SM, MJ Silva, DB Barr, JW Brock, L Ryan, Z Chen, RF Herrick, DC
Christiani and R Hauser 2003. Phthalate Exposure and Human
Semen Parameters. Epidemiology 14:269 –277. [note]
other phhtalate-sperm studies:
experiments with rodents have shown repeatedly that phthalate exposures
can adversely affect sperm quality. Critics have argued that these
results are not relevant to humans, either because of differences
in reproductive physiology or because environmental exposures experienced
by people are beneath those causing effects in rodents.
by scientists from the Centers for Disease Control, Harvard School
of Public Health, the Dana Farber Cancer Institute and Harvard Medical
School, this study dramatically undermines those critics by showing
that men with higher phthalate levels have reduced sperm
counts, lower sperm motility and more deformed sperm. The
levels observed in the men are well within the range of exposures
seen in the American public. Different types of phthalates had different
did they do? Duty et al. obtained sperm and urine
samples from 168 men who were partners in infertile couples coming
for treatment to an infertility clinic at Massachusetts General
Hospital. Participants also responded to a questionnaire about lifestyle
factors and medical history. Responses were used to control for
potentially confounding variables. It was not known at the time
of enrollment whether the couple's infertility was due to male or
semen samples the research team determined sperm concentration (sperm
count), sperm motility and the percentage of deformed sperm in samples.
Urine analysis yielded measurements of the concentrations of 8 different
metabolites. Of those 8, 5 were included in the statistical
analysis. The other 3 were not because in most men levels were quite
low, indeed often undetectable.
5 metabolites measured were:
did they find? In analyzing the men's sperm, Duty et
al. first determined which men had sperm characteristics indicating
fertility problems. They used criteria
established by the World Health Organization, based on sperm count,
sperm motility and sperm morphology.
the 168 men studied, 54% had sperm characteristics lower than WHO
criteria on at least one of the variables measured: 17% had sperm
counts beneath 20 million per ml, 44% had less than 50% motile sperm
and 26% had less than 4% normally-shaped sperm. Some men were suboptimal
on more than one parameter.
of the men were white (77%) and had never smoked. They averaged
34.6 years of age.
study the relationship between phthalate levels and sperm characteristics,
Duty et al. carried out two types of analysis.
the first, they divided the men into two groups based on sperm parameters
(a high group, composed of men with sperm parameters higher than
vs. a low group, i.e., men beneath the median) and two groups based
on phthalate measurements (a high group, composed of men with phthalate
parameters higher than the median, vs. a low group). They then determined
for different sperm measurements whether men in the high sperm group
were more or less likely to be in a high phthalate group.
results of this analysis showed that men with high MBP levels were
more than twice as likely to have low sperm motility (adjusted odds
2.4; 95% CI = 1.1 to 5.0). High MBP levels were also associated
with reduced sperm concentration (OR= 2.4) and higher percentage
of deformed sperm (OR = 1.7).
et al. also found associations between MMP and sperm morphology
and MBzP and sperm count, motility and morphology.
the second round of analysis, Duty et al. looked for dose
response relationships between sperm parameters and phthalate exposure.
To do this, they divided the men into tertiles
based on phthalate levels and then after adjusting for confounding
this analysis, three trends emerged. Men with higher MBzP or higher
MBP were more likely to have lower sperm count. Men with higher
MBP were more likely to have lower sperm motility.
does it mean? These results demonstrate associations
between phthalate levels commonly experienced by the American public
and impaired sperm quality. They are consistent with laboratory
results studying the effects of phthalates in animals, although
they suggest that humans may be more sensitive than rodents.
key point is that there is nothing out of the ordinary for the phthalate
levels observed in the patients studied by Duty et al.
The levels are somewhat lower than those reported in national surveys
by the US CDC. Indeed, while the comparison is complicated because
of differences in how the samples were composed, the CDC data indicate
that American men may often carry levels 2-3x those reported in
this study. This would suggest that if the associations
revealed by Duty et al. are causal
many American men have sperm parameters affected by phthalate exposure.
always, there are ways that this study can be criticized.
of sperm parameters are difficult; single samples of sperm may
not present an accurate snapshot of a man's reproductive condition.
time measurements of phthalates may not be representative of a
man's exposures over time, because phthalates have a relatively
short half-life in the human body.
men in the sample may not be representative of the population...
although there is no reason to suggest they are not representative
of men in couples with fertility problems.
the first two of these potential weaknesses would work against finding
significant relationships within the data, because they introduce
random measurement error into the system. There is no plausible
reason why measurement errors of the sort caused by these limitations
would produce be expected to yield a false
positive. Thus if anything, the underlying pattern of association
between phthalate exposure and sperm parameters is likely to be
stronger than that reported in this article.
an editorial accompanying this article and a
in Epidemiology, Univ. Missouri reproductive epidemiologist Dr.
Shanna Swan notes that the evidence is now good, albeit not certain,
that environmental agents, even at low levels, can impair semen
quality. Teasing apart and proving conclusively the contribution
of any given agent will be especially difficult because of the wide
array of chemicals to which people are regularly exposed, each of
which has been linked by laboratory animals to adverse effects on
comments also place these new results in the broader context of
debate over whether broad declines in sperm
count have occurred, regionally or globally. This debate, kicked
off by an analysis
of global trends carried out by a team of Danish scientists,
ultimately led to the conclusion that no firm conclusion could be
reached even though existing historical data were consistent with
a decline, because of the limitations of a retrospective analysis
of data gathered using different methods for different purposes
over a long period of time. This realization forced scientists to
shift their focus away from long-term trends and toward geographic
variation, because while the past could not be reconstructed, current
geographic patterns could be examined.
studies are currently underway, for example, a recent
report of large differences in sperm count among men from different
regions of the United States. Work on geographic differences, coupled
with work like the current paper by Duty et al., should shed light
on what is causing the geographic patterns and then allow firmer
conclusions to be reached about changes over time.
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