Shift in the Sexes
Are Endocrine Disruptors Changing Birth Ratios?
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According to demographic data compiled by the United
Nations, an average of 105 boys are born for every 100 girls. The male
proportion of births, equal to 0.515, varies slightly between years
and populations, but these factors do not fully explain consistently
shifting ratios in several industrialized countries over recent decades.
A new study examines birth and fetal death sex ratios in Japan and the
United States and reveals significant male-to-female shifts in both
nations [EHP 115:941–946; Davis et al.].
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image: Brent Bossom |
The research team calculated birth and fetal death
sex ratios in Japan based on 1949–1999 data from the Japanese
Vital Statistics Bureau. The proportion of male births varied yearly
before 1970 but declined steadily since then, from 0.5172 to 0.5135.
Between 1960 and 1999, the male proportion of fetal deaths increased
from 56% to 67.7%. The male fetal death rate is approximately four times
higher in Japan than in the United States.
For U.S. calculations, the researchers drew 1983–1995
fetal death data and 1970–2002 birth data from the National Center
for Health Statistics. The proportion of male births dropped in the
United States, from 0.5134 in 1970 to 0.5117 in 2002. There are significant
racial differences, however: between 1970 and 2002 the proportion of
non-Hispanic white male births fell from 0.5143 to 0.5122, whereas the
proportion of black male births rose slightly from 0.5076 to 0.5079.
The male proportion of black fetal deaths also increased, rising from
53.5% to 54.5%; among whites, the male proportion of fetal deaths rose
by less than 0.5%.
Why birth sex ratios differ so much between white
and black women is unknown, but hormonal differences due to race and
to incidence of obesity may be involved. A possible explanation for
the increased ratio among black births may stem from improved prenatal
and obstetric care in general, reducing the overall number of fetal
deaths.
The researchers speculate that parental exposures
to endocrine-disrupting chemicals, including metalloestrogens such as
methylmercury, might be factors undermining the conception and survival
of male children. They suggest particular scrutiny of Japanese body
burden of mercury and other metalloestrogens to understand this difference.
Additionally, future investigations of declining sex ratios should consider
the types and timing of prenatal and parental exposures to endocrine-disrupting
chemicals. The researchers hypothesize that paternal exposures prior
to conception might affect expression of the SRY gene on the
Y chromosome.
Julia R. Barrett
Phthalates and Metabolism
Exposure Correlates with Obesity and Diabetes in Men
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The prevalence of obesity, insulin resistance, and
diabetes has increased considerably in the past few decades. Many plausible
contributing factors have been identified for this increase, among them
low testosterone levels in men. Research has found that exposure to
certain synthetic chemicals adversely affects testicular function in
animals and possibly in humans. A new analysis looked for—and
found—that exposure to one class of these chemicals, phthalates,
correlated with two metabolic abnormalities in men: abdominal obesity
and insulin resistance [EHP 115:876–882; Stahlhut et al.].
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image: Paul Cowan/ShutterStock |
Phthalates are commonly used in products such as
cosmetics, soaps, pesticides, lubricants, plastics, and paints. They
are widespread; indeed, more than 75% of the U.S. population carries
detectable levels of several phthalate metabolites. Studies have also
found associations between some phthalate metabolites and antiandrogenic
effects in humans, including both infant and adult males.
The authors used 1999–2002 data from the CDC
National Health and Nutrition Examination Survey (NHANES) to look for
a connection between phthalate exposure and metabolic disease in adult
men. They compared urine concentrations of six phthalate metabolites
to the participants' waist circumference and measures of insulin
resistance. The analysis controlled for a variety of potential confounders,
including age, ethnicity, fat and calorie consumption, physical activity,
and smoking status.
Four phthalate metabolites were significantly associated
with greater waist circumference and three with increased insulin resistance.
When the authors further controlled their models for measures of participants'
kidney and liver function, the associations decreased somewhat but remained
significant for all but one metabolite.
The authors caution that this first look at phthalates,
obesity, and insulin resistance is limited by the study's cross-sectional
design and the single measurement of urine phthalate metabolites (an
imperfect measure of long-term exposure). In addition, although the
study was based on the hypothesis that phthalates cause metabolic abnormalities
by decreasing androgen levels or function, the authors couldn't
examine this mechanism, because the NHANES data do not contain measures
of sex hormones in men. They note that other mechanisms could also be
involved in a relationship between phthalates and metabolic disease.
If phthalates are eventually shown conclusively
to contribute to obesity or diabetes in men, it's still not clear
how these chemicals would affect the opposite sex, since low testosterone
has been associated with a lower (not higher) prevalence of metabolic
disease in women. If further longitudinal studies confirm that phthalate
exposure contributes to obesity, diabetes, and related disorders, actions
to reduce phthalate exposure could effectively lessen the chemicals'
contribution to metabolic disorders, because phthalates are quickly
metabolized and excreted by the body.
Melissa Lee Phillips
Childhood Leukemia in Germany
Cluster Identified near Nuclear Power Plant
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Childhood leukemia clusters have been observed at
a number of sites near European nuclear facilities. With the identification
of the largest cluster to date, a new German study underscores the need
to clarify the association [EHP 115:947–952; Hoffmann et al.].
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image: vario images GmbH & Co. KG/Alamy |
Between February 1990 and May 1991, five cases of
leukemia were diagnosed in children living within 5 kilometers of the
Krümmel nuclear power plant in Geesthacht and a neighboring nuclear
research operation along the Elbe River in northern Germany. By 2005,
another nine cases of leukemia had been discovered in the area. Most
of the cases were acute lymphatic leukemia in males under five years
of age.
Several expert commissions investigated, and found
moderate levels of cesium in rainwater and air samples, along with plutonium
and americium in household dust near the plant. There was also some
evidence of chromosomal damage to lymphocytes among the local population.
One panel deemed these observations consistent with fallout from a possible
accident at the research facility that would have to have occurred around
September 1986, but so far no such accident has been proved. Another
panel suggested instead that chance or population mixing—the commingling
of local people with newcomers from various places—might have
caused the cluster.
In the current study, researchers compared the number
of observed leukemia cases in the sparsely populated Geesthacht area
to the number of predicted cases based on nearby county and national
incidence rates from 1990 to 2005. The five cases found in 1990 and
1991 significantly exceeded the expected incidence for that period of
0.45 cases. After studying medical records from all treatment facilities
in the vicinity and in Hamburg, the team concluded that the Geesthacht
cluster is the "largest series of childhood leukemia cases reported
to date" among European leukemia clusters near nuclear facilities,
including those at Dounreay, Scotland; LeHague, France; and Sellafield,
England.
The authors state that population mixing is unlikely
to account for the leukemia incidence because the population remained
stable over the years studied. Nor would an alleged one-time release
of radiation in 1986 readily explain the cluster, given that the excess
incidence persisted over at least 15 years. Thus, they conclude, the
elevated incidence of childhood leukemia around Geesthacht remains "another
piece in a growing puzzle" of childhood leukemia's association
with nuclear installations—and its severity and persistence emphasize
the need to keep investigating.
Valerie J. Brown
A Twist in the Ritalin Riddle
Drug-Related Genomic Damage Not Confirmed in Children
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The frequently prescribed central nervous system
stimulant methylphenidate (MPH), better known by brand names that include
Ritalin, does not cause genomic damage in children, contrary to earlier
reports, according to new work published this month [EHP 115:936–940; Walitza et al.]. In use for more than 50 years and now prescribed
more than 5 million times a year in the United States, MPH is the drug
of choice for attention deficit/hyperactivity disorder (ADHD). ADHD
is the most frequently diagnosed psychiatric disorder in children and
adolescents, with an estimated 6–12% of minors worldwide thus
diagnosed.
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image: Calvero, GFDL |
A 2005 report published in Cancer Letters
had showed that gross genomic damage—reflected by chromosome aberrations
including sister chromatid exchanges and formation of micronuclei (smaller-than-normal
cell nuclei containing partial genomes)—was found in nucleated
lymphocytes taken from peripheral circulation of children who had been
taking the drug for only three months. Because large chromosomal breaks
are associated with cancer, the study raised concerns about the potential
for cancer risk in the millions of people who have taken the stimulant.
That 2005 study found an increased frequency of
chromosomal abnormalities in all of the 12 children whose lymphocytes
were examined, lending urgency to future studies. The current study
looked at micronuclei as an indicator of genomic damage in the lymphocytes
of 38 children newly prescribed the drug, following some but not all
of them out to six months.
The children, 29 boys and 9 girls, took a variety
of doses and formulations of the drug. Some subjects were lost to follow-up
during the study; others switched to other medications or dropped out
because they did not respond to the drug. Eight children stayed in the
study through the whole six months.
Overall, there was no significant increase in the
formation of micronuclei at any time point, though some individual children
had elevated numbers of micronucleated lymphocytes at one time point
or another. Further, the lymphocytes of 9 children who had been taking
the drug for more than six months at the start of the study did not
show increased levels of micronucleation compared to the pretreatment
levels seen in drug-naïve children.
The marked difference in results between the 2005
study and the current one raises the possibility of unexplained genetic
differences between the study populations. Whereas the first study population
included six white, four black, and two Hispanic children, the latter
study focused on a more uniform group of ethnically German children.
The authors say further work, especially on the long-terms effects of
MPH, is called for.
Victoria McGovern