Low Testosterone Levels Tied to More Severe COVID in Men

Men with low testosterone levels may be more likely to have more severe illness when infected with COVID-19, according to a new study.

Treating men who have low testosterone with hormone therapy may reduce their risk of serious illness from COVID, researchers said, but it comes with other risks that doctors and patients will need to weigh.

The investigators analyzed the cases of more than 700 men who tested positive for COVID — most before vaccines were available.

Men with low testosterone (low-T) who contracted the virus were 2.4 times more likely to require hospitalization than men with normal hormone levels. But men who had been treated successfully for low-T before catching COVID were not more likely to be hospitalized.

“Low testosterone is very common; up to a third of men over 30 have it,” said study co-author Dr. Abhinav Diwan, a professor at Washington University School of Medicine in St. Louis.

“Our study draws attention to this important risk factor and the need to address it as a strategy to lower [COVID] hospitalizations,” Diwan said in a school news release.

Researchers had previously found that men hospitalized with COVID had abnormally low levels of the male hormone. But they didn’t know whether low-T is a risk factor for severe COVID or a result of it.

For that, they needed to find out whether men with chronically low testosterone levels — before illness or after recovering — were getting sicker than men with normal levels.

From two hospital systems in the St. Louis area, researchers found 723 men with COVID whose testosterone levels were on record. They identified 427 men with normal testosterone levels; 116 with low levels; and 180 who were being successfully treated for low levels.

They had confirmed cases of COVID in 2020 or 2021 and low-T either before or after their infection.

“Low testosterone turned out to be a risk factor for hospitalization from COVID, and treatment of low testosterone helped to negate that risk,” said co-author Dr. Sandeep Dhindsa, an endocrinologist at Saint Louis University.

Dhindsa noted that the risk “really takes off” when levels of testosterone in the blood are below 200 nanograms per deciliter. The normal range is 300 to 1,000.

“This is independent of all other risk factors that we looked at: age, obesity or other health conditions,” Dhindsa said in the release. “But those people who were on therapy, their risk was normal.”

The study suggests, but doesn’t prove, that low testosterone is an independent risk factor for COVID hospitalization, similar to diabetes, heart disease and chronic lung disease. A clinical trial would be needed to prove this link between low-T and severe COVID-19.

Low testosterone levels can cause sexual dysfunction, depressed mood, irritability, difficulty with concentration and memory, fatigue, loss of muscular strength and reduced sense of well-being.

Some doctors treat the condition only if a man’s quality of life is diminished, because testosterone therapy may increase his risk for prostate cancer risk and heart disease.

“In the meantime, our study would suggest that it would be prudent to look at testosterone levels, especially in people who have symptoms of low testosterone, and then individualize care,” said Diwan, a cardiologist. “If they are at really high risk of cardiovascular events, then the doctor could engage the patient in a discussion of the pros and cons of hormone replacement therapy, and perhaps lowering the risk of COVID hospitalization could be on the list of potential benefits.”

The findings were published in JAMA Network Open.

Source: HealthDay

 

 

 

 

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For Women, Greater Exposure to Estrogen in Life May Protect Brain Regions That Are Vulnerable to Alzheimer’s

The drop in estrogen levels that occurs with menopause brings declines in the volumes of “gray matter,” the cellular matter of the brain, in key brain regions that are also affected in Alzheimer’s disease. But a new study from Weill Cornell Medicine researchers, in collaboration with the University of Arizona, suggests that greater cumulative exposure to estrogen in life, for example from having had more children or from having taken menopause hormone therapy, may counter this brain-shrinking effect.

The findings, reported in Neurology, come from an analysis of personal histories, MRI scans and cognitive tests on 99 women in their late 40s to late 50s. The researchers confirmed an earlier finding linking menopause to lower gray matter volume (GMV) in brain areas that are also vulnerable to Alzheimer’s. But they also linked indicators of higher overall estrogen exposure, such as a longer span of reproductive years (menarche to menopause), more children and the use of menopause hormone therapy and hormonal contraceptives, to higher GMV in some of these brain areas.

The study was an observational study rather than a clinical trial, but it adds to the evidence that estrogen may have a protective effect on the female brain, limiting the loss of gray matter that normally comes with menopause, and thereby potentially reducing Alzheimer’s risk.

“Our findings suggest that while the menopause transition may bring vulnerability for the female brain, other reproductive history events indicating greater estrogen exposure bring resilience instead,” said study senior author Dr. Lisa Mosconi, an associate professor of neuroscience in neurology at Weill Cornell Medicine and director of the Women’s Brain Initiative, and associate director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.

Researchers estimate that nearly two thirds of those living with Alzheimer’s in the United States are women. The higher prevalence of Alzheimer’s in women may be due in part to women’s greater longevity, among other reasons. A leading hypothesis is that that vulnerability relates to estrogen.

Receptors for estrogen molecules are found in cells throughout women’s brains, and the sex hormone has long been known not just to help steer brain development and behavior but also generally to have a nourishing and protecting role in the central nervous system. That protection doesn’t last forever, though. Estrogen levels decline steeply during the transition through menopause, and as recent research from Dr. Mosconi and others has shown, women tend to experience significant GMV loss during this transition.

The volume loss occurs especially in brain regions that are the most heavily affected in Alzheimer’s, and at roughly the same time of life when the long, slow process of late-onset Alzheimer’s is believed to start. Thus, women’s mid-life loss of estrogen may be a key factor behind the higher risk of Alzheimer’s.

The flip side of this hypothesis is that more estrogen, in particular a cumulatively greater estrogen exposure, could serve as a counter to the brain-weakening effect of menopause. That possibility is what Dr. Mosconi and her team sought to investigate in the new study.

The analysis covered 99 women aged 46-58 and a comparison group of 29 similarly aged men. It confirmed that the post-menopausal and peri-menopausal (starting menopause) women, compared with the pre-menopausal women and the men, had significantly lower GMV—adjusted for age and head size—in brain areas such as the hippocampus, entorhinal cortex and temporal lobe regions, which are heavily affected by Alzheimer’s.

By contrast, among the women, having more estrogen exposure as implied by various factors was associated with greater GMV in certain brain areas. Longer reproductive span, for example, was significantly linked to more GMV in a cluster of regions near the top of the brain including the superior parietal lobule and precuneus of the left hemisphere. Having had more children was significantly associated with more GMV in inferior and middle frontal gyri, and middle and inferior temporal gyri. Having used hormone replacement therapy was associated with more GMV in superior frontal gyrus and several other brain regions. All these brain regions are known to be affected by aging and Alzheimer’s.

The results support the idea that estrogen can be protective, the researchers say, and suggest that further investigation of the specific biological pathways underlying this effect could yield medical or lifestyle changes that help women reduce their risk of cognitive decline with aging as well as Alzheimer’s dementia risk.

“We’re hoping now to get further into the details of these links between estrogen and GMV, for example by comparing the effects of surgical menopause and spontaneous menopause, and by focusing specifically on certain types of estrogen exposure, such as menopause hormone therapy,” said study first author Eva Schelbaum, research assistant in Dr. Mosconi’s laboratory. “The goal as always is to understand why Alzheimer’s affects more women than men, and how we can reduce that risk.”

Source: Weill Cornell Medicine

Elevated Stress Hormones Linked to Higher Risk of High Blood Pressure and Heart Events

Adults with normal blood pressure and high levels of stress hormones were more likely to develop high blood pressure and experience cardiovascular events compared to those who had lower stress hormone levels, according to new research published today in Hypertension, an American Heart Association journal.

Studies have shown that cumulative exposure to daily stressors and exposure to traumatic stress can increase cardiovascular disease risk. A growing body of research refers to the mind-heart-body connection, which suggests a person’s mind can positively or negatively affect cardiovascular health, cardiovascular risk factors and risk for cardiovascular disease events, as well as cardiovascular prognosis over time.

“The stress hormones norepinephrine, epinephrine, dopamine and cortisol can increase with stress from life events, work, relationships, finances and more. And we confirmed that stress is a key factor contributing to the risk of hypertension and cardiovascular events,” said study author Kosuke Inoue, M.D., Ph.D., assistant professor of social epidemiology at Kyoto University in Kyoto, Japan. Inoue also is affiliated with the department of epidemiology at the Fielding School of Public Health at the University of California, Los Angeles.

“Previous research focused on the relationship between stress hormone levels and hypertension or cardiovascular events in patients with existing hypertension. However, studies looking at adults without hypertension were lacking,” Inoue said. “It is important to examine the impact of stress on adults in the general population because it provides new information about whether routine measurement of stress hormones needs to be considered to prevent hypertension and CVD events.”

Study subjects were part of the MESA Stress 1 study, a substudy of the Multi-Ethnic Study of Atherosclerosis (MESA), a large study of atherosclerosis risk factors among more than 6,000 men and women from six U.S. communities. As part of MESA exams 3 and 4 (conducted between July 2004 and October 2006), white, Black and Hispanic participants with normal blood pressure from the New York and Los Angeles sites were invited to participate in the substudy MESA Stress 1. In this substudy, researchers analyzed levels of norepinephrine, epinephrine, dopamine and cortisol – hormones that respond to stress levels. Hormone levels were measured in a 12-hour overnight urine test. The substudy included 412 adults ages 48 to 87 years. About half were female, 54% were Hispanic, 22% were Black and 24% were white.

Participants were followed for three more visits (between September 2005 and June 2018) for development of hypertension and cardiovascular events such as chest pain, the need for an artery-opening procedure, or having a heart attack or stroke.

Norepinephrine, epinephrine and dopamine are molecules known as catecholamines that maintain stability throughout the autonomic nervous system—the system that regulates involuntary body functions such as heart rate, blood pressure and breathing. Cortisol is a steroid hormone released when one experiences stress and is regulated by the hypothalamic-pituitary-adrenal axis, which modulates stress response.

“Although all of these hormones are produced in the adrenal gland, they have different roles and mechanisms to influence the cardiovascular system, so it is important to study their relationship with hypertension and cardiovascular events, individually,” Inoue said.

Their analysis of the relationship between stress hormones and development of atherosclerosis found:

• Over a median of 6.5-year follow-up period, every time the levels of the four stress hormones doubled was associated with a 21-31% increase in the risk of developing hypertension.
• During a median of 11.2-years of follow-up, there was a 90% increased risk of cardiovascular events with each doubling of cortisol levels. There was no association between cardiovascular events and catecholamines.

“It is challenging to study psychosocial stress since it is personal, and its impact varies for each individual. In this research, we used a noninvasive measure — a single urine test — to determine whether such stress might help identify people in need of additional screening to prevent hypertension and possibly cardiovascular events,” Inoue said.

“The next key research question is whether and in which populations increased testing of stress hormones could be helpful. Currently, these hormones are measured only when hypertension with an underlying cause or other related diseases are suspected. However, if additional screening could help prevent hypertension and cardiovascular events, we may want to measure these hormone levels more frequently.”

A limitation of the study is that it did not include people who had hypertension at the study’s start, which would have resulted in a larger study population. Another limitation is that researchers measured stress hormones via a urine test only, and no other tests for stress hormone measurement were used.

Source: American Heart Association

Does Testosterone Influence Success? Not Much, Research Suggests

It is already known that in men testosterone is linked with socioeconomic position, such as income or educational qualifications. Researchers from the University of Bristol’s Population Health Sciences (PHS) and MRC Integrated Epidemiology Unit (IEU) wanted to find out whether this is because testosterone actually affects socioeconomic position, as opposed to socioeconomic circumstances affecting testosterone, or health affecting both. The findings are published in Science Advances.

To isolate effects of testosterone itself, the research team applied an approach called Mendelian randomization in a sample of 306,248 UK adults from UK Biobank. They explored testosterone’s influence on socioeconomic position, including income, employment status, neighbourhood-level deprivation, and educational qualifications; on health, including self-rated health and BMI, and on risk-taking behaviour.

Dr Amanda Hughes, Senior Research Associate in Epidemiology in Bristol Medical School: Population Health Sciences (PHS), said: “There’s a widespread belief that a person’s testosterone can affect where they end up in life. Our results suggest that, despite a lot of mythology surrounding testosterone, its social implications may have been over-stated.”

First, the team identified genetic variants linked to higher testosterone levels and then investigated how these variants were related to the outcomes. A person’s genetic code is determined before birth, and generally does not change during their lifetime (there are rare exceptions, such as changes that occur with cancer). This makes it very unlikely that these variants are affected by socioeconomic circumstances, health, or other environmental factors during a person’s lifetime. Consequently, any association of an outcome with variants linked to testosterone would strongly suggest an influence of testosterone on the outcome.

Similar to previous studies the research found that men with higher testosterone had higher household income, lived in less deprived areas, and were more likely to have a university degree and a skilled job. In women, higher testosterone was linked to lower socioeconomic position, including lower household income, living in a more deprived area, and lower chance of having a university degree. Consistent with previous evidence, higher testosterone was associated with better health for men and poorer health for women, and greater risk-taking behaviour for men.

In contrast, there was little evidence that the testosterone-linked genetic variants were associated with any outcome for men or women. The research team concluded that there is little evidence that testosterone meaningfully affected socioeconomic position, health, or risk-taking in men or women. The study suggests that – despite the mythology surrounding testosterone – it might be much less important than previously claimed.

Results for women were less precise than results for men, so the influence of testosterone in women could be studied in more detail in the future using larger samples.

Dr Hughes added: “Higher testosterone in men has previously been linked to various kinds of social success. A study of male executives found that testosterone was higher for those who had more subordinates. A study of male financial traders found that higher testosterone correlated with greater daily profits. Other studies have reported that testosterone is higher for more highly educated men, and among self-employed men, suggesting a link with entrepreneurship.

“Such research has supported the widespread idea that testosterone can influence success by affecting behaviour. There is evidence from experiments that testosterone can make a person more assertive or more likely to take risks – traits which can be rewarded in the labour market, for instance during wage negotiations. But there are other explanations. For example, a link between higher testosterone and success might simply reflect an influence of good health on both. Alternatively, socioeconomic circumstances could affect testosterone levels. A person’s perception of their own success could influence testosterone: in studies of sports matches, testosterone has been found to rise in the winner compared to the loser.”

Source: University of Bristol

Close Monitoring for Heart Risk Needed if Breast, Prostate Cancer Treatment Includes Hormones

The hormonal therapies used to treat many breast and prostate cancers raise the risk of a heart attack and stroke, and patients should be monitored regularly and receive treatment to reduce risk and detect problems as they occur, according to a new American Heart Association scientific statement, published today in the Association’s journal Circulation: Genomic and Precision Medicine.

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” said Tochi M. Okwuosa, D.O., FAHA, chair of the scientific statement writing group, an associate professor of medicine and cardiology and director of Cardio-Oncology Services at Rush University Medical Center in Chicago.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common cancers in the United States and worldwide not including skin cancers. As improvements in treatment – including increased use of hormonal therapies – allow people with these cancers to live longer, cardiovascular disease has emerged as a leading cause of illness and death in these patients.

Hormonal treatments for breast cancer include selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). SERMs block estrogen receptors in cancer cells so the hormone can’t spur tumor growth, while letting estrogen act normally in other tissues such as bone and liver tissue; examples of SERMs include tamoxifen and raloxifene. Aromatase inhibitors lower the amount of estrogen produced in post-menopausal women and include exemestane, anastrozole and letrozole. Endocrine treatments for prostate cancer, called androgen deprivation therapy, include some medications that decrease production of testosterone by their action on the brain and others that block testosterone receptors found in prostate cells and some prostate cancer cells.

The writing group reviewed existing evidence from observational studies and randomized controlled trials and found that:

• Tamoxifen increases the risk of blood clots, while aromatase inhibitors increase the risk of heart attack and stroke more than tamoxifen. For breast cancer patients who require more than one type of hormonal therapy because of developed resistance to the initial medication, , there is an improvement in cancer outcomes. However, treatment with multiple hormones is associated with higher rates of cardiovascular conditions such as high blood pressure, abnormal heart rhythms and blood clots.
• Androgen deprivation therapy (to reduce testosterone) for prostate cancer increases cholesterol and triglyceride levels, adds body fat while decreasing muscle and impairs the body’s ability to process glucose (which may result in type 2 diabetes). These metabolic changes are associated with a greater risk of heart attacks, strokes, heart failure and cardiovascular death.
• The longer people receive hormonal therapy, the greater the increased risk of cardiovascular problems. Further research is required to better define the risks associated with duration of treatment.
• The hormonal therapy-associated increase in CVD risk was highest in people who already had heart disease or those who had two or more cardiovascular risk factors – such as high blood pressure, obesity, high cholesterol, smoking or a family history of heart disease or stroke – when they began treatment.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietician, endocrinologist and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” Okwuosa said.

There are currently no definitive guidelines for monitoring and managing hormonal therapy-related heart risks. The statement calls for clinicians to be alert for worsening heart problems in those with prior heart disease or risk factors, and to recognize that even those without pre-existing heart problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Okwuosa said.

The statement also calls for additional research in several areas, including:

• Further evaluation of racial and ethnic disparities among breast and prostate cancer patients who have received hormone therapy. In the few studies that exist, racial and ethnic differences detected may be related to health inequities and other factors, and these are important areas to address.
• Heart disease and stroke outcomes and risks should be added as primary endpoints in randomized trials of hormonal therapies.
• Studies of specific hormonal medications are needed since each one may have different heart risks even if they work in the same way to treat breast or prostate cancer.

Source: American Heart Association