Posts Tagged ‘testosterone’

Even “Mid-low-T” Levels Make Men Depressed

Men referred for borderline testosterone levels may have high rates of depression and depressive symptoms that are under-recognized, according to the results of a new study.

“In an era where more and more men are being tested for ‘Low T’ — or lower levels of testosterone — there is very little data about the men who have borderline low testosterone levels.

We felt it important to explore the mental health of this population,” said lead author Michael S. Irwig, MD, associate professor of medicine and director of the Center for Andrology at the George Washington School of Medicine and Health Sciences in Washington, DC.

The number of testosterone prescriptions has grown exponentially over the past decade.

Along with it has been a corresponding increase in direct-to-consumer marketing about the effects of “Low T” on decreased sexual function and low energy in middle-aged men.

The study included 200 adult men, mean age 48 years, who were referred for borderline total testosterone levels between 200 and 350 ng/dL.

Doctors typically treat men for hypogonadism if they have symptoms of low testosterone and their testosterone levels are below 300 ng/dL.

The researchers gathered information on demographics, medical histories, medication use, signs and symptoms of hypogonadism, and assessments of depressive symptoms and/or a known diagnosis of depression or use of an antidepressant.

All of the study participants who were not diagnosed with depression or who were taking medications for the condition answered standardized test questions aimed at measuring mood.

More Than Half Showed Signs of Depression

The results show that more than half (56%) of the men had depression or depressive symptoms, which is significantly higher than rates seen in general populations.

A recent survey of US adults found that 6% of those who are overweight or obese were depressed.

One-quarter of the men used antidepressants.

Rates of depression were 62% for those in their 20s and 30s, 65% for those in their 40s, 51% for those in their 50s, and 45% for those who were age 60 and higher.

Notably, the men had high rates of overweight or obesity and physical inactivity.

Common symptoms were erectile dysfunction, decreased libido, fewer morning erections, low energy, and sleep disturbances.

Sexual and nonspecific symptoms, such as fatigue, likely prompted measurements of testosterone in this selected population, the researchers pointed out.

They concluded that “clinicians should consider screening for depression/depressive symptoms and overweight and unhealthy lifestyle risk factors in men referred for tertiary care for potential hypogonadism.”

Testosterone replacement therapy can improve the signs and symptoms of low testosterone in these men, the researchers said.

The researchers published their results online on July 1, 2015 in the Journal of Sexual Medicine.

No Added Heart Attack Risk With Testosterone Therapy in Older Men

Testosterone therapy does not increase the risk of heart attack, or myocardial infarction (MI), among older men, according to a comprehensive new study.

“We believe this is a methodologically rigorous study and should be thoughtfully weighed, critiqued, and discussed alongside the other studies of testosterone therapy and cardiovascular outcomes,” said lead author Jacques Baillargeon, PhD, Director, Epidemiology Division and Associate Professor of Preventive Medicine & Community Health at the University of Texas Medical Branch in Galveston.

“Although recent observational studies have reported an increased risk of cardiovascular disease associated with testosterone use, there is a large body of evidence that is consistent with our finding of no increased risk of MI associated with testosterone use,” Dr. Baillargeon said.

He noted that there are cardiovascular risks associated with untreated hypogonadism (a condition in which the body doesn’t produce enough testosterone) and those should be factored into the risk-benefit assessment about testosterone therapy.

INCREASE IN TESTOSTERONE PRESCRIPTIONS

Testosterone prescriptions for older men in the United States have increased more than 3-fold over the past decade.

This trend has been driven by increases in direct-to-consumer marketing; rapid expansion of clinics specializing in the treatment of low testosterone; the development of new drugs and improved delivery mechanisms, particularly dermal gels; and greater diagnostic awareness of hypogonadism, stated Dr. Baillargeon.

The retrospective study used information from 25,000 Medicare beneficiaries aged 66 years and older.

It compared more than 6,300 men treated with testosterone for 8 years with more than 19,000 who were not treated with testosterone.

“We found that use of intramuscular testosterone therapy was not associated with an increased risk of MI,” Dr. Baillargeon said.

In fact, testosterone was associated with a possible protective effect — reduced risk of MI in patients with the highest prognostic risk index.

There were no differences in risk in patients in the lower prognostic risk groups.

HOW TESTOSTERONE AFFECTS THE HEART

There are a number of physiologic pathways whereby testosterone therapy may affect the risk of adverse cardiovascular events.

“Some have reported that testosterone therapy may improve cardiovascular health by way of decreasing fat mass, insulin sensitivity, and lipid profile,” said Dr. Baillargeon.

“Also, testosterone may possess anti-inflammatory and anticoagulant properties.”

He continued, “It is possible that our findings of a protective effect among men in the highest MI prognostic group reflect a process whereby testosterone reduces peripheral vascular resistance, thereby reducing stress on the heart among those who have some degree of coronary artery disease.

It is important to note that there are also postulated mechanisms through which testosterone may increase the risk of cardiovascular disease.

Given the broad range of proposed biologic pathways, it is important to conduct further research on this topic.”

CONCERNS ABOUT TESTOSTERONE THERAPY

Several recent studies have raised concerns about cardiovascular risks associated with testosterone therapy, in particular for older men.

On June 19, the FDA expanded labeling on testosterone products to include a general warning about the risk of blood clots in veins.

The FDA and European Medicines Agency also are further examining the safety of these products.

The researchers reported their results in the July 2, 2014 issue of the Annals of Pharmacotherapy.

Evidence on Testosterone Therapy Does Not Support Cardiac Risk

Does testosterone therapy to treat testosterone deficiency, or “low T,” increase a man’s risk of cardiovascular disease?

No, says a provocative editorial that asserts there are flaws in the cardiovascular risks quoted in recent articles in the scientific literature and mass media.

The public judgment of the overselling of testosterone therapy demands a response, stated the lead author, Martin Miner, MD, Clinical Associate Professor of Family Medicine and Urology, Warren Alpert Medical School of Brown University.

The editorial appeared in the April 8, 2014 issue of Journal of Men’s Health.

NO CREDIBLE EVIDENCE

“As researchers and clinicians with extensive experience with testosterone deficiency and its treatment, we do not find any credible evidence that testosterone prescriptions increase health risks.

We find the assertion that testosterone is prescribed to men ‘who are simply reluctant to accept the fact that they are getting older’ is without foundation, and we object to comments that question the reality of testosterone deficiency, regardless of whether it is called hypogonadism or, as in advertisements, ‘low T,’” Dr. Miner stated.

“In addition, in our opinion, the idea that physicians prescribe testosterone due to pressure from drug companies is irresponsible and not supported by scientific evidence.”

OVER-THE-TOP COMMENTS

Over-the-top comments tend to scare both patients and physicians.

“The FDA announcement that it is investigating the reports of increased cardiovascular risks has only added to the impression that a major study has determined serious problems with testosterone therapy,” he stated.

A case in point is a recent report published in PLoS ONE that investigated the risk of acute nonfatal myocardial infarction (MI), or heart attack, in a retrospective cohort study of a health-claims database.

The authors compared the rates of heart attack within the first 90 days of an initial prescription for testosterone with the rates of heart attack for the 12 prior months in nearly 56,000 men.

They also examined pre- and post-prescription incidence rates for nonfatal heart attack in another large cohort of more than 167,000 men for whom only phosphodiesterase-5 inhibitor (PDE5i) medications (such as Viagra) were prescribed, and after adjusting for potential confounders, compared these results to those of men who received testosterone prescriptions.

The authors concluded that the risk of heart attack following testosterone prescription was “substantially” increased (at least twofold) in older men and younger men with preexisting, diagnosed heart disease.

STUDY IS “TOO FLAWED”

“A close examination reveals that this study is too flawed to provide meaningful information on the cardiovascular risk of testosterone therapy,” stated Dr. Miner.

“First, the overall rate of nonfatal MI in the testosterone-treated group increased in all ages from 3.48 to 4.75 per 1,000 person-years.

This amounts to just greater than 1 additional MI in 1,000 years of exposure to testosterone.

It is misleading to characterize this increase as ‘substantial’ based on relative risk when the absolute risk is so small and clinically meaningless.”

Also, the study duration (90 days) was short, and a true control group would have consisted of men with untreated testosterone deficiency, not those who received PDE5i medications.

The overall risk was low, and the number of events in subgroups was remarkably few, he noted.

More data from larger, longer term studies are needed to assess the potential effects of testosterone therapy on cardiovascular events in men.

Based on the current evidence, he stated, “we can find no foundation for suggesting new restrictions on testosterone therapy in men with cardiac disease.”

Testosterone Tempers Response to Flu Vaccination

Men with high levels of testosterone may have weakened immune systems, which may be the reason why men’s immune systems respond less strongly to vaccinations.

That’s the main result of the first study to show an explicit correlation between testosterone levels, gene expression, and immune responsiveness in humans.

The expression of genes regulating lipid metabolism correlate with differing vaccine responses observed between the sexes, and a number of these genes also have been shown to be immunosuppressive and likely regulated by testosterone, according to lead author David Furman, PhD, Research Associate in the Department of Microbiology and Immunology at Stanford University School of Medicine in Stanford, CA.

“In addition, elevated levels of free testosterone and expression of such gene signatures appear to be highly detrimental for the production of neutralizing antibodies against influenza in men,” he said.

In general, males have less robust immune responses for reasons that are not well-understood.

The researchers published their results ahead of print on December 23, 2013 in the Proceedings of the National Academy of Sciences.

They used a systems analysis to investigate this difference by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli in 87 patients of various ages.

The men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to the flu vaccine.

The researchers also identified a cluster of genes involved in lipid biosynthesis that had been previously shown to be up-regulated by testosterone, which correlated with poor virus-neutralizing activity in men.

The results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses, Dr. Furman said.

“We hypothesize that these genes connected with lipid metabolism and immunosuppressive shunt down the response by generating suppressive monocytes and T cells, and could be activated when a critical concentration of testosterone is reached,” he said.

Testosterone’s effect on the immune system may be linked to a man’s evolutionary role, Dr. Furman said.

“Infection with pathogens constituting evolutionary pressure, such as highly pathogenic influenza virus, SARS infection, or dengue fever, often generates an exacerbated and uncontrolled expansion of immune cells and production of inflammatory cytokines, the so-called cytokine storm, which causes tissue damage, endothelial leakage with pulmonary edema, and lung failure.

Therefore, in these cases of evolutionary pressure one can think that mechanisms of immunosuppression (high production of testosterone) might be beneficial, and therefore selected.”

Dr. Furman added, “Our study strongly indicates that testosterone supplementation is detrimental.

However, it might be positive in cases where the immune response is harmful, for example, in autoimmunity or cytokine storms.”

He noted that “sex steroids have a huge effect in immunity.

Primary care physicians should be aware of this when considering vaccination regimes.”