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Environmental Impacts on Reproductive Health: Foundations of the Science

Environmental Impacts on Reproductive Health: Foundations of the Science. Association of Reproductive Health Professionals www.arhp.org. Expert Medical Advisory Committee. Kathleen Hill Besinque, PharmD, MSEd, FCSHP Maureen Paul, MD, MPH Barbara Sattler, RN, DrPH, FAAN

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Environmental Impacts on Reproductive Health: Foundations of the Science

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  1. Environmental Impacts on Reproductive Health:Foundations of the Science Association of Reproductive Health Professionals www.arhp.org

  2. Expert Medical Advisory Committee Kathleen Hill Besinque, PharmD, MSEd, FCSHP Maureen Paul, MD, MPH Barbara Sattler, RN, DrPH, FAAN Ted Schettler, MD, MPH Michael Thomas, MD (co-chair) Tracey Woodruff, PhD, MPH (co-chair) Sandy Worthington, MSN, WHNP-BC, CNM

  3. Acknowledgment of Support This project is funded through a grant from the Passport Foundation and the Richard and Rhoda Goldman Fund.

  4. Faculty Disclosure Speaker: Kirtly Jones, MD: nothing to disclose Note: Staff and committee disclosures listed in program

  5. Learning Objectives At the conclusion of this course, clinicians should be able to: Appreciate impact of exposure to harmful environmental chemicals and heavy metals on reproductive health Express value of incorporating basic questions about environmental risks into patient history & physical examination more…

  6. Learning Objectives (continued) Use resources that provide information about environmental exposures in their communities & patient populations Refer patients to relevant resources & further information to learn more about environmental risks

  7. Awareness of Environmental Exposures & Impacts Is Growing Air pollution Water contamination Harmful substances in physical structures and workplaces Food contamination Personal care products

  8. Awareness of Reproductive Effects Is Growing ‘ ‘ “…exposures of males and females to foreign substances prior to conception can affect both their ability to conceive and the health of their offspring.” Davis DL, et al.JAMA. 1998

  9. Reproductive Trends in Some Geographic Areas Raise Concerns Increase in testicular cancer incidence Decreasing sperm counts Decline in serum testosterone Earlier pubertal development in girls Fewer males being born Documented increases in certain types of birth defects Bray F, et al. Int J Cancer. 2006; Edmond LD, James LM. MMWR Surveill Summ. 1990; Euling et al. Pediatrics. 2008; Herman-Giddens ME. Int J Androl. 2006; Harris KB. Mol Genet Metab. 2007; Hertz-Picciotto et al. Environmental Health. 2008; Jørgensen N, et al. Int J Androl. 2006; Mackenzie CA. Environ Health Perspect. 2005; Travison TG, et al. J Clin Endocrinol Metab. 2007; Vu LT. J Pediatr. 2008.

  10. Some Reproductive Effects Are Well Known Jones HE, et al. Obstet Gynecol Clin North Am. 1998. EPA. 2008. Woodruff TJ, et al. Fertil Steril. 2008; CDC. 2009; US Surgeon General. 2005.

  11. Content Overview This slide set will review: State of the science Windows of susceptibility Patient counseling Further information and resources

  12. US Chemical Production and Importation Are High 87K 3K 8K Approximate no. of chemicals registered for commerce in US are produced or imported in annual quantities of >1 million pounds --or one-tenth--have been tested for potential health effects* *Among those tested for certain properties, reproductive/environmental effects often have not been assessed. GAO. 2006; EPA. 2008.

  13. Many Complex Factors Interact to Affect the Impact of Exposures Genetic makeup, gene expression Social environments Diet/Nutrition Reproductive/developmental toxicants Reproductive health & fetal/child development Adapted from Hubbs-Tait et al. Psychological Science in the Public Interest. 2005.

  14. Exposure-Effect Continuum Source e.g., air, water, food, soil Biological uptake (exposure) Breathing, eating/drinking, skin contact Target Organ Dose e.g., testis, ovary, transplacental transport Biologic Change/ Clinical Effect CDC. 2009.

  15. ‘ ‘ The Barker Hypothesis “Exposures to adverse insults during critical…windows of development can permanently reprogram normal physiologic responses, and thus give rise to…disorders later in life.” Woodruff TJ, et al.Fertil Steril. 2008 Barker DJ. Trends Endocrinol Metab. 2002; Woodruff TK, Walker CL. Fertil Steril. 2008; Woodruff TJ, et al. Fertil Steril. 2008.

  16. Biomonitoring Can Yield Useful Information Measures chemical levels in body tissues or fluids (e.g., organ tissue, hair, breast milk, blood, urine) One way to document exposures Often accurate at low levels But… Usually unable to identify source Often clinical significance is unclear Sexton K, et al. American Scientist. 2004.

  17. Environmental Exposures and Critical Windows of Susceptibility Woodruff TJ, et al. Fertil Steril. 2008.

  18. Identified Reproductive Endpoints in Animal and/or Human Studies Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.

  19. Environmental Effects Have Multiple Mechanisms Examples: Toxicants Damage to oocytes/sperm Changes to DNA structure/gene expression Interference with cell function more… Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.

  20. Exposure May Affect DNA Structure and Gene Expression 2 1 Functional changes to gene expression Structural changes to DNA sequence more… Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.

  21. Exposure May Affect DNA Structure and Gene Expression 3 4 Functional changes to gene expression Structural changes to DNA sequence Modification of gene expression Chromosomal damage Example: Hormone disruption Example:Gene mutations Examples: Altered hormone levels, early puberty, infertility Example:Birth defects and cancer Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.

  22. Epigenetic Effects Result from Changes in Gene Expression Epigenetic effects: Not caused by internal changes in DNA May be caused by external environmental factors that modify gene activation May be passed to subsequent generations (preliminary evidence) Bird A. Nature. 2007; Cavalli G, et al. Cell. 1998.

  23. DES: An Example of Delayed Effects Given to pregnant women from 1930s to1970s to prevent miscarriage Linked to health effects in offspring Increased cancer risk; reproductive abnormalities more… DES Cancer Network. 2008; Dieckman WJ, et al. Am J Obstet Gynecol. 1999; Herbst AL. N Engl J Med. 1971; NIEHS. 2008; Schrager S, et al. Am Fam Physician. 2004.

  24. DES: An Example of Delayed Effects (continued) Examples of delayed effects in offspring: High-risk pregnancy; miscarriage Increased vaginal, cervical, breast cancer Increased infertility Structural defects in reproductive organs DES Cancer Network. 2008; Dieckman WJ, et al. Am J Obstet Gynecol. 1999; Herbst AL. N Engl J Med. 1971; NIEHS. 2008; Schrager S, et al. Am Fam Physician. 2004.

  25. DES: An Example of Delayed Effects (continued) DES Grandsons DES Granddaughters DES Granddaughters Penis Rete testis* Seminal vesicles* Prostate* Ovaries* Uterus* Immune system* Menstruation Ovaries* Uterus* Women who took DES while pregnant * = Effects in animals DES Sons DES Daughters Adapted from Schwartz JM, Woodruff TJ. Shaping Our Legacy. 2008.

  26. Endocrine-Disrupting Chemicals Certain pesticides, industrial chemicals & byproducts, ingredients in plastics manufacture --Interfere with hormonal levels or functions, including estrogen, testosterone, prolactin, LH, FSH, thyroid, etc. --Demonstrated by rigorous animal studies & epidemiological observations Welshons WV. Environ Health Perspect. 2003.

  27. ‘ ‘ Position Statement on EDCs “Until such time as conclusive scientific evidence exists to either prove or disprove harmful effects of substances, a precautionary approach should be taken in the formulation of EDC policy.” The Endocrine Society, June 2009 Endocrine Society. 2009.

  28. Lessons Learned from EDCs: PCBs Woodruff TJ, et al. Fertil Steril. 2008; Harremoës P, et al. The Precautionary Principle in the 20th Century: Late Lessons from Early Warnings. 2002.

  29. EDC Lessons Learned: PCBs (continued) Examples of potential effects: Altered neurodevelopment as a result of in utero exposure Endometriosis Reduced fertility Decreased semen quality Miscarriage Altered pubertal development Reproductive tract malformations Woodruff TJ, et al. Fertil Steril. 2008.

  30. Conventional Assumptions Are Being Questioned Environmental research indicates: Assumption: Doses below a certain threshold are safe. Effects of very low doses have been underestimated. High-dose testing predicts low-dose results. High-level tests do not necessarily predict low-level impacts. Effects typically increase with dose. Some effects are seen only at low levels. Welshons WV, et al. Environ Health Perspect. 2003.

  31. Most Environmental Health Science Is Based on Animal Studies Most evidence derived from animal studies and epidemiologic observation (e.g., occupational studies) Effects found at “real-life” doses Andrade AJM, et al. Toxicology. 2006; Welshons WV, et al. Environ Health Perspect. 2003; Welshons WV, et al. Endocrinology. 2006.

  32. Many Factors Complicate the Environmental Health Picture Epidemiological studies have limited capacity to identify causal relationships Many factors contribute to the complexity of observed health outcomes Clinical relevance of population exposures are not always clear in the individual “Safe” levels are often based on many factors that can influence the interpretation of the scientific data

  33. “First, Do No Harm” ‘ ‘ “When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause-and-effect relationships are not fully established scientifically.” Wingspread Consensus Statement on the Precautionary Principle. 1998.

  34. Translating Population-Wide Risks into Individual Risks Clinicians work with individuals, not populations Elevated population-wide risks may represent a very small increased risk for an individual more… Stoll C, et a. Arch Fr Pediatr. 1991; CDC. 2009.

  35. Translating Population-Wide Risks into Individual Risks (continued) Modest increases in risk can result in major public health concerns if exposed population is large A large increase in population-wide risk will be increasingly important in individuals, even if not many people are exposed Two times a rare event = still a very rare event

  36. Small Individual Effects Can Have Significant Population Effects Mean = 100 6.0 million: “mentally retarded” 6.0 million: “gifted” 70 130 80 40 60 100 120 140 160 more… IQ Adapted from Weiss B. Neurotoxicology. 1997.

  37. Small Individual Effects Can Have Significant Population Effects (cont.) Mean = 95 9.4 million: “mentally retarded” 2.4 million: “gifted” 70 130 80 40 60 100 120 140 160 57%increase in “mentally retarded” population 60%decrease in “gifted” population IQ Adapted from Weiss B. Neurotoxicology. 1997.

  38. Relevant for Every Patient Assessment of exposure risk is relevant for all patients Particular focus on points of heightened susceptibility: Preconception Pregnancy Childhood Pre-puberty Adolescence

  39. One Tool for Conducting an Environmental History: CH2OPS Occupation/ School Community Home/Hobbies Personal Socioeconomic

  40. CH2OPS: Community Recreational areas Factories Landfills Farms Hazardous waste sites Businesses

  41. “So What Do I Do?” Learn about local environmental issues Incorporate questions about exposures into every health history Suggest alternatives to reduce exposures Give specific guidance to patients who may become pregnant Provide handouts and websites for patients Conduct thyroid screening Work with women to assess workplace exposures

  42. Environmental Health History Should Be Routine Identify and reduce or eliminate potentially harmful exposures The Environmental Health History WHEN? • Vulnerable Stages: • Early childhood • Puberty • Adolescence • Preconception planning (men & women) • Pregnancy HOW? WHY?

  43. Thyroid-Disrupting Chemicals Hypothalamus TRH Free TH Blood Pituitary X TSH Hormone Synthesis X Thyroid Bound TH T3 and T4 Iodine uptake X Adapted from Miller MD. 2009. Iodine Blount BE, et al. Environ Health Perspect. 2006; Boas M, et al. Eur J Endocrinol. 2006; Longnecker MP, et al. Environ Health Perspect. 2003; Steinmaus C, et al. Environ Health Perspect. 2007; Boas M, et al. Eur J Endocrinol. 2006; Brucker-Davis F. Thyroid. 1998; DeVito M, et al. Environ Health Perspect. 1999 Miller MD, et al. Environ Health Perspect. 2009.

  44. Measuring Thyroid Function Allan WC, et al. J Med Screen. 2000; Caturegli P, et al. Endocri Rev. 2005; Glinoer D. Trends Endocrinol Metab. 2998; Endocrine Society. 2007; Pearce EN. Thyroid. 2007; Dosiou C, et al. Eur J Endocrinol. 2008; Environ Health Perspect. 2006; Haddow JE. N Engl J Med. 1999. Image: Wikipedia. 2009.

  45. Community: Guidance for Patients Access community organizations & resources, for information about: Dry cleaners that avoid toxic solvents Salon products without toluene, phthalates, and other toxic chemicals Grocery stores that carry organic products Resource Tip: • Download the What We Can Do: Community Efforts to Protect Our HealthTool Kit from the Women’s Health and the Environment Web site

  46. CH2OPS: Home/Hobbies Pesticides Adhesives Furniture products Cleaners Detergents Gardening products (e.g., pesticides, plant food) more…

  47. CH2OPS: Home/Hobbies, cont. Exposure to: Carbon monoxide Metals Solvents Fishing: Be aware of fish advisories for mercury more…

  48. Home: Guidance for Patients Check for lead paint and pipes; manage dust Avoid canned foods and beverages Avoid certain types of plastics: No. 3:Polyvinyl chloride (PVC) No. 6:Styrene (Styrofoam) No. 7:Polycarbonate (bisphenol A [BPA]) Where possible, avoid food stored in plastic containers or plastic wrap Avoid vinyl products, such as shower curtain liners Center for Health, Environment and Justice. 2008; NRDC. 2008; CDC. 2002.

  49. Home: Guidance for Patients (continued) Use non-polycarbonate plastic or glass baby bottles Drink from unlined stainless steel bottles Eat fresh food when possible - frozen better than canned Buy processed food in cardboard Microwave food in glass or “microwave safe” plastic containers NRDC. 2008.

  50. Home: Guidance for Patients (continued) Avoid using pesticides in homes, lawns, gardens, or on pets Wash fruits and vegetables; buy organic when possible; favor thick-skinned fruits and vegetables Resource Tips: Extensive resources are available to eliminate the use of pesticides or to use less toxic products. Some examples include: • Visit www.beyondpesticides.org • Visit the Pesticide Action Network (PAN): www.pesticideinfo.org • Download the Shopper’s Guide to Pesticides wallet card from the Environmental Working Group

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