Promoting gender-based analysis in environmental health research

Donna Mergler PhD Professor emerita

Center for interdisciplinary studies on health, well-being, society

and environment University of Quebec at Montreal

Principal Investigator

Canadian Institutes for Health Research Team on Gender, Environment and Health

CEC, 2014

– Alice Hamilton (1869 – 1970), the mother of modern occupational health, did much work on lead poisoning

– Studies showed women workers had higher lead levels compared to men and the prevalent notion was that women workers were more susceptible to lead poisoning than male workers.

– By taking into account job category and socio-economic status, she showed that when men and women were doing the same job, there was no difference in their blood lead levels

– Since more women worked in the poorer paying jobs with higher exposures, overall, women had higher blood lead levels as compared to men1.

Hamilton A. Exploring the Dangerous Trades, Little Brown & Co., 1943

Lead poisoning in the 1920’ and 1930’s in the United States

• In 2002, enhanced surveillance of pesticide poisonings in South Africa revealed that, contrary to the official statistics, women had a higher prevalence of pesticide poisonings compared to men1: – higher exposures in women, who did more seasonal work with high exposures

and were likewise more exposed in the home. – women’s pesticide-related health problems were often misdiagnosed because

of the dominant belief that women were not exposed ‘like men’ to pesticides

• In 2004, a field study of 488 migrant workers in Mexico: – women were six times more likely than men to have anemia and asthma,

twice more likely to have parasites and respiratory and gastrointestinal diseases and 38% more likely to suffer from heart disease. Significantly more women than men reported symptoms associated with pesticide poisoning2

Photo: Hanna-Andrea Rother

1. London et al. Int J Occup Environ Health 2002; 8:46-59 2. Palacios-Nava et al. Salud pública de México 2004; 46: 286-293

A similar situation today for pesticide poisonings?

Women Farmworkers in North America

• The percentage of women farm workers is increasing.

– In Mexico, in 1985, the number of women in the total population of agricultural workers was about 20%, by 2004 it was estimated at 42.6%1.

– In California, women make up 26% of the seasonal agricultural workers2

• An important percentage of farming is done by migrant workers (from one state to another or from one country to another), whose working and living conditions are generally very poor. Researchers from Guelph University have carried out studies with women migrant workers in Ontario3 and produced a fact sheet…

1. cited in Ojinaga et al. in Genero, Ambiente y Contaminación por Sustancías Químicas 2012 p 67-78; 2. cited in Habib and Fathallah, Work 2012;41 Suppl 1:4356-62 2012 3. Preibisch & Encalada Grez, 2010; Journal of Women in Culture and Society 35: 289-316

• “In 2006, there were 15,576 SAWP workers in Ontario, 393 were women; 75% came from Mexico

• Most of them are single mothers, in part due to recruitment practices that limit placements in Canada to this group.

• They value highly the wages they earn in Canada; the money serves to support their family in Mexico.

• Women accede to their employers’ demands in order to maintain their employers’ approval and preserve their tenure in the SAWP, even when these put their health and safety at risk or violate their rights.

• Migrant women face greater restrictions on their mobility than men.

• They face considerable barriers in accessing public health care and other social services required to address their gender-specific needs

• They face a number of challenges when trying to parent across borders

• Migrant women are resilient, innovative individuals pioneering a new life for their families”.

Preibisch & Encalada Grez Migrant Workers Fact Sheet, Univerisity of Guelph – Rural Women Making Change 2008

• “Males predominate in behavioral experiments, few such experiments study both sexes, some investigators fail to even describe the sex of their subjects, and in vitro studies tend to wholly ignore sex, even for model systems aimed at neurological disorders that display marked sex differences”.

• “In Volume 29 of Neurotoxicology (2008), the male:female ratio of whole-animal, single sex studies was 40:1. Four were on both sexes”.

Same sex, no sex, and unaware sex in neurotoxicology (Weiss, 2011)

Weiss B. Neurotoxicology. 2011; 32:509-17

Articles in recent volumes of environmental health journals

* 3 were pregnant women

No. of studies

No sex Stratified for

sex/gender

Animal studies

17 2 (12%)

13 (76%)

1 (6%)

1 (6%)

0

Human studies

25 3 (12%)

4 (16%)

5* (20%)

13 (52%)

6 (24%)

Neurotoxicology : vol 39 (2013); vol 40 (2014) Environmental Health Perspectives: vol 121 (1) (2013)

Environmental Research: vol 129 (2014)

Consequences of not examining gender and sex differences

• Under-estimation of the environment-related health problems in one sex or the other (usually women) or both

• Health problems are attributed to other causes (susceptibility, hysteria, complaining)

• Cycle of ignorance : There is less research on the particular situation because it is not viewed as an environmentally-related problem and thus not a “research priority” and thus not studied and if it’s not studied, it’s not a problem

• Prevention strategies that target the source, the transmission or the effects of environmental hazards do not necessarily address the entire population.

Scientific Group on Methodologies for the Safety

Evaluation of Chemicals (SCOPE, WHO, UNEP, IPCS)

2012

1998

Gender Differences in Susceptibility to Environmental Factors: A Priority Assessment

Sex and gender • In 2001, a committee from the Institute of Medicine

provided the following definitions:

– Sex: The classification of living things, generally as male or female, according to their reproductive organs and functions assigned by chromosomal complement. In most studies of nonhuman animals, the term "sex" should be used.

– Gender: A person's self-representation as male or female, or how that person is responded to by social institutions based on the individual's gender presentation. Gender is rooted in biology and shaped by environment and experience

1. Exploring the Biological Contributions to Human Health: Does Sex Matter? Institute of Medicine, 2001

Gender and sex interact throughout the life span

GENDER

SEX

fetal growth and development

Childhood growth and

development

Puberty

Decline of biological functions

Infant and childhood experiences

Adolescence

Working and family life

Retirement

Reproduction

Menopause Andropause

Reproduction, pregnancy, breast-feeding,

CONTACT WITH THE ENVIRONMENT

Fetal growth and development

Childhood growth and

development

Puberty

Decline of biological functions

Infant and childhood experiences

Adolescence

Working and family life

Retirement

Reproduction

Menopause Andropause

Pregnancy Breast-feeding

• DBCP, a pesticide used extensively in banana plantations rendered men sterile; until the cause was known women were often “accused” of infertility

• In utero exposure to many toxics commonly found in our environments will affect developing boys and girls differently

• Childhood playing activities and household chores may differ between boys and girls translating into different exposure patterns

• Several toxic substances modify the chronology of puberty…..

Mothers working in greenhouses with exposure

to pesticides in Denmark

Pregnancy

Fetal growth and development

Childhood growth and

development

Puberty

Breast-feeding

Mean age at breast development was 8.9 years in exposed girls vs. 10.4 years in non-exposed.

Early breast development in girls after prenatal exposure to non-persistent pesticides

Wohlfahrt-Veje et al, Int J Andrology 2012; 35: 272-282

Childhood growth, development and puberty

• Menarche is occurring at a younger age

• The period between the appearance of secondary sexual characteristics and menarche is increasing

• Secondary sexual characteristics are appearing much younger in girls

• Endocrine modifiers may contribute to these changes

Childhood experiences

Pinto, K.. J. Early Adolescence 2007; 27:509-544

• Lead (Pb) • In rats, lead and maternal stress interact differently on male and female

offsprings’ corticosteroid levels, neurotransmitters and behavior. (Cory-Slechta et al, 2005)

• In mice, low level prenatal Pb exposure showed male-specific effects in 1 year old offspring, for motor activity and brain dopamine metabolism; effects were non-linear, with the largest effects at the lower doses (Leasure et al, 2011)

• Polychlorinated Biphenyl (PCB) congeners • Sex-specific differences have been reported for motor activity and

neurotransmission (Boix et al, 2011), as well as on the retina (Kremer et al, 1999)

• Polybrominated diphenyl ethers (PBDE) • No sex differences were observed in male and female mice prenatally

exposed to PBDE (Viberg et al, 2004)

Some examples of sex differences in animal studies with pre-natal exposures

Birth cohort studies • Some studies have examined sexes separately and reported

differences for some functions but not for others. – Several studies have reported stronger associations between prenatal

Pb exposure and poorer cognitive performance and behavioral disorders for boys compared to girls1,2; others have not observed differences3

– Poorer motor performance was reported in relation to prenatal mercury in boys, while other functions were similar4

– Boys presented greater risk for behavioral disorders in relation to prenatal exposure to phthaltes5.

– Boys presented greater risk for early childhood symptoms of attention disorders in relation to mothers’ exposure to pesticides6,7, while others have not observed differences8

. 1. Ris et al, 2004; 2. Jedrychowski et al, 2009; 3. Kim et al, 2001; 4. Grandjean et al, 1998 ; 5.

Engel et al, 2010; 6. Marks et al, 2010; 7. Fortenberry et al. 2014; 8. Bouchard et al, 2010

50 75 100 125 150

Percentage of children

Intellectual deficits and behavioural disorders in children

(adapted from Rice, 1998)

median score

Country Mn source

Quebec1 Well water

Brazil2 Airborne (Mn alloy production)

Mexico3 Airborne (mines and transformation)

Cognitive performance and environmental Mn exposure in primary school children

1. Bouchard et al, 2011 3. Riojas-Rodriguez et al. 2010 2. Menezes-Filho et al, 2011

Low hair manganese : <2µg/g Quebec Brazil Mexico

High hair manganese : ≥2µg/g Quebec Brazil Mexico

Combined analysis of the relation between hair Mn and Full IQ in primary school children

Quebec (n = 377)

Mexico (n = 195)

Brazil (n – 82)

p

% girls 53.7 48.7 46.3 ns

Age 9.1 ± 1.78 9.42 ± 1.45 8.74 ± 1.61 0.007

Full IQ 104 ± 12 78.5 ± 14 85.2 ± 14 0.0001

• Adjusted Full IQ Score for each study separately on mothers’ Raven score, mothers’ education, z-score of height for age

• Examined association with hair Mn, taking into account study, age and sex

• Stratified for sex, taking into account study and age

Estimate : -2.62 (-4.10 - -1.13) Estimate boys: - 1.08 (-3.21 – 1.05) Estimate girls: - 4.19 (-6.19 - -2.07)

In a study of manganese-exposed adult mice, long-lasting differences in neuronal morphology were observed in females, but not in males, in the absence of differences in manganese accumulation in the brain (Madison et al., 2011).

In a recent study in the same region in Brazil, externalizing behaviors and attention problem scores were significantly associated with girls' hair manganese levels but not with boys’ (Menezes filho et al. In press)

The cycle of environmental disease

Using Indicators to Mesure Progress on Environmental Health, WHO ,UNEP, 2002

Mothers’ exposures, working and living

conditions

Newborn underweight

0 – 6 months

Further exposure through breast milk,

but also benefits

6 months – 2 y

Poverty and lack of parental

knowledge. Environmental

exposure

Age 3

Developmental delays. Child does

not demand stimulation.

Frequent illnesses

Age 6 Lack of energy, poor school

performance

Teenager to adult : school drop-out, low

paid job, further exposure

For teenage girls, this often translates into

early pregnancies

For boys and men, this can likewise translate into higher prevalence of anti-social, delinquent and criminal behavior Ex: In a longitudinal study of crime arrests in young adults in relation to prenatal and childhood Pb : the attributable risk for 6-y blood lead rate was 0.85 arrests/year for males and 0.18 for females (Wright et al, 2008).

• Toddlers’ activities may differ between boys and girls – A study of farm workers’ children showed that boys had more

frequent contacts with their environment while girls contact objects for longer durations.

– The authors point out that “Understanding how frequency and duration contribute to dermal and non-dietary ingestion exposure could increase understanding of the potential difference in exposure between the genders”. (Beamer et al, 2008)

• Childhood playing activities and household chores may differ between boys and girls translating into different exposure patterns: • In a study around a dumpsite, boys roamed in contaminated areas

more than girls (Steegmann and Hewner, 2000) • Girls may be more exposed to more household contaminants.

Childhood exposures

Childhood socialization : gender identity

Rock Star Make Over

Room Clean-up

Extreme Hair Make Over

Spider-3-rescue

Choose-your-weapon Tank 2008

http://www.free-online-games-to-play.net/games/girlgames/page/3/

• Googled boys and girls e-games

Biologic differences and exposure

• A study of serum PCB concentration in adolescents1:

– Girls : positively with milk consumption fat intake , the duration of breast-feeding, and the concentrations of serum triglycerides and cholesterol and negatively with body fat,

– Boys: fat intake and serum triglycerides, and marginally with the duration of breast-feeding and negatively with body fat.

– Similar and significant estimates for external exposure – Sex-related differences in the serum PCB concentration

disappeared after allowing for calculated body fat content – The authors discuss the role of changes in body fat and PCB

concentrations throughout the lifespan in women

1. Nawrot et al, 2002

• Analysis of Data from the Canadian Health Measures Survey: Bisphenol A (BPA)

– Males had higher volume-based urinary BPA concentrations than did females, but lower creatinine-standardized urinary concentrations of BPA.

– The reversal in the sex difference was attributed to the higher urinary creatinine concentrations

– The authors conclude : “Differences between the sexes in urinary BPA concentrations may reflect differences in exposure and in pharmacokinetic factors, the relevance of which is not currently known”

Gender, sex or both?

Bushnik et al, 2010

Urinary Bisphenol-A: data from the Canadian Health Measures Survey

0

0.5

1

1.5

2

6 - 11y 12- 19y 20 - 39y 40 - 59y 60- 79y0

0.5

1

1.5

2

2.5

6 - 11y 12- 19y 20 - 39y 40 - 59y 60- 79y

µg/L µg/g cr

(geometric means)

Different functions/different exposures

Table 638. Average Hours pers Week Spent Doing Unpaid Household Work and Paid Work by Sex and Age (US Census Bureau, The 2011 Statistical Abstract; The National Data Book) http://www.census.gov/compendia/statab/cats/labor_force_employment_earnings.html

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

15 - 24years

25 - 34years

35 - 44years

45 - 54years

55 - 64years

65 - 74years

75 yearsold and

over

Series2

Series3

Series6

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

15 - 24years

25 - 34years

35 - 44years

45 - 54years

55 - 64years

65 - 74years

75 yearsold and

over

Series1

Series4

Series5

Men Women

unpaid

total paid

From the Hänninen twin study

Hänninen et al, 1991

• Partition analysis identified activities with respect to blood Pb

Informal work

• A surprising result from our studies on mercury exposure in the Brazilian Amazon : high blood Pb: mean: 13.1 µg/dL range: 0.59 - 48.3 µg/dL

• Highest levels were observed among young men and older women

Barbosa et al, 2009

Working together

Natural Sciences & Engineering

Health Sciences

Social Sciences & Humanities

Community

Cancer among women plastics workers: an interdisciplinary study1

• Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study (Brophy et al 2012)1,2 – Many investigators (researchers and community) from different disciplines – Mixed-method research approach (quantitative and qualitative)2

• women in the study area held a wide range of jobs in the plastics industry dating back to the 1960s;

• the majority of automotive plastics manufacturing workers in the study area are women;

• the work environment is heavily contaminated with dust, vapours and fumes; • there has been a historic failure by government regulators to control

exposures; • workers receive a steady dose of mixtures of chemicals through inhalation,

absorption and ingestion; • workers are getting sick; and society is largely unaware of their plight.

1. De Matteo et al, New Solutions 2012: 22:427-448 2. Brophy et al. Environmental Health. 2012; 11:87. 3. Winner of the American Public Health Association Scientific Award in Occupational Health

Gender and sex: not an afterthought

• Taking gender and sex into account begins with the research question

• Some questions … – Are different disciplines and concerned parties providing input? – Is the situation similar for both sexes ? – What are the differences and similarities ? – If just one sex is involved, this should be stated up front

(including animal and cell studies1)

1. Ritz et al. First steps for integrating sex and gender considerations into basic experimental biomedical research FASEB J. 2014;28:4-13

Study or Intervention Design: a non-exhaustive list of questions

• If there is exposure assessment, are the activities and habits of both genders adequately considered?

• If it involves working populations (including informal work), is there a good description of the work activities?

• Is the sample size sufficient to demonstrate possible differences?

• Are there sex and/or gender-related factors that could influence the relation between exposure and biomarkers of exposure?

• Are the outcome measurements relevant for males and females?

• Could gender differences influence the outcomes?

• Have the individual outcome measures been validated for males and females?

• Are the social consequences of effects equally relevant for both genders?

Data presentation & analyses

USA National Health and Nutrition Survey (2009) Canadian Health

Measures Survey (2010)

Report on Urinary Bisphenol A (µg/g creatinine)

0

0.5

1

1.5

2

6 - 11y 12- 19y 20 -39y

40 -59y

60- 79y0

0.51

1.52

2.5

6 - 11y 12- 19y 20 -39y

40 -59y

60- 79y

µg/L µg/g cr

( Urinary Bisphenol A geometric means)

Complex analyses • In studies seeking to examine the associations between exposure

and health outcomes, sex/gender is included in multiple regression analyses as any other co-variable like: age, income, and many others…

• Some studies suggest that this may not fully capture the sex/gender differences.

• Stratifying analyses by sex/gender can help to understand both similarities and differences (both exposure patterns and effect can be different)

• Mixed methods, cluster analysis, multi-level analyses have been proposed to examine the complex interrelations between social, physical and biological factors and health outcomes

Sources of exposure

Biomarkers of

exposure

Biomarkers of effect

Health outcomes

Social impact

• There is growing awareness of the importance of including gender.

• There is no simple "recipe" for integrating gender and sex in environmental health research - or in examining these complex interrelationships

• It requires a change in paradigm to take into account and to promote a bettering understanding of sex and gender in environmental health

biosphere global ecosystem

regional ecosystem local ecosystem

community workplace

home

geophysical milieu

biological factors

socio-political situation

economy

culture

toxic substances

Health & well-being

An Ecosystem Approach to Human Health