Environmental Impacts on
Reproductive Health:
Foundations of the Science
Association of Reproductive Health
Professionals
www.arhp.org
Expert Medical Advisory Committee
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•
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•
•
•
•
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
Acknowledgment of Support
This project is funded through a grant from the
Passport Foundation and the Richard and
Rhoda Goldman Fund.
Faculty Disclosure
Speaker: Kirtly Jones, MD: nothing to disclose
• Note: Staff and committee disclosures listed in
program
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…
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
Awareness of Environmental
Exposures & Impacts Is Growing
• Air pollution
• Water contamination
• Harmful substances in
physical structures and
workplaces
• Food contamination
• Personal care products
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
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.
Some Reproductive Effects Are
Well Known
High exposure to:
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.
Content Overview
This slide set will review:
•
•
•
•
State of the science
Windows of susceptibility
Patient counseling
Further information and resources
US Chemical Production and
Importation Are High
87K 3K
Approximate no. of
chemicals
registered for
commerce in US
are produced or
imported in annual
quantities of
>1 million pounds
8K
--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.
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.
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.
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.
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.
Environmental Exposures and
Critical Windows of Susceptibility
Woodruff TJ, et al. Fertil Steril. 2008.
Identified Reproductive Endpoints in
Animal and/or Human Studies
Female
• Effects on:
 Oocyte & follicle development
& function
 Ovary formation, cell organization
 Uterine development
 Corpus luteum development &
function
 Pubertal development
 Menstrual & ovarian function
Male
• Effects on:
 Sertoli cell differentiation
 Spermatogonia formation, sperm
count
 Testis, prostate, penis development
• Increased risk of testicular germ
cell cancer
• Low serum testosterone levels
• Increased risk of:
 Cervical/vaginal cancer
 Infertility
 Miscarriage
Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
Environmental Effects Have
Multiple Mechanisms
Examples:
Toxicants
Damage to
oocytes/sperm
Interference
with cell function
Changes to DNA
structure/gene expression
more…
Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
Exposure May Affect DNA Structure
and Gene Expression
Structural changes
to DNA sequence
Functional changes
to gene expression
more…
Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
Exposure May Affect DNA Structure
and Gene Expression
Structural changes
to DNA sequence
Functional changes
to gene expression
Chromosomal damage
Modification of
gene expression
Example:
Gene mutations
Example:
Hormone disruption
Example:
Birth defects and cancer
Examples:
Altered hormone levels,
early puberty, infertility
Casarett and Doull’s Toxicology: The Basic Science of Poisons. 2007.
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.
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.
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.
DES: An Example of Delayed Effects
(continued)
Women who took DES while pregnant
* = Effects in animals
DES Sons
DES Daughters
Ovaries
Fallopian tubes
Uterus
Cervix
Vagina
Breast
Fertility
Pregnancy
Hormonal balance
Menopause
Bones
Immune system
Testes
Penis
Prostate
Epididymis
Fertility
Sperm*
Seminal vesicles*
DES
Granddaughters
DES
Grandsons
DES
Granddaughters
Menstruation
Ovaries*
Uterus*
Penis
Rete testis*
Seminal vesicles*
Prostate*
Ovaries*
Uterus*
Immune system*
Adapted from Schwartz JM, Woodruff TJ. Shaping Our Legacy. 2008.
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.
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.
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; Harremoës P, et al. The Precautionary
Principle in the 20th Century: Late Lessons from Early Warnings. 2002.
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.
Conventional Assumptions Are
Being Questioned
Assumption:
Environmental
research indicates:
Doses below a certain threshold
are safe.
Effects of very low doses have
been underestimated.
High-dose testing predicts lowdose 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.
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.
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
“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 causeand-effect relationships are not fully established
scientifically.”
Wingspread Consensus Statement on the Precautionary Principle. 1998.
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
Stoll C, et a. Arch Fr Pediatr. 1991; CDC. 2009.
more…
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
Small Individual Effects Can Have
Significant Population Effects
Mean = 100
6.0 million:
“mentally
retarded”
6.0 million:
“gifted”
40
80
60
70
100
IQ
Adapted from Weiss B. Neurotoxicology. 1997.
120
140
130
160
more…
Small Individual Effects Can Have
Significant Population Effects (cont.)
Mean = 95
57%
increase in
“mentally retarded”
population
60%
decrease in
“gifted”
population
9.4 million:
“mentally
retarded”
2.4 million:
“gifted”
40
80
60
70
100
IQ
Adapted from Weiss B. Neurotoxicology. 1997.
120
140
130
160
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
One Tool for Conducting an
Environmental History: CH2OPS
Community
Occupation/
School
Home/Hobbies
Personal
Socioeconomic
CH2OPS: Community
Recreational areas
Farms
Hazardous waste
sites
Factories
Landfills
Businesses
“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
Environmental Health History Should
Be Routine
The Environmental Health History
WHY?
HOW?
WHEN?
Identify and reduce
or eliminate
potentially harmful
exposures
Vulnerable Stages:
 Early childhood
 Puberty
 Adolescence
 Preconception planning
(men & women)
 Pregnancy
Thyroid-Disrupting Chemicals
Hypothalamus
TRH
Pituitary
TSH
Thyroid
Hormone
Synthesis
X
Blood
Free TH
X
Bound TH
Iodine uptake
X
Iodine
Adapted from Miller MD. 2009.
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; BruckerDavis F. Thyroid. 1998; DeVito M, et al. Environ Health Perspect. 1999 Miller MD, et al. Environ Health Perspect. 2009.
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.
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 Women’s Health and the Environment Web site
CH2OPS: Home/Hobbies
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•
•
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•
•
Pesticides
Adhesives
Furniture products
Cleaners
Detergents
Gardening products
(e.g., pesticides, plant food)
more…
CH2OPS: Home/Hobbies, cont.
Exposure to:
• Carbon monoxide
• Metals
• Solvents
Fishing:
• Be aware of fish advisories
for mercury
more…
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.
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.
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
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 Women’s Voices for the Earth Web site or
www.care2.com
Home: Guidance for Patients
(continued)
Species to Avoid
Safer Choices
Shark
Trout
Swordfish
Salmon
King mackerel
Tilapia
Tilefish
Sardines
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.
Hobbies: Guidance for Patients
• Understand mercury
present in recreationally
caught fish
• Use glue and solvents in
well-ventilated spaces
• Garden with organic
products
CH2OPS: Occupation/School
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•
•
•
Chemicals
Radiation
Biological agents
Pesticides in schools
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”
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 EPA’s Healthy School Environments
Web site to learn more about creating a healthier school environment
CH2OPS: Personal
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•
•
•
Dietary history
Alcohol use
Tobacco use
Prescription & nonprescription medications
• Substance abuse
• Insect repellants
• Cosmetics; personal
care products
Personal: Guidance for Patients
Advise patients:
•
•
•
•
Don’t 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
CH2OPS: Socioeconomic
• Living in higher levels
of air pollution
• Exposure to lead,
asbestos
• Limited access to
nutritious food
• Vulnerability to other
factors
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
Case Study: Jennifer
• 30 year old, married
• Contemplating pregnancy in
next year
• Lab technician at polymer
manufacturing company
• Presents for annual wellwoman exam
• Occasional headaches
What Questions Should You
Ask?
• When do headaches occur?
• Which chemicals?
• What protection does she
use?
Material Safety Data Sheets
Material Safety Data Sheets. 2009.
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
Advocating for Workplace Safety
An Important Take-Home Message
Identifying and reducing exposures to
potentially harmful toxicants now
increases the likelihood of a
successful pregnancy outcome.
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
more…
--Adolescence
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
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
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 >5,000 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…
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
Visit CORE (www.arhp.org/core) to
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