214 Autism and Exposure to Environmental Chemicals
exposures by permutation analysis, an association between the level of chlorin
ated pesticides in breast milk and risk of cryptorchidism in offspring was
found. Greenhouse workers exposed to pesticides during pregnancy were also
shown to have an increased risk of cryptorchidism. Phthalate levels in breast
milk were not associated with cryptorchidism risk, but they were linked to an
increased LH‐to‐free testosterone ratio in the son at the age of 3 months, sug
gesting testicular impairment during lactation. It is clear that there is a need for
more research as there are large gaps in our understanding of this problem.
In addition to clinical experience in humans, experimental animal studies
show that exposure to anti‐androgenic EDCs lead to cryptorchidism, similar to
the effect of these compounds on hypospadias (Figures 7.14 and 7.15).
Hypospadias is a birth defect of the urethra where the urinary opening is not at
the usual location on the head of the penis. It is the second most common birth
abnormality found in male newborns, and this affects 1:250 males at birth. In
the majority of cases, the opening is on or near the head of the penis (Figures 7.14
and 7.15), while in rare cases hypospadias will be located near or within the
scrotum. In addition to anti‐testosterone chemicals, compounds that act like
estrogen (estrogenic) can also lead to cryptorchidism. Thus, a mixture effects
of EDCs may be due to their various estrogenic and anti‐androgenic proper
ties. There is no reason why the same mechanisms do not apply to humans,
who share the same biological mechanisms of testicular descent as rodents.Early Puberty in Males
Skakkebaek et al. [129] also have clearly shown that there is another alarming
trend – males as well as females are reaching puberty earlier. Early puberty in
females is well documented but this trend appears to be present in males also.
Several well documented studies suggest a significant downward trend in
male pubertal timing. For example, a European study of 21,612 boys born
in 1935–1969 showed a downward trend in age at peak height velocity (PHV),
although other European studies did not find such changes.
Male puberty marks the transitional period during which the infantile boy
achieves reproductive capacity and develops into a matured man. Puberty
usually starts at 11.5 years of age, although with large inter‐individual variability.
A boy generally reaches puberty between 9 years and 14 years of age and any
one falling outside of this range is considered pathological and requires clinical
evaluation to exclude underlying pathologies. The timing of puberty is deter
mined by genetic as well as environmental factors such as body composition,
physical fitness, nutritional and socioeconomic status, ethnicity, residence,
foreign adoption, and exposure to endocrine disrupters. Testosterone pro
duced by the Leydig cells in the testes is the major male sex steroid that deter
mines the timing of male puberty. Production of testosterone is stimulated by