Endocrine Disruptors in the News, Again

The Guardian Unlimited has a provocative
article on the role of
endocrine disruptors in increasing the ratio of girl babies to boy
babies in the Arctic.  



I've written about the topic before ( href="http://scienceblogs.com/corpuscallosum/2007/02/endocrine_disruptors.php">1
2)
as have href="http://scienceblogs.com/terrasig/2007/02/lavender_and_tea_tree_oils_may.php">Abel
and href="http://scienceblogs.com/pharyngula/2006/12/satans_perfect_food_tofu.php">PZ.
 James Hrynyshyn, on Island of Doubt, has
already commented on
the Guardian article: href="http://scienceblogs.com/islandofdoubt/2007/09/two_girls_for_every_boy.php">Two
girls for every boy
.  



In this post, I will address
some of the skepticism that has been expressed about the topic.



Endocrine disruptors are chemicals in the environment that disrupt
normal regulation of hormones.  Some are artificial chemicals,
such as href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1569763"
rel="tag">polychlorinated biphenyls (PCBs). Some
are natural chemicals that are concentrated and used unwisely.
 Examples include lavender and tea tree oils used in cosmetic
products, which can result in href="http://en.wikipedia.org/wiki/Gynecomastia">gynecomastia
(abnormal
breast enlargement) in males.



With that as background, let's turn to the article:



href="http://www.guardian.co.uk/international/story/0,,2166996,00.html">Man-made
chemicals blamed as many more girls than boys are born in Arctic


Paul Brown in Nuuk, Greenland

Wednesday September 12, 2007

The Guardian


>· High levels can change sex of child
during pregnancy


·
Survey of Greenland and east Russia puts ratio at 2:1





Twice as many girls as boys are being born in some Arctic
villages because of high levels of man-made chemicals in the blood of
pregnant women, according to scientists from the Arctic Monitoring and
Assessment Programme (Amap).



The scientists, who say the findings could explain the recent excess of
girl babies across much of the northern hemisphere, are widening their
investigation across the most acutely affected communities in Russia,
Greenland and Canada to try to discover the size of the imbalance in
Inuit communities of the far north...



The scientists measured the man-made chemicals in women's blood that
mimic human hormones and concluded that they were capable of triggering
changes in the sex of unborn children in the first three weeks of
gestation. The chemicals are carried in the mother's bloodstream
through the placenta to the foetus, switching hormones to create girl
children...





Judging from the comments at
James Hrynyshyn's
post, there is a tendency for some people to disbelieve the findings.
 Some doubt the significance of the correlation between the
level of endocrine disruptors and the alteration in sex ratio.
 There is also skepticism about the potential for chemicals to
alter the sex of the developing fetus.



Consider the first point, that some doubt the significance of the
correlation.  Certainly it is true that correlation is not
causation, or more accurately, that correlation does not prove
causation.  But here we have an extremely unusual
circumstance, in the alteration of the sex ratio.  Not only
that, but it is occurring to a very large extent.
 We also have chemicals that are known to have effects on the
part of the endocrine system that regulates development of sexual
characteristics.  (See the links to the previous posts, by
Abel and me, for the evidence.) While it is true that the correlation
does
not constitute proof, I see little room for skepticism here.



To add to the evidence base, I note that similar, but less extreme, href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1281326">alteration
of the sex ratio has occurred in the Great Lakes region.
 This is an area where PCBs linger decades after they were
(mostly) banned.



Now consider the second point, that it seem incredible that the
chemicals could change the sex of the fetus.  It is true that
the genotypic sex is determined at conception.  That is, if
the sperm delivers a Y chromosome, the fetus will be genetically male.
 That does not change.  What the article fails to
clarify, is that a fetus with one X and one Y chromosome in each cell,
while genotypically male, can develop in such a way
that is it
morphologically (phenotypically) female (at least to
external inspection).  



Unfortunately, the article neither clarifies this, nor provides any
links for the reader to obtain clarification.  I notice also
that the organization that produced the study (
href="http://www.amap.no/">Arctic Monitoring and Assessment
Programme) does not have the report up yet on their website.
 So going to the original source is not yet possible.



The key point is that the genetic makeup of an individual
does not
always determine what the person will look like
.  It
is
possible for a person to have two X chromosomes in each cell, yet have
all the external features of a male.  This occurs in href="http://ghr.nlm.nih.gov/condition=21hydroxylasedeficiency">virilizing
21-hydroxylase deficiency:



Simple virilizing 21-hydroxylase
deficiency causes a buildup of potent androgens that leads to the
masculinization (development of male characteristics) of external
genitalia in females at birth. The development of the internal
reproductive organs (uterus and ovaries) in these patients is normal.



The opposite can occur, in href="http://www.emedicine.com/ped/topic2222.htm" rel="tag">androgen
insensitivity syndrome:



Androgen insensitivity syndrome (AIS),
formerly known as testicular feminization, is an X-linked recessive
condition resulting in a failure of normal masculinization of the
external genitalia in chromosomally male individuals. This failure of
virilization can be either complete androgen insensitivity syndrome
(CAIS) or partial androgen insensitivity syndrome (PAIS), depending on
the amount of residual receptor function.




Both individuals with PAIS and individuals with CAIS have
46,XY karyotypes. Individuals with CAIS have female external genitalia
with normal labia, clitoris, and vaginal introitus. The phenotype of
individuals with PAIS may range from mildly virilized female external
genitalia (clitorimegaly without other external anomalies) to mildly
undervirilized male external genitalia (hypospadias and/or diminished
penile size).



Persons with CAIS are href="http://health.nytimes.com/health/guides/disease/androgen-insensitivity-syndrome/overview.html">infertile.
 They have female external genitalia, but no uterus.
 Persons with
virilizing
21-hydroxylase deficiency, are, likewise, infertile.  They
have a penis but no sperm.  
In fact,
the conditions are sometimes discovered during medical evaluation of
infertility, or in cases of CAIS, the workup of amenorrhea.



The bottom line, is that one needs to have a bit of background in
biomedical sciences in order to assess the credibility of the Guardian
article.  Of course it would have been good if the author had
provided just a few more sentences to provide the necessary background.
 



As to the implications of the article, I think it means that we are
well on the way to really screwing up the environment.  Many
of the chemicals that act as endocrine disruptors are highly persistent
in the environment.  Although it is reasonable to have a
healthy degree of skepticism about these things, it is good to get a
little background information to temper one's skepticism.  




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Yes, I know one can be genetically male but morphologically female. That's not adequate evidence to conclude that environmental chemicals are "chang[ing] the sex of children before birth."

Yet, according to the Guardian article, that's exactly what one of the researchers claimed.

I repeat my objections from James Hrynyshyn's blog: that's an unwarranted conclusion, and if the researchers really did make that leap, it's reason to doubt their competence.

P.S. With a PhD in molecular biology and a 20 year career in biotech, I hope I can claim the requisite bit of background in biomedical sciences. I freely admit that endocrinology and reproduction aren't my fields, but I know more than enough to spot conclusions that aren't supported by the data.

OK, I won't argue with your qualifications. What I will say is this: we can argue all day about it, but in the end, we are hampered by the fact that the actual research is not on the Internet yet, at least that I could find. So what we are left with is a journalist's take on the subject. Most likely, what is in the article is only a subset of what information the scientists gave to the journalist.

It is easy to reach opposite conclusions when two people are arguing from a very limited data set.

My take on it is this: I start with the assumption that the scientists are reasonably competent. If you don't start with that assumption, and just look at what is in the article, I suppose I could understand a higher level of skepticism.

As you point out, the article would be more convincing, if we had access to the karyotypes and to details of the anatomy of the affected persons.

On the other hand, the findings reported in the Guardian article are consistent with animal studies on endocrine disruptors, and they are consistent with the Great Lakes data.

Now, we are not going to get proof at the beyond-a-reasonable-doubt level. To get that, we would need to do randomized, double-blind controlled trials on humans exposed to endocrine disruptors. Obviously we are not going to get that; it would be unethical to do any such study. But what level of evidence to you want to see before you get worried, or before you think some action should be taken to protect the environment?

As for the CIA factbook data, I doubt they studied the issue as the scientists, and I doubt tehy were looking at the same population. Probably most of their data come from hospital records in more Westernized areas, where the diets are not so strongly affected by accumulated lipophilic compounds.

I think there's a fairly well-established link between PCBs and abnormalities of sexual organs in other organisms. Like many issues involving human exposure to pollutants, it's unethical to test hypothesis in vivo, so you're left with correlations and animal models.

It's pretty easy to do some DNA testing to determine if XY children are outwardly female. Hopefully the full study will be posted shortly.

Joseph,

If the data showing a 2:1 sex ratio is robust, and not reasonably explained away as just some statistical anamoly, then that's worrying all by itself.

Independent of that, anywhere that PCBs or other chemicals are present in levels high enough to have toxic effects on animals (human or otherwise), that's also worrying and deserves corrective action.

I agree we're hampered by a dearth of information, but we're not reaching opposite conclusions. I'm arguing we cannot reach any conclusions. We can't even conclude that the reported sex ratio bias is real.

I wouldn't normally wonder about the basic competence of the researchers involved. The only reason I do in this case is the supposed quote where one researcher claimed chemicals were changing the sex of fetuses in utero. Do you honestly think that's a scientifically supportable conclusion?

Hopefully that's a misquote by the reporter. If so, it's unfortunate but not the researcher's fault. If it's an accurate quote, then you already know my opinion.

@Gerard Harbison:

I'm not sure we can say much based on the CIA Factbook data. The AMAP study looked at a specific population of only 480 families. That population could have a very skewed sex ratio, without having a noticeable effect on the sex ratio for all of Greenland.

I'd say this: the absence of a conclusion is not directly opposite from my conclusion, but it is an important difference. If you conclude that the preponderance of the evidence indicates that endocrine disruptors are a problem, then it would stand to reason that we ought to be doing something about it. If, on the other hand, you think no conclusion is warranted, then it would stand to reason that nothing should be done...except more research.

I assume we all agree that more research should be done, but do we all agree that mitigation of pollution is in order?

Let me be clear. I think no conclusion is warranted at this time regarding the AMAP study.

I don't have an opinion whether the literature as a whole allows us to reasonably conclude that pollutants can change human sex ratio (much less change fetal sex in utero). I haven't seen any compelling data so far, but I don't claim to know this literature.

The study you mention in the Aamjiwnaang First Nation has some reasonably strong data on changing sex ratio, but they show no data linking that to pollutants (other than the fact that the study population lives in a polluted area). They cite other studies that claim to link pollutants to human sex ratio, but different studies appear to reach contradictory conclusions, sometimes even when studying the same class of pollutants.

To reiterate, I'm not arguing for or against any conclusions about pollutants and human sex ratios in general. I'm arguing we can't make conclusions regarding the groups studied by AMAP (because we haven't seen any of their data). I'd also argue we can't conclude pollutants altered the sex ratio in the Aamjiwnaang (because there's no direct data demonstrating a link).

In fact, it's not just wrong to reach conclusions in the above cases, I think it's irresponsible. From the data I've seen, there's a real possibility that something else is affecting sex ratio in these populations. If we hastily blame pollutants, the actual cause(s) may go untreated.

In spite of all that, I agree mitigation of pollutants is in order. As I said in my previous comment, we can reach that conclusion independent of whether and how they affect human sex ratio.