Front Matter

Effects of Testosterone or AR Mimicking EDCs 213

levels [136]. High phthalate exposure was associated with a decline in free
testosterone and an increase in LH concentration, again suggesting an anti‐
androgenic effect (Figure 7.13).
The key question to ask is: is human exposure to one or a mixture of many
of  EDCs enough to introduce disruptions of male programming and brain
engineering? In experimental animals, when a mixture of the chemicals is
introduced (to mimic the real life daily exposure to these agents in humans),
these chemicals can induce the double or triple jeopardy manner (additive
effect) and render harmful effects. The experimental results from exposing
animals to mixtures of chemicals can impart dose–response curves of the indi­
vidual chemical. Estrogenic chemicals and dioxins can also cause cryptorchidism.
In humans, exposure to the synthetic estrogen DES was linked to increased
rate of cryptorchidism, but environmental estrogens are typically much less
potent. However, together with anti‐testosterone they might act in a synergistic
manner and deliver a double effect [128,137].
Epidemiological studies that can link exposures to endocrine disruptors and
cryptorchidism have analyzed single chemicals or chemical groups, and only a
few have attempted to integrate these data (Figure 7.15). Exposures have been
measured in blood, urine, placenta, and breast milk that serve as a biomarker
to a woman’s levels of chemicals during pregnancy. In some cohort studies,
careful ascertainment of the diagnosis has been combined with exposure
measurements. The results vary according to the experimental design. The
breast milk level of polybrominated flame retardants was associated with an
increased risk of cryptorchidism. Similarly, dioxin levels in breast milk of
Danish women were associated with an increased risk of cryptorchidism [129].
The effects of exposure to multiple chemicals have been analyzed in only a
limited number of studies. After combining data from several pesticide

Abdominal (15%)

Inguinal canal

(25%)

High scrotal

(60%)

Normal Subcoronal MidshaftPenoscrotal

Figure 7.15 cryptorchidism and hypospadias in newborn boys. Source: http://img.tfd.com/
mk/C/X2604‐C‐73.png.