201.
33. Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham
G, Matsumoto AM, Weber T, Berman N. Transdermal testosterone
gel improves sexual function, mood, muscle strength, and body
composition parameters in hypogonadal men. J Clin Endocrinol Metab
2000;85:2839 –2853.
34. Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley
JE. Oral testosterone supplementation increases muscle and decreases
fat mass in healthy elderly males with low-normal gonadal status. J
Gerontol A Biol Sci Med Sci 2003;58:618–625.
35. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson
EJ, Klibanski A. Increase in bone density and lean body mass during
testosterone administration in men with acquired hypogonadism.
J Clin Endocrinol Metab 1996;81:4358–4365.
36. Marin P. Testosterone and regional fat distribution. Obes Res 1995;4:
609–612.
37. Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S.
Androgens stimulate myogenic differentiation and inhibit adipogenesis
in C3H 10T1/2 pluripotent cells through an androgen receptormediated
pathway. Endocrinology 2003;144:5081–5088.
38. Tan KC, Shiu SW, Pang RW, Kung AW. Effects of testosterone
replacement on HDL subfractions and apolipoprotein A-I containing
lipoproteins. Clin Endocrinol (Oxf) 1998;48:187–194.
39. Ozata M, Yildirimkaya M, Bulur M, Yilmaz K, Bolu E, Corakci A,
Gundogan MA. Effects of gonadotropin and testosterone treatments on
lipoprotein(a), high density lipoprotein particles, and other lipoprotein
levels in male hypogonadism. J Clin Endocrinol Metab 1996;81:3372–
3378.
40. Bhasin S, Bagatell CJ, Bremner WJ, Plymate SR, Tenover JL, Korenman
SG, Nieschlag E. Issues in testosterone replacement in older men.
J Clin Endocrinol Metab 1998;83:3435–3448.
41. Malkin CJ, Pugh PJ, Jones RD, Jones TH, Channer KS. Testosterone
as a protective factor against atherosclerosis—immunomodulation and
influence upon plaque development and stability. J Endocrinol 2003;
178:373–380.
42. Zgliczynski S, Ossowsli M, Slowinska-Srzednicka J, Brzezinska A,
Zgliczynski W, Soszynski P, Chotkowska E, Srzednicki M, Sadowski
Z. Effect of testosterone replacement therapy on lipids and lipoproteins
in hypogonadal and elderly men. Atherosclerosis 1996;121:35– 43.
43. Dobs AS, Bachorik PS, Arver S, Meikle AW, Sanders SW, Caramelli
KE, Mazer NA. Interrelationships among lipoprotein levels, sex hormones,
anthropometric parameters, and age in hypogonadal men
treated for 1 year with a permeation-enhanced testosterone transdermal
system. J Clin Endocrinol Metab 2001;86:1026 –1033.
44. Kenny AM, Prestwood KM, Gruman CA, Fabregas G, Biskup B,
Mansoor G. Effect of transdermal testosterone on lipids and vascular
reactivity in older men with low bioavailable testosterone levels. J
Gerontol a Biol Sci Med Sci 2002;57:M460.
72M The American Journal of Cardiology (www.AJConline.org) Vol 96 (12B) December 26, 2005
2012pharmaceutical
Amandeep Kaur
Aashir Awan, Phd
Abhisar Anand
Adina Hazan
Alan F. Kaul, PharmD., MS, MBA, FCCP
alexcrystal6
anamikasarkar
apreconasia
aviralvatsa
David Orchard-Webb, PhD
danutdaagmailcom
Demet Sag, Ph.D., CRA, GCP
Dror Nir
dsmolyar
Ethan Coomber
evelinacohn
Gail S Thornton
Irina Robu
jayzmit48
jdpmd
jshertok
kellyperlman
Ed Kislauskis
larryhbern
Madison Davis
marzankhan
megbaker58
ofermar2020
Dr. Pati
pkandala
ritusaxena
Rick Mandahl
sjwilliamspa
Srinivas Sriram
stuartlpbi
Dr. Sudipta Saha
tildabarliya
vaishnavee24
zraviv06
zs22
Leave a Reply