PFCs and menopause among women from NHANES
Environmental Health Perspectives
0.46; between PFOA and PFNA, r = 0.55.
In the present study, Spearman correlations
ranged from 0.19 between PFOS and PFNA
to 0.65 between PFOS and PFOA (p < 0.001
for all correlations). We considered the use
of a total (summed) exposure measure of all
four PFC congeners; however, serum levels of
PFOS were much higher than those of PFOA,
PFHxS, and PFNA, suggesting that the com-
bined analysis would dis proportionately reﬂect
Early menopause is associated with a num-
ber of adverse health impacts. For example,
results from a meta-analysis demonstrated that
menopause before 50 years of age was asso-
ciated with a 25% increased risk of cardio-
vascular disease (Atsma et al. 2006) and
menopause before age 46 has been associated
with increased risk of coronary heart disease
and stroke (Lisabeth et al. 2009; Wellons et al.
2012). If PFC levels are predictors of earlier
menopause, exposure may also be responsible
for increased risk of other serious health out-
comes (e.g., cardio vascular disease and stroke).
Our examination of reverse causality
indicated positive associations between all
four of the PFCs we examined and the rate
of hysterectomy, and showed that these
PFC levels increased with time since natural
menopause. Taken together, the results of
these two additional analyses suggest that the
association between PFCs and menopause
may reﬂect the accumulation of PFCs among
women who were not excreting them through
menstruation. However, because of the cross-
sectional natural of our data, we cannot
confirm the direction of these associations.
Prospective human studies evaluating the
onset of menopause are necessary to better
assess potential causality.
Using data from the large, U.S. representa-
tive NHANES sample allowed us to explore
the association between PFCs and the haz-
ard of natural menopause while adjusting for
potential confounding by a number of vari-
ables. Unlike previous analyses of PFCs and
natural menopause, NHANES collected infor-
mation on the time since natural menopause
and surgical hysterectomy, which allowed us
to address the potential for reverse causality.
e cross-sectional nature of data collection
does not allow us to establish temporality
because menopause status, age at menopause,
and PFC measurements were taken at the
same time. PFC measurements were based on
a single serum sample. Any misclassiﬁcation
from single measures would tend to decrease
power and under estimate the real strengths
of association (Pearce et al. 2007). Although
a single sample may be more reliable for com-
pounds with long half-lives, samples collected
at several time points would be more accu-
rate for classifying exposure in future studies
(Melzer et al. 2010).
e consistency and robustness of our ﬁndings
suggest a relationship between PFCs and
menopause, although the under lying mecha-
nism of that association remains unknown.
In these cross-sectional data, it is not clear
whether the association observed between
PFCs and menopause is causal, if results are
due to non causal influences such as biases
from confounding or misclassification, or
if results are due to accumulation of PFCs
after menopause. Regardless of the under lying
cause, women appear to accumulate PFCs
more rapidly after they are no longer menstru-
ating. ese results, along with the ubiquitous
nature of exposure and persistence of PFCs in
the environment, support the need for contin-
ued monitoring of serum levels in the general
popu lation as well as further studies of the
reproductive health eﬀects of PFCs.
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