Enzyme 'switch' clue to infertility and miscarriage

BBC News

The findings could help some couples trying to have a baby

Scientists have identified a "fertility switch" protein which appears to increase infertility if levels are too high and fuel miscarriage if too low.

An Imperial College London team took samples from the womb lining of more than 100 women.

Writing in Nature Medicine they said women with unexplained infertility had high levels of the enzyme SGK1, while those who miscarried had low levels.

One fertility expert said the research offered new avenues for research.

About one in six women have difficulty getting pregnant, and one in 100 women trying to conceive experience recurrent miscarriages, defined as the loss of three or more consecutive pregnancies.

The Imperial team also carried out mouse studies which found levels of SGK1 in the womb lining decline during the window of time during which they can fall pregnant.

When extra copies of the SGK1 gene were implanted into the womb lining, these mice were unable to get pregnant.

The researchers say this suggests a fall in SGK1 levels is essential for making the uterus receptive to embryos.

However, if low levels of SGK1 persist into pregnancy, this appears to cause different problems.

When the researchers blocked the SGK1 gene, mice had no problem getting pregnant but they had smaller litters and showed signs of bleeding, suggesting a lack of SGK1 made miscarriage more likely.

'Focus for research'

Prof Jan Brosens, who led the research at Imperial's Institute of Reproductive and Developmental Biology, said: "Our experiments on mice suggest that a temporary loss of SGK1 during the fertile window is essential for pregnancy, but human tissue samples show that they remain high in some women who have trouble getting pregnant.

"I can envisage that in the future, we might treat the womb lining by flushing it with drugs that block SGK1 before women undergo IVF."

“"It's all very well to measure something that is missing - whether or not you can correct it is the next step”

Prof Richard Fleming Glasgow Centre for Reproductive Medicine

After an embryo is implanted, the lining of the uterus develops into a specialised structure called the decidua.

The team say lab tests show low levels of the enzyme may impair the ability of cells in the decidua to protect themselves against oxidative stress, a condition in which there is an excess of reactive chemicals inside cells.

Dr Madhuri Salker, who also worked on the study, said: "We found that low levels of SGK1 make the womb lining vulnerable to cellular stress, which might explain why low SGK1 was more common in women who have had recurrent miscarriage.

"In the future, we might take biopsies of the womb lining to identify abnormalities that might give them a higher risk of pregnancy complications, so that we can start treating them before they get pregnant."

Prof Richard Fleming, of the Glasgow Centre for Reproductive Medicine, said the research was "encouraging".

"To have something as clear as this, with a specific enzyme, is great. It is giving us something to focus on."

But, Prof Fleming, who is also a member of the British Fertility Society, warned it would be some time before the discovery translated into day-to-day practice.

"It's all very well to measure something that is missing - whether or not you can correct it is the next step.

"But at least we know somewhere that's directly involved, and can explore that.

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Breast cancer prevention drugs 'should be prescribed'

BBC News

Breast density could be a risk factor of breast cancer

Women at high risk of developing breast cancer should be given preventative drugs, according to an international panel of cancer experts.

Writing in the Lancet Oncology, they said drugs such as tamoxifen could reduce the chances of developing breast cancer.

Such a policy would be similar to prescribing statins to patients at risk of heart disease, they suggest.

However, tamoxifen has been linked with womb cancer, blood clots and stroke.

In the UK, 46,000 women are diagnosed with breast cancer each year.

Two drugs, tamoxifen and raloxifene, have been approved in the US for the prevention of breast cancer. However, they are not available as a preventative measure in the UK.

Professor Jack Cuzick, who chaired the panel and is an epidemiologist at Queen Mary, University of London, told the BBC: "The two drugs should be approved in the UK. The evidence for them is overwhelming."

He estimates that for every 1000 women given tamoxifen there would be 20 fewer breast cancers, but there would also be three more womb cancers and six more cases of deep vein thrombosis.

To balance the risks, the panel agreed that women who had a greater than 4% chance of developing breast cancer in the next 10 years should be offered preventative therapy.

Predicting risk

In heart disease, there are well-known risk factors such as blood pressure and cholesterol, which can inform treatment.

The challenge for any preventative breast cancer treatment would be identifying similar "markers" of risk.

The panel suggests breast density. They say patients with more than 75% "dense breast tissue" had at least four times the risk of developing breast cancer than patients with mainly non-dense tissue.

Professor Cuzick said: "Increased breast density is one of the leading risk factors for breast cancer and early trial results suggest that where tamoxifen is shown to decrease density, the risk of cancer decreases.

"If this is confirmed in long-term studies, breast density could become a powerful way to identify high-risk women who could benefit from preventive treatments."

He suggests the risk of getting breast cancer should be determined during cancer screening.

Dr Lesley Walker, from Cancer Research UK, said: "Our scientists were behind some of the first trials showing the long term benefits of tamoxifen for preventing breast cancer in women with a greater than average risk of the disease.

"Being able to accurately predict breast cancer risk and who will respond to preventative drugs like these is a crucial step in ensuring women get the most suitable treatment."

Meg McArthur, senior policy officer at Breakthrough Breast Cancer said: "It is vital that we find effective ways to prevent breast cancer, especially in women with a high risk. However, as preventative therapy may have negative side effects it would not be appropriate for everyone.

"We welcome studies investigating the best treatments to be used for breast cancer prevention. It's also crucial to identify those at high-risk who would benefit the most from this form of therapy."

Female Sexual health

Heart fears over common chemical

BBC News

Bisphenol A is commonly used in food packaging

Higher levels of a chemical often found in plastic food and drink packaging are associated with cardiovascular disease and diabetes, a study has suggested.

The group with the highest levels of Bisphenol A (BPA) in their urine were found to be more than twice as likely to have diabetes or heart disease.

But the Journal of the American Medical Association research did not show that Bisphenol A caused the conditions.

And a UK toxicology expert stressed the study's findings were "preliminary".

Over two million tonnes of BPA were produced in 2003, although usage of the chemical is starting to decline.

BISPHENOL A Used in the industrial production of plastics, two types in particular: Polycarbonate plastic: A lightweight, rigid and reusable plastic used in products including CDs and DVDs, electronics equipment, sports equipment and reusable food and drink containers Epoxy resins: Used in protective coatings, paints and adhesives, and protective liners for metal food and drink cans

As well as being present in packaging, people are exposed to BPA through drinking water, on their skin and in household dust.

Previous research in the US found detectable levels of BPA in more than 90% of the population.

Animal tests had raised concerns about the possible effects in humans - such as disruption to hormone production - but were inconclusive because people process the chemical differently.

The study by researchers from the UK's Peninsula Medical School in Exeter looked at BPA levels in the urine of 1,400 US adults, and whether they had ever been diagnosed with one of eight major diseases, including arthritis, stroke and thyroid disease.

No strong link was found aside from that with cardiovascular disease and diabetes, although higher BPA concentrations were associated with clinically abnormal concentrations of three liver enzymes.

Obesity link

People who were obese, and therefore already at a higher risk of cardiovascular disease and diabetes, had higher BPA levels - and the researchers said it was possible that eating more was simply linked to a higher intake of the chemical.

TESTING AND SAFETY Some lab and animal tests have suggested potential problems, with BPA disrupting hormone balance in the body Specifically BPA has been found to mimic the female sex hormone oestrogen - with implications for development and reproduction Lobby groups, mainly in Canada and US have called for a ban Canada has become the first country to move towards reducing levels of BPA exposure in the population

But they said the link between higher levels of the chemical and the conditions remained true, even when they took body mass index levels and waist measurements into account,

Dr David Melzer, who led the study, said: "These findings add to the evidence suggesting adverse effects of low-dose BPA in animals.

"Independent replication and follow-up studies are needed to confirm these findings and to provide evidence on whether the associations are causal."

He added: "Given the substantial negative effects on adult health that may be associated with increased BPA concentrations and also given the potential for reducing human exposure, our findings deserve scientific follow-up."

Hearing

The study is being published to coincide with a hearing on BPA by the influential US Food and Drug Administration (FDA).

A spokesperson from the UK's Food Standards Agency said an expert panel was keeping the safety of BPA under review.

"The FSA will continue to closely monitor scientific reports about the health effects of BPA in the body and will take action to further protect consumers if it becomes necessary."

Professor Alan Boobis, a toxicology expert based at Imperial College in London, said the study did not fit with previous research into the chemical.

"It's an interesting finding, which we can't ignore. But it is preliminary, and requires following up."

He added: "It may be that the association is the inverse of what they are suggesting; not that the BPA is causing cardiovascular disease and diabetes, but that these diseases result in a higher level of BPA, or that there may be a common cause - like something going wrong with the kidneys.

"Or it could be a chance finding."

Professor Richard Sharpe, of the University of Edinburgh, said for some people a raised risk of cardiovascular disease and diabetes could simply be down to drinking too many high sugar canned drinks.

These people would also be exposed to higher levels of BPA from the lining of drinks cans - but that could be purely incidental.

He said more research was needed to tease out the truth before BPA could be labelled as the prime suspect.

In a joint statement, the British Soft Drinks Association (BSDA) and the Food and Drink Federation (FDF) said bisphenol A had been approved as safe for use in food and drink containers by the regulatory authorities, and its use was closely monitored and regulated.

Levels of bisphenol A in food and drink can linings that did include the chemical were well below safety levels set by the European Food Safety Authority.

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