Environmental dioxins and endometriosis.

[Guest guest]

http://www.ourstolenfuture.org/NewScience/reproduction/Endometriosis/2002/2002-1\

215rierandfoster.htm

 

Rier, S and WG Foster. 2002. Environmental dioxins and endometriosis.

Toxicological Sciences 70:161-170.

 

 

 

Rier and Foster review evidence from animal and human studies indicating that

dioxin (and other dioxin-like compounds) causes endometriosis via its ability to

disrupt immune and endocrine system function. They conclude that existing data

support this interpretation but that the details of the mechanisms are not yet

clear.

 

They also show that human exposure to dioxin is significantly higher than that

associated with endometriosis in monkeys., and cite published work which

concludes that current public health standards are not strong enough to provide

guarantees against the potential for dioxin causing endometriosis.

 

What does this mean? Dioxins are highly likely to be involved in the causation

of endometriosis. Many people carry dioxin body burdens that animal experiments

predict should cause endometriosis. The disease itself has likely increased

dramatically in prevalence over the past century, the same period over which

human dioxin body burdens grew. In the US alone, endometriosis forces over

100,000 hysterectomies each year, with health care costs for the disease

exceeding $1 billion annually. Strong measures to reduce dioxin exposures are

warranted.

 

Key parts of their review:

 

A summary of the action of dioxin and dioxin-like compounds:

 

 

This group of chemicals, the polyhalogenated aromatic hydrocarbons (PHAHs),

includes not just dioxins (PCDDs) but also furans (PDDFs) and biphenyls (PCBs).

PHAH compounds bind with the aryl hydrocarbon receptor (AhR), migrate to the

nucleus and activate genes, including several involved in controlling cell

growth, differentiation and inflammation.

Evidence demonstrates that different dioxins can act additively via this

mechanism. To assess the effects of dioxin mixtures, scientists have developed a

dioxin " toxic equivalency factor " (TEF) based upon the relative potency of

different congeners compared to TCDD(2,3,7,8-tetrachlorodibenzo-p-dioxin) the

most potent of the compounds, and then used the summed TEFs to calculate the

total TCDD equivalency (TEQ).

Most human exposure to dioxin comes via food. " In developed countries, blood

levels typically run 1-5 parts per trillion TCDD and 25 ppt TEQ, at least for

people without industrial exposure.

" Although the toxic effects of TCDD in animals are unequivocal, its effects

in humans are less clear. "

 

 

A review of data on dioxin-endometriosis links in monkeys:

 

 

The first hard data linking endometriosis and dioxin came from Rier et al.'s

1993 work with rhesus monkeys. They discovered, 10 years after TCDD exposure was

ended, that exposed monkeys had developed endometriosis: the more dioxin, the

greater the incidence and severity of the disease. Exposures were in the low

parts per trillion.

Subsequent studies with monkeys have strengthened this conclusion. For

example, a study of cynomolgus monkeys found that TCDD exposure increased the

implantation rate of endometrial tissue.

And in 2001, Rier et al. published additional work with rhesus monkeys

showing that higher TEQ levels were associated with a higher prevalence of

endometriosis. Disease severity was positively related to PCB congeners, but not

to TCDD itself. In this study, the animals were exposed to PHAH compounds

through food, as are people.

 

 

Comparison of exposures of people to those of the monkeys in these experiments:

 

 

Their comparison reveals that the body burdens in people living in the real

world are 2 to 20-fold higher than the monkeys in the experiments.

 

Rier and Foster cite a Japanese calculation that " protection against

development of endometriosis cannot be guaranteed by current regulatory

safeguards, since exposure to dioxin and dioxin-like compounds in certain

at-risk populations, such as local residents living near incinerators or who are

heavy fish consumers are greater than the levels for which adverse effects have

been documented in rhesus monkeys. "

 

 

It would thus seem that if human endometriosis has a comparable dose response

relationship to that revealed by the experiments with monkeys, then it is not

surprising that endometriosis is as widespread in people as data currently

indicate.

 

Evaluation of the value of animal models for understanding human endometriosis:

 

 

Only menstruating species like people and monkeys develop endometriosis.

Rhesus endometriosis closely resembles the human form.

Surgical transplantation of endometrial tissues in other species, such as

rodents, can be used to study the factors that affect the chances that the

tissue will thrive in other locations, but not of the the earliest stages of

development of endometriosis.

New approaches are being developed that transplant endometrial tissues into

immune-deficient mice. The implants resemble endometrial lesions in people. This

may allow more cost-effective and rapid research than studies with monkeys.

 

 

Human studies on dioxin and endometriosis:

 

 

Four hospital based case-control studies have been published. Results are

mixed. None of the studies are ideal, all with small sample sizes. Two (both

negative) failed to confirm surgically that the control population did not have

endometriosis. A third negative study used a chemical assay that probably

underestimated TEQ. The one positive study found that infertile women with

endometriosis were more likely to have detectable levels of TCDD than fertile

women without endometriosis.

 

 

Potential mechanisms by which dioxin could cause endometriosis:

 

 

Rier and Foster begin this section summarizing studies showing that the

dioxin stimulates gene activation in endometrial tissue through binding with the

Ah receptor.

They then propose that this gene activation may promote endometriosis through

three pathways:

 

First, by inducing an enzyme that increases estrogen levels and results in

" chronic exposure of the endometrium to growth-promoting estrogen. "

 

Second, by stimulating certain cytokines (immune system proteins) involved in

immune system responses and in the regulation of cycles of cell division and

death, thereby inducing inflammation and immune dysfunction.

 

Third, by interfering with progesterone. This hormone normally helps block

formation of endometrial lesions.

 

They conclude: " Although preliminary work suggests a potential involvement of

exposure to dioxins in the pathogenesis of endometriosis, much work remains to

clearly define cause and effect and to understand the potential mechanism of

toxicity. "

 

 

 

 

 

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