Foetal oestrogens and autism

High Levels of Sex Hormones in The Womb Linked to Autism Once More

A small new study has once again found a link between elevated hormone levels in the womb and the likelihood of developing autism. But this time, instead of major androgens such as testosterone, researchers are pointing the finger at estrogen, medicalxpress and sciencealert report. Image.

Abstract

Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.

“In conclusion, we have demonstrated that prenatal oestradiol, oestriol and oestrone are elevated in in boys who went on to develop autism. This extends our previous finding of elevated prenatal steroidogenesis in the same cohort and provides further evidence for the prenatal steroid theory of autism. High levels of prenatal oestradiol contribute to a greater degree to autism likelihood than other prenatal sex steroids, including testosterone. We conclude that prenatal oestrogenic excess is a characteristic of autism and may interact with genetic predisposition to affect neurodevelopment.”

See studies in ref to DES and autismADHDDown’s syndrome.

Evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing

Pubertal development after unintended intrauterine exposure to oral contraceptives: a nationwide cohort study

2019 Study Abstract

Objective
To study the associations between exposure to oral contraceptives before conception and early in pregnancy and pubertal timing in boys and girls.

Design
Population-based cohort study.

Setting
Not applicable.

Patient(s)
Overall, 15,800 children (70%) born during 2000–2003 into the Danish National Birth Cohort were categorized according to maternal use of combined oral contraceptive pills or progestin-only pills reported around gestational week 17: no exposure (reference), exposure 4 months before conception, and exposure in early pregnancy. Children self-assessed pubertal status using Web-based questionnaires from 11 years and biannually throughout puberty.

Intervention(s)
None.

Main Outcome Measure(s)
Adjusted mean age differences (months) for attaining individual pubertal milestones and overall pubertal timing. Proportion mediated by prepubertal body mass index.

Result(s)

  • In boys, intrauterine exposure to oral contraceptives showed a tendency toward slightly earlier mean age for voice break (months, −3.8; 95% confidence interval [CI] −6.5, −1.0) and first ejaculation (months, −2.9; 95% CI −5.9, 0.1) and a mean difference of −1.4 months (95% CI −3.3, 0.4) for overall pubertal timing.
  • Girls with intrauterine exposure tended to have slightly earlier age at menarche (months, −1.9; 95% CI −4.0, 0.3) and Tanner breast stages and had a mean difference of −0.9 months (95% CI −2.7, 1.0) for overall pubertal timing.
  • Exposure before conception was not associated with pubertal timing. Prepubertal body mass index did not play a mediating role.

Conclusion(s)
This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing.

Anti-inflammatory drugs and contraceptive pills polluting our waters – A 20year systematic review

Monitoring, sources, receptors, and control measures for three European Union watch list substances of emerging concern in receiving waters, 2017

2017 Study Abstract

Pollution of European receiving waters with contaminants of emerging concern (CECs),

  1. such as with 17-beta-estradiol (a natural estrogenic hormone, E2),
  2. along with pharmaceutically-active compounds diclofenac (an anti-inflammatory drug, DCL)
  3. and 17-alpha-ethynylestradiol (a synthetic estrogenic hormone, EE2))

is a ubiquitous phenomenon. These three CECs were added to the EU watch list of emerging substances to be monitoring in 2013, which was updated in 2015 to comprise 10 substances/groups of substances in the field of water policy.

A systematic literature review was conducted of 3952 potentially relevant articles over period 1995 to 2015 that produced a new EU-wide database consisting of 1268 publications on DCL, E2 and EE2. European surface water concentrations of DCL are typically reported below the proposed annual average environmental quality standard (AA EQS) of 100ng/l, but that exceedances frequently occur. E2 and EE2 surface water concentrations are typically below 50ng/l and 10ng/l respectively, but these values greatly exceed the proposed AA EQS values for these compounds (0.04 and 0.035ng/l respectively). However, levels of these CECs are frequently reported to be disproportionately high in EU receiving waters, particularly in effluents at control points that require urgent attention.

Overall it was found that DCL and EE2 enter European aquatic environment mainly following human consumption and excretion of therapeutic drugs, and by incomplete removal from influent at urban wastewater treatment plants (WWTPs). E2 is a natural hormone excreted by humans which also experiences incomplete removal during WWTPs treatment. Current conventional analytical chemistry methods are sufficiently sensitive for the detection and quantification of DCL but not for E2 and EE2, thus alternative, ultra-trace, time-integrated monitoring techniques such as passive sampling are needed to inform water quality for these estrogens. DCL appears resistant to conventional wastewater treatment while E2 and EE2 have high removal efficiencies that occur through biodegradation or sorption to organic matter.

There is a pressing need to determine fate and behaviour of these CECs in European receiving waters such as using GIS-modelling of river basins as this will identify pressure points for informing priority decision making and alleviation strategies for upgrade of WWTPs and for hospital effluents with advanced treatment technologies. More monitoring data for these CECs in receiving waters is urgently needed for EU legislation and effective risk management

Environmental impact of estrogens on human, animal and plant life: A critical review

Water Pollution Caused by Birth Control Poses Dilemma – Environment International, 2017

2017 Study Abstract

Background
Since the inception of global industrialization, steroidal estrogens have become an emerging and serious concern. Worldwide, steroid estrogens including estrone, estradiol and estriol, pose serious threats to soil, plants, water resources and humans. Indeed, estrogens have gained notable attention in recent years, due to their rapidly increasing concentrations in soil and water all over the world. Concern has been expressed regarding the entry of estrogens into the human food chain which in turn relates to how plants take up and metabolism estrogens.

Objectives
In this review we explore the environmental fate of estrogens highlighting their release through effluent sources, their uptake, partitioning and physiological effects in the ecological system. We draw attention to the potential risk of intensive modern agriculture and waste disposal systems on estrogen release and their effects on human health. We also highlight their uptake and metabolism in plants.

Methods
We use MEDLINE and other search data bases for estrogens in the environment from 2005 to the present, with the majority of our sources spanning the past five years. Published acceptable daily intake of estrogens (μg/L) and predicted no effect concentrations (μg/L) are listed from published sources and used as thresholds to discuss reported levels of estrogens in the aquatic and terrestrial environments. Global levels of estrogens from river sources and from Waste Water Treatment Facilities have been mapped, together with transport pathways of estrogens in plants.

Results
Estrogens at polluting levels have been detected at sites close to waste water treatment facilities and in groundwater at various sites globally. Estrogens at pollutant levels have been linked with breast cancer in women and prostate cancer in men. Estrogens also perturb fish physiology and can affect reproductive development in both domestic and wild animals. Treatment of plants with steroid estrogen hormones or their precursors can affect root and shoot development, flowering and germination. However, estrogens can ameliorate the effects of other environmental stresses on the plant.

Conclusions
There is published evidence to establish a causal relationship between estrogens in the environment and breast cancer. However, there are serious gaps in our knowledge about estrogen levels in the environment and a call is required for a world wide effort to provide more data on many more samples sites. Of the data available, the synthetic estrogen, ethinyl estradiol, is more persistent in the environment than natural estrogens and may be a greater cause for environmental concern. Finally, we believe that there is an urgent requirement for inter-disciplinary studies of estrogens in order to better understand their ecological and environmental impact.

Dry olive leaf extract attenuates DNA damage induced by DES in human peripheral blood cells in vitro

The protective potential of dry olive leaf extract could arise from the synergistic effect of its scavenging activity and enhancement of the cells’ antioxidant capacity

2018 Study Highlights

  • Antigenotoxic potential of DOLE was investigated on the human whole blood in vitro, using comet assay.
  • E2 and DES were used as DNA damage inducers, expressing a genotoxic effect.
  • DOLE exhibited antigenotoxic properties.

Abstract

Phenolic groups of steroidal or nonsteroidal estrogens can redox cycle, leading to oxidative stress, where creation of reactive oxygen species are recognized as the main mechanism of their DNA damage properties.

Dry olive (Olea europaea L.) leaf extract is known to contain bioactive and antioxidative components and to have an ability to modulate the effects of various oxidants in cells.

The main goal of this study was to investigate antigenotoxic potential of a standardized dry olive leaf extract on DNA damage induced by 17β-estradiol and diethylstilbestrol in human whole blood cells in vitro, using comet assay.

Our results indicated that both hormones showed a genotoxic effect at a concentration of 100 μM (P < 0.05, n = 6).

Dry olive leaf extract was efficient in reducing number of cells with estrogen-induced DNA damage at tested concentrations (0.125, 0.5 and 1 mg/mL) (P < 0.05, n = 6) and under two experimental protocols, pre-treatment and post-treatment, exhibiting antigenotoxic properties.

Analysis of antioxidant properties of the extract revealed moderate ABTS radical scavenging properties and reducing power.

Overall, our results suggested that the protective potential of dry olive leaf extract could arise from the synergistic effect of its scavenging activity and enhancement of the cells’ antioxidant capacity.

DES DiEthylStilbestrol Resources

Endocrine Disrupting Chemicals and Behavior

Special issue of Hormones and Behavior, Volume 101, Pages 1-148, May 2018

The peer-reviewed journal Hormones and Behavior, Volume 101, Pages 1-148 (May 2018), raises concern about how many of the 90,000+ chemicals in use today may disrupt our most basic endocrine systems with significant consequences for neurodevelopment, neurophysiology, healthy brain aging, and behavior.

Several articles address bisphenol A :

About PDBEs, triclosan, and other replacement chemicals :

Other studies included in this special issue address behavioral effects of voluntary taken pharmaceuticals, including birth control pills, and pain medications.

About DES and the BRAIN :

All species are exposed to EDCs and at risk for adverse neurodevelopmental outcomes

Behavioral and molecular analyses of olfaction-mediated avoidance responses of Rana (Lithobates) catesbeiana tadpoles: Sensitivity to thyroid hormones, estrogen, and treated municipal wastewater effluent

2018 Study Highlights

  • Olfaction is critical in tadpoles for predator avoidance and food location.
  • Thyroid hormones (THs) change olfactory tissues dramatically during metamorphosis.
  • T3 & municipal wastewater effluent, but not T4 or E2, disrupt avoidance behavior.
  • Thra and thibz mRNAs are significantly higher in T3 versus T4 olfactory epithelium.
  • Further bioindicator candidates are needed to link to adverse behavior outcomes.

Abstract

Olfaction is critical for survival, facilitating predator avoidance and food location. The nature of the olfactory system changes during amphibian metamorphosis as the aquatic herbivorous tadpole transitions to a terrestrial, carnivorous frog. Metamorphosis is principally dependent on the action of thyroid hormones (THs), l-thyroxine (T4) and 3,5,3′-triiodothyronine (T3), yet little is known about their influence on olfaction during this phase of postembryonic development.

We exposed Taylor Kollros stage I-XIII Rana (Lithobates) catesbeiana tadpoles to physiological concentrations of T4, T3, or 17-beta-estradiol (E2) for 48 h and evaluated a predator cue avoidance response.

The avoidance response in T3-exposed tadpoles was abolished while T4- or E2-exposed tadpoles were unaffected compared to control tadpoles. qPCR analyses on classic TH-response gene transcripts (thra, thrb, and thibz) in the olfactory epithelium demonstrated that, while both THs produced molecular responses, T3 elicited greater responses than T4. Municipal wastewater feed stock was spiked with a defined pharmaceutical and personal care product (PPCP) cocktail and treated with an anaerobic membrane bioreactor (AnMBR). Despite substantially reduced PPCP levels, exposure to this effluent abolished avoidance behavior relative to AnMBR effluent whose feed stock was spiked with vehicle. Thibz transcript levels increased upon exposure to either effluent indicating TH mimic activity.

The present work is the first to demonstrate differential TH responsiveness of the frog tadpole olfactory system with both behavioral and molecular alterations. A systems-based analysis is warranted to further elucidate the mechanism of action on the olfactory epithelium and identify further molecular bioindicators linked to behavioral response disruption.

Fetal Origin of Adult Disease

Abstract from “Environmental Exposures and Adverse Pregnancy Outcomes: A Review of the Science”

During the last two decades, chronic disease has replaced infectious disease as the major focus of public health concern. The top 4 leading causes of death in the United States are chronic diseases. There remains much unknown about the etiology of many chronic conditions, which in most cases is probably multifactorial. Studies from the 1990s found that effects on the fetal environment, such as through poor or inadequate nutrition, can result in an increased risk of adult onset of chronic conditions, such as coronary heart disease. This has been called the fetal origins hypothesis (also known as the Barker theory), which proposes that external influences on the fetal environment can increase the risk of later disease in adulthood.

Diethylstilbestrol (DES)—a synthetic estrogen given to US women between 1938 and 1971 to prevent pregnancy complications illustrates the fetal origins of later in life disease. In utero DES exposure left mature female offspring at increased risk of clear cell adenocarcinoma of the vagina and cervix, breast cancer, structural reproductive tract anomalies, an increased infertility rate, and poor pregnancy outcomes, while male offspring have an increased incidence of genital abnormalities and a possibly increased risk of prostate and testicular cancer. These observed human effects have been confirmed in numerous animal models, which have also predicted changes later found in DES-exposed humans, such as increased incidence of uterine fibroids, oviductal malformations, and second generational effects such as increased menstrual irregularities and possibly ovarian cancer in DES granddaughters and increased hypospadias in DES grandsons.

Diethylstilbestrol shows the adverse effects of fetal exposures to synthetic chemicals may not be apparent at birth or even for many years afterward, and that continued monitoring of this cohort of exposed children and grandchildren is necessary to inform potential effects of prenatal exposures to other contaminants.

Reference. Image credit Hush Naidoo.

DES DiEthylStilbestrol Resources

Less plastic use help decrease harmful chemicals in the body

The ReThink Plastic Pilot Study Community Report, 2018

A new pilot study has shown that women who reduce their exposure to plastic see a decrease in estrogen-mimicking chemicals in their bodies within a month.

The chemicals used in the manufacture of many plastics are known to mimic estrogen activity. There is strong scientific evidence linking these “environmental estrogens” to breast cancer. The ReThink Plastic study was designed to reduce exposure to these chemicals using simple, practical behavior change and to build a coalition of plastic use reduction by spreading the study messages. This approach could result in broad benefits by effectively reducing exposure to harmful chemicals in plastic and thus protecting against breast cancer and protecting the environment against plastic pollution.

Specifically, the objectives of the study were to:

  1. Inform participants about the harmful effects of chemicals that are in plastic
  2. Teach participants simple ways to reduce the use of plastic in order to reduce the potential for harmful health effects
  3. Ask participants to spread the message to other friends and family
  4. Evaluate the effectiveness of the study:
    • Examine changes in “plastic use” behavior before and after the study
    • Examine changes in estrogenic activity before and after the study in a small sub-study of post-menopausal women.

Reference.

Staying with the Trouble : Making Kin in the Chthulucene

Donna J. Haraway’s poetic guide to finding connection in a time of crisis, 2016

Description

In the midst of spiraling ecological devastation, multispecies feminist theorist Donna J. Haraway offers provocative new ways to reconfigure our relations to the earth and all its inhabitants. She eschews referring to our current epoch as the Anthropocene, preferring to conceptualize it as what she calls the Chthulucene, as it more aptly and fully describes our epoch as one in which the human and nonhuman are inextricably linked in tentacular practices. The Chthulucene, Haraway explains, requires sym-poiesis, or making-with, rather than auto-poiesis, or self-making. Learning to stay with the trouble of living and dying together on a damaged earth will prove more conducive to the kind of thinking that would provide the means to building more livable futures. Theoretically and methodologically driven by the signifier SF—string figures, science fact, science fiction, speculative feminism, speculative fabulation, so far—Staying with the Trouble further cements Haraway’s reputation as one of the most daring and original thinkers of our time.

Awash in Urine,” chapter 5, begins with personal and intimate relations, luxuriating in the consequences of following estrogens that connect an aging woman and her elder dog, specifically, me and my companion and research associate Cayenne. Before the threads of the string figure have been tracked far, remembering their cyborg littermates, woman and dog find themselves in histories of veterinary research, Big Pharma, horse farming for estrogen, zoos, DES feminist activism, interrelated animal rights and women’s health actions, and much more. Intensely inhabiting specific bodies and places as the means to cultivate the capacity to respond to worldly urgencies with each other is the core theme.

More Information

  • Introduction and customer reviews on amazon and goodreads.
  • Donna Haraway lectures at the San Francisco Art Institute, April 25, 2017.
  • Chapter 5 Awash in Urine DES and Premarin in Multispecies Response-ability is lightly revised from Women’s Studies Quarterly 40, nos. 3/4 (spring/summer 2012): 301 – 16.
DES DiEthylStilbestrol Resources