25 July 1996 Environmental chemicals – a friend or foe to sex hormones and health

Certain man-made chemicals found in the environment and some naturally occurring plants can produce oestrogen-like effects in our body. But evidence of a cancer inducing effect or a real threat to human reproductive health from exposure to environmental chemicals and oestrogenic plants, at levels we are exposed to in New Zealand, is far from conclusive, says Lincoln University toxicologist Dr Ravi Gooneratne.

Our society is hooked on chemicals. We use many chemicals in our daily life. The soaps, creams, detergents (washing powders and dish washing liquids), fly sprays and weed killers, all contain chemicals. These chemicals are an essential component of the lifestyle we enjoy in New Zealand. But chemicals, if not used properly, are dangerous to health and also the environment. Hardly a week goes by without a discussion in the news media about a chemical that potentially threatens our health; we hear about pesticide residues in the food we eat, pollutants in the air we breathe, toxic chemicals leaking into the water we drink and, in recent months, unleaded Super 96 petrol causing sickness in truck drivers.

There is a new wave of concern in the scientific literature worldwide that some toxic chemicals in the environment as well as substances in some plants can act like the female sex hormone oestrogen and be responsible for decreasing sperm counts, increasing breast, prostate and testicular cancers and affecting reproduction in wildlife. Chemicals like DDT, PCBs and dioxins and plants like soybean are cited as the major culprits. Pesticides in general are singled out. But evidence is far from conclusive. These chemicals act like, or interfere with the actions of some hormones.

What are hormones?

Hormones are chemicals produced by certain cells in the body. They are released into the blood and travel to different parts of the body where they cause changes in cell structure or function. The cells can only respond to the hormone if they have special sites where the hormone can attach or bind to. These sites are called receptors. The hormone and receptor fit together like a key in an ignition and cause very specific changes to take place in the tissue. Examples of hormones in our body include growth hormone, thyroid hormone, insulin, cortisol and the sex hormones (oestrogen, testosterone).

What are sex hormones?

Oestrogen is the major female sex hormone and is produced in the ovaries. The major male sex hormone, testosterone, is produced in the testes. The production of these sex hormones in correct amounts at the right times is responsible for the basic differences between males and females. Sex hormones are important for:

• formation of sex organs in the foetus
• development of sex characteristics at puberty
• control of menstrual cycle in women
• control of sperm production in men
• sexual behaviour after puberty

Males also produce a small amount of oestrogen and females produce small amounts of testosterone in the adrenal glands. The roles of oestrogen in men and testosterone in women are poorly understood. However. it is known that too much oestrogen in males can have a feminizing effect, while too much testosterone in females can have a masculinizing effect.

Chemicals and sex hormones

The idea that chemicals can alter hormone production is not new. Over the years, many drugs have been developed for treating hormone imbalances in humans:

• Drugs can increase hormone activity by binding to the hormone receptor, turning on the response. Such drugs are called mimics or agonists. Certain other drugs can increase hormone activity by stopping the breakdown of the hormone in the body prolonging its effect. Ethinyloestradiol is a synthetic oestrogen mimic that is widely prescribed in birth control pills.
• Drugs can decrease hormone activity by inhibiting production of the hormone or by increasing the rate of breakdown of the hormone. Other drugs, called antagonists bind to the hormone receptor, but like a rusty key cannot turn the ignition. Instead, by occupying the receptor, antagonists block the natural hormone from binding and thereby block hormone activity. Tamoxifen, a drug widely used in breast cancer, is an example of an oestrogen receptor antagonist that blocks the action of oestrogen.

Scientists have found many different types of chemicals that can increase or decrease hormone levels in animals. For example, scientists have known for some time that the pesticide DDT had high oestrogen like activity when injected into rats. Since then, many different chemicals including other pesticides (methoxychlor, kepone), industrial chemicals like some PCBs (polychlorinated biphenyls) and some dioxins and industrial effluent, some surfactants, some spermicides, have all been reported to produce oestrogen like effects in laboratory experimental animals. However, compared to the natural oestrogen produced by the body, most of these chemicals have very weak oestrogenic activity.

Therefore, some scientists believe the chemicals which exhibit weak oestrogenic compounds can in fact have an opposite effect (that is, anti-oestrogenic activity) because they block the effects of highly potent oestrogenic compounds produced by the body activating the receptors.

There are also a number of dietary and environmental compounds which themselves have no oestrogenic activity, but can exhibit anti-oestrogenic activity. Some polyaromatic hydrocarbons such as by­ products of combustion of organic compounds in cigarettes (during smoking) and foods (during barbecuing), can contribute significantly to the average daily intake of anti-oestrogens.

Oestrogenic Plants (phyto-oestrogens)

Many naturally occurring chemicals found in a variety of plants can also alter hormone activity when eaten. Phyto-oestrogens are plant-derived chemicals that bind to oestrogen receptors. They are found in plants such as soybeans, broccoli, clovers, Lucerne, to name a few. The potency of these phyto­ oestrogens is usually weak compared to the activity of the natural hormone and oestrogen drugs.

Professor Cliff Irvine, a reproductive endocrinologist at Lincoln University has shown that potentially high levels of two phyto-oestrogens (genistein and daidzein) are found in baby soy products (milk formulae and cereals) and cautions feeding these to infants and because it is fed at a time in life when critical brain-sex hormone links are made.

But how powerful these soybean phyto-oestrogens is not known. Soybeans also contain other chemicals (such as trypsin inhibitors and phytic acid) which can interfere with protein digestion and absorption of minerals (calcium. zinc, iron). The potential toxicity of infant soy products needs to be further looked at and research is currently underway in New Zealand. One approach would be to remove all undesirable chemicals from soymilk and the technology is available to do that.

Some plants also contain anti-oestrogenic compounds like indole-3-carbinol. Brussels sprouts, cauliflower and cabbage, all contain indole-3-carbinol and are therefore sources of dietary anti­oestrogens.

Certain fungi (for example, fusarium species) can infect grains and pasture plants and produce toxins (for example zaeralenone) which have oestrogenic activity in animals (including wildlife) and especially in pigs, feeding on these.

Oestrogenic chemicals and reproductive health

In male adults, unless testosterone production is suppressed, any possible feminising effect of extra oestrogen is likely to be over-ridden by the much greater influence of testosterone. In contrast, small amounts of chemical dioxin given to pregnant rats has been shown to result in smaller sex organs, delayed sexual maturity, reduced sperm production and change the sexual behaviour of the male offspring.

Some wildlife populations have also been found to have reproductive problems. There is evidence of feminisation in males (for example, alligators in Florida's Lake Apopka following a pesticide spill in 1980's, birds and fish in Great Lakes in USA, rainbow trout in waters near a sewage treatment plant in UK). There is widespread speculation these effects were caused by man-made chemical pollutants.

Currently, however, there is little scientific evidence there has been exposure to such chemicals in amounts sufficient to induce such effects.

Reports of declining sperm counts have received much publicity recently. Some estimates indicate that human sperm counts have declined by almost 50% over the last century.

Two recent reports from Denmark have shown that men on organic diets had higher sperm counts. A study at Christchurch Women's Hospital (by Drs Peter Berry, Iris Sin and Anoma Gooneratne) in 1994 did not find a difference in sperm count between men on organic diets and other diets, but men on organic diet had a significantly lower percent of abnormal sperms (72%) compared to the rest (84%).

But evidence is far from conclusive because studies in laboratory animals have shown that exposure to some chemicals like dioxin results in reduced sperm production, whereas exposure to other chemicals like PCB's can increase sperm production. Rats exposed to PCBs via mother's milk have shown no changes in semen quality.

We are exposed to a whole range of chemicals but with our current understanding of chemicals and plants showing both oestrogenic and anti-oestrogenic activity it is difficult to estimate what the overall effect of exposure might be.

The drop in sperm count in men over the past century may be due to factors other than oestrogenic chemicals, such as: lifestyle changes (smoking, alcohol consumption), dietary factors (high fat and low fibre consumption), wearing tight briefs instead of loose underwear (increased temperature of the testicles can inhibit sperm production).

Exposure to other non-oestrogenic environmental contaminants have also been shown to affect sperm production (for example radiation and lead).

Methods of collecting and quantifying sperm counts have changed over the past century and therefore sperm counts done now may not be easily compared with those done many years ago.

Oestrogen chemicals and cancer

The first evidence of chemically induced cancer came from studies of diethyl stilbesterol (DES), a synthetic oestrogen used to prevent miscarriages for over two decades. DES was banned in 1971 after it was linked to vaginal cancers of women who took it. Current scientific evidence does not fully support the view that hormones cause cancer, but rather under certain circumstances, they may promote the growth of cancer; that is, cancer appears at a younger age or grows faster.

Studies suggest that oestrogen plays a role in the development of breast cancer and the lining of the womb (endometrium). These two areas in the body have many oestrogen receptors and are therefore susceptible to any cancer inducing effects of oestrogen. But our understanding of oestrogen and cancer is far from complete because Tamoxifen. a drug that blocks oestrogenic receptors prevents breast cancer but not endometrial cancer.

Women whose diets are rich in phyto-oestrogens do not have an increased risk of breast cancer and some studies in fact show a reduced cancer risk as in Asian women who consume lots of soybean. The oestrogenic potency of these phyto-oestrogens is much lower than natural oestrogen, so it is hypothesised that these weaker plant oestrogens, just like some environmental chemicals, probably act as antagonists to block the cancer-promoting effects of natural oestrogen. The report that women exposed to dioxins following an accident in Seveso, Italy in 1976, have a below-normal incidence of breast and endometrial cancer support this idea.

Scientific opinion on a link of pesticides (for example DDT or DOE, a metabolite of DDT) or industrial chemicals (such as PCB) exposure and development of breast cancer is not consistent and the issues seem very complex. Some human studies show a cause and effect link while some others do not.

Animal studies have not shown consistent evidence to connect breast cancer to these chemicals. It is heartening to note that a report of total diet survey of pesticides carried out in New Zealand in 1991 and published last year show our daily intake of pesticides to be well below acceptable daily intakes.

The incidence of testicular and prostate cancer is increasing in the industrialised countries. However, except for an association between age and prostate cancer, very little is known about the risk factors for development of these cancers.

In summary, certain man-made chemicals found in the environment and some naturally occurring plants can produce oestrogen-like effects in our body. The issue is highly complex. Evidence of a cancer inducing effect or a real threat to human reproductive health from exposure to environmental chemicals and oestrogenic plants at levels we are exposed to in New Zealand is far from conclusive. But the effects of infant soy products on reproductive health needs further investigation to provide a peace of mind to the parents and to those who were fed soy products during their childhood.

Dr Ravi Gooneratne is a senior lecturer in toxicology at Lincoln University. He has recently been admitted to the Membership of the Royal College of Pathologists (MRCPath) in UK.