Sarah J. Janssen

Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing

OBJECTIVE To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. DESIGN Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. CONCLUSION(S) The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which womens health can be improved.

Health Effects of the Gulf Oil Spill

The oil spill in the Gulf of Mexico poses direct threats to human health from inhalation or dermal contact with the oil and dispersant chemicals, and indirect threats to seafood safety and mental health. Physicians should be familiar with health effects from oil spills to appropriately advise, diagnose, and treat patients who live and work along the Gulf Coast or wherever a major oil spill occurs.

Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points for Improved Risk Assessment and Decision-Making

Background Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an “adverse effect” in the context of hazard identification and risk assessment. Objectives Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available. Discussion Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects. Conclusions For certain classes of early perturbations, sufficient information on the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population.

Environmental impacts on reproductive health and fertility

1. Introduction Tracey J. Woodruff and Linda C. Giudice 2. Environmental contaminants and exposure Mary A. Fox and Yutaka Aoki 3. Development and maturation of the normal female reproductive system: 3.1. Ovary Laxmi A. Kondapalli and Teresa K. Woodruff 3.2. Oviduct and uterus Leo F. Doherty and Hugh S. Taylor 3.3. Breast Maricel V. Maffini, Carlos Sonnenschein and Ana M. Soto 4. Development and maturation of the normal male reproductive system Richard M. Sharpe 5. Modern genetics of reproductive biology Taisen Iguchi and Tamotsu Sudo 6. Mechanisms of endocrine disruption K. Leigh Greathouse and Cheryl L. Walker 7. Developmental exposures and implications for early and latent disease Retha R. Newbold and Jerrold J. Heindel 8. Wildlife as sentinels of environmental impacts on reproductive health and fertility Heather J. Hamlin and Louis J. Guillette Jr 9. Environmental contaminants and effects on timing and progression of human pubertal development Annette Mouritsen, Julie Damm, Lise Aksglaede, Kaspar Sorensen and Anders Juul 10. Environmental contaminants and impacts on healthy and successful pregnancies Remy Slama and Sylvaine Cordier 11. Environmental contaminants and the reproductive and fertility effects in the male: 11.1. Introduction Sarah J. Janssen 11.2. Environmental contaminants and male reproductive health: possible role of fetal exposure Jorma Toppari, Helena E. Virtanen and Niels E. Skakkebaek 11.3. Environmental contaminants and male reproductive health: adult exposure and effects on fertility John D. Meeker and Russ Hauser 12. Environmental contaminants, female reproductive health and fertility Pauline Mendola and Germaine M. Buck Louis 13. Environmental contaminants and related systems that have implications for reproduction: 13.1. The neuroendocrine system Andrea C. Gore 13.2. The thyroid system R. Thomas Zoeller and John D. Meeker 13.3. The immune system Robert W. Luebke and Dori R. Germolec 14. Environmental contaminants and cancers of the reproductive tract Gail S. Prins and Esther L. Calderon 15. Communicating with patients and the public about environmental exposures and reproductive risk Gina M. Solomon and Sarah J. Janssen 16. Interpreting science in the policy context Tracey J. Woodruff and Sarah J. Janssen 17. Conclusions - what does all this mean and where are we going? Shanna H. Swan, Patricia Hunt and Linda C. Giudice Index.

Outcomes of the California ban on pharmaceutical Lindane: clinical and ecologic impacts

Introduction There are increasing concerns over the presence and implications of pharmaceutical agents in water. In 2002, California banned pharmaceutical use of lindane because of concerns about water quality, as lindane treatment for head lice and scabies was found to be a significant factor adversely affecting wastewater quality. Objectives In this article we describe the effects the ban has had on wastewater quality, unintentional exposures, and clinical practice. This is the first time that a pharmaceutical has been outlawed to protect water quality. As such, this ban provides a rare opportunity to evaluate the possible or potential outcomes of future public health interventions aimed at reducing pharmaceutical water contamination. Methods We compiled data on lindane in wastewater treatment plant effluent for several large plants in California and one outside of California. Data on exposures to lindane were obtained from records of the California Poison Control System. We assessed the impact on clinical practice via a survey of 400 pediatricians Results Wastewater treatment plant monitoring showed that lindane declined in California after the ban. Similarly, unintentional exposure calls declined. Most physicians were aware of the ban (81%) and had used lindane previously (61%), but they did not notice any difficulties with the ban (78%). Conclusions The California experience suggests that elimination of pharmaceutical lindane produced environmental benefits, was associated with a reduction in reported unintentional exposures, and did not adversely affect head lice and scabies treatment. This ban serves as a model for governing bodies considering limits on the use of lindane or other pharmaceuticals.

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation

Background Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk. Methods Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC. Results The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist. Conclusions This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor β activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases. Citation Schwarzman MR, Ackerman JM, Dairkee SH, Fenton SE, Johnson D, Navarro KM, Osborne G, Rudel RA, Solomon GM, Zeise L, Janssen S. 2015. Screening for chemical contributions to breast cancer risk: a case study for chemical safety evaluation. Environ Health Perspect 123:1255–1264; http://dx.doi.org/10.1289/ehp.1408337

Talking With Patients and the Public About Endocrine-Disrupting Chemicals

Health care providers often discuss issues of risk and uncertainty with patients in the context of surgery, diagnostic tests, immunizations, or treatment. Communication of potential risks and benefits before making a voluntary decision is the foundation of informed consent (1). Communication about environmental health risk differs from medical informed consent in that the hazard usually involves involuntary exposure, may be unfamiliar, provides no benefit to those exposed, and there often is much less known about the potential risks. Health care providers may not know where to find information to answer questions related to environmental health generally, or endocrine disruption specifically. Even when scientific information is available about the health effects of chemical exposure, it is almost never enough to answer questions pertaining to individual risk (as opposed to population risk) and rarely addresses issues related to the long-term effects of poorly quantified exposure during vulnerable periods of development of the fetus, young child, or adolescent (2). Despite the paucity of relevant information, health care providers have an important role to play in communication of risks associated with endocrine disruptors and

Endocrine Disruption and Reproductive Outcomes in Women

Infertility and associated problems of the female reproductive tract, such as endometriosis, abnormal menstrual cycles, and premature menopause, are diagnosed in women of reproductive age. For this reason, reproductive problems are usually considered to be “adult” conditions. Whereas, some female reproductive problems are the result of contaminant exposures during adulthood, there is increasing evidence that exposures early in life can result in permanent and irreversible changes to the reproductive tract, which are not manifest until decades later. A growing body of scientific evidence suggests that exposure to endocrine-disrupting chemicals (EDCs) early in life may alter development of the reproductive tract and hormonal responsiveness in adulthood (1,2). Coupled with this evidence are a number of disturbing trends in some geographic regions, including a reduction in fertility, an increase in hormone-sensitive cancers, an earlier age of puberty in girls, and a decrease in the number of boys being born. Evidence from animal studies indicates that these conditions are likely to originate during the prenatal period. Exposures to environmental contaminants early in life are