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In a paper published in the journal PLOS ONE, researchers have studied the association which exposure to endocrine-disrupting chemicals (EDCs) in women may have with the onset of menopause. The researchers report that high levels of 15 EDCs were associated with an earlier onset of menopause, and suggest that these EDCs warrant further attention.
Dr Crispin Halsall, Reader in Environmental Chemistry at Lancaster Environment Centre, Lancaster University, said:
“The study includes a large number of chemicals with widely varying potency with regards to mimicking or disrupting hormones. To add to this the concentration ranges in the serum of these women also varies enormously, so while the study appears to reveal an association between chemical exposure and the onset of menopause, the underlying reasons are really quite obscure. We can’t be complacent about long-lived synthetic chemicals that we are exposed to in our daily lives, but considerable research is required to tease out a mechanism to explain this effect. In addition, several chemicals listed in this paper, including PCBs, mirex and b-HCH are already banned in the UK.”
Prof. Warren Foster, CIHR/Ontario Women’s Health Council Professor & Director, McMaster University, said:
“To my knowledge dioxins, PCBs, and pesticides studied in this report have been banned. It is important to recognize that the dioxins are produced as a by-product of pesticide manufacture, waste incineration, and also occur naturally via forest fires. Several phthalates are being phased out and use has been restricted for use in some applications.
“We cannot fail to appreciate that analytical chemistry methods have improved over the last several decades to the point that we can measure sparingly small concentrations of chemical residues in human tissues and fluids. If we were to track chemical exposures over time we would undoubtedly find that exposures today are substantially lower than they were decades previously and are profoundly lower than accidental or occupational exposures. Moreover, while adverse effects have been documented in animal studies, the concentrations are quite large in comparison to human exposure. Indeed, the literature for these chemicals involving exposure, metabolism, distribution to target tissues, cellular and molecular mechanisms of effects is heavily nuanced and should not be over interpreted.”
Also:
“I have read the paper with interest. Overall the paper shows that there is a correlation between the concentrations of several environmental contaminants and age of menopause. However, as the author’s acknowledge they do not establish a causal association. Rather, this study is best characterized as a hypothesis generating study designed to highlight any chemicals that can be measured in human serum or urine that might be linked to menopause and worthy of further investigation in further studies designed to examine the causal relationship. The data do not support a conclusion that the chemicals identified are causally linked with menopause and cannot be used to affect policy or suggest changes in behaviour. These types of correlation are common and are just as likely the result of spurious findings. The old example used to explain this concept to students is: there are more storks in the city and more babies are born in the city therefore storks bring babies. Similar misleading correlations have been catalogued in recent years such as increased organic food consumption is positively correlated with a rise in population weight and therefore eating organic food is linked to the obesity epidemic. In the study being released today, the authors examined the relationship between 111 chemicals and menopause. Simply looking at this many chemicals alone increases the likelihood of finding several that are statically linked with the outcome of interest, associations that are more likely the consequence of statistical chance than actual meaningful association.
“Another important issue with this paper that were not brought out by the authors includes the following. Concentrations for persistent organic pollutants such as the dioxins, PCBs, and chlorinated organic pesticides studied in this paper have been falling in the environment. Similarly, the concentrations in human tissues and fluids have also been falling. The data reported in this study are for early NHANES study cycles as data for more recent cycles was not available. It will be interesting to see if the links remain as the more recent data becomes available.”
Prof. Richard Sharpe, Group Leader of Male Reproductive Health Research Team University of Edinburgh, said:
“Attempting to establish if exposure to environmental chemicals affects the risk of having an earlier menopause in women is an important question to answer, but poses quite a challenge. Menopause is determined by the age at which the ovaries become depleted of oocytes (eggs), and the number of oocytes is established during the foetal period (i.e. whilst the woman was a foetus in the womb). This study has used a cohort of menopausal women who are representative of the US population to ask whether their current exposure to a wide range of environmental chemicals is associated with them having had an earlier menopause. They found that women with the highest exposure to chemicals that are persistent in the body (PCBs, DDE, HCB) or to a ubiquitous non-persistent plasticiser (the phthalate DEHP) had a significantly earlier menopause (by 1.9-3.8 years).
“Whilst the study is generally well-conducted it has serious limitations, most of which are not mentioned. These include: (1) association does not prove cause and effect, (2) diet, in particular a high-fat diet, is an important determinant of exposure to the persistent chemicals that were measured, and to DEHP, but no allowance for this potential confounding was undertaken (i.e. the associations could reflect differences in diet not chemical exposures), (3) current chemical exposure may not accurately reflect exposures earlier in life or at points in life when any effect on oocyte number is likely, (4) the study would have been far more convincing if the authors had an internal positive control, for example by replicating the established adverse effect of smoking and earlier menopause, (5) the socioeconomic analyses seem very limited, considering their importance in relation to some of the factors being measured.”
Prof. Charles Tyler, Professor of Environmental Biology, University of Exeter, said:
“There are many studies of this nature now and the difficulty is they are all correlative…that is lots of health conditions associate with chemical burdens in humans. Separating out which ones are key in the disorders and which ones are not is almost impossible based on epidemiology data alone.
“Many previous studies have shown correlations between hormone (especially oestrogen) dependent processes and ‘adverse’ health outcomes. Here now for menopause. Other studies have linked various EDCs with obesity, heart infarctions etc. Much of the data/associations reported are marginal. The huge challenge here is trying to establish the significance on all of these findings (if anything).
“ I think the main message this sends to me is that although it is extremely difficult to assign a cause –effect relationship between any chemical or class of chemicals (EDCs or otherwise) and a specific health condition in humans from epidemiological studies, increasingly associations (correlations) are being drawn between chemical body burdens and unfavourable health outcomes. This study, like so many before on humans, and even more so for studies on wildlife, raise consciousness that persistent chemicals in the environment is not a good thing.”
Prof. Ashley Grossman, Professor of Endocrinology, University of Oxford, said:
“There are a lot of chemicals in our environment which have been suspected of causing significant hormonal (endocrine) changes, although much of the evidence comes from animal studies. In this paper a retrospective survey of a large number of women in the US suggested that suspected ‘endocrine-disrupting chemicals’ may shift the age of the menopause forward by between 2 and 4 years. Although a relatively small change, this could have a significant impact on fertility. However, the authors investigated up to 111 chemicals and, as this was more of a pilot study, did not make any allowance for multiple comparisons; it is always possible that comparing lots of different things will suggest a statistically significant effect when it purely arises by chance. There is also evidence that many of these chemicals have already been removed from industrial processes. Even so, it would be sensible to try and reduce environmental contaminants even further, particularly plastic bottles. Perhaps many of those walking around and continually sipping (expensive) bottled water will decide it might be healthier to abandon this unnecessary habit altogether.”
‘Persistent organic pollutants and early menopause in U.S. women’ by Grindler et al. published in PLOS ONE on Wednesday 28th January 2015.
Declared interests
Prof Warren Foster: I am not familiar with this study group and have no competing interest. Ongoing research studies in my laboratory are designed to better define human exposure to environmental contaminants and characterize the cellular and molecular mechanisms underlying reproductive effects on fertility in women. My research funding is provided by through the Canadian Institutes of Health Research. I do not hold any industry supported research contracts or grants. I have previously been retained as an expert witness for the plaintiffs in a case brought against a chemical company.
No other interests declared