Endocrine disrupting chemicals and menopause – experts respond

Credit: Eric Young

Women whose bodies have high levels of hormone mimicking chemicals found in plastics, personal-care products, common household items and the environment appear to experience menopause earlier than women with lower levels of these chemicals, according to a new US study.

Researchers analysed the blood and urine of almost 1,500 menopausal women and identified 15 chemicals – nine PCBs, three pesticides, two phthalates and a furan (a toxic chemical) – that warrant closer evaluation because they were significantly associated with earlier ages of menopause and could potentially have detrimental effects on ovarian function. The research was published in the journal PLOS One today.

Our colleagues at the UK and Australian SMCs collected the following expert commentary. Feel free to use these quotes in your reporting. If you would like to contact a New Zealand expert, please contact the SMC (04 499 5476; smc@sciencemediacentre.co.nz).

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:

“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.”

ADDITIONAL COMMENT from 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.”

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.”

From the Australian Science Media Centre

Dr Ian Musgrave is a Senior Lecturer in the Faculty of Medicine, School of Medicine Sciences, within the Discipline of Pharmacology at the University of Adelaide

“A number of chemicals that are persistent pollutants in the environment such as polychlorinated biphenyl’s (PCB’s) and phthalates can weakly mimic estrogen or testosterone. As they are easily absorbed and can accumulate in the body, these chemicals may accumulate to levels that have adverse effects on human health.

“This study looks at the occurrence of early menopause in a sample of US women with levels of a variety of persistent organic pollutants that can mimic estrogens’ effects. The study found that women who had high levels of PCB’s, some pesticides or phthalates in their urine, higher than 90 per cent of women in the general community, went through menopause between 6 months to three years earlier than women in the general community. The amount menopause was shifted by, and the statistical strength of the association, varied quite a bit even in the same chemical class. When the researchers tried to control for the length of time the women had been exposed to these chemicals, the association disappeared for phthalates and some of the pesticides, but remained for PCB’s.

“While the associations are suggestive, correlation studies suffer from the problem that other factors may be involved. However, these results are concerning and should be carefully considered with a view to reducing PCB exposure in people with the highest levels of PCB’s. This is already occurring to some extent, the latest US National Health and Nutrition Examination Survey shows that exposures to phthalates at least has fallen by around 45 per cent from the levels examined in this study.”

Dr Anna Callan is a lecturer in the School of Medical Sciences, Faculty of Health, Engineering and Science at Edith Cowan University

“Endocrine disrupting chemicals are substances that interfere with the normal hormonal processes in the body. This study used a relatively small sub-sample from a large US population based study to investigate whether exposure to endocrine disrupting chemicals such as pesticides and polychlorinated biphenyls were associated with an earlier age of menopause.

“Fifteen organic pollutants were identified as being associated with an early menopause – with the earlier onset in those with the highest exposure ranging from 1.9 to 3.8 years, depending on the specific chemical. The study was cross sectional and so cannot demonstrate cause and effect, however it does provide an important starting point for future research.

“Chemicals that affect ovarian function could have serious implications for women’s health and fertility at the population level. To date there has been limited research in Australia on the exposure of individuals to organic pollutants and other endocrine disrupting chemicals. More research is needed to identify the sources of exposure – to pinpoint where these chemicals are found in our diets or home environments – as well as to measure any potential associated health effects.”

Professor Susan Davis is a National Health and Medical Research Council (NHMRC) Principal Research Fellow and Professor of Women’s Health in the School of Public Health and Preventive Medicine at Monash University

“This is an important paper and adds to the growing evidence that there are a number of environmental chemicals that disrupt the balance of reproductive hormones and reproductive function.

“Whether the observed effect of an earlier menopause represents organ-specific effects (i.e. that these compounds are toxic to the ovaries) or a general toxicity of these compounds is not yet known.

“A limitation to the study is that it relied on women’s recall of when their menopause occurred. The authors have suggested that such recall is pretty accurate but in the study they quoted, 25 per cent of women were at least 2 years out in their recall of when their menopause actually occurred. As that study included women who had experienced a surgical menopause (these women may have been more accurate in their recall) there is a concern that more than 25 per cent of the women may have made an incorrect recall of at least 2 years, give or take.

“However, the findings reported here are consistent with another recent study that reported that higher phthalate levels were associated with lower testosterone levels in women aged 40-60 years (Meeker et al. 2014).

“These compounds are ubiquitous in our 21st century environment, and as the authors say research into the health consequences of exposure to these endocrine disrupting chemicals should be prioritised.  These chemicals not only pose a potential threat to human health, but to the health of all living creatures.”

Professor Ian Rae is an Honorary Professorial Fellow at the University of Melbourne and Former President of the Royal Australian Chemical Institute

“The good news is that most of the chemicals involved in this study have been banned for almost a decade under the Stockholm Convention and their concentrations in the environment – and in our body burdens! – are declining.

“Looking at the reported results, I think that age at menopause could be affected by many things, not just those that the researchers controlled for when they surveyed their populations. Industrial chemicals could be involved but as with epidemiological studies of this type, all that can be observed is an ‘association. The authors do say this but their enthusiasm is sometimes misplaced, since 45-55 are hardly prime years for expression of fertility.”