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Title: 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.

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
High exposure to Can Increase the Risk of Can Increase the Risk of
Tobacco smoke Miscarriage Infertility Preterm delivery Low semen quality Low birth weight Neurodevelopmental abnormalities in offspring
Alcohol use Fetal alcohol syndrome Mental retardation Behavioral problems Birth defects
Heavy metals (lead) Miscarriage Infertility Menstrual irregularities Abnormal sperm Altered pubertal onset
Toluene (e.g., in paint thinner, solvents) Fetal solvent syndrome
DBCP (pesticide) Low sperm count Other male reproductive effects
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
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.
13
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.
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
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.
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
Female Male
Effects on Oocyte follicle development function Ovary formation, cell organization Uterine development Corpus luteum development function Pubertal development Menstrual ovarian function Increased risk of Cervical/vaginal cancer Infertility Miscarriage Effects on Sertoli cell differentiation Spermatogonia formation, sperm count Testis, prostate, penis development Increased risk of testicular germ cell cancer Low serum testosterone levels
Casarett and Doulls 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 Doulls Toxicology The Basic
Science of Poisons. 2007.
20
Exposure May Affect DNA Structure and Gene
Expression
more
Casarett and Doulls Toxicology The Basic
Science of Poisons. 2007.
21
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.
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)
Women who took DES while pregnant
Effects in animals
DES Sons
DES Daughters
Testes Penis Prostate Epididymis Fertility Sperm Seminal vesicles
Ovaries Fallopian tubes Uterus Cervix Vagina Breast Fertility Pregnancy Hormonal balance Menopause Bones Immune system
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
Name Polychlorinated biphenyls (PCBs)
Uses Coolants and lubricants in electrical equipment before 1977
Route of Exposure Mainly food contamination body burden levels had been decreasing but recently have leveled off
Woodruff TJ, et al. Fertil Steril. 2008
Harremoes 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
more
IQ
Adapted from Weiss B. Neurotoxicology. 1997.
37
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.
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
Factories
Recreational areas
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
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 Health Tool Kit from the Womens
    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 Shoppers Guide to Pesticides wallet
    card from the Environmental Working Group

51
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

52
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.
53
Hobbies Guidance for Patients
  • Understand mercury present in recreationally
    caught fish
  • Use glue and solvents in well-ventilated spaces
  • Garden with organic products

54
CH2OPS Occupation/School
  • Chemicals
  • Radiation
  • Biological agents
  • Pesticides in schools

55
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

56
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

57
CH2OPS Personal
  • Dietary history
  • Alcohol use
  • Tobacco use
  • Prescription non-prescription medications
  • Substance abuse
  • Insect repellants
  • Cosmetics personal care products

58
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

59
CH2OPS Socioeconomic
  • Living in higher levels of air pollution
  • Exposure to lead, asbestos
  • Limited access to nutritious food
  • Vulnerability to other factors

60
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

61
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

62
What Questions Should You Ask?
  • When do headaches occur?
  • Which chemicals?
  • What protection does she use?

63
Material Safety Data Sheets
Material Safety Data Sheets. 2009.
64
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

65
Advocating for Workplace Safety
66
An Important Take-Home Message
Identifying and reducing exposures to potentially
harmful toxicants now increases the likelihood of
a successful pregnancy outcome.
67
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
68
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

69
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

70
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
71
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

72
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