Watch out, oestrogen about

"Warning: the plastic wrapper round your sandwich may contain certain 'gender-bending' chemicals". Is this a proven menace or a wild hypothesis? Liz Hunt reports
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The Independent Online
It is the ultimate environmental horror story: a scenario in a Stephen King novel, scripted by Greenpeace and Friends of the Earth. It is worse than global warming, more alarming than any hole in the ozone layer: the future of mankind threatened in the most fundamental way by "gender-bending" chemicals in everyday use.

These chemicals are, it is claimed, causing sperm counts to fall worldwide, and triggering a rise in the number of defective sperm. And the cunning twist in this particular plot line? The female hormone, oestrogen, appears to be to blame.

More precisely, it is the scores of man-made chemicals in plastics, detergents, electronics and pesticides which mimic the action of oestrogen that are now to be put under closer government scrutiny, among them phthalates, used in food packaging and plastics.

John Gummer, Secretary of State for the Environment, yesterday accepted the findings of scientific advisers who concluded that there "may" be a link between chemicals in the environment and falling sperm counts in men, defects of the reproductive tract in both sexes, and rising rates of testicular cancer and breast cancer.

Professor Lewis Smith, director of the Institute for Environment and Health at Leicester University, conducted a review of data from around the world. He found an abundance of circumstantial evidence for what has become known as the "oestrogen hypothesis" - but no causal link.

The oestrogen hypothesis holds that these "false" oestrogens present in chemicals latch on to hormone receptor sites present in males and females, disrupting the action of naturally occurring hormones, and switching on or turning off important biochemical pathways. They are difficult to break down and persist in body fat longer than natural oestrogen, to levels 100 or 1,000 times greater than background levels. The result can be devastating for oestrogen-sensitive tissues in the body: the reproductive tract, the breast and womb, and, most worryingly, the developing foetus.

The starting point for the oestrogen hypothesis was a wildlife haven, Lake Apopka, near Orlando in Florida. Between 1980 and 1984, the death rate for alligator eggs on the lake was found to be running at around 96 per cent, compared to a figure of 57 per cent for other lakes in the area.

Dr Louis Guillette, a reproductive physiologist from the University of Florida, was called in to investigate. He found sterile male alligators with shrunken, useless, penises, and drastically reduced levels of the the male hormone testosterone. Dr Guillette and his team made a tentative link with an accidental spill of thousands of gallons of DDT into Lake Apopka in 1980.

Throughout the Eighties, researchers surveying the Great Lakes of North America found that some of the offspring from 16 species living on the shores were failing to reach adulthood, or were sterile or hermaphrodite. They all ate fish from the lakes whose waters were known to be heavily contaminated with chemicals.

Closer to home, on the south coast of Britain, female dogwhelks, a species of mollusc, were found to be developing "pseudo-penises", and a chemical present in the paint used to protect the bottom of boats was found to be the cause. There were reports, too, of "feminised" male fish found near the sewage outlets in British rivers. Tests revealed that one or more chemicals in the outfall were exerting such a strong oestrogenic effect on male rainbow trout that they were producing large quantities of an egg protein usually found only in females.

These findings helped the environmentalists' cause, but it wasn't until human sperm moved centre-stage that the story grabbed the headlines. Professor Niels Skakkebaek, a Danish scientist, is credited with first alerting the world to the possibility of falling male fertility levels in 1992, when he showed that sperm counts in healthy men appeared to have dropped by more than half in 50 years.

He and his team in the Department of Growth and Development at Copenhagen University reviewed 61 international studies involving almost 15,000 men between 1938 and 1992. They found that the average sperm count fell from 113 million per millilitre in 1940 to 66 million in 1990. During this same period, the definition of a "normal" sperm count fell from 60 million per millilitre to 20 million in the same period.

The findings received worldwide attention and ridicule. Other scientists who re-examined the Skakkebaek data pointed out fundamental flaws in the analysis which ruled out any significant decline. But last year, two studies in France and Belgium confirmed and strengthened Skakkebaek's conclusion.

The irony was that these studies had set out to prove Skakkebaek wrong. A survey of 1,350 healthy sperm donors in Paris found a decline in sperm counts over 20 years with the youngest men having the poorest-quality semen. This demonstrated for the first time a connection between falling sperm counts and a man's age group. In fact, Pierre Jouannet of the Central University of Bicetre and his team found that men in Paris are losing on average 1 million sperm from each millilitre of semen each year.

In Ghent, researchers had found that the number of men with low levels of "grade A" sperm - which swims fastest and straightest to the nearest egg - had risen from 5 to 40 per cent over a 17-year period. They also found a rise in the number of defective sperm produced by the group of 360 men.

Professor Skakkebaek and a leading British scientist, Dr Richard Sharpe, a male fertility specialist at the Medical Research Council's Reproductive Biology Unit in Edinburgh, collaborated on developing the oestrogen hypothesis. They argued that exposure to more than the normal level of oestrogen in the womb at a critical period of development could be responsible for abnormalities of the testes. They pointed to the "DES" experience as supporting evidence.

DES or diethylstilboestrol, is a synthetic oestrogen, which was given to millions of women between 1945 and 1971 to prevent miscarriage. Some of the children born to these women had genital abnormalities which were later shown to be due to the drug. In boys, these included decreased semen volume and sperm counts, undescended testes and urethral abnormalities.

The work of Dr John McLachlan, scientific director of the National Institute of Environmental Health Sciences in North Carolina, was also central to the hypothesis. He contacted Professor Skakkebaek following publication of the sperm count findings. He wanted to share his research, in which he exposed pregnant mice to DES and obtained hermaphrodite, sterile offspring.

There are several other factors which have increased oestrogen uptake and exposure to the hormone, natural and synthetic, which may be significant, too. The intake of hormone-rich dairy produce has risen since the Forties; there are synthetic oestrogens in the contraceptive Pill and other drugs, and there are environmental contaminants such as DDT, PCBs, and exhaust fumes. They are among more than 30 man-made chemicals with oestrogen-like effects identified so far.

It is a complex jigsaw, but the pieces seem to fit well enough for the environmental lobby, which is demanding that some of the oestrogen-like chemicals are banned with immediate effect. Professor Lewis says such a move is premature, that if certain chemicals are banned in the absence of definitive evidence then "if you've guessed badly you have left behind the chemicals in the environment doing the damage". He for one, then, will happily continue to buy plastic-wrapped food, one presumes.