bisphenol A Archives - Hormones Matter

Early BPA Exposure Doubles Risk for Prostate Cancer

Published on July 27, 2017

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Bisphenol A or BPA is ubiquitous in the modern environment. Used to form plastics for array of products (and found in fracking waste water, as we just learned), BPA exposure is almost unavoidable these days. A study in 2008, showed just how unavoidable demonstrating high levels of BPA in 93% of the individuals tested. Like many environmental endocrine disruptors, BPA is estrogenic in nature. When exposure to environmental estrogens occurs during pregnancy or during early life, those estrogens affect male and female reproductive and neurological development significantly. Adding to the body of research against BPA and other estrogenic environmental endocrine disruptors (here, here, and here), a new study, Bisphenol A Promotes Human Prostate Stem – Progenitor Cell Self – Renewal and Increases in vivo Carcinogenesis in Human Prostate Epithelium links developmental BPA exposure to a significantly increased risk of prostate cancer for men later in life.

The study, conducted by researchers from the University of Chicago, Illinois, was rather unique in its approach. Researchers cultivated prostate stem cells from young, disease-free men and then conducted a series of both in vitro and in vivo exposure tests. In the in vitro tests they exposed the human cells, in culture, to the various levels of hormones over differing periods. With the in vivo tests, however, the researchers took those same human prostate progenitor cells and grafted them to host rats. The host rats were then exposed to the different hormones for different time periods. Hormones tested included: native testosterone, estradiol and BPA, the environmental estrogen that mimics native estradiol. In both series of experiments researchers were interested in the timing and length of hormone exposure on prostate carcinogenesis. What they found was striking.

Male prostate tissue, though dependent on testosterone for development, is also susceptible to native and environmental estrogens. Both types of estrogen receptors are present. Moreover, the timing and duration of estrogen exposure impacts prostate health health. Specifically, treatment of the host rodents for 1-4 months with native testosterone plus estradiol produced a relatively small incidence of cancer, only 13%. Treatment of the host rodents with BPA, however, increased the rate to 33-45%, with higher rates of carcinogenesis linked to longer exposures.

This study provides further evidence that early developmental exposure to environmental estrogens negatively affects male prostate health.

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This post was published originally on Hormones Matter on January 10, 2014.

Evaluating Endocrine Disruptor Research

by Chandler Marrs, PhD

Published on July 30, 2015

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Every now and again, we see a flurry of press releases flooding social media about new research purporting to prove that endocrine disruptors are safe. Most recently, the press has been focused Bisphenol A or BPA. New FDA proclamations suggest that it has no impact on health. When one reads the actual research upon which these statements are based, it says no such thing. Unless of course, the research is funded by industry, then it is almost always positive. A report in Newsweek found:

In 2013, for example, the American Chemistry Council spent more than $11 million on lobbying expenses, according to the Center for Responsive Politics. Industry groups have also funded, and in some cases written up, research done by governmental scientists. One 2008 investigation, by the Milwaukee Journal Sentinel, found that “a government report claiming that bisphenol-A is safe was written largely by the plastics industry and others with a financial stake in the controversial chemical.”

The report goes on to state that the FDA

…dismissed as irrelevant the vast majority of the BPA safety studies its own scientists reviewed in preparation for that official position statement. According to the FDA, for example, all of the 48 epidemiological studies reviewed had ‘no utility’ for the agency’s risk assessment, the formal process it undertakes to decide if a chemical is safe for human health or not.

With such contradictory claims about safety, who should we believe? How do we evaluate the safety research about endocrine disruptors? Here is a primer.

Industry Sponsored Research Is Biased

In a mini-review of research on bisphenol A (BPA) – the endocrine disruptor in plastics, of the 115 studies published on adverse effects of BPA 81.7% (94) reported significant adverse health effects (2004). However, upon review, it was found that 90% of the government funded, academic research found significant adverse effects while 100% of the industry-sponsored research found no ill-effects of BPA – none. This is a common theme across all industries – pharmaceutical included. When billions of dollars are on the line, industry sponsored studies will show favorable results more often than not. Always check the author’s conflict-of-interest disclosures at the back the article. If none are reported though, don’t assume they do not exist. Not all conflicts of interests are disclosed. You may have to do additional digging to identify conflicts.

FDA or EPA Approved Does not Mean Safe or Risk-Free

Both agencies have long histories of approving and then failing to recall dangerous chemicals, drugs and devices from the market. Their work is particularly incompetent in reproductive (endocrine) and women’s health: thalidomide, DES, Yasmin/Yaz, HRT, Mirena, Prolift to name but a few that have garnered the seal of approval by the FDA. Phthalates, BPA, Glyphosate for the EPA. Remember the EPA doesn’t even study the female reproductive dangers unless research shows that a chemical impacts the male reproductive system.

Research Methods Matter

Perhaps more so than in any other field of science, endocrine research requires serious consideration of all aspects of the study protocol. This means that you cannot rely on a press release about the research to determine the study’s relevance. You must read the original research and evaluate the methods. (Reading original research is a good habit to have for all matters that affect your health and well-being). Once you pull the research, here are some things to consider.

Length of study. Most hormone reactions are longer term and span generations. If the study is short duration, as in the case with the industry sponsored GMO research or doesn’t include third generation effects, as with BPA research – question the results.
Population studied. Whether one is investigating a chemical or a drug in humans or in rodents, the sample population matters. Ascertaining safety of efficacy by testing only healthy young men, when the drug or chemical is meant for the real world where women, children, elderly, healthy and not so healthy individuals reside, is common practice and recipe for disaster. Same is true for rodent research – the strain, sex, age and health of the animal must be considered if the work is to be extrapolated to real humans. I read one study claiming that BPA was safe, but they used a strain of rats that was resistant to environmental estrogens. Of course, BPA’s estrogens would not affect these estrogen-resistant rodents.
Outcomes measured. What does the study measure and how does it evaluate change? More often than not, industry sponsored research will not measure the appropriate endpoints or reproductive dangers. Sometimes this is sleight of hand, other times it is simply ignorance of the endocrine system’s far-reaching regulatory control. In either case, one has to evaluate what the study actually measures before determining its validity. Here, you can use a bit of personal experience – what systems, organs or behaviors are affected by your hormones? If the study didn’t measure any of these variables, then it’s probably not a very solid protocol.
‘Gold-standard’ protocols are not always golden. It takes years, decades even for ‘gold-standards’ to become the accepted methods – often well after their utility has run out and newer, more sophisticated tools have reached the market. This has been the case for endocrine testing and endocrine disruptor evaluation. If a study rests all of its findings using a gold standard, it may not be using the most sensitive testing methods.
Clinical significance is not the same as statistical significance. Clinical significance means the chemical/drug has some meaningful impact on the health or well-being of the individual or animal. Statistical significance is just a math equation. A simple increase in sample size while limiting or ‘restructuring’ outcome variables is all it takes to derive statistical significance in most research. Does that mean the drug or chemical has clinically relevant health effects – not necessarily. The opposite is also true. Want to obfuscate the dangers of a drug/chemical? Do a huge study (preferably by combining dozens of poor quality individual studies into a meta analysis), throw everything but the kitchen sink into the analysis, do simple stats and highlight the lack of statistical significance in the death or injury rates. Only a small fraction of the study population died – but it wasn’t statistically significant, so the drug/chemical is considered safe. If the study does not study distinguish between clinical and statistical significance or downplays the death and injury rates as statistically insignificant, approach cautiously.
Hormone reactions do not conform to linear statistics. Damn it, how dare our complex physiology not conform to the simplicity of linear statistics. A common dose-response curve is highly linear, where a small dose elicits a similarly small response and a larger dose increase the response size. This is not case when dealing with endocrine disruptors. Hormone systems are complex and highly non-linear. Hormone dose-response curves are often in the shape of an inverted U where low doses elicit huge responses, mid-level doses elicit minimal responses and high doses again elicit huge responses. And so, any study measuring hormone effects using simple, linear, dose response calculations is bound to miss the effects entirely.
Hormones have metabolites (as does everything else). Metabolites evoke their own reactions. We know that some of the metabolites from BPA are stronger, 1000X stronger in fact, than BPA itself. Studies that don’t address the full complement of hormone products that circulate in our bodies as a result of exposure to something like BPA will severely underestimate the safety issues.

In a nutshell, we have to do our homework. There is no simple ‘Good Housekeeping Seal of Approval’ for products that impact health and well-being. We wouldn’t trust the marketing put out by car manufacturers or, worse yet, a car salesmen, about the safety, gas efficiency, repair history and comfort of a new/used car; why do we trust the makers of chemicals to give us the straight story. We shouldn’t. We have to become educated consumers of health research in order to protect ourselves.

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This article was published previously in March 2013 and updated and edit for republication in 2015.

BPA and Other Gender Bending Plastics

by Chandler Marrs, PhD

Published on February 2, 2015

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An oft repeated theme in this journal is that measurement matters. From the basic concept that one cannot manage what is not measured to the more specific notion that research protocols in the lab should attempt to mimic real life as much as reasonably possible, we believe measurement is critical. In matters of health and hormones where complex systems with a myriad of ever-changing variables are the norm, this is difficult at best. Sometimes, however, the simple act of measuring these variables opens a world of insight. This is the case with BPA and other estrogenic plastics.

BPA and Estrogens

Bisphenol-A (BPA), the estrogenic activator leaching sperm from our men and damaging the ovaries of women came to the world’s attention several years ago after a vocal and strident outcry from moms. The FDA subsequently remitted, prohibiting BPA from baby bottles and sippy cups and a slew of newer ‘safer’ BPA-Free plastic products emerged, but are they really safer? Maybe not.

Simulating Real Life Usage: Measurement Matters

Until recently, no one had measured the estrogenic activity of the other compounds used to plasticize our food containers. Nor had anyone measured these compounds under real-world stressors, such as UV-radiation (sunlight), microwave radiation or in the dishwasher or with different types of solvent (to represent the food/drinks contained by these plastics). Indeed, as is often the case, we were lulled into a false sense of safety. We believed that since BPA was removed from plastics, the endocrine disruptors were also removed, when in fact the other compounds had simply not been measured.

As one might expect, once those tests were conducted, researchers found that most plastic products on the market today release chemicals that are estrogenic – even those marketed as BPA-Free. Baby bottles, where much of the BPA outcry began, can leech as many as 100 different chemicals especially when exposed to real-life stressors, sunlight, microwaves and dishwashers, all estrogenic in nature.

Sunlight, in particular, was especially adept at maximizing the release of estrogenic chemicals into the solvent. Who hasn’t left their water bottle in the car? And when the plastics were tested in both polar and non-polar solvents (most foodstuffs/drinks are a combination of both), the majority showed reliably detectable estrogenic activity.

What to Do With All of These Estrogens

Not to worry, according to the authors of the study, there are ways to create plastics that don’t elicit estrogenic activity and they don’t cost any more or require different manufacturing than those that do. It’s simply matter of choosing to utilize those plasticizers and associated chemicals instead of what we currently use. The question is whether major plastics manufacturers will pay heed to these warnings and make the switch. Did I mention the man-boobs and infertility from the extra estrogens?

The study: Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved

Postscript

The article above was published originally in October 2012. Over two years later, I am sad to say that not much has changed. Industry has repeatedly denied the safety issues with BPA and the other, presumably safe, BPA-free plastics. The current campaigns, much like those of the tobacco industry, proffer industry financed research as proof of product safety while discrediting any scientist who brings evidence to the contrary. It’s a common script followed by all chemical manufacturers; one that has yet to be successfully curtailed.

BPA Exposure Linked to Egg Maturation Errors and Infertility

by Chandler Marrs, PhD

Published on August 9, 2013

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Bisphenol A (BPA), the polycarbonate, endocrine disrupting plastic is pervasive in the environment. A recent National Health and Nutrition Examination Survey detected BPA in the urine of 95% of the participants. Along with other toxins, BPA has been found in the placenta and follicular fluid of pregnant women. Given its estrogenic actions and its ability to disrupt the normal equilibrium of maternal and placental hormones, scientists have begun to investigate what role BPA might have on infertility, pregnancy complications and fetal development. What they are finding is not good.

In the most recent set of experiments, researchers from Brigham and Women’s in Boston, found that in vitro BPA exposure to human eggs – oocytes, prevented the egg’s ability to mature and disrupted chromosome alignment and organization at the lowest dose possible; a dose lower than levels normally found in women’s ovaries.

The experiment used eggs discarded from patients undergoing IVF/ICSI cycles. The eggs were divided into two groups, those to be exposed to varying doses of BPA and a control group. Sibling pairs, eggs from the same mom, were placed into both the BPA and the control groups equally to reduce the possibility that any maturation errors in egg development might be linked other factors related to maternal infertility, such as age, weight or general health.

The eggs exposed to even the lowest doses of BPA failed to mature appropriately and higher doses were linked to an increased rate of error and maturation failure. Researchers note that this was preliminary study, but that their findings indicate BPA exposure might be linked into infertility at the most basic level – egg health and maturation.

From our perspective, this study suggests that couples contemplating pregnancy should eliminate BPA and other environmental toxicant exposure well before attempting to conceive. For couples having difficulties conceiving, it might be worth testing urinary BPA and other endocrine disruptors such as phthalates and reducing exposure to these chemicals prior to undergoing costly fertility treatments. Here are the four most effective ways you can minimize your exposure to BPA:

Drink filtered tap water. This helps avoid water that has leached BPA from plastic containers.
Use stainless steel water bottles or certified “BPA-free” containers.
Avoid all canned foods, which are often lined with BPA containing resins. Eat fresh, non-processed, organic foods and avoid storing in plastic bags.
Avoid the use of plastic utensils and dishes.

BPA is likely not the only source of endocrine disruptors. All plastics under normal conditions release estrogenic compounds. It may be wise to avoid plastics in general. Additional research on removing BPA and other chemicals from your diet can be found here.

Of BPA and Endocrine Disruptors: New Research, Same Flaws

by Chandler Marrs, PhD

Published on April 3, 2013

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Bisphenol A or BPA is the ubiquitous estrogenic compound used to create plastics. It leaches into our food stuffs and because of its hormone-like qualities elicits a myriad of health issues in adults but especially in children and most especially when exposed in utero or during key developmental phases.

As we cover the expanding research base on BPA, it becomes increasingly clear that traditional methods of toxicology do not work for understanding endocrine disruptors – the man-made chemicals that alter our hormone pathways . A case in point, the latest research on BPA.

Exposure in Adults

A report published online in June of 2011 and presented at a prominent toxicology conference in February 2013, measured BPA exposure levels over a 24-hour period in adults fed a high BPA diet (lots of canned food and water from plastic bottles). The report showed that the concentration of BPA measured from blood was below the level of detection in most of the study participants, even though urine concentrations were extremely high and indicated exposure levels above the 95th percentile of the US population.

From urine tests, researchers were able to detect an average 84% – 97% of the dosed BPA and its metabolite, BPA glucuronide – indicating a high rate of clearance from the body. The ranges varied widely by time of day (morning tests showed significantly less clearance) and gender of participant (women did not process the hormone as well as men).

The researchers argue that their failure to detect BPA in blood, combined with the high concentration in the urine meant that risk was minimal. Their reasoning, even though BPA exposure was high, most of the BPA was cleared from the body rapidly and efficiently; no harm, no foul.

Medical and science marketers latched on to this and soon every major and minor media outlet was reporting that risks were minimal. Here are just a few headlines.

No Ill Effects Found in Human BPA Exposure, says the Wall Street Journal

Majestically Scientific Federal Study on BPA has Stunning Findings: So Why is the Media Ignoring it? – says Forbes

No toxic effects from controversial food packet, says expert – the Guardian

Ahh, where to begin?

Flaws in the Research

Conflicts of interest. Always look for industry sponsorship of for research, see my previous post on evaluating endocrine research for details. The relationship between the investigators in the present study and industry are muddled, but they do exist. For more information, click here.

Below the level of detection. When researchers report that their tests are unable to detect a visible pathology or measure a particular compound that any reasonable person would expect to be present, the test is likely at fault. Below the level of detection, means just that. It does not mean the compound was not present or that it was not exerting effects, only that the tests were not sensitive enough to measure the compound. This was case here and I suspect as testing methods improve, we’ll see higher detection levels in blood.

High clearance is not the same as never exposed. In this study, not all of the hormone was recovered in the urine, only an average of 84% – 97%. That sounds like a lot. With hormones, however, small amounts do great damage. Why? Because steroid hormones are stored in fat (and other tissues). They accumulate over time and metabolize into a myriad of different hormones (metabolites), some more potent than the parent compound. After the initial exposure and certainly after repeated exposures, our bodies become little (or big) hormone factories, storing and creating more and more hormones and hormone metabolites.

Metabolites matter. Hormones are shape shifters. Every time they meet an enzyme, the interaction between the enzyme and the hormone creates a new, similar, but differently shaped hormone. Hormones are never ‘one and done’ metabolizers. Even though a large percentage of the original hormone and its primary clearance metabolite were measured from urine in the present study, one cannot assume that there were not still other metabolites circulating within the body and wreaking havoc.

BPA has metabolites. This is critical and often ignored in toxicology research. BPA is a hormone like substance and as such, it metabolizes into many different forms. BPA has metabolites that are more potent than BPA itself. New research shows that BPA metabolizes into a compound called 4-methyl-2,4-bis(4-hydroxyphenl)pent-1-ene or MBP for short. MBP is 1000-fold stronger than BPA in its estrogenic effects. MBP binds strongly to both types of estrogen receptors (ERa and ERb) and may change the activity of the cell, displacing native or endogenous estradiol. So within that 3%-16% range of BPA not cleared, comes a compound 1000 times stronger than the BPA itself. As the research progresses, who knows how many other active and potent metabolites from BPA or MBP we’ll see. With hormones, nothing is simple or straightforward.

What this Means

Avoid medical marketing, it’s usually incorrect. Learn how to evaluate endocrine disruptor research. Once you get the hang of it, you’ll be able to dismiss faulty research at a glance. More importantly, learn about hormone systems and environmental hormone disrupting chemicals. Otherwise, our children will bear the brunt of our ignorance.

A good review article: Bisphenol A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption.

The Bottom Line: BPA and Endocrine Disruptors

by Laurel Pritchard, PhD

Published on October 21, 2012

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Unless you have been living under a rock for the past ten years, you probably know about BPA. Bisphenol A is a chemical used in the manufacturing of some hard plastics and liners for canned foods, including infant formula. In recent years, more and more plastic products, especially items like baby bottles, have adopted the “BPA-free” label. Why? It turns out that BPA mimics some effects of estrogens in the body. BPA and chemicals like it, known collectively as endocrine disruptors, have been implicated in a disturbing variety of health problems, ranging from early puberty to cancer. The U.S. Food and Drug Administration banned the use of BPA in manufacturing of baby bottles and sippy cups in July, 2012. However, its use in can liners and other plastic products is still essentially unregulated. The science of endocrine disruptors is still in its infancy, and consumers are left to decide what constitutes an acceptable level of exposure. So, how concerned should we be?

Is BPA Safe?

This turns out to be a complicated question. The vast majority of studies on BPA and other endocrine disruptors have been done in rodents, whose endocrine systems are not equivalent to those of humans. Many of the early studies of these compounds exposed animals to doses much higher than humans might ever experience or administered the compounds via routes that were unlikely in humans (e.g. intravenously). There was also a widespread lack of consistent methodology across studies, with different labs examining different endpoints, so that results were nearly impossible to compare and interpret. Recent efforts by the FDA, National Institutes of Health and Centers for Disease Control have helped to coordinate multiple, large scale studies and improve methodology.

The Good News and the Bad News about BPA

Based on these more recent studies, there’s good and bad news. The good news: recent estimates of exposure levels for infants are 10-fold lower than previous estimates (0.24 micrograms/kg body weight/day vs. 2.4 micrograms/kg body weight per day) [1]. This may be partly due to increased inaccurate assumptions about how parents prepare bottles. Also, studies in primates, whose endocrine metabolism is closer to humans, suggest that most orally-administered BPA is rapidly metabolized to an inactive form and excreted [2].

Now, the bad news. A recent study, in which pregnant rhesus monkeys were exposed continuously to low concentrations of BPA, similar to those found in human tissues, found that the ovaries of female fetuses had more unenclosed follicles [3]. This could mean that the female offspring of exposed monkeys would have fewer viable eggs and diminished reproductive success as adults, though this study did not follow the offspring to adulthood. Another study examined the effects of BPA on human breast epithelial cells grown in culture [4]. BPA increased expression of genes involved in DNA repair, including the BRCA1 and BRCA2 genes. Women who carry specific mutations in these genes are at five times greater risk for developing breast and ovarian cancers than the general population. The study suggests that women who carry these mutations may be unable to repair DNA damage induced by BPA and may be especially vulnerable to its effects on estrogen-sensitive tissues.

How Concerned Should We Be about BPA?

So, back to our original question: how concerned should we be? While exposure levels are probably fairly low, and much of the BPA we ingest is likely metabolized, there are certain populations, including pregnant women, infants and women at high risk for breast and ovarian cancer, who should be especially concerned. In the absence of tighter regulatory controls on BPA use in manufacturing, there are simple steps consumers can take to reduce their exposure. Bottom line, am I going to stop buying canned foods? Not entirely, but fresh is always nutritionally superior to canned anyhow. Do I buy BPA free bottles for my infant son? Absolutely. Do I spend a lot of time worrying about my family’s exposure to BPA? No. Not because it’s not important, but because there are many other known endocrine disruptors in our environment, and probably many more that haven’t yet come to our attention. BPA is just a small piece of a very complex puzzle.

References

[1]Department of Health and Human Services. Memorandum: Exposure to Bisphenol A (BPA) for infants, toddlers and adults from the consumption of infant formula, toddler food and adult (canned) food. 2009

[2]Doerge D.R., Twaddle N.C., Woodling K.A., Fisher J.W. Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys, Toxicology and Applied Pharmacology 2010; 248: 1–11.

[3] Hunt P.A., Lawson C., Gieske M., Murdoch B., Smith H., Marre A., Hassold T., Vandevoort C.A. Bisphenol A alters early oogenesis and follicle formation in the fetal ovary of the rhesus monkey. PNAS USA; 2012 Sep 24. [Epub ahead of print].

[4] Fernandez S.V., Huang Y., Snider K.E., Zhou Y., Pogash T.J., Russo J. Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. International Journal of Oncology 2012; 41(1): 369-77.

bisphenol A

We Need Your Help

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Industry Sponsored Research Is Biased

FDA or EPA Approved Does not Mean Safe or Risk-Free

Research Methods Matter

We Need Your Help

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BPA and Estrogens

Simulating Real Life Usage: Measurement Matters

What to Do With All of These Estrogens

Postscript

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Exposure in Adults

Flaws in the Research

What this Means

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Is BPA Safe?

The Good News and the Bad News about BPA

How Concerned Should We Be about BPA?

References

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