By Peter Montague
Two important British scientific journals have published editorials calling for more research into environmental chemicals that may be harming the reproductive health and sexual development of men throughout the industrialised world.
Nature said on June 15, "The case for research to be conducted urgently is overwhelming". The medical journal Lancet was much more explicit, making the following points:
- Industrial chemicals that mimic sex hormones (or xeno-oestrogens, as they are sometimes called) "may be responsible for a massive decrease in male sperm counts and semen quality since 1940", Lancet said.
- "Female infertility is the subject of intense research and an unfailing source of headlines for the popular press. Male reproductive health has not been studied nearly so thoroughly, and little attention was paid to a series of observations indicating that the frequency with which a male factor is responsible for a couple's infertility has increased in recent years from about 10% to 25%."
- "Numerous compounds in daily industrial, agricultural, or domestic use have oestrogenic effects, but the endocrine effects of the tens of thousands of man-made chemicals with which we come into daily contact have been studied in only a few instances, and then by accident rather than design ... For most chemical pollutants we do not know whether they are oestrogenic or not, what their effects are singly or together, or even the degree of our exposure ... They will remain in the environment for generations, and even small amounts of such contaminants can lead to the accumulation of considerable quantities in animal and human tissues."
- "It is the mother's lifetime exposure [prior to pregnancy] that determines the foetal dose, not just her exposure during pregnancy", Lancet said.
Both these journals called for urgent research to learn more about the male reproductive system, the chemicals that we encounter in our daily lives, and the effects those chemicals may have, singly or in combination, on male reproductive health.
The research task is formidable. It is well known that sexual differentiation is initiated by the presence of the Y chromosome, which sets in motion male development; absence of the Y chromosome sets in motion female development. All further steps are controlled by chemicals called hormones — oestrogens are the "female" hormones and androgens are the "male" hormones.
But the development of gender, with all its physical and behavioural aspects, depends upon both oestrogens and androgens in both males and females; it is the balance of these chemicals, in combination, that produces normal differentiation and development. All females contain some androgens, and all males contain some oestrogens.
Over the past 30 years, it has been discovered that many industrial chemicals mimic oestrogens. An "oestrogen hypothesis" has been proposed to explain why each year more men in the industrialised world are getting cancer of the testicles, birth defects affecting the penis, lowered sperm count, lowered sperm quality and undescended testicles. The oestrogen hypothesis suggests that all of these effects can be traced to one cause: industrial chemicals mimicking hormones, affecting male children while they are still in the womb.
However, in the last two years, a different set of concerns has been raised: some chemicals that don't mimic oestrogens can still interfere with sexual differentiation and development in laboratory animals; they do it by interfering with the action of androgens. Since it is the balance of oestrogens and androgens that creates one gender or another, anti-androgens can interfere with male development as effectively as excessive oestrogens can.
In Nature June 15, William Kelce, a researcher at the US Environmental Protection Agency (EPA), reported that a breakdown by-product ("metabolite") of the pesticide DDT (called p,p'-DDE) is a powerful anti-androgen. Anti-androgen drugs (developed as therapy for human prostate cancer), when given to animals before and shortly after birth, can cause reproductive tract disorders, including small penis, hypospadias (the urethra remains open for a certain distance on the underside of the penis, and this has to be corrected surgically) and undescended testicles.
DDT has been banned in the US, but many countries still allow its use, including its use on food products. Furthermore, despite the ban, many ecosystems remain heavily contaminated from past DDT use.
Therefore, the research task requires us to know not only which chemicals mimic oestrogens, but also which chemicals interfere with androgens. For example, a common pesticide, Vinclozolin, was recently discovered to be a powerful anti-androgen. Dosing a pregnant female rat with Vinclozolin at a level that caused no toxicity in the mother, gave rise to baby male rats which all appeared to be female at birth. The newborn male rats developed nipples (which, in rats, only females normally have), and they all had the hypospadias birth defect and undescended testicles. Furthermore, they were all sterile.
In the US today, Vinclozolin is legal for use on cucumbers, grapes, lettuce, onions, bell peppers, raspberries, strawberries, tomatoes and Belgian endive. EPA has no published plans for banning Vinclozolin.
In the cases of both DDT and Vinclozolin, the chemical itself has certain gender-bending properties, but the breakdown by-products (metabolites) have even more powerful anti-androgenic properties. For example, the M1 metabolite of Vinclozolin is 100 times more powerful than Vinclozolin itself. Therefore, researchers will need to study not only the main chemicals but all of their important metabolites.
The problem of chemical combinations is even more difficult. Several prominent researchers calling for urgent work on gender-benders have suggested that combinations of chemicals might be important. For example, the editorial from Lancet April 15: "For most chemical pollutants we do not know whether they are oestrogenic or not, what their effects are singly or together, or even the degree of our exposure ..."
Suppose we wanted to study only the possible two-chemical combinations among the commonest 500 industrial chemicals. To do this, we would have to run 124,749 different experiments. To study all the different three-chemical combinations among the 500 would require 20.7 million experiments — an impossible task. Even testing all three-chemical combinations among only 100 chemicals would require 161,700 experiments.
If we were worried about 500 chemicals, each with one metabolite, for a total of 1000 chemicals, and we wanted to study all possible two-chemical combinations, we'd have to run 499,500 experiments.
Finally, recent research on dioxin reveals that, at dose levels not toxic to the mother, both male and female offspring of dioxin-exposed pregnant rats and hamsters have their sexual development stunted. In females, the external genitalia were malformed; in males, testicles were reduced in weight, and sperm count was reduced by more than 50%.
These effects were not caused by oestrogen-mimicking, nor by an anti-androgen mechanism. Some entirely different mechanism, not understood, allows dioxin to interfere with sexual development of mammals at extremely low levels of exposure. Are there other chemicals like dioxin in this regard? It seems a fair question.
How can we avoid exposure to dioxin and to all the other gender-benders found in pesticides, detergents, paints, plastics, and so on? After they are made and released into the environment, there is no avoiding them. Therefore, we must prevent their manufacture in the first place. This is the life-and-death challenge of our age.
[From Rachel's Environment & Health Weekly.]