Thyroid Hormone Use May Raise Death Risk in Older Adults

Thyroid hormone replacement therapy in older adults is associated with a higher risk of death compared with no treatment, a large study finds. The study results were accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

When people have too little thyroid hormone, called hypothyroidism, they usually require lifelong treatment with levothyroxine to supplement the body’s thyroid hormone, thyroxine (T4). Some people have subclinical hypothyroidism, which occurs when the thyroid gland needs more stimulation to produce adequate thyroid hormone levels. These individuals will have modest elevations in thyroid-stimulating hormone (TSH), which stimulates thyroid hormone production.

Subclinical hypothyroidism is a mild or early form of thyroid disease, and these patients also routinely receive thyroid hormone replacement, said the study’s principal investigator, Jennifer Mammen, M.D., Ph.D., an assistant professor at Johns Hopkins University in Baltimore, Md. However, Mammen notes that this interpretation of high TSH with normal T4 levels may not be correct in all older adults.

“Many older adults have an elevation in TSH with normal thyroid levels. Our earlier research showed that this can reflect developing hypothyroidism in some, while in others, it is a form of adaptation to age-related changes in health instead of thyroid disease,” Mammen said. “As a result, some of these older people may be receiving inappropriate or excessive thyroid hormone therapy, treatment that may counteract important adaptations needed for healthy aging.”

The researchers studied the effects of levothyroxine therapy on survival in adults ages 65 and older. They used data from 1,054 participants of the Baltimore Longitudinal Study of Aging, a long-running observational study from the National Institute on Aging. All participants had at least one TSH and T4 measurement since 2003. Mammen’s research team looked at the risk of dying during one-year intervals from 2003 to 2018 and adjusted their statistical analyses for multiple demographic and health factors that may influence survival.

They found that among older adults, use of thyroid hormone increased risk of death 60% year over year (hazard ratio 1.6). They also limited the analysis to compare individuals with normal TSH levels, reflecting normal thyroid function, to those on thyroid hormone with normal TSH levels, who were therefore treated to target, and found those on treatment had almost double the risk of dying compared with untreated persons (hazard risk 1.9), Mammen reported.

Despite studies showing that hormone treatment of an isolated high TSH may not benefit older people, Mammen said, “we were surprised that we were able to demonstrate harm associated with thyroid hormone supplementation. Our work supports the growing calls to use age-specific TSH reference intervals to determine the threshold for thyroid hormone treatment.”

Mammen also recommended repeating testing after finding an isolated elevation of TSH in older adults, because levels can fluctuate. “We advocate being cautious and conservative when considering thyroid hormone treatment,” she said.

Source: Endocrine Society

High Testosterone Levels Have Different Health Impact for Men and Women

Steven Reinberg wrote . . . . . . . . .

High levels of the sex hormone testosterone may trigger different health problems in men and women, a new study reveals.

In women, testosterone may increase the risk for type 2 diabetes, while in men it lowers that risk. But high levels of testosterone increase the risk for breast and endometrial cancer in women and prostate cancer in men, the researchers reported.

“Our findings provide unique insights into the disease impacts of testosterone. In particular, they emphasize the importance of considering men and women separately in studies, as we saw opposite effects for testosterone on diabetes,” said lead researcher Katherine Ruth, of the University of Exeter in the United Kingdom.

“Caution is needed in using our results to justify use of testosterone supplements until we can do similar studies of testosterone with other diseases, especially cardiovascular disease,” Ruth explained in a University of Cambridge news release.

Dr. Joel Zonszein, an emeritus professor of medicine at Albert Einstein College of Medicine in New York City, said there is a “sweet spot” of normal values for men and women. “Too much is not good, and too little is also bad,” he explained.

“Testosterone supplementation is widely used in both men and women with normal values with no good evidence of benefit. Testosterone replacement in truly deficient individuals is something else,” said Zonszein, who had no role in the study.

For the study, British researchers collected genetic data on more than 425,000 men and women listed in the UK Biobank. The investigators found more than 2,500 genetic variations associated with levels of testosterone and the protein that binds it — sex hormone-binding globulin.

The researchers checked their results with analyses of other relevant studies and used a randomization method to see if associations between testosterone and disease are causal.

In women, a high level of testosterone was tied to a 37% increased risk for type 2 diabetes and a 51% increased risk for polycystic ovary syndrome.

In men, however, a high testosterone level was linked to a 14% lower risk of developing type 2 diabetes, the findings showed.

“The findings in men that higher testosterone has a protective effect and reduces the risk of type 2 diabetes is news to me,” Zonszein said. “This needs to be shown by other studies and its mechanism needs to be elucidated.”

Dr. Minisha Sood, an endocrinologist at Lenox Hill Hospital in New York City, said that testosterone may not be as protective in women because it converts to estradiol, which is related to the risk for breast cancer.

“High levels of testosterone in women have also been shown to increase visceral fat, which is linked to the components of metabolic syndrome,” Sood said.

That men with high testosterone are at lower risk of developing type 2 diabetes is likely related to having more lean muscle mass, which improves insulin sensitivity and reduces the likelihood of type 2 diabetes, she said.

But Sood isn’t a fan of men using testosterone supplements to ward off diabetes.

“Testosterone therapy comes with potential risks, including a high red blood cell count and higher rates of high-grade prostate cancer if a man is already predisposed to develop prostate cancer,” she said.

Obese men or those with type 2 diabetes would benefit more from lifestyle changes to improve testosterone levels, namely, weight loss, healthy diet and exercise.

“This approach is preferred in that population over testosterone replacement whenever possible,” Sood said.

The report was published in the journal Nature Medicine.

Source: HealthDay


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Testosterone Supplements Won’t Help Most Men, Doctors’ Group Says

Amy Norton wrote . . . . . . . . .

Testosterone therapy is no fountain of youth for older men, though it might help some who are impotent.

That’s according to new guidelines from the American College of Physicians — the first from the group to address the issue of treating age-related “low T.”

It’s known that men’s testosterone levels decline with age. And for years industry has promoted the idea that men suffer a range of symptoms caused by what’s sometimes described as “male menopause.” The list includes fatigue, weakness, muscle loss, dulled memory and thinking, depression, and dampened libido and erectile dysfunction.

Yet for nearly all of those problems, there is no good evidence testosterone therapy helps, the college found in a research review.

The only area where there is some benefit, the group says, is in treating sexual dysfunction. On average, studies have found “small improvements” in sexual and erectile function.

The lackluster performance in clinical trials is “a bit surprising,” said ACP president Dr. Robert McLean. But, he pointed out, the fact that testosterone wanes with age does not automatically mean that’s behind men’s health issues. And that means replacing testosterone will not necessarily help.

That never stopped manufacturers of supplemental testosterone, however. For years, they launched aggressive marketing campaigns warning men of the health effects of age-related declines of the male hormone.

Between 2009 and 2013, the number of U.S. men on testosterone shot up from 1.3 million to 2.3 million, according to the U.S. Food and Drug Administration. And most, the agency said, were not using it for an established indication — namely, certain medical conditions that cause testosterone deficiency.

Instead, they were using it to counter the aging process.

The tide has turned in more recent years. One study found that Americans’ testosterone use dropped substantially between 2013 and 2016 after questions were raised about the risks of heart disease or prostate cancer.

“The enthusiasm for it is less than it used to be,” said Dr. Victor Adlin, an endocrinologist from the Lewis Katz School of Medicine at Temple University in Philadelphia.

Still, it remains something men ask about, Adlin said. He wrote an editorial published with the guidelines Jan. 7 in the Annals of Internal Medicine.

Two other medical groups — the Endocrine Society and the American Urological Association — have guidelines on treating age-related low testosterone, Adlin said. And they agree with the ACP on the central point: Testosterone might help some men with sexual dysfunction, but it should not be prescribed for vague symptoms like fatigue and low energy.

The ACP recommends trying injection testosterone over patches or other skin preparations. Both methods are similarly effective, McLean said, but injection therapy is far cheaper: $156 per year, versus $2,135, based on Medicare claims.

As for safety, the overall evidence from 20 studies suggests that testosterone does not raise the risks of heart problems, blood clots or prostate cancer, McLean said. Those studies followed men for up to 10 years, he added, so it’s not possible to say what the risks are beyond that.

How can men with sexual dysfunction know if they do, in fact, have low testosterone? Blood levels of the hormone should be measured on two separate days to confirm the results, Adlin said. And both should be done in the morning, he added. Testosterone levels fluctuate and are typically highest early in the day.

“If you have confirmed low levels, and your sexual symptoms are bothersome enough to need treatment, it’s reasonable to start testosterone,” Adlin said. “But don’t start it and forget it.”

The ACP says men should have their symptoms reevaluated within a year — and if they are not better, stop using testosterone. Adlin said the six-month mark can be a good time for that check-in.

Low testosterone is very common among older men, according to the ACP. It’s seen in 20% of U.S. men over age 60, 30% of those over age 70, and half of men older than 80.

But based on the evidence, only select men will gain any benefit from taking testosterone.

“It is not a fountain of youth,” McLean said.

Source: HealthDay


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Study: New Findings on Postmenopausal Hormone Replacement Therapy

Amy Norton wrote . . . . . . . . .

The ongoing debate about postmenopausal hormone therapy and breast cancer risk may have turned even more muddy: A large, new study suggests that two different types of hormone therapy have opposite effects on women’s long-term risk of the disease.

The researchers found that combined hormone replacement therapy (HRT) — with estrogen and progestin — increases the risk of breast cancer, with effects that last for years after women discontinue the therapy.

On the other hand, women who take estrogen alone appear to have an equally long-lasting decrease in their breast cancer risk.

The findings come from a long-term follow-up of the Women’s Health Initiative (WHI) — a major U.S. government-funded project begun in the 1990s that tested the health effects of hormone replacement therapy. One trial randomly assigned over 16,000 women aged 50 to 79 to take either combined HRT or placebo pills. The other involved close to 11,000 women the same age who were given either estrogen therapy alone or placebos.

Before the WHI, doctors had thought that menopausal hormone therapy — which helps control hot flashes — had other health benefits, including a lower risk of heart disease.

But the initial findings from the WHI made waves when they instead uncovered higher disease risks: Combined HRT raised women’s odds of developing heart disease, stroke, blood clots and breast cancer.

The picture was different with estrogen-only therapy: It raised the risk of blood clots and stroke, but did not increase heart risks. In addition, it seemed to lower the odds of developing breast cancer.

But only certain women can take estrogen-only therapy, namely, those who’ve had a hysterectomy, since using estrogen by itself raises the risk of uterine cancer.

As if that weren’t complicated enough, things have gotten murkier over the years. A number of observational studies — which followed women in the “real world” who opted for hormone therapy or not — have found that estrogen-only therapy is associated with a higher breast cancer risk.

Enter these latest findings from the WHI. They show that for years after stopping combined HRT, women continue to face an increased risk of breast cancer. Meanwhile, the reduced risk seen with estrogen-only therapy also continued.

“So, who’s right? This big clinical trial or those large observational studies?” asked Dr. Rowan Chlebowski, the lead researcher on the new analysis.

Unfortunately, there is no clear answer, according to Chlebowski, chief of medical oncology at Harbor-UCLA Medical Center, in Los Angeles.

He is to present the findings Friday at the annual San Antonio Breast Cancer Symposium. Such research is considered preliminary until published in a peer-reviewed journal.

“Overall,” Chlebowski said, “this information suggests that combined HRT is a little worse than we’d thought, and estrogen alone is probably a little safer than we’d thought.”

Trial participants on combined HRT typically used it for about five years. Over 18 years of follow-up, those women were 29% more likely to develop breast cancer.

Women on estrogen-only typically used it for seven years. Over 16 years, they were 23% less likely to be diagnosed with breast cancer, the findings showed.

So what does it all mean? Given the overall body of evidence, experts have long advised women against using hormone therapy to prevent any disease.

And that advice still stands, Chlebowski said.

“You should not use hormone therapy to lower chronic disease risks,” he said. “If your menopausal hot flashes are bad enough that you want to try hormone therapy, talk with your doctor about the benefits and risks to you.”

Susan Brown is senior director of education and patient support at the nonprofit Susan G. Komen. The new findings give women another piece of information “to make informed decisions about their health,” she agreed.

“Large population studies are needed to understand the complex impact menopausal hormone therapy has on breast cancer risk and incidence,” Brown said. “We’re encouraged to see the results of research like this.”

Source: HealthDay


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High Levels of Two Hormones in the Blood Raise Prostate Cancer Risk

Men with higher levels of ‘free’ testosterone and a growth hormone in their blood are more likely to be diagnosed with prostate cancer, according to research presented at the 2019 NCRI Cancer Conference.

Other factors such as older age, ethnicity and a family history of the disease are already known to increase a man’s risk of developing prostate cancer.

However, the new study of more than 200,000 men is one of the first to show strong evidence of two factors that could possibly be modified to reduce prostate cancer risk.

The research was led by Dr Ruth Travis, an Associate Professor, and Ellie Watts, a Research Fellow, both based at the University of Oxford, UK. Dr Travis said: “Prostate cancer is the second most commonly diagnosed cancer in men worldwide after lung cancer and a leading cause of cancer death. But there is no evidence-based advice that we can give to men to reduce their risk.

“We were interested in studying the levels of two hormones circulating in the blood because previous research suggests they could be linked with prostate cancer and because these are factors that could potentially be altered in an attempt to reduce prostate cancer risk.”

The researchers studied 200,452 men who are part of the UK Biobank project. All were free of cancer when they joined the study and were not taking any hormone therapy.

The men gave blood samples that were tested for their levels of testosterone and a growth hormone called insulin-like growth factor-I (IGF-I). The researchers calculated levels of free testosterone – testosterone that is circulating in the blood and not bound to any other molecule and can therefore have an effect in the body. A subset of 9,000 of men gave a second blood sample at a later date, to help the researchers account for natural fluctuations in hormone levels.

The men were followed for an average of six to seven years to see if they went on to develop prostate cancer. Within the group, there were 5,412 cases and 296 deaths from the disease.

The researchers found that men with higher concentrations of the two hormones in their blood were more likely to be diagnosed with prostate cancer. For every increase of five nanomoles in the concentration of IGF-I per litre of blood (5 nmol/L), men were 9% more likely to develop prostate cancer. For every increase of 50 picomoles of ‘free’ testosterone per litre of blood (50 pmol/L), there was a 10% increase in prostate cancer risk.

Looking at the population as a whole, the researchers say their findings correspond to a 25% greater risk in men who have the highest levels of IGF-I, compared to those with the lowest. Men with the highest ‘free’ testosterone levels face a 18% greater risk of prostate cancer, compared to those with the lowest levels.

The researchers say that because the blood tests were taken some years before the prostate cancer developed, it is likely that the hormone levels are leading to the increased risk of prostate cancer, as opposed to the cancers leading to higher levels of the hormones. Thanks to the large size of the study, the researchers were also able to take account of other factors that can influence cancer risk, including body size, socioeconomic status and diabetes.

Dr Travis said: “This type of study can’t tell us why these factors are linked, but we know that testosterone plays a role in the normal growth and function of the prostate and that IGF-I has a role in stimulating the growth of cells in our bodies.”

“What this research does tell us is that these two hormones could be a mechanism that links things like diet, lifestyle and body size with the risk of prostate cancer. This takes us a step closer to strategies for preventing the disease.”

Dr Travis and Ms Watts will continue examining the data from this study to confirm their findings. In the future, they also plan to home in on risk factors for the most aggressive types of prostate cancer.

Professor Hashim Ahmed, chair of NCRI’s prostate group and Professor of Urology at Imperial College London, who was not involved in the research said: “These results are important because they show that there are at least some factors that influence prostate cancer risk that can potentially be altered. In the longer term, it could mean that we can give men better advice on how to take steps to reduce their own risk.

“This study also shows the importance of carrying out very large studies, which are only possible thanks to the thousands of men who agreed to take part.”

Source: National Cancer Research Institute


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