The oestrogen jigsaw: What have Florida alligators, pesticides and men with low sperm counts in common? Scientists who think they know the answer meet for the first time next week, and the topic under discussion will be a female hormone. Liz Hunt reports

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At a medical conference in Montreal next week three scientists with seemingly diverse research interests will share a conference platform to tell the latest instalment in an intriguing tale.

Dr Louis Guillette of the University of Florida, who describes himself as a 'reptile gynaecologist', will talk about alligators with tiny, useless penises that live on a lake near Orlando. Dr John McLachlan is an American environmental health expert, whose interest lies with hundreds of chemicals in daily use in plastics, detergents, pesticides and electronics, and their effect on the gender of baby rodents. The third is Professor Niels Skakkebaek, the Danish scientist who in 1992 first alerted the world to the possibility of falling male fertility levels when he showed that sperm counts in healthy men appeared to have dropped by more than half in 50 years.

There is growing evidence that these scientists are working on pieces of the same complex jigsaw. Together, the work of all three has far-reaching implications for human reproduction, some common cancers and the increase in abnormalities of the male reproductive tract being reported worldwide. Testicular cancer has tripled in America and the UK to become the most common cancer in young men; prostate cancer has doubled in a decade and there is an increase in the incidence of undescended testes in baby boys and urethral deformities. Breast and womb cancers are also increasing in most countries. The key to completing the puzzle may be the female hormone oestrogen - or more precisely, man-made chemicals that mimic its action.

Oestrogen is essential for normal female sexual development and healthy functioning of the reproductive system. In men, the adrenal glands produce a small amount and there are 'receptor' sites for the hormone although it has no known specific function. Over the past four years it has become clear that hundreds of chemicals designed in the laboratory have an oestrogenic effect.

The hypothesis runs that these 'false' oestrogens latch on to hormone receptor sites in the body, possibly blocking the action of the naturally occurring hormone. Another explanation is that the chemicals may mimic its action, switching on or turning off biochemical pathways, and hanging around in the body far longer than natural oestrogen. The result is potentially devastating effects on oestrogen-sensitive tissues in both sexes, such as the reproductive tract, the breast and womb, and particularly on a developing foetus.

It will be the first time that three key players in this unfolding story will have addressed a major international medical conference - the World Congress of Obstetrics and Gynaecology - together. It marks acceptance by mainstream medicine of what had been dismissed by many as the latest whinge of environmental lobbyists, backed up with questionable data on sperm counts. Professor Skakkebaek's work on sperm counts, published in 1992, attracted worldwide publicity at first - and then ridicule. He and his team in the Department of Growth and Development at Copenhagen University had reviewed 61 international studies involving 14,947 men between 1938 and 1992. They found that the average sperm count had fallen from 113 million per millilitre in 1940 to 66 million in 1990. In addition, the definition of a 'normal' sperm count fell from 60 million per millilitre to 20 million in the same period.

Critics who reanalysed the Danish data pointed out a fundamental flaw in the calculations which, they said, ruled out any significant decline. But two subsequent studies in France and Belgium, published this year, have confirmed and strengthened Skakkebaek's findings. A survey of 1,350 sperm donors in Paris found a decline in sperm counts over 20 years, with the youngest men having the poorest-quality semen. In Ghent, researchers found a dramatic increase in the number of defective sperm produced over a 17-year period in a group of 360 men.

The significance of these two studies is that they had set out to disprove Skakkebaek but could not. 'The criticisms of the original study were a statistical argument that didn't stand up,' says Dr Richard Sharpe, a male fertility specialist at the Medical Research Council's Reproductive Biology Unit in Edinburgh.

In May last year Professor Skakkebaek and Dr Sharpe published a paper in the Lancet medical journal proposing a possible explanation for falling sperm counts, and also for the increased abnormalities of the male reproductive tract. Enter the oestrogen connection. Exposure to more than the normal level of oestrogen in the womb at a critical period of foetal development could be responsible for these abnormalities and there was evidence to support this, the scientists said. A drug known as DES (diethylstilbestrol) had been given to 6 million pregnant women worldwide to prevent a miscarriage between 1945 and 1971. It was a synthetic oestrogen, and genital abnormalities in the children of some of these women were subsequently linked to its use. In boys the abnormalities included decreased semen volume and sperm counts, undescended testes and urethral abnormalities.

And there was the work of Dr McLachlan, scientific director of the National Institute of Environmental Health Sciences in North Carolina and one of the speakers in Montreal. He exposed pregnant mice to DES during experiments in the early Nineties and obtained hermaphrodites, sterile offspring with both male and female characteristics.

Professor Skakkebaek and Dr Sharpe cited several factors in their paper that may have increased oestrogen uptake and exposure since the Forties: dietary changes with increased consumption of hormone-rich dairy produce; synthetic oestrogens in the contraceptive Pill and other drugs, and a wide-range of chemicals that have been identified as having oestrogenic activity. They include environmental contaminants such as DDT, PCBs (used in electronics), and exhaust fumes.

The dietary theory of oestrogen exposure is interesting but difficult to pin down and, although far from discounted, it is the environmental theory that has grabbed the headlines. There is a good deal of circumstantial evidence, in laboratory data and graphic descriptions of wildlife apparently affected by these oestrogen-like contaminants.

Between 1980 and 1984 the mortality rate for alligator eggs on Lake Apopka in Florida was around 96 per cent compared with 57 per cent for other lakes in the area. Dr Guillette, a reproductive physiologist, and his team, were asked to investigate and found sterile males with penises up to half the normal size and drastically reduced testosterone levels. He made a tentative link with a spill of thousands of gallons of a DDT pesticide into the lake in 1980. 'My feeling was, and still is, that we were seeing the tip of an iceberg. From what we know about embryonic development, from lab data, and from the chemistry of pesticides and other chemicals, there are problems for human health generally and we should be worrying about them,' Dr Guillette said.

Other researchers surveying the Great Lakes in the late Eighties found that members of 16 animal species that fed on fish from the lakes known to be contaminated with some of the oestrogen-like chemicals were failing to reach adulthood, or were sterile. Many were hermaphrodite.

In Britain, too, there have been reports of 'feminised' male fish found near sewage outlets. Tests revealed that one or more chemicals in the outfalls were exerting such a strong oestrogenic effect on male rainbow trout that they were producing large quantities of an egg protein normally produced only by females.

Since 30 per cent of drinking water comes from rivers, these findings - suppressed for almost 15 years by the Department of the Environment - led to concerns about drinking water. A report published earlier this year by Dr Jean Ginsburg, a fertility specialist at the Royal Free Hospital in London, suggested that men in the Thames Water Authority area had poorer-quality sperm and were less fertile than men in other areas. However, Professor John Sumpter, a fish physiologist at Brunel University who is leading research into the sewage effluent, says that drinking water is unlikely to be linked with a decrease in sperm counts 'simply because we don't drink enough water'.

He and his team are 'tracking' the oestrogenic activity of effluent and are close to identifying the chemical or chemicals responsible, most likely a constituent of a detergent present in a range of industrial and domestic products. 'The problem may not be what you are drinking, but what you are exposed to in your home, some plastics could be a source. We know the consequences to fish. The question we have only recently learnt we need to ask is, what are the consequences for humans?'

In Montreal next week, Professor Skakkebaek and his colleagues hope their attendance will attract more money for essential research from medical groups, who have been sitting on the sidelines. Only by chance have the scientists become aware of what others were doing. 'This research is in danger of disappearing through the cracks,' Professor Skakkebaek said yesterday. 'The environmentalists believe it is the health bodies that should be backing it, and vice versa. So far, people have been talking and talking. We have facts and we have hypotheses; it is important that we get together and find the real answers.'

(Photograph omitted)

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