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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Major Study Gives Women More Guidance on Hormone Therapy During Menopause

Women who receive hormone therapy to help ease menopausal symptoms have an increased risk of breast cancer, which can persist long after they stop the therapy, a new study confirms.

The new review — which included data from 58 studies involving nearly 109,000 women from around the world — is the latest chapter in the ongoing story of these hormone therapies.

“Since the Women’s Health Initiative [study] identified in 2002 that women who took hormone replacement therapy were at an increased risk for the development of breast cancer, we have seen a marked decline in their use,” noted Dr. Lauren Cassell, a breast surgeon at Lenox Hill Hospital in New York City. She wasn’t involved in the new report.

“Patients who were on hormone replacement went off them [after the 2002 study], and physicians were more cautious in prescribing them,” Cassell said.

The new report, published Aug. 29 in The Lancet, “again reinforces that known increased risk, but more importantly, it identifies that the risk persists even after the therapy is stopped, and is affected by the length of time that the patient takes hormone replacement,” Cassell said.

The new analysis was performed by a global team of experts known as the Collaborative Group on Hormonal Factors in Breast Cancer. They pored over data from 58 studies conducted worldwide between 1992 and 2018. These studies included nearly 109,000 women with breast cancer, with an average age of 65 at diagnosis.

Half of the women had received hormone therapy for menopause, the researchers noted. The average age at menopause was 50 and the average age at starting hormone therapy was also 50. Women took hormone therapy for an average of 10 years, in current users, and for seven years in past users, the team said.

For women of average weight living in Western countries who have never used hormone therapy, the average risk of developing breast cancer between ages 50 to 69 was about 6.3 per 100 women, according to the study.

However, the risk rose for women who received hormone therapy, and the formulation used seemed key to an uptick in risk.

For example, for women who took treatments involving estrogen plus daily progestogen for five years, the rate of breast cancer was 8.3 per every 100 women. It was slightly lower for women taking estrogen plus intermittent progestogen — 7.7 per 100.

The rate was lower — but still elevated — for women who used an estrogen-only therapy: 6.8 cases per 100, the findings showed.

Duration of use mattered, as well. The rise in breast cancer risk was about twice as high for women who used hormone therapy for 10 years rather than five years, the study found.

Conversely, there was little increased risk of breast cancer after using any form of hormone therapy for less than a year, the researchers said.

One major finding was just how long hormone therapies left their mark for women who used the treatment for five years; any elevation in breast cancer risk didn’t fully subside until 15 years after stopping the therapy.

The findings suggest that all types of hormone therapy for menopause — with the exception of topical vaginal estrogens — are associated with an increased risk of breast cancer, the study authors said.

“Our new findings indicate that some increased risk persists even after stopping use of menopausal hormone therapy,” study co-author Valerie Beral, a professor at the University of Oxford in England, said in a journal news release.

The use of hormone therapy for menopause rose sharply in the 1990s, fell by half in the early 2000s and stabilized in the 2010s. Currently, there are about 12 million users in Western countries — about 6 million in North America and 6 million in Europe.

Ten years of use was once common, but about five years of use is now more likely, the researchers said.

Dr. Alice Police directs breast surgery at Northwell Health Cancer Institute in Sleepy Hollow, N.Y. Looking over the study, she said that as time goes by, research like this is giving women better guidelines on what is or is not safe when it comes to hormonal therapies.

For example, “we now know that topical vaginal creams do not increase the risk of breast cancer as they mostly work locally and absorption is minimal. This is great news for many women who depend on these therapies to prevent UTIs [urinary tract infections] and vaginal dryness,” Police said.

“We also know which medications, in what combinations, are the most dangerous,” she added. “For example, estrogen alone is safer than estrogen and progesterone together.”

For her part, Cassell said that, going forward, “oral hormone replacement therapy should be prescribed judiciously for patients who are having intolerable symptoms of menopause and understand the increased risk for breast cancer.”

That means, “the use of progesterone should be minimized and the length of the hormone replacement should be as short as possible,” Cassell said.

Source: HealthDay


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Testosterone Therapy May Threaten the Heart

Taking testosterone might sound like a good idea for an older man, but a new study suggests the treatment might be bad news for his heart.

Men who took it showed a slightly increased risk of heart attack and stroke in the first few years.

“Our findings show that the use of [testosterone therapy] was associated with an increased risk of stroke, TIAs [mini-strokes], or cardiac arrest during the first two years of use,” said study author Dr. Christel Renoux. She is from the departments of epidemiology, biostatistics, and occupational health, and the department of neurology and neurosurgery at McGill University in Montreal.

“There is limited evidence on the long-term clinical benefits of [testosterone therapy] to effectively treat the modestly declining levels of [natural] testosterone levels of aging but healthy men,” Renoux said. “We strongly recommend that clinicians proceed with caution when considering prescribing [testosterone therapy] and first discuss both the potential benefits and risks with patients.”

The team analyzed data from about 15,400 British men, aged 45 and older, with age-related low testosterone levels.

Those who took testosterone replacement therapy had a 21% higher risk of cardiovascular events such as heart attack, stroke or mini-stroke than those who did not take the therapy. That increased risk translated into 128 more cardiovascular events.

However, the increased risk declined after two years of testosterone treatment, according to the study published recently in The American Journal of Medicine.

Further studies should be conducted to confirm this study’s findings, Renoux recommended.

“Until such time, the potential cardiovascular risk of [testosterone therapy] should be weighed against the perceived and expected benefits among aging men,” she said in a journal news release.

While reported rates of low testosterone have remained stable, prescriptions for testosterone replacement therapy have soared in the last 20 years.

Increasingly, testosterone replacement therapy is prescribed to treat general symptoms of aging, including fatigue and slight declines in sexual functioning.

One of the other study findings was that current use of testosterone replacement therapy was associated with a lower risk of death from any cause, while past use was associated with an increased risk.

While this suggests that testosterone replacement therapy may reduce the risk of death, it could also be because doctors halt the therapy in men with declining health, the researchers noted.

Source: HealthDay


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Testosterone: the Sex Hormone that Affects both Men and Women

Anthea Rowan wrote . . . . . . . . .

The sex hormone testosterone plays important roles in health and disease. We talked to experts and studied recent research findings to dispel some common misconceptions about the hormone that is vital in reproductive activity.

Only men make testosterone

No. Both men and women do.

Testosterone is an androgen hormone, which means it stimulates the development of male characteristics. Women with small breasts and narrow hips are often called “androgenous”.

The hormone is made in the testes of men and the ovaries of women, and in the adrenal glands, located above the kidneys, in small quantities in both men and women. Normal levels for women are 5 to 7 per cent of those for men.

Total testosterone levels vary throughout the day. They are highest in the morning and lower towards the end of the day. In healthy adult men, levels would be around 240 to 950 nanograms per decilitre, and 8 to 60 ng/dl in women.

Women whose levels are too high may develop facial hair, some balding and acne.

Taking testosterone supplements makes men more virile

No. It may make their muscles pop, but it also makes their testes shrivel – called “testicular atrophy” – which makes them less fertile.

“Taking testosterone is almost male contraception,” says Dr Brian Levine, a director at CCRM New York Fertility Clinic.

High doses of testosterone decrease a man’s sperm count significantly, he explains. This is because the more the brain senses testosterone in the blood, the less it signals for the testes to produce more on their own.

Testosterone promotes fertility in women

Yes – oddly, and in a roundabout way, because it affects egg development, according to research by the University of Rochester Medical Centre in New York.

It is believed that testosterone prevents the premature “death” of the egg at an early stage of development. That’s because testosterone in the ovaries may help make follicles more sensitive to the hormone FSH – follicle-stimulating hormone – that helps to mature ovulated eggs. Clever huh?

Testosterone develops muscle mass in women

Yes. If it does in men, of course it’s going to in women, too.

Men produce more testosterone, so their muscle mass is going to be greater. But one of the reasons muscle mass in women begins to decline with the menopause is because of declining testosterone.

And while we’re on testosterone and muscle mass in men – many body builders shave their heads to replicate the baldness associated with high testosterone counts.

Very high testosterone levels in men lead to baldness, ergo bald men are more virile

Yes, this is true – but only in part. Dihydrotestosterone, or DHT, is a derivative of testosterone and is found in skin, hair follicles and the prostate. It’s the actions of DHT and the sensitivity of hair follicles to it that leads to hair loss.

Oddly, a man can have low levels of testosterone in his system but too much DHT. So the adage that a bald man is a virile one because of high levels of testosterone is potentially both true and false.

Is there really a male menopause?

Yes – the “manopause” really is a thing, though it is technically an “andropause” rather than a menopause and may be experienced by men starting around the age of 40.

Just as in women, it’s all about hormone decline; for men, it’s due to a slow drop in testosterone levels. And just as with menopause in women, there may be physiological manifestations: loss of bone mass, loss of muscle mass, tendency to expanding waistlines, plummeting libidos, anxiety, depression and insomnia. But not the hot flushes.

Keeping fit and not smoking may help delay andropause, or make it less acutely felt. Most men manage perfectly well – it’s a natural part of human ageing after all – even if women dismiss grumpy partners as having a midlife crisis and “manopausal”.

But men who suffer with very low moods or erectile dysfunction should see their doctors; there are good treatment options available just as there is HRT for women.

Testosterone turns us all on

Yes. It does. Even women.

The link between testosterone and our sex drive is well known. Although there is some research to suggest extra testosterone may improve sexual function in some women – especially post-menopause when women may be prescribed testosterone creams or gels to apply to the skin – the jury is still out on this.

“Having less testosterone can have three effects that women notice,” says Hong Kong-based Dr Sue Jamieson. “This may be less sex drive, generally low energy levels, and also muscle mass. Some women notice that even though they exercise to the same extent, the muscles become more flabby and less firm.”

Testosterone can boost a woman’s libido because it targets receptors in the brain responsible for sexual activity. But there are risks associated with synthetically adding testosterone post-menopause, and it won’t make any difference if there aren’t other positive things going on – good relationships and good health, for a start.

Women in love have more testosterone, which is handy when kick-starting a new relationship. Strangely, the opposite is true for men; single men or those with a long-term partner have more than the recently hooked-up.

Men have a higher pain threshold because of testosterone

Apparently they do. Studies suggest that the female hormone oestrogen may lower a person’s pain threshold whereas testosterone appears to make people more pain tolerant. This does not explain, however, how women manage to endure childbirth while attendant fathers faint…

Testosterone is why men can read maps and women can read moods

It’s true. Testosterone is good for the memory and particularly associated with spatial intelligence. Empathy, though, is all about being able to read people well (and then, often, being able to react sensitively). Higher testosterone levels make for interpreting body language less fluently.

Fat can lower testosterone and testosterone can lower fat

Fat men tend to have lower testosterone levels than leaner ones, possibly because obesity promotes a state of widespread inflammation in the body and the downing of tools in the testosterone factory.

Upping a man’s testosterone levels may help men drop the spare tyre – not that it’s advocated as a dietary technique.

Source: SCMP


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Hormone Treatment for Prostate Cancer Linked to Heightened Alzheimer’s Risk

E.J. Mundell wrote . . . . . . . . .

Soon after a man is diagnosed with prostate cancer, drugs that lower levels of testosterone are often offered as treatment, since testosterone fuels the cancer’s growth.

But a major new study suggests that this approach might have an unwanted side effect: Higher odds for Alzheimer’s disease and other dementias.

“Our results suggest that clinicians need to raise their awareness about potential long-term cognitive effects of hormone therapy and discuss these risks with their patients,” said study author Ravishankar Jayadevappa.

He’s a research associate professor of geriatrics at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.

One expert said it does raise troubling questions.

“Most of us are becoming as afraid of getting Alzheimer’s as we are of getting cancer,” said Dr. Elizabeth Kavaler, a urology specialist at Lenox Hill Hospital in New York City. “When a study pits one debilitating condition against another, it instills fear in patients.”

But the treatment — called androgen-deprivation therapy — remains the “gold standard” for many cases of prostate cancer, according to Kavaler. Therefore, the new data means “tough decision-making” for patients and their physicians, she said.

In the new study, Jayadevappa’s group took a look back at U.S. National Cancer Institute data on over 154,000 prostate cancer patients who were diagnosed between 1996 and 2003. About 62,000 received hormone-depleting therapy within two years of their diagnosis, while about 92,000 did not.

In total, 13% of men who had received the therapy went on to develop Alzheimer’s disease over eight years of follow-up, compared to 9% who hadn’t gotten the treatment, the study found. According to the researchers, the lifetime prevalence of Alzheimer’s disease in men generally is about 12%.

When the team looked at diagnoses of all forms of dementia, 22% of those who’d received the therapy received such a diagnosis, compared to 16% of those who hadn’t undergone hormonal therapy.

Jayadevappa’s team noted that earlier, smaller studies have found similar trends.

However, “to our knowledge, this is one of the largest studies to date examining this association, and it followed patients for an average of eight years after their prostate cancer diagnosis,” he said in a university news release.

As the researchers noted, androgen-deprivation therapy is an effective means of slowing the progress of prostate cancers. However, it is now typically only used in cases of advanced disease, or cases where the chances of a tumor recurrence are high.

The approach also has other deleterious side effects, including impaired sexual function, and potential harm to bones and cardiovascular health.

The study also can only point to an association between hormonal treatment and raised odds for dementia, it cannot prove cause and effect. But Jayadevappa’s team noted that they tried to account for other factors, such as age, the presence of other medical conditions and the severity of the prostate cancer.

Dr. Maria Torroella Carney is chief of geriatric and palliative medicine at Northwell Health in New Hyde Park, N.Y. Looking over the findings, she said they warrant further study, but it’s not time for men who’ve gotten hormonal therapy to panic.

Carney stressed that the study couldn’t prove cause and effect, and other factors might account for the higher risk of dementia.

Men receiving hormonal therapy tended to be “older, sicker and had more advanced prostate cancer,” Carney noted, and sicker patients already have higher odds of dementia.

In addition, the study didn’t reveal whether or not men who got the therapy lived longer than those who didn’t. If they did live longer, their odds of dementia would also increase over time, Carney explained.

Study co-author Dr. Thomas Guzzo agreed that no one should make rash decisions on prostate cancer care based on this study alone.

“I think we need to look at these patients on an individual level,” said Guzzo, who is chief of urology at the University of Pennsylvania. “Certainly, there are patients who need hormonal therapy and benefit from it greatly,” he said in a university news release. “There are others where the evidence is less clear, and in these patients, we should consider the risk of hormonal therapy versus the benefit in treating their prostate cancer. This should be a shared decision-making process with the patient.”

The study was published online in JAMA Network Open.

Source: HealthDay


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