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  SILENT SPERM

Condensed from an article by Lawrence Wright.

Recently, both the quantity and the quality of the human sperm population have come into question. Almost everywhere, the normal sperm count - from 20 million to 300 million per millilitre of semen - is falling. Although a decline in sperm count has been noted before, in one part of the world or another - and generally dismissed - several new studies report a high proportion of damaged or misshapen sperm and depressed sperm counts in many countries.

The apparent drop in the sperm count is so sudden and steep that some scientists have wondered whether the human species is approaching a fertility crisis. Their views, amplified by alarming press articles, have triggered a debate that occupies scientific journals and conferences around the world. While sceptical scientists claim there is not yet enough evidence to indicate a crisis, others are calling for bans on chemicals that may inhibit sperm production.

The current concern is complicated by the fact that most research on human reproduction has focused on the female, because women bear the children, and because it was thought that men are not usually the source of infertility in a relationship. Thus andrology, the study of male reproductive disorders, is a new and relatively small field, usually undertaken by doctors who were trained as gynaecologists and paediatricians.

In 1990, Danish paediatric endocrinologist Niels E. Skakkebaek set up a department at the NationalUniversity Hospital in Copenhagen to study the phenomenon of male infertility and children's growth disorders. In the 1970s Skakkebaek gained a wide reputation for his brilliant studies of testicular cancer, a formerly rare disease in which there has been a startling rise in the last 50 years, and which is particularly common in Denmark, where nearly one in a hundred men are affected with it. Skakkebaek demonstrated that cells similar to precursor testicular cancer cells can be found even in germ cells of aborted foetuses, indicating that the cancer might be caused by some prenatal event, although the disease doesn't reach its pathological state until after puberty. In his paediatric practice, Skakkebaek was seeing many boys with genital malformations, and others with undescended testicles - a condition that may lead to sterility and a higher rate of testicular cancer. As sperm banks in Denmark were having difficulty in establishing a core of donors, Skakkebaek and his colleagues decided to study the sperm of Danish men. They found that even supposedly healthy men had surprising low-quality sperm. For decades it had been believed that the average man produced about 100 million sperm per millilitre, and of that about 20 percent was expected to be immobile. Skakkebaek's study, however, revealed a situation far worse than he had anticipated: 84 percent of the men had sperm quality below the low standards set by the World Health Organisation, although the men themselves seemed to be normal in every other respect.

Skakkebaek was not the first to discover something wrong with the sperm population. In 1974, two Iowa University physicians, C. M. Kinloch Nelson and Raymond G. Bunge produced a study of the semen quality of men who were about to undergo vasectomies, and was presumably above average in fertility since most of those accepted for vasectomies at the clinic had fathered two or more children. Yet only 7 percent had sperm concentrations above 100 million.

When Nelson and Bunge looked back at the records of men who had come to hospital 20 years before for infertility evaluations, they found that a large proportion of those supposedly infertile men in the 1950s had higher sperm counts than the fertile men seeking vasectomies in the seventies. In their report the two physicians speculated that "an environmental factor to which the entire population has been exposed" might be involved.

This report and other studies in Philadelphia and Houston, which also found low sperm counts and poor semen quality, caught the interest of John MacLeod, an eminent retired anatomist whose work in the fifties had set the modern standards for fertility and semen quality. In 1979, MacLeod and his colleague Ying Wang published a critique of the work of Nelson and Bunge who had dared to suggest that these standards could no longer be met. While acknowledging a decline in sperm counts in fertile males since the thirties, MacLeod and Wang rejected the notion of a larger, overall decline, citing analytical error in the study.

And there the matter rested for over a decade until 1992, when Skakkebaek and his Danish colleagues decided to review all published studies of sperm counts around the world. In 61 studies going back as far as 1938, they found that although the average sperm count varied from country to country, the clear trend was toward lower sperm counts in the present - a decline in average sperm density from 113 million per millilitre in 1940 to 66 million in 1990.

Following the Skakkebaek study, new data from other researchers around the world confirmed low sperm counts nearly everywhere.

But Skakkebaek's study had its critics, one of whom was Pierre Jouannet, a reproductive biologist at the Hopital Cochin in Paris, who with his co-workers had used the same sperm-testing procedures for 20 years and had built up an impressive database. Jouannet believed that their accumulated information would overturn the hypothesis of a general decline in the quality and quantity of sperm - at least in Paris.

So in 1993, when the French researchers analysed their data, they were astonished to discover that the concentration of sperm had actually declined on average more than 2 percent a year - from 89 million in 1973 to 60 million in 1992. If the decline were to continue at the same rate, Jouannet says gravely "it will take 70 or 80 years before it goes to zero".

Likewise, Edinburgh gynaecologist Stewart Irvine initially had doubts about the Skakkebaek survey. But in conducting a survey of Scottish males, he found that men born in the forties had an average sperm count of 128 million, whereas those born in the second half of the sixties averaged only 75 million - a decline of more than 40 percent in a single generation.

Why is the human sperm count declining? There is not one widely accepted theory, but a bewildering array of hypothetical culprits which range from the residues of birth control pills in drinking water to the stress of urban living.

From the sperm's perspective, modern life abounds with perils. Common antibiotics like penicillin and tetracycline can wipe out a sperm harvest. Tobacco, marijuana and alcohol can affect sperm production. The effects of these chemicals are usually limited to a brief period following exposure; a man who stops smoking marijuana will probably see an improvement in the quality of his sperm within a few months. The testes are acutely sensitive to X-rays: even a modest exposure can dampen sperm production for months. Chlamydia is a fertility-impairing venereal disease, and viruses like mumps and chickenpox can also devastate sperm counts. Men who work where they inhale lead-laden gasoline fumes risk lower counts as do agricultural workers who handle certain pesticides. One chemical in particular, dibromochloropropene, or DBCP, causes sterility. It has been banned in the US but continues to be used as a pesticide in a number of other countries. DBCP has allegedly caused epidemics of childlessness among plantation workers.

In 1987, before the current discussion about declining sperm counts began, a group of scientists led by Ralph C. Dougherty, a professor of chemistry at Florida State University, attempted to correlate the drop in sperm count with a number of variables. They found that lower counts were strongly correlated with an area's production of synthetic chemicals, number of automobiles, and consumption of meat, fat and alcohol.

Urban stress may adversely affect sperm production. John MacLeod in his many studies of semen among various populations found one group with "phenomenally high" sperm counts: long-term prisoners whose lives are presumably well regulated and stress-free. Skakkebaek, however, sees the source of the problem as more ominous than the stresses of modern life. Whatever is happening to men, he believes some part of it must take place during the early stages of human development - in the womb or else shortly after birth - because damage to the male urogenital system is evident even in some very young patients.

In Skakkebaek's opinion, the most likely villains are chemicals in the environment which masquerade as the female hormone, oestrogen. These chemicals, which can have a temporary effect on adults, can cause permanent damage in boys whose sexual organs are not yet fully developed. There is a provocative model for this theory in the children of mothers who had taken diethylstilbestrol (DES), a synthetic oestrogen widely prescribed in the US from the 1940s to the early seventies, because it was thought to prevent miscarriage. A number of the daughters of these women developed a rare form of vaginal cancer at an early age. Some of the sons of these DES mothers also developed alarming problems - low sperm counts, undescended testicles and deformations of the penis - many of the same problems that were later found in Danish males. DES has now been banned in most countries.

In line with Skakkebaek's observations, Richard M. Sharpe, research physiologist with the Medical Research Council in Edinburgh, began to search for sources of oestrogens in the environment that might disrupt the body's hormonal balance. He learned that many different synthetic oestrogens are still commonly used as growth promoters for livestock. They also produce meat that is as much as 20 percent lower in fat. The suggestion that powdered milk could be a source of oestrogen for infants weighed on Sharpe's mind until he was assured by a Cambridge professor who had done experiments on milk that the higer levels of oestrogen weren't present once the milk had been powdered before being blended into baby formula. The question of where the oestrogen had gone remained unanswered.

Like Skakkebaek, Sharpe thinks that the decline in sperm is linked to some event affecting the endocrine system which governs the body's hormones, and that this must happen either in the womb or shortly after birth. This is when the male's sperm-producing capacity is established. Even a small amount of synthetic oestrogen crossing the mother's placental boundary at a critical moment and invading the body of a developing foetus could have a devastating impact on male sexual development.

Sharpe tested this assumption on pregnant rats by introducing minute amounts of DES and other synthetic oestrogens into their drinking water. Sperm production in male offspring was reduced by 5 to 15 percent. Sharpe and Skakkebaek reported these findings in The Lancet of 29 May 1993.

That same year, John Sumpter, a fish biologist at Brunel University, reported that a number of fish in British rivers and streams had developed unusual genitalia, with elements of both sexes. Below sewage outfalls in Northern England investigators had found that one in twenty fish were hermaphrodites.

At first Sumpter and his colleagues suspected ethynyl estradiol, the main form of oestrogen found in the contraceptive pill. Ethynyl estradiol is an extremely potent oestrogen; the effect on male trout is evident at doses too small to be measured. The Pill is so widely used in western cultures that its residue can be found in treated sewage. But it has not been ascertained whether it is also present in drinking water, and Sumpter decided to test other compounds.

In addition to synthesised oestrogens, more than a hundred thousand industrial chemicals are widely used in the environment and about a thousand new ones are introduced each year. These chemicals and their byproducts have been tested only for their potential to cause cancer and birth defects - not for their ability to mimic human hormones.

Although the impact of a highly oestrogenised environment on humans is uncertain, it is well known that men who work directly with oestrogens tend to become feminised.

In 1993, Sharpe and Sumpter decided to test various common chemicals to determine whether they had an oestrogen effect - Sharpe with pregnant rats and Sumpter with male trout. Among the compounds tested were octylphenol and butyl benzyl phthalate - both very common. Octylphenol belongs to a class of sturdy compounds called alkylphenol ethoxylates (APEs), which have been found in river water at rather high levels. APEs are used as emulsifiers and are found in detergents, paints, pesticides, plastic wraps, textiles and cosmetics. Phthalates, which make plastic flexible, are the most abundant manmade chemicals in the environment, and are present in the human diet. When Sharpe and Sumpter tested these chemicals on animals at levels approximating human exposure, they found effects similar to those of DES. It appears that industrial chemicals can actually mimic hormones.

It is also possible that other chemicals in the environment may affect the hormonal balance by blocking either the oestrogen receptors or the androgen receptors or both. It is possible that those chemcials are even more potent in their effect than environmental oestrogens. Dioxin, which is a byproduct of chemical manufacturing and of the pulp-and-paper industry, is present at low levels nearly everywhere in the environment, and it can cause an incredible amount of damage. In rats a single dose of dioxin during pregnancy reduced sperm counts in males by about 60 percent.

Even Richard Sharpe, whose research did so much to advance the environmental-oestrogen hypothesis, admits that it remains unproven. For Sharpe and many other scientists, the search for the cause of declining sperm counts is far from over.


Source: The New Yorker, 15 January 1996.

 
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