Environmental Impacts on Reproductive Health: Foundations of the Science

1
Environmental Impacts on Reproductive
HealthFoundations 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.

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Faculty Disclosure

• Speaker Kirtly Jones, MD nothing to disclose
• Note Staff and committee disclosures listed in
  program

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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
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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

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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
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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.
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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.
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Content Overview

• This slide set will review
• State of the science
• Windows of susceptibility
• Patient counseling
• Further information and resources

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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
gt1 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.
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Many Complex Factors Interact to Affect the
Impact of Exposures
Reproductive health fetal/child development
Adapted from Hubbs-Tait et al. Psychological
Science in the Public Interest. 2005.
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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.
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The Barker Hypothesis
Exposures to adverse insults during
criticalwindows of development can permanently
reprogram normal physiologic responses, and thus
give rise todisorders 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.
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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.
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Environmental Exposures and Critical Windows of
Susceptibility
Woodruff TJ, et al. Fertil Steril. 2008.
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Identified Reproductive Endpoints in Animal
and/or Human Studies
Casarett and Doulls Toxicology The Basic
Science of Poisons. 2007.
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Environmental Effects Have Multiple Mechanisms
Examples
Toxicants
Damage to oocytes/sperm
Changes to DNA structure/gene expression
Interference with cell function
more
Casarett and Doulls Toxicology The Basic
Science of Poisons. 2007.
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Exposure May Affect DNA Structure and Gene
Expression
more
Casarett and Doulls Toxicology The Basic
Science of Poisons. 2007.
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Exposure May Affect DNA Structure and Gene
Expression
Casarett and Doulls 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.
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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.
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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.
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DES An Example of Delayed Effects (continued)
Women who took DES while pregnant
Effects in animals
DES Sons
DES Daughters
Adapted from Schwartz JM, Woodruff TJ. Shaping
Our Legacy. 2008.
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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.
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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.
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Lessons Learned from EDCs PCBs
Woodruff TJ, et al. Fertil Steril. 2008
Harremoes P, et al. The Precautionary Principle
in the 20th Century Late Lessons from Early
Warnings. 2002.
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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.
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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.
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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.
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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

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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.
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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.
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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

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Small Individual Effects Can Have Significant
Population Effects
more
IQ
Adapted from Weiss B. Neurotoxicology. 1997.
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Small Individual Effects Can Have Significant
Population Effects (cont.)
57 increase in mentally retarded population
60 decrease in gifted population
IQ
Adapted from Weiss B. Neurotoxicology. 1997.
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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

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One Tool for Conducting an Environmental History
CH2OPS
Occupation/ School
Community
Home/Hobbies
Personal
Socioeconomic
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CH2OPS Community
Factories
Recreational areas
Landfills
Farms
Hazardous waste sites
Businesses
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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

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Environmental Health History Should Be Routine
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.
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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.
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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 Health Tool Kit from the Womens
  Health and the Environment Web site

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CH2OPS Home/Hobbies

• Pesticides
• Adhesives
• Furniture products
• Cleaners
• Detergents
• Gardening products (e.g., pesticides, plant
  food)

more
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CH2OPS Home/Hobbies, cont.

• Exposure to
• Carbon monoxide
• Metals
• Solvents
• Fishing
• Be aware of fish advisories for mercury

more
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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.
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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.
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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 Shoppers Guide to Pesticides wallet
  card from the Environmental Working Group

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Home Guidance for Patients (continued)

• Read labels on cleaning products
• Use ammonia and chlorine bleach sparingly, with
  ventilation
• Avoid mixing ammonia and chlorine
• Use inexpensive, nontoxic products such as
  vinegar and baking soda

• Resource Tip
• Find nontoxic cleaning recipes on the Womens
  Voices for the Earth Web site or www.care2.com

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Home Guidance for Patients (continued)

• Resource Tips
• Learn about local fish advisories from the EPA
• Download a regional fish seafood-watch pocket
  guide from Seafood WATCH

FDA. 2009 EPA 1999 NRDC 2009.
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Hobbies Guidance for Patients

• Understand mercury present in recreationally
  caught fish
• Use glue and solvents in well-ventilated spaces
• Garden with organic products

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CH2OPS Occupation/School

• Chemicals
• Radiation
• Biological agents
• Pesticides in schools

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Occupation Guidance for Patients

• Become familiar with all chemicals used or
  encountered at work
• Learn about toxic properties of these chemicals
• Wash any exposed skin change from work clothes
  at night wash exposed clothes separately
• Take extra care if pregnant (or planning
  pregnancy)
• Use protective gear with toxic substances or
  radiation

• Resource Tip
• Learn more from the CDC report, The Effects of
  Workplace Hazards on Female Reproductive Health

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Occupation (Schools) Guidance for Patients

• Advise patients
• Practice non-pesticide insect management inform
  parents if pesticides used
• Use fruit vegetables for snacks avoid junk
  foods in cafeterias
• Avoid pressure-treated woods (arsenic) in
  playground equipment

• Resource Tip
• Visit the Healthy Schools Network Web site and
  EPAs Healthy School Environments Web site to
  learn more about creating a healthier school
  environment

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CH2OPS Personal

• Dietary history
• Alcohol use
• Tobacco use
• Prescription non-prescription medications
• Substance abuse
• Insect repellants
• Cosmetics personal care products

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Personal Guidance for Patients

• Advise patients
• Dont trust dermatologist-tested, natural,
  organic
• Learn about skin products that are safe for
  children
• Avoid tobacco use exposure to 2nd-hand smoke
• Use alcohol in moderation

• Resource Tips
• Check the safety of your own personal care
  products at the Skin Deep Cosmetic Safety
  Database and the Campaign for Safe Cosmetics
• Download the Safety Guide to Children's Personal
  Care Products from the Environmental Working
  Group
• Visit www.HealthyToys.org to find toy rankings
  and a safer toy shopping list

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CH2OPS Socioeconomic

• Living in higher levels of air pollution
• Exposure to lead, asbestos
• Limited access to nutritious food
• Vulnerability to other factors

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Socioeconomic Guidance for Patients

• Advice for patients
• Know tenant citizen rights
• Work with community organizations, government
  agencies to ensure risk awareness knowledge

• Resource Tip
• Visit the Alliance for Healthy Homes Web site for
  tools and tips on reducing environmental hazards
  in homes and communities

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Case Study Jennifer

• 30 year old, married
• Contemplating pregnancy in next year
• Lab technician at polymer manufacturing company
• Presents for annual well-woman exam
• Occasional headaches

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What Questions Should You Ask?

• When do headaches occur?
• Which chemicals?
• What protection does she use?

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Material Safety Data Sheets
Material Safety Data Sheets. 2009.
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Next Step?

• Order pregnancy test
• Carefully explore her options for transferring
  out of the lab to a less toxic work environment
• Offer to write a letter to her employer with
  recommendations for improved safety protections
• Consider an occupational health consult

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Advocating for Workplace Safety
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An Important Take-Home Message
Identifying and reducing exposures to potentially
harmful toxicants now increases the likelihood of
a successful pregnancy outcome.
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Summary

• Environmental exposures have been linked to
  reproductive health effects and may affect future
  generations
• Exposures may have more significance at critical
  points
• --Preconception
• --Pregnancy
• --Childhood
• --Pre-puberty
• --Adolescence

more
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Summary (continued)

• Clinicians can help by offering guidance,
  counseling, and resources
• Emphasize preconception care
• Incorporate an environmental/occupational history
  as part of patient health history
• Be aware of risks in your community
• Work with community groups to reduce exposure
  levels
• Provide education and information sources

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ARHP Resources

• Learn more at the ARHP Web site
• Click on Environmental and Reproductive Health
  topic area
• www.arhp.org/topics/enviro-repro-health
• --Fact Sheet Environmental and Reproductive
  Health Resources for Health Care Providers
• --Patient handout Health Matters The Connection
  Between Your Health and the Environment

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Resources for Clinicians

• Critical Windows of Development
  (www.endocrinedisruption.com) Online tool from
  The Endocrine Disruption Exchange (TEDX)
• ReproTox (www.reprotox.org) Summaries on the
  effects of gt5,000 agents and exposures on
  pregnancy, reproduction, and development
• TOXNET (http//toxnet.nlm.nih.gov/) Databases on
  toxicology, hazardous chemicals, environmental
  health, and toxic releases

more
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Resources for Clinicians (continued)

• American College of Occupational and
  Environmental Medicine (www.acoem.org)
• Collaborative on Health and Environment (CHE)
  database (http//database.healthandenvironment.org
  /)
• EnviRN (www.envirn.umaryland.edu)
• Local environmental health specialists
• Occupational and environmental health departments
  in universities

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