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Endocrine Disruptors

CITATION:  Solomon, G.M. and Schettler, T.  (2000).  Environment and health: 6. Endocrine disruption and potential human health implications. CMAJ: 163 (11).

SUMMARY:

During the past 50 years, tens of thousands of chemicals have been synthesized and released into the general environment. Some of these chemicals inadvertently interfere with hormone function in animals and, in somecases, humans. The public health implications of these so-called endocrine disruptors have been the subject of scientific debate, media interest and policy attention over the past several years. The current scientific debate centres on whether there is evidence of significant risks to the general human population.1

The health care community should be familiar with this issue because it is increasingly a subject of the popular press and is a topic of concern to patients, who may present with questions. But health policy decisions are currently being made with little input from the medical and public health community. In this article we review the history of environmental endocrine disruption, the mechanisms of action of endocrine disruptors and the current evidence of effects on reproduction, infant development and neurobehavioural function. Finally, we discuss health policy activities worldwide that are relevant to endocrine-disrupting chemicals in the environment.

Table 1: Examples of endocrine-disrupting chemicals

Chemical

Use
Mechanism
Health effect
References
DES
Synthetic estrogen
Estrogen receptor agonist
Humans (prenatal exposure): vaginal
cancer, reproductive tract abnormalities
(females); cryptorchidism, hypospadias,
semen abnormalities (males)
4
Methoxychlor
Insecticide
Metabolite is an estrogen
receptor agonist
Rodents: accelerated puberty, abnormal
ovarian cycling (females); aggressive
behaviour (males)
7,13
DDT
Insecticide
Metabolite (DDE) is an androgen
receptor antagonist
Rodents (males): delayed puberty,
reduced sex accessory gland size,
altered sex differentiation
14
Vinclozolin
Fungicide
Androgen receptor antagonist
Rodents (males): feminization, nipple
development, hypospadias
15
PCBs
No longer manufactured;
still in electrical
transformers, capacitors,
toxic waste sites, food chain
Accelerated T4 metabolism,
decreased T4 levels, elevated
TSH levels
(high doses: thyromimetic)
Humans (in utero exposure): delayed
neurological development; IQ deficits
16,17
Atrazine
Herbicide
Reduces gonadotropin-releasing
hormone from hypothalamus,
reduces pituitary LH levels,
interferes with metabolism of
estradiol, blocks estrogen
receptor binding
Rodents (females): mammary tumours,
abnormal ovarian cycling
Humans: some evidence of breast and
ovarian tumours
18–22
Dioxin
By-product of industrial
processes including waste
incineration; food
contaminant
Aryl hydrocarbon receptor
agonist; increases estrogen
metabolism, decreases estrogenmediated
gene transcription,
decreases estrogen levels,
decreases testosterone levels by
interfering with HPG axis
Rodents (in utero exposure): delayed
puberty, increased susceptibility to
mammary cancer (females); decreased
testosterone, hypospadias,
hypospermia, delayed testicular
descent, feminized sexual behaviour
(males)
Humans: decreased T3 and T4 levels,
decreased testosterone levels,* cancer*
23–27
Note: DES = diethylstilbestrol, DDT = dichlorodiphenyltrichloroethane, PCBs = polychlorinated biphenyls, T4 = thyroxine, TSH = thyroid stimulating hormone, IQ = intelligence quotient, LH =
luteinizing hormone, HPG axis = hypothalamic–pituitary–gonadal axis, T3 = triiodothyronine.
*Exposures in adults.

Table 2: Trends in human health effects potentially related to endocrine function

End point

Region
Trend
Degree of change
Reference
Hypospadias
Canada
US
Increasing incidence
4.3% per year
3.3% per year
37
Cryptorchidism
Canada
US
Increasing incidence
3.5% per year
1.6% per year
37
Sperm count
Canada
US
Europe
Decreasing
–0.7%/mL per year*
–3%/mL per year
–5.3%/mL per year
38
39
39
Testicular cancer
Canada
US
Europe
Increasing incidence
2.1% per year
2.3% per year
2.3%–5.2% per year†
40
41
42
Prostate cancer
Canada
US
Increasing incidence‡
3% per year
5.3% per year
43
44
Breast cancer
Saskatchewan
US
Increasing incidence
3.3% per year
1.9% per year
45
46
Sex ratio
Canada
US
Shift toward females
–1.0 males/10 000 per year
–0.5 males/10 000 per year
47
Age at breast
development
US
Shifting earlier
11.2–9.96 years in white
population
48
*This trend disappears when data from before 1984 are included.
†Range is dependent on country, with Sweden at the lower and the former East Germany at the upper end of the range.
‡International trends in prostate cancer are complicated by the introduction of the prostate specific antigen screen, but prostate cancer mortality also increased (by about 1% per year through 1995 in the US and Canada), implying that improved diagnosis may not fully explain the rising incidence trends.

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