CHEMICAL EXPOSURE AND MENSTRUAL REGULATION

by

Kyley Shanneen Drach
B.Sc., Thompson Rivers University, 2019

A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF
MASTER OF SCIENCE IN ENVIRONMENTAL SCIENCES

In the Department of Biological Sciences

Thesis examining committee:
Heidi Huttunen-Hennelly (PhD), Associate Professor and Co-Supervisor, Chemistry
Kingsley Donkor (PhD), Professor and Co-Supervisor, Chemistry
Mark Rakobowchuk (PhD), Associate Professor and Committee Member, Biological Sciences
Mary Jung (PhD), Associate Professor and External Examiner, Health and Exercise Sciences

June 2023
Thompson Rivers University

Kyley Shanneen Drach, 2023

Thesis Co-Supervisors: Associate Professor, Heidi Huttunen-Hennelly and Professor, Kingsley
Donkor

1

ABSTRACT

It is estimated that individuals are exposed to hundreds of harmful chemicals at any given
time, where it is nearly impossible to find unexposed populations anywhere in the world. Exposure
routes include eating, drinking, breathing, and dermal absorption. After chemicals enter the body,
their impact depends on their properties, whether they are excreted or stored, and their rates of
entry and excretion. Endocrine disrupting chemicals (EDCs) are of particular concern, as they may
impact metabolism and interfere with homeostatic feedback regulation of various endocrine organs
by interfering with hormone production. In women, this may increase the risk of negative
reproductive health outcomes, such as during the menstrual cycle. Despite the inevitable exposure
to EDCs, there is limited research that examines exposure routes and assesses which may have the
greatest impact on female reproductive health. Therefore, the purpose of this study is to see if
different levels of chemical exposure can cause menstrual irregularities and if additional factors
modulate these effects.
Using an online survey, we collected information about lifestyle, nutrition, health status,
and chemical exposure in women aged 18-35 who experience a menstrual cycle. The survey
included questions regarding reproductive health, product use, general health, mental health, work,
and additional factors that are known to impact reproductive health. The survey data was analyzed
using a regression analysis to see which exposure routes, health statuses, or additional factors may
contribute to menstrual irregularities, and which may not.
A correlation was found between increase in age and a decrease in the risk of experiencing
dysmenorrhea from 56% to 45% (p=0.016, OR=0.907). A correlation was found between high
chemical exposure and a decrease in the risk of experiencing dysmenorrhea from 56% to 14%
(p=0.015, OR=0.274). A correlation was found between menstruation that lasts eight or more days
and an increase in the risk of both dysmenorrhea and menorrhagia from 56% to over 100%
(p=0.014, OR=3.969) and 20% to over 100% (p<0.001, OR=17.943), respectively. A correlation
was found between moderate alcohol consumption and a decrease in the risk of experiencing
menorrhagia from 20% to 2% (p=0.001, OR=0.106). A correlation was found between moderate
to heavy drug use and a decrease in the risk of experiencing menorrhagia from 20% to 4%
(p=0.010, OR=0.210), and a correlation was found between moderate stress and a decrease in the
risk of experiencing menorrhagia from 20% to 4% (p=0.016, OR=0.220).
Our study aims to encourage future research in the field of women’s health, where research
in this area is often limited, especially regarding research looking at women’s health under a more
holistic lens.

Keywords: Chemical exposure, Endocrine Disrupting
Dysmenorrhea, Menorrhagia, Female reproductive cycle.

Chemicals

(EDCs), Lifestyle,

1
II

TABLE OF CONTENTS
ABSTRACT .................................................................................................................................. II
ACKNOWLEDGEMENTS ..................................................................................................... VII
LIST OF FIGURES ................................................................................................................. VIII
LIST OF TABLES ................................................................................................................... VIII
1.0

INTRODUCTION: ENDOCRINE DISRUPTING CHEMICALS .............................. 1

1.1 PAIN AND THE MENSTRUAL CYCLE ........................................................................................ 4
1.2 BLEEDING AND THE MENSTRUAL CYCLE ............................................................................... 6
1.3 THE FEMALE BODY AND REPRODUCTIVE HEALTH ................................................................. 7
1.3.1 EARLY LIFE AND MENSTRUAL IRREGULARITIES ................................................................. 7
1.3.2 FEMALE ANATOMY, HORMONES, AND THE MENSTRUAL CYCLE......................................... 8
1.3.2.1 THE OVARIAN CYCLE ...................................................................................................... 9
1.3.2.2 THE MENSTRUAL CYCLE ............................................................................................... 11
1.4 THE ROLE OF LIFESTYLE, NUTRITION, SOCIOECENOMIC STATUS, AND MEDICAL CONDITIONS
ON REPRODUCTIVE HEALTH ...................................................................................................... 12

1.4.1 CONSUMER PRODUCT USE AND REPRODUCTIVE HEALTH ................................................. 13
1.4.2 DIET AND REPRODUCTIVE HEALTH ................................................................................... 19
1.4.2.1 DIETARY INTAKE AND CHEMICALS ................................................................................ 19
1.4.2.2 EFFECT OF DIET ON MENSTRUAL IRREGULARITIES ........................................................ 21
1.4.2.3 DISORDERED EATING AND REPRODUCTIVE HEALTH ...................................................... 22
1.4.3 EXERCISE AND REPRODUCTIVE HEALTH ........................................................................... 24
1.4.4 SMOKING AND REPRODUCTIVE HEALTH ........................................................................... 25
III

1.4.5 ALCOHOL AND REPRODUCTIVE HEALTH ........................................................................... 26
1.4.6 SLEEP AND REPRODUCTIVE HEALTH ................................................................................. 27
1.4.7 WORKPLACE AND REPRODUCTIVE HEALTH ..................................................................... 28
1.4.8 ETHNICITY AND SOCIOECONOMIC STATUS AND REPRODUCTIVE HEALTH ......................... 28
1.4.9 MENTAL HEALTH AND REPRODUCTIVE HEALTH............................................................... 30
1.4.10 CONFOUNDING VARIABLES ............................................................................................. 30
1.5 OBJECTIVES ......................................................................................................................... 32
2.0

STUDY DESIGN AND PARTICIPANTS .................................................................... 34

2.1 ONLINE SURVEY .................................................................................................................. 34
2.2 ANALYSIS ............................................................................................................................ 35
3.0

RESULTS ........................................................................................................................ 38

3.1 PAIN DURING MENSTRUATION ............................................................................................. 38
3.1.1 PAIN VARIABLE SUMMARY ............................................................................................... 38
3.1.2 AGE................................................................................................................................... 39
3.1.3 CHEMICAL EXPOSURE ....................................................................................................... 40
3.1.4 LENGTH OF MENSTRUATION ............................................................................................. 40
3.1.5 ADDITIONAL VARIABLES .................................................................................................. 40
3.2 BLEEDING DURING MENSTRUATION .................................................................................... 42
3.2.1 BLEEDING VARIABLE SUMMARY ...................................................................................... 42
3.2.2 CYCLE REGULARITY ......................................................................................................... 43
3.2.3 ALCOHOL CONSUMPTION .................................................................................................. 44
3.2.4 DRUG USE ......................................................................................................................... 44
IV

3.2.5 STRESS LEVELS ................................................................................................................. 44
3.2.6 LENGTH OF MENSTRUATION ............................................................................................. 45
3.2.7 ADDITIONAL VARIABLES .................................................................................................. 45
4.0

DISCUSSION .................................................................................................................. 47

4.1 DYSMENORRHEA .................................................................................................................. 47
4.2 MENORRHAGIA .................................................................................................................... 49
4.3 STRENGTHS AND LIMITATIONS ............................................................................................. 52
4.4 FUTURE DIRECTIONS ............................................................................................................ 52
5.0

CONCLUSION ............................................................................................................... 54

6.0

REFERENCES................................................................................................................ 55

7.0

APPENDIX ...................................................................................................................... 67

V

Acknowledgements
I would like to acknowledge and thank my supervisor, Dr. Heidi Huttunen-Hennelly, for
her support and encouragement for me to pursue my master’s project. Thank you for your
constant support and mentorship during both my master’s and undergraduate degrees. Without
your assistance, I would not be where I am today, and for that I am eternally grateful.
To Dr. Mark Rakobowchuk, thank you for your immense support, especially when my
master’s project changed from a more chemistry-based project to a biological project. Without
your encouragement, knowledge, and guidance I would not have been able to complete this
project. I am honored to have had the chance to work closely with you during this time after
everything I have learned from you in undergrad.
To Dr. Kingsley Donkor, thank you for your support, flexibility, and encouragement
throughout this project, as well as during my undergrad. Your positivity and love of science have
been inspiring to me and encouraged me to keep going, even when my project changed multiple
times.
To my friends, Lynnea Carr and Jesse Biddlecombe, who were constant supporters
during my masters and provided me with their wealth of knowledge, positivity, and
encouragement. Without Jesse’s wisdom and resources from her own master’s experience and
Lynnea’s wealth of knowledge in statistics and R Studio, I would not have been able to complete
my project. Thank you for everything!
To my family, especially Mom and Dad, thank you for your support, understanding, and
assistance during all my years of school. None of this would have been possible without your
generosity and love. Thank you!
Thank you to the Canadian Institute of Health Research – Canadian Graduate Scholarship
Masters, British Columbia Graduate Scholarship, Ken Lepin and family, and TRU Graduate
Student Research Mentor Award for financial support. Approval for the study was granted by
Thompson Rivers University Research Ethics Board (ID 102783).

VI

List of Figures
FIGURE 1. IMPACT OF VARIABLES ON DYSMENORRHEA WITH 95% CONFIDENCE INTERVALS ........ 39
FIGURE 2. IMPACT OF VARIABLES ON MENORRHAGIA WITH 95% CONFIDENCE INTERVALS ........... 43

List of Tables
TABLE 1. PARTICIPANT PAIN EXPERIENCE .................................................................................... 38
TABLE 2. PARTICIPANT BLEEDING EXPERIENCE ............................................................................. 42
TABLE 1A. ANDERSCH AND MILSON PAIN SCALE ......................................................................... 98
TABLE 2A. REASONS FOR EXCLUSION OF POTENTIAL PARTICIPANTS ............................................ 98
TABLE 3A. QUESTIONS EXCLUDED DUE TO INSUFFICIENT DATA .................................................... 99

VII

Chapter 1: Introduction

1

Endocrine Disrupting Chemicals
Individuals are constantly exposed to potentially harmful chemicals in almost every aspect of

daily life at home, in the workplace, and at school.1,2 It is estimated that individuals are exposed
to hundreds of harmful chemicals at any given time, where it is nearly impossible to find
unexposed populations anywhere in the world.3 Chemical contaminants are found in indoor and
outdoor air, soil, water, food, dust, and many consumer products.1 Exposure routes include eating,
drinking, breathing, and dermal absorption.1
One such group of chemicals that individuals are exposed to on a regular basis are endocrine
disruptors, or endocrine disrupting chemicals (EDCs). EDCs affect the endocrine system, which
includes the adrenal glands, the thyroid gland, the pituitary gland, the hypothalamus, and the male
and female gonads.1 and is responsible for regulating growth, sexual development, reproduction,
and metabolism.4 The organs of the endocrine system secrete hormones that travel to various parts
of the body through the blood within the cardiovascular system.1 EDCs specifically interfere with
these hormones5,6 by affecting their production and release, transport throughout the body,
metabolism, and elimination, among other mechanisms of action.1,7,8 Many EDCs can mimic
estrogen and bind to estrogen receptors, having either estrogenic or anti-estrogenic effects.8,9 EDCs
are often found in plastics, pesticides, and industrial chemicals,2,10 as well as in foods through
processing and storage5. Exposure to hormone disrupting chemicals may increase the risk of
women experiencing negative reproductive health outcomes through their direct or indirect affects
on the reproductive system.1,10
Unfortunately, for many chemicals a safe exposure threshold is not known.1 Many chemicals
do not go through rigorous scientific testing, meaning that many are lacking information regarding
their possible negative effects, including to the reproductive system.2,3,5,11 In fact, most
commercially used chemicals have not been tested for endocrine disrupting effects, so there are
still many unknown sources of EDC exposure.3 For a chemical to be considered dangerous
according to toxicological standards, the chemical must cause adverse health effects that are
proportional to an increasing dose, though EDCs do not follow this trend.5 EDCs follow a
nonlinear U-shaped dose response curve due to the many different means through which they can
1

disrupt the endocrine system,3 meaning that they can have differing effects at various doses.1 For
example, organochlorine pesticides such as methoxychlor and chlorpyrifos have been found to
enhanced gonadotropin releasing hormone (GnRH) gene expression at low doses and inhibition of
this same gene at high doses.12 Specifically, some EDCs only cause adverse health effects at low
doses and not at high doses by affecting the endocrine system’s ability to respond through highdose inhibition.5,6 Even low doses of a harmful chemical can affect an individual6 depending on
how many other chemicals they are exposed to and in what doses, as well as whether the individual
has any underlying health issues.2 For example, the effects caused by phthalate exposure may be
cumulative.13 EDCs may also have different impacts during different parts of the life cycle
depending on when in the life cycle the exposure occurs10 and for how long6. In some
circumstances, low doses of EDCs may be more harmful than high doses4,10 and the effect of
exposure to several EDCs at once may be more pronounced than the effect of each EDC
individually3,14. For this reason, even small additions, or subtractions of EDC exposure at low
doses can have significant impacts on reproductive health as compared to high doses.6 This also
means that current safe exposure levels may not reflect true safe exposure levels for low dose
exposures, as a threshold exposure level may not exist.6
There may also be a difference in absorption of chemicals based on sex, where researchers
McCormick and Abdel-Rahman found that absorption of certain chemicals through the skin were
twice as great in female rats as opposed to male rats, as sex hormones can affect absorption and
transport of chemicals.15 It is impossible to avoid all exposure to harmful chemicals, but an
individual can minimize their exposure so that enough of these chemicals do not enter the body or
disrupt normal function.1 After harmful chemicals enter the body, their impact is dependent upon
their individual chemical properties and whether they are excreted from the body or stored, as well
as how much of the chemical entered the body over a particular time period.1 The amount of a
chemical that remains inside the body is known as the body burden.1 There are many chemicals
that can begin to accumulate in the body that increase body burden, such as lipophilic chemicals
that accumulate in adipose tissue.1 An example of a lipophilic chemical is di(2-ethylhexyl)
phthalate (DEHP), which is an endocrine disruptor that has been found in sanitary pads.16 DEHP
is part of a class of chemicals called phthalates, which are commonly found in plastics and various
2

personal care products.1 They are also commonly found within the environment in water, soil, air,
and dust and can enter the body through absorption, ingestion, and inhalation.1 Organochlorine
pesticides and dioxins or dioxin-like compounds are other such chemicals that are readily stored
in adipose tissue, where they remain for extended periods of time.1 Both organochlorine pesticides
and dioxins are considered persistent organic pollutants (POPs), which persist within the body for
extended periods of time1 and more easily accumulate over time as a result.
In addition, individuals vary in their capability to absorb, metabolize, and excrete chemicals,
meaning that some individuals are more susceptible to the effects of harmful chemicals, such as
those with nutrient deficiencies or pre-existing illnesses.1 If a chemical that enters the body is not
stored, it can be metabolized or may simply be excreted right away.1 Excretory pathways include
exhalation; tears; shedding of dead skin, nails, and hair; saliva; sweat; urine, feces, and breast
milk.1 The half-life of a harmful chemical will also impact the body burden, where the longer the
half-life of a chemical, the longer it remains in the body. For example, polychlorinated bisphenols
(PCBs), which are lipophilic, can have a half-life of several years in humans.17
Exposure to any harmful chemical can come from more than one source, so it is important to
consider all possible exposure routes.1 For example, some endocrine disruptors are found in both
menstrual products and food, so both diet and consumer products should be considered to reduce
exposure to endocrine disruptors. This will be discussed in later sections. In addition, the timing
of exposure can have a huge impact on reproductive function.10 For example, exposures during
development have been seen to cause long term health effects, even as a zygote.1 Chemicals can
enter the placenta and fetus from the pregnant mother and cause adverse health effects in her
offspring.2 Woodruff et al. found that pregnant women in the United States between 2003 and
2004 were exposed to a minimum of 43 harmful chemicals while pregnant, where these chemicals
may have even greater effects on the fetus than the mother if these chemicals accumulate within
the fetus.18 A more recent study in 2011 by Sutton et al. had similar findings, where researchers
found that almost all pregnant women in the United States had several types of harmful chemicals
in their body that included phthalates, pesticides, PCBs, and bisphenol A (BPA), among others;
some of these chemicals, such as phthalates, were found in high enough levels to be associated
with adverse health effects in humans.11 In a meta-analysis done by Mendola et al., researchers
3

found that exposure to certain pesticides after birth can lead to reproductive developmental issues
in females that can impact puberty and menopause, ovulation and fertility, and menstruation.19
Due to the inevitable exposure to EDCs and previous research that indicates negative impacts
on reproductive health, our research aims to see which areas of exposure may contribute the most
to these issues by looking at the pain and bleeding women experience during menstruation and
comparing their experiences with chemical exposure routes and additional factors that may
increase or decrease chemical exposure and/or pain and bleeding during menstruation.

1.1

Pain and the Menstrual Cycle
Painful menstruation, also known as dysmenorrhea, is extremely common in reproductive aged

women and has been reported to affect anywhere from 16 to 95% of these women.20–28 The World
Health Organization (WHO) considers dysmenorrhea as the number one source of chronic pelvic
pain in women.20 This pain occurs during menstruation, though it can start before and is
characterized by a throbbing pain in the lower abdomen and pelvis.22 It is often the most severe on
the first day of menstruation24 when the menstrual flow is at its heaviest. Nieczuia-Dwojacka et
al. found that that women with primary dysmenorrhea often have more days between periods and
a longer period of bleeding.29
Dysmenorrhea can be classified into two categories: primary dysmenorrhea and secondary
dysmenorrhea.20,21 Primary dysmenorrhea refers to menstrual pain that does not have an
underlying cause and originates in the uterus.23,30 Pain caused by primary dysmenorrhea typically
lasts for 2-3 days after the onset of the menstrual cycle.21,24 This type of dysmenorrhea often
appears soon after the onset on menarche and usually improves after a woman has experienced 30
years of menstruation28 or has given birth to children30. Dysmenorrhea is most common in women
in their early twenties.21
Primary dysmenorrhea is thought to be caused by a decrease in blood flow to the
uterus23,26,31 and an increase in spastic uterine contractions,23,26 both of which may be caused by
an overproduction of prostaglandins27 (specifically prostaglandins E2 (PGE2) and F2 (PGF2)21).
Increased levels of prostaglandins can also increase pain sensitivity,21,24,26 which is thought to be
4

caused by myometrial and endometrial innervation in the uterus.23 In a study by Proctor and
Farquhar, they found that women with severe dysmenorrhea have higher concentrations of
prostaglandins than women with lesser or no dysmenorrhea, with the first two days of menstruation
having the highest concentrations of prostaglandins found in the menstrual flow.28 Other research
shows the overproduction of prostaglandins by the endometrium is a cause of primary
dysmenorrhea,21,24,32 as well as some of the other associated symptoms.33 Concentrations of both
PGF2α34 and PGE2 are higher in women who suffer from dysmenorrhea than in women who do
not,35 and pain intensity increased proportionally to PGF2α increase,36 PGF2α and PGE2 have also
been linked to reduced blood flow to the endometrium of the uterus, increased myometrial
contractions, and decreased oxygen to the uterus, all of which can cause pain.37
Although the main cause of primary dysmenorrhea is uterine inflammation, the sensitization
of the peripheral and central nervous systems is thought to play an important role.38 Extended
periods of pain in the peripheral nervous system that travels to the central nervous system can alter
the structure and function of the nervous system, which results in sensitization.38 Together, the
peripheral and central nervous systems may then cause hyperalgesia, allodynia, and spontaneous,
ongoing pain.38
Secondary dysmenorrhea refers to menstrual pain that results from an identified cause, such as
endometriosis or ovarian cysts, and may appear long after menarche.21,23 Secondary dysmenorrhea
is less common in younger girls as compared to older women, as these causative conditions
typically occur later in life.30 The pain caused by secondary dysmenorrhea can start as much as
two weeks before menstruation and can continue several days afterwards.21 The pain experienced
in primary and secondary dysmenorrhea, however, are very similar.21
Dysmenorrhea has a serious impact on the quality of life of women that have this
condition.21,24,27,28 Dysmenorrhea is a frequent cause of missed school and work, where Tu,
Bettendorf, and Shay found that up to one-half of women with dysmenorrhea in their study had
absenteeism due to their pain.21 Even when women suffering from dysmenorrhea choose to go to
work or school, the pain experienced may cause difficulty concentrating.32 In another study, 3240% of women with dysmenorrhea experienced absences and trouble functioning socially due to
5

their pain.22 Dysmenorrhea can also impact sleep, where women are often unable to get adequate
rest due to pain.32
When pain becomes chronic, the changes made to the nervous system may cause pain to occur
independently from the stimulus or even in its complete absence.38 Women who experience
dysmenorrhea experience an increase in visceral and muscular sensitivity, as well as increased
pain sensitivity, outside of the uterus even when dysmenorrhea is absent and a woman is not
menstruating.23,39 These changes to the nervous system are perhaps why suffers of chronic pain
typically also suffer from mental health issues or are more likely to suffer from additional chronic
pain conditions.38 In fact, the changes seen in the brains of women with dysmenorrhea are
consistent with other chronic pain conditions.23
Risk factors for developing dysmenorrhea include early menarche,13,14,23 late menarche,22
younger age,13,23 irregular or prolonged menstrual flow,21–25,30 smoking,21–23,30 low body mass
index (BMI),21–23,30 high BMI;23 pelvic infections,21 previous abortions,21,22 somatic complaints
around the time of menstruation,21 psychological disturbances,21,30 a history of sexual
assault,21,23,30 nulliparity,30 inadequate exercise,22,32 stress,22,32 mental illness,22,23,32 genetics,22,23
and low socioeconomic status.22 However, there are also many protective factors that may reduce
the risk of developing dysmenorrhea or lessening pain, some of which will be discussed in future
sections. These protective factors include exercise, oral contraceptives, higher equality, a stable
relationship, and certain dietary choices.21 Many of these risk factors were taken into consideration
for our research and data collection.

1.2

Bleeding and the Menstrual Cycle
Heavy menstrual bleeding, or menorrhagia, is another common menstrual issue that as

many as 50% of the female population suffers from.40 Typical blood loss during menstruation is
30 mL on average but may range anywhere from 13-80 mL.41,42 Menorrhagia is classified as either
a menstrual flow of more than 80mL per cycle43 or a heavy menstrual flow lasting for more than
seven days44.

6

Symptoms that often accompany menorrhagia aside from iron deficiency or anemia include
pain in the abdomen, breasts, and back; headaches; pressure and weakness in the pelvis; and
distension of the abdomen.45 Menorrhagia may be caused primarily, where the underlying cause
is not known, or secondarily because of another disorder.40 For example, women with congenital
bleeding disorders or platelet disorders42 may have a heavy menstrual flow as a symptom of their
disorder. Such disorders include hemophilia A and B, Von Willebrand disease, Bernard-Soulier
syndrome, and Glanzmann’s thrombastenia.40
Fifty to eighty percent of menorrhagia cases have no underlying pathology46 and may
instead be caused by abnormally high levels of prostaglandins40 and increased fibrinolysis47 in the
endometrium48, though the mechanism of menorrhagia is not well understood. Excessive uterine
blood loss may be a result of increased levels of PGE2 and decreased levels of prostaglandin F2α
(PGF2α)49 and increased levels of prostacyclin, which is a vasodilator and platelet aggregation
inhibitor.50
The endometrium may also become inflamed, which is caused by leukocytes,
macrophages, and natural killer cells. These cells breakdown the endometrial epithelium and cause
vasodilation of capillaries in the endometrial epithelium, which increases bleeding.51 This heavy
level of bleeding may not only impact the health of the individual, but also impacts quality of life
and interrupts routine activities.

1.3

The Female Body and Reproductive Health

1.3.1 Early Life and Menstrual Irregularities
As mentioned previously, prenatal exposure to chemicals can have an affect on health later in
life. The human reproductive system is especially vulnerable to chemicals during infancy,
childhood, and adolescence due to the many developmental changes that occur during this time.11
For example, exposure to certain harmful chemicals during fetal development may increase the
risk of childhood cancers, while postnatal exposure to certain pesticides during development may
interfere with developmental stages of reproductive function in women8 such as puberty,
menstruation, and menopause, and can also affect fertility.2 Exposure to EDCs during fetal
7

development or infancy may also lead to the development of disease later in life1–3, where the lag
time between exposure and disease onset can be years or decades.10
Females may also be reaching puberty much earlier than previously documented, where the
average age of menarche has been shown to be decreasing by about 3 months per decade since
1977.52 At the same time, there has also been an increase in reproductive system diseases.53
Females who experience menarche before they are 12 years old may have an increased chance of
experiencing breakthrough bleeding between periods as well as shorter, more frequent periods,
while those who experience menarche when they are 15 years or older may be more likely to
experience longer and irregular cycles.54 The change in the average age of menarche may be
associated with chemical exposure, as exposure to EDCs may impact the starting time of puberty.55

1.3.2 Female Anatomy, Hormones, and the Menstrual Cycle
Both the uterus and the ovaries play a major role in the ovarian and uterine cycles associated
with menstruation. The uterus is supplied with blood by the uterine arteries and contains many
blood vessels, lymphatic vessels, and parasympathetic and sympathetic autonomic nerve fibres.56
The shedding of the endometrium results in large, exposed areas of wounds on the uterine walls,
which may act as a pathway for chemicals from women’s sanitary products57 or other sources to
enter the bloodstream and the circulatory system.
For most women, the average menstrual cycle is about 28 days,58 where the first day of the
cycle is the first day of menstruation.33,41,42,56 Menstruation typically lasts from one to seven days56
and generates anywhere from 5-80 mL of blood per cycle, with an average blood loss of 30 mL
per cycle.41 The menstrual cycle typically starts in pubertal females between the ages of 11 and 12
(but can range from 9-16) and continues until menopause is reached between 45-55 years of age.42
The menstrual cycle is the most irregular during adolescence and just prior to menopause.58 Since
menstrual cycle characteristics, such as cycle length, are associated with fertility and reproductive
health, the menstrual cycle can be used to determine a woman’s reproductive and endocrine system
health.59
8

The menstrual cycle consists of three uterine phases and two ovarian phases.33,56 The
uterine menstrual phase and the proliferative phase occur during the follicular phase in the ovaries,
while the secretory phase in the uterus corresponds with the luteal phase in the ovaries.33,56 To
understand the menstrual cycle, both the ovarian and uterine phases must be considered, as,
although the uterus is where menstruation occurs, the uterine events leading up to menstruation
are caused by changes in the secretion of hormones in the ovaries, which is in turn influenced by
the ovary’s interactions with the hypothalamus and the anterior pituitary gland, often referred to
as the hypothalamic-pituitary-ovarian axis.33,41,56 If the uterine and ovarian cycles are not
synchronized or hormonal communication is disrupted, reproductive functions may be
compromised.56,60

1.3.2.1 The Ovarian Cycle
Ovarian function is controlled by a cascade of hormones that starts in the hypothalamus,
where gonadotropin-releasing hormone (GnRH) is released41 into surrounding blood vessels in
pulsating secretions that change in frequency and amplitude over the menstrual cycle33,56,58,70,
which begins for the first time at puberty42.
The ovaries are responsible for ejecting a single oocyte that travels to the uterus during
each menstrual cycle60, as well as the secretion of estrogen and progesterone, the female sex
hormones, and inhibin35 and activin, which inhibit and stimulate the anterior pituitary gland to
release follicle stimulating hormone (FSH), respectively.42 These inhibitory and stimulatory
actions are achieved by down or upregulating the anterior pituitary gland’s GnRH receptors,42
where estrogen increases, and progesterone decreases pulsatile secretions of GnRH.56 GnRH
travels through the blood to the anterior pituitary gland and binds to receptors; initiating the
pulsatile secretion of FSH and luteinizing hormone (LH)41,42,58,60 into surrounding blood vessels,
though the anterior pituitary gland’s response to GnRH also varies over the course of the menstrual
cycle.33,56 For example, depending on the pulse frequency of GnRH secretions, the anterior
pituitary gland may only primarily release FSH at one frequency, and LH at another frequency.56
When GnRH pulsatile secretions are low, FSH is released from the anterior pituitary gland,
9

whereas when GnRH pulsatile secretions are high, LH is released from the anterior pituitary
gland.60 Additionally, if GnRH were constantly released without pulses, no FSH or LH would be
secreted from the anterior pituitary gland, just as if no GnRH were being produced at all.56
Regardless, FSH and LH both travel through the bloodstream to the ovaries, whose response to
FSH and LH also change throughout the menstrual cycle.33,56
When FSH and LH reach the ovaries, they bind to receptors in the granulosa cells of
ovarian follicles, which contain the oocytes.41,60 These granulosa cells secrete estrogen and inhibin
during the follicular phase,60 as well as small amounts of progesterone33,56 just before ovulation.42
As the follicles mature, the granulosa cells differentiate into theca, which also synthesizes
estrogen.33,56,58 Between 3-30 follicles mature during each cycle, and usually only one of these
follicles will continue to develop41 after the first week of the cycle.33,56,58 Between days five to
seven of the cycle, one follicle becomes the dominant follicle, and by day eight it begins to
stimulate its own growth while supressing the growth of the other follicles.58 This follicle will
continue to mature, as well as the oocyte, until eventually the wall of the follicle breaks and
releases the oocyte, which travels to the fallopian tube; this results in ovulation41 at around day 14
of the menstrual cycle.33,60 The granulosa cells of the leftover follicle then grow to create the corpus
luteum structure, which secretes estrogen, progesterone,60 and inhibin. This structure continues to
develop for another ten days, at which time it begins to degrade unless fertilization occurs.33 If
fertilization does not occur and degeneration continues, it will result in menstruation and the start
of the next menstrual cycle.33,60 Therefore, the follicular phase that occurs in the ovaries consists
of the development of follicles up until the oocyte is released into the fallopian tubes at ovulation,
and the luteal phase occurs when the leftover follicle becomes the corpus luteum after ovulation
until its degeneration and the start of menstruation.33,56,60 The follicular phase and the luteal phase
each last about 14 days,56,60, though the follicular phase has more variation in length38,41,58 and can
affect the length of the menstrual cycle.42
The disruption of ovarian function can lead to many reproductive issues, such as infertility,
anovulation, and abnormal secretion of estrogen.61 For example, exposure to DEHP may affect the
ovaries, likely through mono-(2-ethyl-5-hexyl) phthalate (MEHP), by reducing estrogen levels and

10

thus slowing follicle growth.61 DEHP may also cause oxidative stress, which further inhibits
follicular growth and may also lead to follicular death.61

1.3.2.2 The Menstrual Cycle
The first phase of the menstrual cycle is the menstrual phase. During this phase,
menstruation occurs and typically lasts for three to five days. Menstruation is a result of the
shedding of the functional layer of the endometrium as it degenerates,33,41,42,62 which occurs in
patches.56
After the functional layer of the endometrium is shed during the menstrual phase, it must
be restored; this occurs during the proliferative phase56 in response to estrogen38,42 and is marked
by the regeneration and thickening of the functional layer of the endometrium from the basal layer.
33,41,56

There is an increase in estrogen levels during the proliferative phase, whose hormonal

actions sustain this phase and causes the endometrium to grow,41,42,56 along with the myometrium,
leading to progesterone receptor synthesis in endometrial cells.33 The full function of the
endometrium is restored after the restoration of the vasculature41 and uterine glands.42,56 The
proliferative phase lasts for roughly ten days and ends with ovulation, after which the secretory
phase begins.33
During the secretory phase after ovulation, progesterone begins to bind to the progesterone
receptors of the endometrial cells, changing the endometrium into a secreting tissue.33 This causes
the glands of the endometrial epithelium to dilate and produce mucus.33 Enzymes also begin to
accumulate in the connective tissue before angiogenesis occurs.33 This is to provide a hospitable
environment for a potential embryo if fertilization occurs.33 The uterine environment is further
made hospitable to a possible fetus through the inhibitory action of progesterone, which works
against estrogen58 and prostaglandins, so contractions of the myometrium do not occur, allowing
implantation of a fertilized egg in the uterus.33
Secretions from uterine glands are highest around 12 days after ovulation, where the
secretory phase typically lasts 14 days.56 If fertilization does not occur and the corpus luteum
11

begins to degenerate, decreases in estrogen and progesterone cause the endometrium to synthesize
prostaglandins.33 These prostaglandins build up in the endometrial tissue32 and cause
vasoconstriction (so the blood and oxygen supply to the endometrium is reduced and it begins to
degenerate)41,58,62, rhythmic myometrial contractions28,33,58, inflammation63, and lowered pain
thresholds21. Specifically, PGE2 inhibits platelet aggregation and acts as a vasodilator, while PGF2α
causes smooth muscle contractions, leading to pain; both cause inflammation.63 The reduction in
blood flow to the endometrium causes a reduction in oxygen and nutrients to the tissue and a
buildup of wastes, resulting in degeneration.56,58 All but a very thin, underlying layer of the
endometrium, the basal layer, will degenerate.33,41,56,62 The basal layer does not degenerate because
it is still richly supplied with blood from the straight arteries, which do not undergo
vasoconstriction56 by prostaglandins. The basal layer will regenerate the endometrium again for
the following cycle.33,41,56,62
Soon after the vasoconstriction caused by prostaglandins occurs in the endometrium,
vasodilation of these arteries follows and the weakened capillaries hemorrhage. This blood, along
with the sloughed endometrium, makes up the menstrual flow.33,41,57 The immune system also
plays a role in menstruation and regulates the inflammatory response, tissue breakdown, and pain
experienced during menstruation, as well as the repair of the functional layer of the endothelium.23
Within the first two days of the new menstrual cycle, new follicles within the ovaries begin
to secrete estrogen, which leads to vasoconstriction within the uterus and clot formation on the
basal layer of the endometrium, allowing the functional layer of the endometrium to regenerate.58

1.4

The Role of Lifestyle, Nutrition, Socioeconomic Status, and Medical Conditions on
Reproductive Health
Menstrual irregularities may be attributed not only to EDCs, but also to additional factors

such as diet and exercise. It is important to understand the many ways in which the menstrual cycle
may be affected, as this helps to reduce variables when studying the effects of EDCs on the
menstrual cycle. For this reason, the following sections will discuss how consumer product use,
diet, ethnicity, socioeconomic status, exercise, smoking, alcohol consumption, sleep, the
12

workplace, mental health, and other medical conditions may have an impact on the menstrual
cycle. Outside of these topics, there are still many areas of study that may impact the menstrual
cycle, both positively and negatively.

1.4.1 Consumer Product Use and Reproductive Health
Many consumer products, including personal care products and cosmetics, contain a
variety of chemicals, including EDCs. Some of the most common EDCs found in these products
include phthalates, parabens, dioxins, volatile organic compounds (VOCs), and pesticides. Women
are exposed to these products daily and exposure can come from multiple sources. For example,
phthalates are found in many fragrances13,57,64, deodorants13,57, skin and hair products13,57, nail
polish13,57, and cosmetics13,57 in various concentrations, which add to total exposure levels. They
are also used during food processing7,13, which can introduce these chemicals into food. These
chemicals are often ingested, inhaled, and absorbed through the skin on dermal contact;7,13,61,65–67
these routes are considered major exposure pathways for phthalates.65 In fact, phthalates can
enhance skin penetration and have been found in personal care products and women’s sanitary
products.16 Phthalates are also used in industrial processes and are found in many common
products,64–66,68 such as medical devices and various personal care products.7,13,61,69 Other products
include lubricants, food, pharmaceuticals, resins, and products containing polyvinyl chloride
(PVC).16 Phthalates, such as DEHP, are used in the plastic industry to make plastics more
flexible14,61,68 and soft14,57,65, such as in food packaging64 and sanitary pad production. Phthalates
have been shown to cause fertility problems along with other reproductive health issues.54,57,66,67
For example, Liu et al. found that phthalates were the cause of multiple reproductive health issues
in rats, including spontaneous abortion, follicular development disorders, hormone imbalances,
ovarian issues, vaginal bleeding issues, and cancer, to name a few.54 Phthalates have been found
in personal care products in several countries, including Canada16, the United States16, and China57.
Because DEHP is not covalently bonded to the plastics it is found in, DEHP can leach from these
products through the heating, cleaning, and general use of plastic products.61 For this reason,
DEHP and other phthalates can also migrate from these products to soil, sediment, water, dust, and
13

air so that exposure may not only be by dermal absorption, but inhalation and ingestion.13 The
French Agency for Food, Environmental, and Occupational Health and Safety also found
phthalates in feminine hygiene products.74,84
Parabens have also been found in women’s sanitary products, food, and other personal care
products within the United States.16,31 These chemicals are typically used as antimicrobial
preservatives in such products.31 Bisphenols, a type of paraben, have been found in women’s
sanitary products, where bisphenol F (BPF) was found in many tested brands of pads and panty
liners and BPA was found in pads, tampons, and panty liners.16 These bisphenols likely come from
the plastics sanitary products as made from in the form of impurities or additives.16 BPA has also
been found in food, consumer products, and packaging, where exposure can occur through
ingestion, absorption, or inhalation.7 Examples of these include food containers, cellphones,
laptops, hospital equipment, and water pipes.70 BPA, a very well-known EDC and estrogen
mimetic, causes nervous system issues71 and reproductive issues as well as other adverse health
effects4 even at extremely low doses that are below regulatory safety standards in the United
States.70 These adverse effects include endometriosis85 and ovarian cysts.86
A safe BPA dose has yet to be determined, as BPA may have different adverse effects
depending on the organ or organ system exposed to it.71 Parabens are generally excreted from the
body quite quickly, yet these chemicals are found in most of the United States population.31 A
study by Smith et al. found more than 92% of individuals had parabens in their urine, suggesting
exposure to parabens is continuous and chronic.31 As of 2013, there have been no studies looking
at paraben concentrations found in urine and their association with female reproductive health, as
parabens are also endocrine disruptors.31
Dioxins are known endocrine disruptors that can affect reproductive function, among its
many other effects on various body systems.87 In a study by De Vito and Schecter, they tested
tampons from 1997 and found dioxins and furans present in low concentrations.73 However, the
materials used in the production of sanitary pads and tampons may have changed greatly since
1997, making it unclear of dioxin and furan levels are lower or higher than those found in this
study, as Woo et al. in a more recent 2019 study still found dioxins present in sanitary products.74
14

These chemicals, along with furans, are produced through the bleaching process, where the highest
level of dioxins produced comes from elemental chlorine bleaching.73 It is likely that dioxin levels
have decreased in sanitary products, as many manufacturers have changed their bleaching
processes to safer alternatives.75 The dioxins, dioxin-like compounds, and furans that have been
found in sanitary products include polychlorinated dibenzodioxins (PCDDs), PCBs, and
polychlorinated dibenzofurans (PCDFs).74 Triclocarban (TCC), a source of dioxins and other
harmful substances,76 has also been found in pads, tampons, panty liners, cleansing lotions, bar
soaps, and feminine wipes and bactericidal creams.16 Regardless of this, the major contributor to
dioxin exposure is likely through the consumption of animal products and dairy, where
bioaccumulation of dioxins is high.73
Volatile organic compounds (VOCs) have been found in a variety of consumer products, such
as feminine hygiene products, including women’s sanitary products; vaginal washes, sprays,
powders, wipes, and moisturizers.77 VOCs within these products typically act as binders,
fragrances, adhesives, moisture barriers, or adsorbents.77 These chemicals are easily absorbed by
the skin, though other exposure pathways include ingestion and inhalation.78
There are several VOCs that have been identified to be endocrine disruptors including toluene,
xylene, and methylene chloride, all of which have been identified in at least some sanitary pad
brands from Finland, Japan, Greece, France, Korea, and the United States.67 Another report by
Women’s Voices for the Earth identified styrene, chloroform, and chloromethane in well-known
Procter & Gamble’s Always sanitary pads through an independent product test done by Paradigm
Environmental Services.79 Unsurprisingly, Lin et al. found that scented sanitary pads and tampons
contained higher amounts of terpenes and aromatic compounds (such as ethylbenzene, toluene,
xylene, styrene, and benzene) than unscented products.77 What was surprising, however, was that
store brands often had lower levels of VOCs than non-store brands and organic disposable sanitary
pads and tampons did not have a significant difference in VOCs levels as compared to non-organic
disposable products (the same was found for products with “sensitive skin” and “natural” labels).77
Regarding “organic” labels, this may be due to the lack of controls placed on manufacturers, as
this term lacks regulation or definition outside of the production of organic food by the United
States Department of Agriculture (USDA).77 Differences in store and non-store brand VOC levels
15

may be due to differences in manufacturing practices and sourcing of materials.77 In addition, the
concentrations and types of VOCs present in sanitary products can vary by country due to different
VOC use standards.74 Many of the chemicals found in disposable sanitary pads and tampons are
also found in other feminine hygiene products.77
Organic farming practices, including the farming of not only food and livestock, but also cotton
and other plant and animal products not regularly consumed, prohibits the use of synthetic
pesticides, fertilizers, and growth hormones, as well as antibiotic use, aside from when necessary.80
Regarding plants specifically, they are not allowed to contain chemical food additives, be
irradiated, or be grown from genetically modified organisms (GMOs).80
Synthetic pesticides, such as the organophosphates malathion81 and chlorpyrifos81, are often
used in food and plant production (such as non-organic cotton).1 Organophosphates do not persist
in the environment, but their residues on the products that they are used on contribute to exposure
in individuals.1 In fact, Lu et al. found that organophosphates were present in soil, food, and indoor
air and dust in both agricultural and non-agricultural communities, while these chemicals were
also found on toys and on children’s hands in agricultural communities.83 Pesticide exposure may
come not only from the use of pesticides, but also through the diet by consuming contaminated
animal products, rice, fruits, and vegetables.8 For example, DEHP has been found in meat and
dairy products at extremely high concentrations.61 These products may contain over 300 𝜇g/kg of
DEHP, where 50 𝜇g/kg/day of DEHP can cause endocrine disruption, specifically testicular
toxicity, according to the European Food Safety Authority.61
A surprising place that pesticides may be found are within women’s sanitary products. A report
by Women’s Voices for the Earth suggests that third-party testing they had done found several
pesticides in a specific brand of tampon,83 including malathion, methidathion, malaoxon,
mecarbam, fensulfothion, pyrethrum, and procymidone, where exposure to these chemicals
through the vagina has not yet been studied.75 However, it is unclear what sort of quality control
was used in the lab.83 The French Agency for Food, Environmental, and Occupational Health and
Safety also found glyphosate, hexachlorobenzene, lindane, and quintozene in some sanitary
products.74,84 Interestingly, quintozene and lindane have been prohibited in the European Union
16

since 2000, and hexachlorobenzene has been prohibited since 2004, yet the products tested in 2016
still contained these pesticides.84 This may be dependent on where the manufacturers of these
products source their cotton, as these pesticides may not be banned in other countries.
Unfortunately, most studies on the risks of pesticide exposure have not considered
exposure to more than one pesticide at a time or the presence of pesticide by-products.8 This is
concerning, since some pesticide by-products are more harmful than the parent compound,
including aldicarb-sulfoxide and oxons of chlorpyrifos, methyl-parathion, and diazinon, while the
combination of some pesticides has greater toxic effects than all of them used separately.8 These
pesticides may be ingested or inhaled and cause various female reproductive issues.88 Research
suggests that postnatal exposure to certain pesticides can also cause issues with developmental
stages (puberty84, menstruation89,90, ovulation91,92, menopause93, etc.) in adult females regarding
reproductive function.
Nearly seven years of a female’s life is spent menstruating when the average length of a
period (five days)42 and female reproduction (40 years)94 are considered. Typically, the average
woman will experience 450 menstruation events in her lifetime.43 A typical sanitary product, such
as a pad or tampon, absorbs between 5-15 mL of blood when saturated, where normal blood loss
can range anywhere from 13-80 mL of blood per cycle.43 It has been estimated that the average
woman may use upwards of 10,000 sanitary pads or tampons during her menstruating years.77,83
Therefore, over their lifetime, women have chronic exposure to sanitary products. This is
concerning, as many chemicals have been found in women’s sanitary products that cause adverse
health effects including dioxins,73,83,94 plasticizing chemicals,94 phthalates,83,94 and VOCs.94 These
sanitary products contact the sensitive skin and vaginal mucosa, which is highly permeable with
high absorption capabilities.77
Women’s sanitary products, such as menstrual pads, tampons, and panty liners, may expose
women to several plasticizers.16 The manufacturing practices used to create these products has the
potential to leave chemicals within the product, such as through the bleaching process or the use
of non-organic cotton that may contain pesticide residues. In addition, these products are largely
made of plastics, such as polypropylene (PP) and polyethylene (PE), which are themselves made
17

of chemicals and may also contain plasticizers, such as phthalates.16 In 2019 Woo et al. found that
residual organic solvents from the manufacturing process present in sanitary pads can increase
health risks, including reproductive harm through their toxic effects.74
In a recent 2020 study by Gao and Kannan, they tested various women’s sanitary products
from the United States from both popular and generic brands and found that all products tested
contained the phthalates Dess-Martin periodinane (DMP), diethyl phthalate (DEP), dibutyl
phthalate (DBP), diisobutyl phthalate (DIBP), DEHP, and the parabens 2-C-Methylerithritol 4phosphate (MeP), and ethylparaben (EtP).16 Tampons were found to contain the highest DEHP
levels, while panty liners had the highest levels of DMP, DBP, DIBP, and DEP.16 Phthalates,
parabens, and many other such chemicals are EDCs that are used as plasticizers and antimicrobial
agents and have been found not only in women’s sanitary products, but other personal care
products and even food.16 DEHP specifically has been known to cause uterine bleeding, among
other things.53 The high levels of phthalates found in these sanitary products likely came from the
plastics they were made of, the plasticizing process, and the hot-melt adhesive process.16,57 The
hot-melt adhesive process serves to glue all the various layers of sanitary products together, though
the high temperatures required may cause leaking of chemicals into other layers of the product as
well, even if those layers are not made of plastics themselves.16,57 For example, Gao et al. found
that the concentration of phthalates present in sanitary pads that had a top layer of cotton still had
just as many phthalates present in the top layer as those found in other non-cotton top layer
materials. This was likely caused by the absorption of phthalates into the cotton layer during the
production process from plastics and the hot-melt adhesive process.57 They also found that 98%
of sanitary pads tested in China contained phthalates, where DEP, DBP, and DEHP accounted for
more than 60% of phthalates tested, while sanitary pads with fragrance also had greater amounts
of DIBP than in pads without fragrance.57 Park et al. also found that sanitary pads had significantly
higher phthalate levels than did other commercial plastic products and found DBP, DEHP, and
DEP in the sanitary pads tested.67
Gao and Kannan found that phthalate levels in women’s sanitary products were much
higher than any other chemicals analyzed in their study.16 The study estimated that dermal
absorption from the use of women’s sanitary products accounted for anywhere from 3-15% of an
18

individual’s total phthalate exposure, though transfer rates of the chemicals tested in this study are
unknown for women’s sanitary products and the absorption rate of phthalates varies greatly in
human skin.16 Gao et al. estimated that sanitary products account for around 8% of phthalate
exposure doses in women.57 However, the vulvar absorption rate of phthalates is not yet known
and an absorption rate of two times that of the epidermis was arbitrarily used and the study did not
consider menstrual blood being used to transfer phthalates into the bloodstream.57 In addition, this
study did not look at vagina absorption rates of phthalates from tampons, which are in much closer
proximity to the mucosa than sanitary pads are, increasing phthalate transfer risks.57 As such,
further research is required to determine if these calculations are an under- or over-estimation.
Many of the chemicals found in sanitary products are known for their adverse health
effects, including the promotion of inflammation and endometriosis95 and menstrual
irregularities.96 To avoid most of these harmful chemicals, the use of reusable pads made of 100%
organic, unbleached cotton may be a preferred option, though testing on these products has not
been done to confirm they do not contain EDCs or other harmful substances.

1.4.2 Diet and Reproductive Health
Chemical exposure may also occur through the diet and likely plays a larger role than the
chemical exposure that occurs through sanitary product use. This topic is considered in the
following section.

1.4.2.1 Dietary Intake and Chemicals
Aside from chemicals found in personal care products, there may be many other avenues
of exposure to chemicals that impact reproductive health. Diet may also impact the chemicals an
individual is exposed to, as well as an individual’s use of personal hygiene products and
medications. Lu et al. in 2006, found that organic diets significantly reduced the intake of
organophosphorus pesticides like malathion and chlorpyrifos (which are regularly used in
agricultural production and are known for their neurologic effects) to undetectable levels in
19

children.97 These pesticides may be found in fruits and vegetables, and products made with them,
as well as wheat and corn products, such as pasta and cereal.97 A meta-analysis by Smith-Spangler
et al. in 2012 further supported these findings, as they found that eating organic foods (animal and
plant products) not only reduces exposure to pesticide residues, but it also reduces exposure to
antibiotic-resistant bacteria.80
Diet may also be a main source of exposure to phthalates and BPA, which are known
EDCs.64,68 Aside from diet, these EDCs have also been found in water and consumer products as
well as in the air and dust.64,68 They are most likely introduced into foods that individuals consume
through the use of plastics in the manufacturing process, including through processing, storing,
and transporting these foods, as well as through an individual’s use of plastic containers, cutlery,
dinnerware and consumption of canned foods.68 In fact, Sathyanarayana et al. showed that
consumption of fresh, un-canned food that was not exposed to plastic packaging or prepared in
plastic containers led to a significant decrease in phthalate and BPA concentrations found in
urine.68 In another study, Rudel et al. found the consumption of fresh food as opposed to foods
exposed to plastics (canned foods, frozen foods, foods microwaved in plastic, food covered in
plastic films, food from restaurants, and drinks from cans or polycarbonate bottles) led to a
significant decrease in DEHP and BPA metabolites found in urine.64 DEHP, BPA, and other EDC
may also be introduced to foods such as milk through the use of PVC tubing when milking cows
and have even been found in whole eggs in Asia.64 Exposure to dioxins may also come primarily
from the diet, where consumption of animal meat and dairy products may account for up to 95%
of dioxin exposure in humans.73
It may not only matter what individuals eat, but where their food is grown. Zhang et al.
found that vegetables grown in plastic greenhouses was a major source of phthalate exposure for
people in China, where phthalate exposures were higher in individuals from urban areas as
compared to individuals from rural areas.98 Of these phthalates, DEHP made up 55% of total
phthalate concentrations found in these vegetables, followed by di-n-butyl phthalate (DnBP) and
DiBP.98

20

Diet may not only be a major source of chemical exposure, but it may also have a positive
impact on reproductive health. Ji et al. found that antibiotic and phthalate exposure were lower in
individuals on vegetarian diets than on unrestricted diets.66 Specifically, of the phthalates tested,
there was a significant correlation between the concentration of MEHP metabolites in the urine
and the consumption of dairy products.66 MEP, mono-n-butyl phthalate (MnBP), and monoisobutyl phthalate (MiBP) also all significantly decreased in individuals on a vegetarian diet.66

1.4.2.2 Effect of Diet on Menstrual Irregularities
There is some evidence that an individual’s nutrition and metabolism may have a large
impact on the menstrual issues women experience. A set of studies by Barnard et al. in 2000 found
that a vegan diet (consisting of grains, vegetables, legumes, and fruits), with an approximate fat
intake of 10% and a protein intake between 10-15% of an individual’s daily caloric intake,
decreased participants cramps and weight and improved sleep, digestion, and perceived energy.99
They also found low-fat, vegetarian diets improved glycemic management, blood pressure, and
serum lipids.99 In a follow-up study, Barnard et al. also found that the duration of menstrual pain
(dysmenorrhea) and intensity were significantly lower in women on a vegan diet as opposed to an
unrestricted diet, as were some premenstrual symptoms.100 The researchers suggest their results
might be caused by dietary effects on estrogen activity, where an increase in sex-hormone binding
globulin or a decrease in serum estrogen may reduce estrogenic stimulation of the endometrium to
limit tissue proliferation that produces prostaglandins.99 Vegetables, fruits, and legumes also have
a profound effect on omega-3 and omega-6 fatty acid ratios, which can affect what type of
prostaglandins are formed from these precursor molecules.100 These animal-product-free foods
have a low-fat content but are often rich in omega-3 fatty acids in relation to other types of fat,
whereas diets containing cooking oils and animal fats have a greater proportion of omega-6 fatty
acids.100 This is an important distinction, as 3-series prostaglandins are formed from omega-3 fatty
acids and have anti-inflammatory properties, while the 2-series prostaglandins PGE2 and PGE2α
are formed from omega-6100 and PGE2 is involved in inflammation, swelling, and pain.101 Barnard
et al. found that a higher intake of omega-3 or a higher omega-3 intake as compared to omega-6
was associated with a decrease in pain from menstruation in women100 In a recent meta-analysis
21

conducted by Isaza, they also found omega-3 could improve dysmenorrhea,102 though nausea and
an increase in acne were associated with omega-3 intake.21 These findings were also confirmed in
other studies, but more research is still needed.28

1.4.2.3 Disordered Eating and Reproductive Health
Disordered eating and eating disorders may have an impact on the menstrual cycle.
According to the American Psychiatric Association, these chronic illnesses typically start around
adolescence and young adulthood and are common in young women.103 If the body does not
receive enough energy and nutrients, it can impact the onset of puberty and menarche, as well as
regular menstruation after menarche.104 It is also typical to see comorbid conditions in individuals
with disordered eating, some of which include reproductive issues and decreased bone health.104
Disordered eating that leads to low weight, along with excessive exercise and high stress levels,
may result in hypothalamic amenorrhea, where menses stops or does not start in the first place.104
Hypothalamic amenorrhea results from a decrease in GnRH secretion, which ultimately causes a
decrease in estrogen secretion.105 In addition to causing amenorrhea, a decrease in estrogen
secretion also leads to decreased bone mineral density, infertility, painful intercourse, and vaginal
and breast atrophy.104 GnRH secretion may also be impacted by stress, as increasing cortisol levels
inhibit this secretion.104
As low weight may lead to a later onset of menarche, girls with a high BMI that are
considered obese may have a earlier onset of menarche.106 Being overweight may also lead to
irregular and infrequent periods.55,106 Interestingly, exposure to the DEHP metabolite MEHP may
be associated with a higher BMI and waist circumference.61 Also, women who experience
menstrual irregularities are more likely to have a larger waist circumference and higher BMI than
those who do not experience menstrual irregularities.106 This may be related to the higher insulin
and testosterone levels and the lower sex hormone-binding globulin (SHBG) found in obese
women, which leads to hormonal changes that may cause menstrual irregularities.107 In addition,
stress plays a role in obesity by altering the bodies ratio of androgens to estrogens, which in turn
can cause abdominal obesity in women.38 Stress causes increased levels of cortisol in the body,
22

inhibiting lipid mobilization in adipose tissue, especially in visceral adipose tissue, which has a
high number of cortisol receptors.38
Adipose tissue is important for various physiological functions, one of which is the
function of the endocrine system.108 Adipocytes can secrete endocrine factors that regulate
inflammation and produce substances that can influence vascular function, immune function, and
hormonal status.108 In addition, adipose tissue is responsible for the storage of substrates in the
body, but it is also capable of storing chemicals108 such as persistent EDCs due to their high lipid
solubility.10 This suggests that individuals who have more fat tissue may have greater body burdens
of various chemicals, such as persistent organic pollutants (POPs).109
POPs, most of which are endocrine disruptors and are resistant to metabolism, have a high
affinity for lipids and can be stored in adipose tissue,109 which in the short term can protect various
other tissues and organs in the body from being exposed to these chemicals.108 Some of these POPs
include

some

organochlorine

pesticides17,108,

polychlorinated

biphenyls

(PCBs)108,109,

dioxins108,109, and furans108,109. DEHP, DBP, and other phthalates may also accumulate in adipose
tissue to a lesser extent, though they are generally non-persistent109 due to their half-life of around
five hours and their ability to be metabolized into more easily excretable substances.13 Despite
their short half-lives, phthalate exposure is detected in most populations worldwide likely due to
chronic exposure, but it may also be due to bioaccumulation.13 However, differences in body
composition and metabolism can affect the half-life, persistence, and degradation of EDCs in
tissues and bodily fluids.10
Other lipophilic xenobiotics are also capable of accumulating in adipose tissue and other
tissues with high lipid content.110 However, this sequestering of lipophilic chemicals increases the
total body burden through bioaccumulation and may have long term negative effects through
continual internal exposure.108 These chemicals will be released into the bloodstream slowly over
time, which may be further exacerbated during weight loss.108,110 Fortunately, for some POPs, the
POP body burden may decrease by 15% through weight loss.108,110

23

1.4.3 Exercise and Reproductive Health
As weight effects menstrual patterns, several studies have looked at exercise as a possible
treatment for both heavy bleeding and painful periods in women.24,27 Atta et al. found that 54.6%
of female students that did not exercise at all or had low physical activity suffered from
dysmenorrhea.32 Although it seems exercise has a positive impact on dysmenorrhea, the type of
exercise varies greatly in such studies, as do their results. In 2017, Banu et al. found that there
seemed to be no association with heavy bleeding and BMI; instead, they found that secondary
causes of menorrhagia were more likely, such as uterine fibroids.45 However, Mariam et al. found
abnormal uterine bleeding to be the main cause of menorrhagia, which may be a result of the age
of the participants, as older women are less likely to develop fibroids than younger women.111 In
other studies Mohebbi Dehnavi et al. and Motahari-Tabari et al. found that regular and continuous
aerobic exercise or stretching may reduce or eliminate heavy menstrual bleeding.24,27 Additionally,
physical activity may increase the length of the menstrual cycle so that there are a greater number
of days between menses.112 This increase in cycle length could be caused by a decrease in FSH,
which in turn causes follicles to mature more slowly and thus increase the length of the follicular
phase, ultimately delaying ovulation.112 In another study Nieczuia-Dwojacka et al. found that
women have shorter menstrual cycles when they are physically active.29
It seems more studies have been done on the effect of exercise on primary dysmenorrhea.
Mohebbi Dehnavi et al. found that primary dysmenorrhea may be reduced through moderate
intensity aerobic exercise, though improvement is only seen when an individual exercises
consistently three times a week for thirty minutes or more.24 This effect is likely due to the decrease
in serum aldosterone levels seen in women when active, which is caused by decreased levels of
renin and increased levels of estrogen and progesterone.24 Additionally, sports exercise may
increase blood circulation to the pelvis, resulting in the elimination of wastes and prostaglandins
from the uterus more effectively during exercise, resulting in a delayed onset of pain.24,27 This
increase in blood circulation also increases endorphins due to a decrease in stress levels
experienced while exercising.24 The timing of exercise may also be important, as Motahari-Tebari
et al. found that the prevalence of dysmenorrhea was reduced in women that had regularly
exercised before the onset of menarche.27 Stretching exercises that consisted of a five-minute
24

warmup and ten-minutes of stomach and pelvic stretches three times a week were also found to
reduce dysmenorrhea just as well as mefenamic acid.27 However, exercise took longer to reduce
pain and was not as effective as mefenamic acid until after one month of consistent exercise.27
Although it seems regular exercise can be effective at reducing pain from primary dysmenorrhea,
its effectiveness largely depends on the duration of exercise, as well as the intensity and quality of
exercise done, where more vigorous exercise causes the greatest decrease in pain intensity.27 These
stretching exercises are thought to increase endorphin levels and cause hormonal changes in the
epithelial tissues of the uterus.27 Exercise in general helps the body to maintain homeostasis in
relation to regulation of hormones and the menstrual cycle.32
Exercise may also be beneficial by inducing perspiration, as may eliminate some phthalates
from the body, including DEHP and MEHP.13 Other activities that induce perspiration, such as
sauna use, may also be beneficial at eliminating these chemicals.13 In addition, the loss of fat that
is often a result of regular exercise and caloric restriction may result in the mobilization of stored
chemicals from adipose tissue to the fat stores of the skin, which may act as an alternative storage.13

1.4.4 Smoking and Reproductive Health
Smoking may also have an impact on the menstrual cycle, where smoking may increase
the risk of dysmenorrhea28 and a longer, heavier menstrual flow.113 Some researchers have found
that this risk increases the longer an individual has been a smoker and the more they smoke.37,113
Ju et al. found that the earlier an individual starts smoking the greater the risk of developing chronic
dysmenorrhea, where girls who started smoking before menarche and girls 13 or younger had up
to 60% higher odds.37 However, there is some evidence that dysmenorrhea symptoms caused by
smoking may be reversed after cessation of smoking, though further research is needed.37 Smoking
likely contributes to dysmenorrhea because smoking causes vasoconstriction and may limit blood
flow to the endometrium.37,113 Additionally, by increasing the duration of menstruation,
individuals are at an increased risk for experiencing dysmenorrhea.37,113 This longer period of
menstruation may be caused by smoking’s effect on the endocrine system.37 Other researchers
have found that smoking may cause shorter, more frequent menstruation54, leading to early
25

menopause.107,112 This early menopause is likely due to an increase in FSH, which causes follicles
to mature more quickly and results in the early depletion of oocytes.112 There are several other
suggested theories as to why smoking may cause dysmenorrhea, such as through interference with
the binding of estrogens to its receptors, enhancing the metabolism of alternative estrogen sources
that are not produced by the body itself, or by reducing the conversion of androgens in the body to
estrogens.37 There are also other less plausible theories, such as smoking causes ovarian atrophy,
which is unlikely since the cessation of smoking can reverse dysmenorrhea symptoms experienced
due to smoking.37

1.4.5 Alcohol and Reproductive Health
The consumption of alcohol in even moderate amounts may cause menstrual and
reproductive irregularities such as infertility, amenorrhea, and early menopause.114,115 Liu et al.
found that the cycle length of women who consumed alcohol was shorter than those who did not,
which can cause more frequent menstruation.112 Alcohol disrupts the reproductive system through
hypothalamic-pituitary-ovarian axis dysfunction, ovarian dysfunction, and the dysfunction of
various regulation mechanisms.114 Augustyńska et al. found that prolactin levels were significantly
increased in alcoholic women during the entire cycle.114 This increase in prolactin disrupts the
pituitary-ovarian axis, which in turn disrupts reproductive function and stimulates a decrease in
LH secretion.114 Additionally, many of the women studied were found to have increased
progesterone levels during the follicular phase and decreased LH levels during the ovulation
phase.114 Testosterone levels also increased during the luteal phase and were positively associated
with the length of time of alcohol dependency prior to the study.114 Decreased LH secretion, or
lack thereof, leads to anovulation or irregular ovulation and is a common cause of infertility.114,115
Testosterone can also influence the hypothalamic-pituitary axis, leading to dysfunction of the
menstrual cycle.114 This increase in testosterone may be further increased when alcohol is
consumed while taking oral contraceptives.114 Estrogen levels may also increase due to alcohol,
likely due to metabolic dysfunction in the liver, leading to an increase in nicotinamide adenine
dinucleotide (NAD) + hydrogen (H) (NADH) that affects estradiol-estrone conversion.114 Schliep
26

et al. found that consumption of wine and liquor led to an increase in estradiol, testosterone, and
LH when one or more alcoholic drinks were consumed per day, while beer and spirits seemed to
have no effect.116 These results were further magnified when binge drinking was involved.116
Parazzini et al. also found that the heavy consumption of wine and/or beer may decrease an
individual’s risk of dysmenorrhea113, though this is likely due to the cessation of a period
altogether, as other researchers have found the consumption of alcohol to cause dysmenorrhea.28
Alcohol consumption may also impact puberty, where Emanuele et al. found that low
levels of estrogen in 12- to 18-year-old girls that remained low for up to two weeks after moderate
drinking, which may impact the maturation of the reproductive system.115 In research done with
rhesus monkeys, alcohol increased the time between menstruations, which may result in the
development of irregular menstrual patterns.115

1.4.6 Sleep and Reproductive Health
Sleep may also have an impact on the menstrual cycle, where circadian rhythm disruption
can affect menstrual function.117,118 A disrupted circadian rhythm, such as in shift workers, may
cause irregular and longer menstrual cycles.117 Baker and Driver found that 50% of menstruating
women doing shift work reported menstrual irregularities, as compared to 20% in the general
population.117 These menstrual irregularities may be caused by changes in the amplitude and
frequency of the pulsatile secretions of LH and dysfunction of the hypothalamic-pituitary-ovarian
axis due to added stress on the body.117 Sleep causes a natural nocturnal decrease in LH levels, as
well as a decrease in LH pulsatile frequency during the follicular phase.117 However, shift work
disrupts this pattern, as most shift workers get less sleep that is more fragmented.117 Short sleep
duration may also lead to menstrual irregularities.13 Figà-Talamanca also found that women
working irregular hours or shift work increased their risk of spontaneous abortion, along with other
reproductive issues.118 However, this was not the case if women working nights had consistent
sleep schedules.118

27

1.4.7 Workplace and Reproductive Health
Stress and anxiety may be linked to dysmenorrhea, where Atta et al. found that female
students who suffered from stress and anxiety were 81.8% more likely to have dysmenorrhea.32
Also, Nieczuja-Dwojacka et al. linked high stress levels with dysmenorrhea, where dysmenorrhea
was more severe and frequent in those with high stress levels than in those who were not highly
stressed.29 Other researchers found high levels of stress in the work environment caused
anovulation and changes in menstrual cycle length, as well as spontaneous abortion and preterm
births.118
The workplace may also impact chemical exposure, where many jobs, such as energy
production or manufacturing, often use chemicals during production that are retained within the
products, exposing both workers and consumers.1 Women working in the plastic industry are also
at higher risk of chemical exposure than men, as women often have lower positions with more
chemical exposure risk.4 Chemicals women are exposed to in the plastic industry may have
estrogenic effects and cause endocrine disruption.119 DEHP is one such chemical and has been
found in workers at significantly higher levels than in the general population, even when air
samples at the workplace found DEHP in trace amounts below typical exposure standard levels.120
This is because DEHP has a low evaporation rate.61 Another high-risk job is agricultural work,
where exposure to pesticides and other chemicals is common.1,2 Immigrant workers are at even
greater risk of chemical exposure, as they often work jobs with high hazardous exposure levels in
greater numbers than do a country’s own citizens.2 It has been documented that pesticide exposure
in women can cause health problems in offspring, infertility, and spontaneous abortion, among
other issues.118 Other high-risk industries with regular chemical exposure include dry cleaners, nail
salons, hair salons, house cleaning, health care, and factory work.121

1.4.8 Ethnicity and Socioeconomic Status and Reproductive Health
Ethnicity and socioeconomic status may also impact dysmenorrhea, though this area is less
studied. For example, although dysmenorrhea prevalence in women of reproductive age ranges
from 16 to 91%, a meta-analysis and systematic review by Saei Ghare Naz et al. found that for
28

Iranian women, this statistic is closer to 71%.20 Banikarim et al. found that Hispanic teenage girls
had higher rates of dysmenorrhea compared to previously reported rates in African American and
Caucasian girls by up to three times their pain.122
Socioeconomic status of women in South Korea was associated with education and
household income, where women who had lower education or women with high household
incomes were found to have the highest rates of menstrual irregularities.123 A higher education is
likely associated with a decreased risk of dysmenorrhea due to an individual having more access
to information, medical services, greater medical service quality, better living conditions, and
better occupational and housing environments.123 However, an individual’s job may also have an
impact on dysmenorrhea, where high stress jobs with poor working conditions, temporary
employment, or irregular hours may increase an individual’s risk of developing menstrual
irregularities.123 Though surprising at first, Kwak et al. found that women with higher incomes had
greater rates of menstrual irregularities, though this was attributed to the types of jobs women with
high incomes usually have.123 For example, many high paying jobs are managerial or specialized
in nature and are often high stress positions; these types of jobs are known for their irregular
schedules and can cause mental and physical exhaustion, dietary changes, and sleep issues.123
Women who had not gone through childbirth and women who were either unmarried, widowed,
divorced, or not living with their spouse may also be more likely to suffer from menstrual
irregularities than women with children or were married living in the same household.123
Culture may have an impact on menstrual pain as well. For example, most women in
Western cultures say they experience menstrual pain, while only one-quarter of rural Mayan
women do.21 This may not necessarily mean than Mayan women experience less menstrual pain
than women from Western cultures. Cultural influences can have a profound impact on how the
menstrual cycle is perceived, which may affect the number of women who report experiencing
menstrual pain.21 For instance, some cultures may consider discussing the menstrual cycle as
taboo23 or may consider a menstruating woman impure and thus unable to partake in certain
religious practices, which may lead to under reporting of dysmenorrhea.21 With this in mind, De
Sanctis et al. reviewed the prevalence of dysmenorrhea from around the world between 2010 and

29

2015, which varied greatly between countries, ranging from as high as 94% in Oman and as low
as 0.9% in Korea.123
In addition to dysmenorrhea, race and status may also play a role in the amount of chemical
exposure an individual experiences. For example, according to the American Lung Association,
poorer people and certain ethnic groups have the highest exposure to pollutants.125 This disparity
can be attributed to the living situation of many minority groups, who often live in poor
neighborhoods with lower quality housing due to a range of factors including racism, class bias,
and low social position, among others.125

1.4.9 Mental Health and Reproductive Health
Mental health status may also be associated with menstrual irregularities.126 Mental health
may impact the menstrual cycle, where Patel et al. found that as levels of anxiety and depression
increased, so did pain caused by dysmenorrhea.127 Women who have experienced emotional
disturbances38 or high levels of somatization may also experience higher rates of dysmenorrhea,
though studies on these topics are generally small.21 Rowland et al. found that women suffering
from depression often had longer and more irregular cycles than those without depression and they
also experienced bleeding between menses.54 These menstrual irregularities could be attributed to
several factors, including depression itself, the medical treatment for depression, or the stress
associated with depression.54

1.4.10 Confounding Variables
Treatments for dysmenorrhea typically involve relieving pain or other symptoms either by
masking them or by directly affecting the mechanisms involved in causing the pain, such as by
reducing or inhibiting prostaglandin synthesis.28 Some of these treatments are also affective in
reducing bleeding.

30

There are many drugs or treatment options that can, for reasons mentioned above, impact
the results of our study. There are also drugs or treatments for other unrelated conditions that have
secondary effects that can impact the menstrual cycle. These include, but are not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs)128, oral contraceptives26,30, GnRH agonists129,
aromatase inhibitors129, antispasmodics129, calcium channel blockers28,129, vasopressin antagonists
28,130

, nitroglycerin28,129, antifibrinolytic drugs46, and progestins129.
In terms of contraceptives, combined oral contraceptives (both continuous and cyclical)

both work to treat primary dysmenorrhea after six months of use, though the use of continuous
oral contraceptives for secondary dysmenorrhea is more effective.26 However, not all
contraceptives are effective at reducing dysmenorrhea and may even increase menstrual pain and
bleeding. The use of a copper intrauterine device (IUD), which is inserted into the vagina, is one
such example.128,131 Common side effects of copper IUDs include increased menstrual flow and
duration, pelvic pain128, and dysmenorrhea.28,131 These side effects are often the cause of
discontinued use and premature removal of copper IUDs.25,128,131 An alternative to the copper IUD
is the hormonal IUD, which reduces prostaglandin synthesis in the endometrial tissue.40 This may
lead to a decrease in dysmenorrhea and menorrhagia through the reduction of uterine blood flow
and a decrease in endometrial thickness.21,25 Another type of contraceptive that may decrease
dysmenorrhea and menorrhagia is the depot medroxyprogesterone acetate (DMPA) injection,132
which is injected intramuscularly every three months; this results in anovulation for seven to nine
months.21 However, there is a chance of increasing uterine bleeding through the use of the DMPA
shot in the short-term, though amenorrhea becomes more likely after three months.132 Since the
use of contraceptives is quite common among women and have varying affects on the menstrual
cycle, women who use these contraceptives were still included in our study.
There are many secondary causes of dysmenorrhea, menorrhagia, and other menstrual
irregularities. Secondary dysmenorrhea is associated with many other issues including painful
intercourse21,133, pelvic inflammatory disease21,28, adenomyosis21,28, uterine fibroids21,28,
endometriosis21,28, ovarian cysts21, intrauterine polyps21, inflammation of the cervix21, and
bleeding between periods21. Other possible causes of secondary dysmenorrhea include neural or
hormonal issues.21
31

Some evidence suggests that exposure to phthalates61 and PCBs74 may increase the risk of
developing endometriosis.1,10,61,74 Polycystic ovary syndrome (PCOS), another common disorder
that can cause dysmenorrhea, may be associated with fetal exposure to some EDCs.10 Endocrine
hormones also help to regulate the function of the immune system and EDCs may disrupt their
effect on this system1 and lead to immune system disorders.3 Inflammation is often linked with
diseases that cause infertility, such as pelvic inflammatory disease, and EDCs such as dioxin-like
PCBs have been associated with an increased risk of developing endometriosis.1
Heavy menstrual bleeding may also be caused by many other conditions which include
ovarian cysts, uterine cancer, uterine polyps, bleeding disorders, cervical inflammation, and
uterine prolapse, to name a few.45 Many hormonal conditions can also have an impact of the
menstrual cycle. Hyperthyroidism and hypothyroidism, both thyroid disorders, can lead to altered
menstrual function58,134,135 by impacting the metabolism of androgens and estrogens.136
Type two diabetes mellitus may also cause menstrual irregularities, where diabetes has
been found to increase the odds that a woman will experience an irregular and longer cycle.54
Additionally, women who had either an irregular cycle or a long cycle were twice as likely to
develop type two diabetes mellitus than women who did not experience an irregular or long cycle.54
It is important to note that DEHP exposure may increase insulin resistance in elderly populations61
and many DEHP metabolites have been positively linked to insulin resistance and diabetes.109
Aside from the above-mentioned conditions, there are many other illnesses and diseases
that can have an impact on the menstrual cycle, as can the medications that are often used to cope
with such conditions. For these reasons, individuals with certain medical conditions were excluded
from our study.

1.5

Objectives
The objective of the proposed research is to see which exposure routes and additional

factors may contribute to menstrual irregularities, and which may not. Each category will also be
ranked to see which have the greatest positive and negative effects on reproductive health.
32

This research addresses the hypothesis that higher levels of exposure to harmful EDCs are
more likely to result in higher reports of reproductive issues in women, such as increased pain and
bleeding during menstruation, compared to women with low EDC exposure levels, where high
chemical exposure is defined as exposure to chemicals in large quantities, for long periods of time,
and/or in high frequencies. High chemical exposure was chosen as our measure due to multiple
EDCs mentioned previously having known reproductive effects at high doses, such as phthalates,
while low doses are not often considered. This research also addresses the hypothesis that various
factors can either increase or decrease a woman’s risk of experiencing pain and/or can increase or
decrease bleeding during menstruation.
This research will provide insight into the effect of EDCs and other chemicals on the female
reproductive system, in particular the menstrual cycle.

33

Chapter 2: Methods
2

Study Design and Participants
Approval for the study was granted by the Thompson Rivers University Research Ethics Board

(ID 102783). Written informed consent was given by all participants.
We aimed to recruit between 2000-3000 menstruating women volunteers between the ages of
18-35 for our study, which consisted of a one-time online survey. Our sample population ended
up being 178, after a total of 97 participants were excluded for various reasons, which can be found
in table 2A. The participants in this study had to be between the ages of 18 and 35, currently
experience a menstrual cycle, and could not be pregnant during the time of completing the survey.
Additionally, only women who lived in Canada and had access to a computer with internet were
considered for participation in the study. Women who had a medical condition that could impact
the reproductive system on its own or through medication use for treating the condition were also
excluded post survey in the data analysis phase of the study.
Women were recruited through online advertising, which was sent to all major universities
across Canada. In addition, further advertisement was done through local and provincial news
outlets and the researcher’s Facebook and Instagram pages. A copy of this ad can be found in the
appendix.

2.1

Online Survey
The survey link was provided to potential participants and included a consent form for

potential participants to review before partaking in the survey. This consent form outlined what
was expected of participants and can be found in the appendix. The survey also contained a builtin screening process, where anyone who was not female, menstruating, and was not between the
ages of 18-35 were automatically excluded. The survey itself contained just over 95 questions and
was estimated to take between 45-60 minutes to complete. The survey did not have to be completed
in one sitting and participants could edit their answers prior to submission. Any surveys that were
not fully completed were not considered for data analysis. Questions included in the survey
34

covered socioeconomic status, reproductive health, general health, mental health, product use, and
additional factors. This survey is contained in the appendix. Within the survey, pain was measured
using the Andersch and Milson Pain Scale (AMS) (which is a scale used to assess the severity of
menstrual pain), and stress levels were measured using the Perceived Stress Scale (PSS). Both of
these scales can be found in the appendix (A4, A5). The AMS was used to assess pain due to its
simplistic, easy to interpret design that could easily be included in our survey without adding
multiple questions to the already broad survey.

2.2

Analysis
After survey results were collected, questions that pertained to a single variable, such as

alcohol consumption, were combined into a single score. Each response was ranked, where, in our
example of alcohol consumption, 0 would indicate low use and a higher number, such as 2, would
indicate high use. Questions were normalized so that each question pertaining to a single variable
were weighted the same. For example, the number of standard alcoholic drinks an individual has
in a week was weighted the same as how many years an individual has been drinking for, so that
both contribute equally to the overall alcohol consumption score used for data analysis.
By condensing questions into a single score, we used a total of 21 variables in our analysis.
These variables were age, BMI, hormone medication use, age at menarche, cycle regularity, vaping
status, alcohol consumption, drug use, sleep, caffeine use, stress, chemical exposure, smoking
status, psychological medication use, relationship status, place of residence (urban, rural, etc.),
pregnancy history, sexual activity, number of days between menstrual cycles, number of days the
menstrual cycle lasts, and stress levels.
Alcohol consumption was calculated based on a participant’s alcohol use status, if
participants consumed alcohol before their first period or when they were younger than 18, how
many drinks they had per week, and how long they have consumed alcohol for.
Drug use was calculated based on a participant’s drug use status, if participants used drugs
before their first period or when they were younger than 20, and how long they have used drugs
for.
35

Stress scores were calculated based on the PSS that can be found in the appendix (A4).
Chemical exposure was calculated based on a participant’s menstrual product use
(inorganic/organic, scented/unscented), use of other vaginal hygiene products, use of personal care
products, diet type (vegetarian/vegan/unrestricted, organic/unrestricted), consumption of canned
foods/foods and beverages stored in plastic bags/bottles/containers, and frequency of consumption
of canned/plastic exposed foods.
Vaping status, Drug status, and smoking status all had small sample sizes for moderate and
high use, so these categories had to be collapsed into one category of moderate/high use in order
to run the logistic regression model that was used. The smallest vaping category was moderate use
with 8 participants, the smallest drug use category was high use with 18 participants, and the
smallest smoking category was high use with 3 participants. As a result, a binary comparison was
made where we compared low/no use in these three categories with moderate/high use.
Several questions from our survey were not used in our analysis for a variety of reasons.
Some questions were excluded due to having insufficient data for analysis, such as having too
many “I am unsure” responses or blank answers, while others were excluded due to being outside
the scope of our study. Other questions were excluded due to the questions not being specific
enough and a high likelihood of misinterpretation by participants (such as “how frequently are you
exposed to chemicals at work, home, or school,” where the participant may not know they are
exposed to chemicals at all and no further information was provided to participants to help them
provide an informed response).
After survey results were condensed into 21 total variables, the data collected was analyzed
using a proportional odds logistic regression model to see if chemical exposure and different
additional factors may contribute to menstrual irregularities, and which may not. Separate analyses
were done for pain and bleeding, respectively. The absolute risk of significant variables was also
calculated to see which variables may have the greatest effects on reproductive health within our
participants. The effect size of all variables was visualized using a Forest Plot.
Relative risk of experiencing dysmenorrhea was obtained by taking the average percentage of
women affected by dysmenorrhea in multiple studies, which ranged from 16 to 95% of
36

reproductive aged women, to get 56%.20–28 Relative risk of experiencing menorrhagia was based
on the CDCs assessment that 20% of American women experience heavy menstrual bleeding.137

37

Chapter 3: Results
3

Results

3.1

Pain During Menstruation
In our study, less than 6% of participants experience no pain during their menstrual cycles.

Most participants experience moderate pain (40%), followed by some pain (35%), and severe pain
(19%).
Table 1. Participant pain experience.
Participant Response

Number of Participants

No Pain

10

Some pain

62

Moderate pain

72

Severe pain

34

Outside of our study, dysmenorrhea is reported to affect anywhere from 16 to 95% of
reproductive aged women,20–28 resulting in an average of 56% of these women, which was used as
an estimate in our risk assessments below.

3.1.1 Pain Variable Summary
A summary of dysmenorrhea results is visualized in Figure 1, where the number of days
of menstrual bleeding, high chemical exposure, and age were the only variables considered that
were found to have a correlation with dysmenorrhea experienced in the study population.

38

Figure 1. Impact of variables on dysmenorrhea with 95% confidence intervals.

Figure 1 illustrates the correlation of each of our study variables with dysmenorrhea with
95% confidence intervals. The x axis shows the log odds ratio of each variable, where any
variable that crosses the 0.000 line do not have an impact on dysmenorrhea in our study
participants. Any variables that do not cross the 0.000 line on the left decrease dysmenorrhea and
any variables that do not cross the 0.000 line on the right increase dysmenorrhea.

3.1.2 Age
Age was negatively correlated with the pain experienced during menstruation, where the
odds of experiencing pain during menstruation are reduced as age increases (p=0.016, OR=0.907).
With an average of 56% of reproductive aged women experiencing dysmenorrhea, the risk of
39

experiencing dysmenorrhea is reduced to 45% (odds ratio*absolute risk = relative risk: 0.907*56%
= 45%) as age increases in our study population.

3.1.3 Chemical Exposure
High chemical exposure was negatively correlated with the pain experienced during
menstruation, where the odds of experiencing pain during menstruation are reduced with high
chemical exposure (p=0.015, OR=0.274) compared to low chemical exposure. With an average of
56% of reproductive aged women experiencing dysmenorrhea, the risk of experiencing
dysmenorrhea is reduced to 14% (odds ratio*absolute risk = relative risk: 0.274*56% = 14%) with
high chemical exposure in our study population.

3.1.4 Length of Menstruation
Menstruation that lasted eight or more days was positively correlated with the pain
experienced during menstruation, where the odds of experiencing pain during menstruation was
increased with periods that last eight or more days (p=0.014, OR=3.969) compared to menstruation
lasting 7 or less days. With an average of 56% of reproductive aged women experiencing
dysmenorrhea, the risk of experiencing dysmenorrhea is increased to 100% (odds ratio*absolute
risk = relative risk: 3.969*56% = 100%) with menstruation events eight or more days long in our
study population.

3.1.5 Additional Variables
BMI was not correlated to pain experienced during menstruation in our study population
(underweight (p=0.107), overweight (p=0.454), obese (p=0.600)). Hormone medication use was
not correlated with pain experienced during menstruation in our study population (use of
combination birth control or hormonal IUD (p=0.290), use of copper IUD (p=0.477)). Cycle
regularity was not correlated with pain experienced during menstruation in our study population
40

(p=0.856). Vape status was not correlated with pain experienced during menstruation in our study
population (p=0.343). Alcohol consumption was not correlated with pain experienced during
menstruation in our study population (moderate consumption (p=0.152), high consumption
(p=0.270)). Drug use was not correlated with pain experienced during menstruation in our study
population (p=0.094). Sleep was not correlated with pain experienced during menstruation in our
study population (irregular sleep or more/less than 7-9 hours (p=0.863), irregular sleep and
more/less than 7-9 hours (p=0.099)). Caffeine consumption was not correlated with pain
experienced during menstruation in our study population (<2 coffees (p=0.544), 2-4 coffees
(p=0.226), 4+ coffees (p=0.163)). Stress levels were not correlated with on pain experienced
during menstruation in our study population (moderate stress (p=0.080), high stress (p=0.109)).
Smoking status was not correlated with pain experienced during menstruation in our study
population (p=0.775). Psychological medication use was not correlated with pain experienced
during menstruation in our study population (p=0.794). Relationship status was not correlated with
pain experienced during menstruation in our study population (dating but not living together
(p=0.686), married/civil union/cohabitation (p=0.572)). Place of residence was not correlated with
pain experienced during menstruation in our study population (suburban (p=0.913), rural
(p=0.863)). Previous experience with pregnancy was not correlated with pain experienced during
menstruation in our study population (p=0.858). Sexual activity was not correlated with pain
experienced during menstruation in our study population (p=0.927). The length of time between
cycles was not correlated with pain experienced during menstruation in our study population
(p=0.629). Stress levels were not correlated with pain experienced during menstruation in our
study population (p=0.085).

41

3.2

Bleeding During Menstruation
In our study, less than 8% of participants experience heavy bleeding during their menstrual

cycles. Most participants experience light bleeding (72%), followed by moderate bleeding (20%).

Table 2. Participant bleeding experience.
Participant Response

Number of Participants

Light bleeding

128

Moderate bleeding

36

Heavy bleeding

14

Outside of our study, menorrhagia is reported to affect 20% of reproductive aged
women,137 which was used as an estimate in our risk assessments below.

3.2.1 Bleeding Variable Summary
A summary of menorrhagia results is visualized in Figure 2, where the number of days of
menstrual bleeding, moderate stress, moderate to high drug use, moderate alcohol consumption,
and irregular periods were the only variables found to be correlated with bleeding experienced in
the study population.

42

Figure 2. Impact of variables on menorrhagia with 95% confidence intervals.
Figure 2 illustrates the correlation of each of our study variables on menorrhagia with 95%
confidence intervals. The x axis shows the log odds ratio of each variable, where any variable
that crosses the 0.000 line do not have an impact on menorrhagia in our study participants. Any
variables that do not cross the 0.000 line on the left decrease menorrhagia and any variables that
do not cross the 0.000 line on the right increase menorrhagia.

3.2.2 Cycle Regularity
Having an irregular cycle was positively correlated with the bleeding experienced during
menstruation, where the odds of experiencing menorrhagia was increased with irregular cycles
(p=0.010, OR=4.480) compared to regular cycles. With an average of 20% of reproductive aged
women experiencing menorrhagia, the risk of experiencing menorrhagia is increased to 90% (odds
43

ratio*absolute risk = relative risk: 4.480*20% = 90%) with cycle irregularity in our study
population.

3.2.3 Alcohol Consumption
Alcohol consumption was negatively correlated with the bleeding experienced during
menstruation, where the odds of experiencing menorrhagia was decreased with moderate alcohol
consumption (p=0.001, OR=0.106) compared to low or no alcohol consumption. With an average
of 20% of reproductive aged women experiencing menorrhagia, the risk of experiencing
menorrhagia is decreased to 2% (odds ratio*absolute risk = relative risk: 0.106*20% = 2%) with
moderate alcohol consumption in our study population.

3.2.4 Drug Use
Drug use was negatively correlated with the bleeding experienced during menstruation,
where the odds of experiencing menorrhagia was decreased with moderate to high drug use
(p=0.010, OR=0.210) compared to low or no drug use. With an average of 20% of reproductive
aged women experiencing menorrhagia, the risk of experiencing menorrhagia is decreased to 4%
(odds ratio*absolute risk = relative risk: 0.210*20% = 4%) with moderate to high drug use in our
study population.

3.2.5 Stress Levels
Moderate stress was negatively correlated with bleeding experienced during menstruation,
where the odds of experiencing menorrhagia was decreased with moderate stress (p=0.016,
OR=0.220) compared to low stress. With an average of 20% of reproductive aged women
experiencing menorrhagia, the risk of experiencing menorrhagia is decreased to 4% (odds
ratio*absolute risk = relative risk: 0.220*20% = 4%) with moderate stress in our study population.

44

3.2.6 Length of Menstruation
Menstruation that lasted eight or more days was positively correlated with the bleeding
experienced during menstruation, where the odds of experiencing menorrhagia was increased with
periods that last eight or more days (p<0.001, OR=17.943) compared to menstruation that lasts 7
or less days. With an average of 20% of reproductive aged women experiencing menorrhagia, the
risk of experiencing menorrhagia is increased to over 100% (odds ratio*absolute risk = relative
risk: 17.943*20% = 100%) with menstrual events that last eight or more days long in our study
population.

3.2.7 Additional Variables
Age was not correlated with menorrhagia experienced during menstruation in our study
population (p=0.102). BMI was not correlated with menorrhagia experienced during menstruation
in our study population (underweight (p=0.106), overweight (p=0.130), obese (p=0.146)).
Hormone medication use was not correlated with menorrhagia experienced during menstruation
in our study population (use of combination birth control or hormonal IUD (p=0.060), use of
copper IUD (p=0.604)). Vape status was not correlated with menorrhagia experienced during
menstruation in our study population (p=0.161). Sleep was not correlated with menorrhagia
experienced during menstruation in our study population (irregular sleep or more/less than 7-9
hours (p=0.296), irregular sleep and more/less than 7-9 hours (p=0.473)). Caffeine consumption
was not correlated with menorrhagia experienced during menstruation in our study population (<
2 coffees (p=0.697), 2-4 coffees (p=0.644), 4+ coffees (p=0.273)). Chemical exposure was not
correlated with menorrhagia experienced during menstruation in our study population (moderate
chemical exposure (p=0.272), high chemical exposure (p=0.686)). Smoking status was not
correlated with menorrhagia experienced during menstruation in our study population (p=0.496).
The use of psychological medications was not correlated with menorrhagia experienced during
menstruation in our study population (p=0.590). Relationship status was not correlated with
menorrhagia experienced during menstruation in our study population (dating but not living
together (p=0.560), married/civil union/cohabitation (p=0.865)). Place of residence was not
45

correlated with menorrhagia experienced during menstruation in our study population (suburban
(p=0.768), rural (p=0.084)). Previous experience with pregnancy was not correlated with
menorrhagia experienced during menstruation in our study population (p=0.444). Sexual activity
was not correlated with menorrhagia experienced during menstruation in our study population
(p=0.224). The length of time between cycles was not correlated with menorrhagia experienced
during menstruation in our study population (p=0.171). Stress levels were not correlated with
menorrhagia experienced during menstruation in our study population (p=0.129).

46

Chapter 4: Discussion
4

Discussion

4.1

Dysmenorrhea
In our study, eight or more days of menstrual bleeding, high chemical exposure, and age

were correlated with dysmenorrhea experienced in the study population.
Age seems to reduce an individual’s risk of experiencing dysmenorrhea, where those who
are younger have a higher risk of dysmenorrhea than those who are older. In our study population,
risk of experiencing dysmenorrhea decreased from 56% to 45% as age increased. This finding is
supported with previous research.13,23,28 After a woman has experienced roughly 30 years of
menstruation28, or has given birth to children30, menstrual pain caused by primary dysmenorrhea
typically decreases. This decrease in pain is likely caused by hormone shifts that occur with age,
specifically, a decrease in estrogen levels. Reduction in estrogen concentrations may reduce its
stimulating effects on the endometrium, thus limiting the growth of tissues that play a role in
prostaglandin synthesis.100
Unexpectedly, high chemical exposure also seems to reduce an individual’s risk of
experiencing dysmenorrhea compared to those who had low or moderate chemical exposure. In
our study, risk of experiencing dysmenorrhea decreased from 56% to 15% with high chemical
exposure as compared to low chemical exposure in our study population. It is surprising that we
did not see a difference in effect between moderate chemical exposure in comparison to low
chemical exposure, since EDC effects are known to follow a nonlinear U-shaped dose response
curve.3 All evidence previously presented seems to contradict our results. However, it is important
to note that EDCs do not only affect the reproductive system, but also other systems in the body
where hormones are present. One of these systems is the immune system, which is closely linked
to the reproductive system. EDCs may act as estrogens or antiestrogens138 and they can interfere
with cytokine and immunoglobulin synthesis, inflammatory mediators, and activation and survival
of immune cells.139 As a result, EDCs may reduce or increase the bodies natural immune
response139, which includes the inflammatory response. Interestingly, estrogen has both proinflammatory and anti-inflammatory influence, which may play a role in our results. Novella et al.
47

(2012) found that the effect of estrogen is bidirectional in certain inflammatory biomarkers based
on age in postmenopausal women.140 It was found that estrogen had anti-inflammatory effects on
the arteries of women in their early stages of menopause and pro-inflammatory effects on the
arteries of women in late menopause, which may be associated with estrogen receptor-β
expression. As far as we are aware, research has not been done on estrogen’s anti-inflammatory
effects on premenopausal women. As inflammation plays a role in the menstrual pain women
experience, it is possible that the specific EDCs our participants were exposed to have an antiinflammatory effect, though it is unclear what other health impacts these EDCs might have had on
our participants. Further research regarding the estrogenic effects EDCs can have in premenopausal women is needed.
Menstruation that lasts 8 or more days seemed to increase an individual’s risk of
experiencing dysmenorrhea, where those that menstruate for 8 or more days have a higher risk of
menorrhagia than those who menstruate for less than 8 days. In our study, risk of experiencing
dysmenorrhea increased from 56% to 100% with menstruation that lasts 8 or more days in our
study population. Since both heavy menstrual bleeding, either in quality or duration, and
dysmenorrhea can be caused by hormone imbalances, 21,24,32,141 it does stand to reason that both
menorrhagia and dysmenorrhea would occur at the same time. Excessive uterine blood loss as well
as primary dysmenorrhea can both result from increased levels of PGE2,21,27,28,49 so it is likely that
study participants who experience menstruation that lasts 8 or more days have elevated PGE2
levels.
Of the significant variables, it seems high chemical exposure has the biggest impact on
reducing pain, with increasing age having a much smaller affect. Long menstruation events that
last eight or more days was the only variable found to increase the risk of experiencing pain.
Many variables tested were not correlated in our study population, although other researchers
mentioned in chapter 1 have found contradictory results. These differences may be due to small
sample sizes, small control sizes (or heavily skewed compared to sample size), not having a
representative sample population, and counting each normalized question as just as powerful as
any other for a variable. Despite reaching out to universities across Canada and multiple news
48

outlets, we were unsuccessful in reaching our desired sample size of roughly 30 participants per
study question, only getting a fraction of the participants we had hoped for. As a result of this,
control and sample sizes for some variables were skewed, where the control was typically the
“null” response (e.g. low/no alcohol consumption, low stress, etc.). With a larger sample size, each
variable would have had a more even representation of participants. In addition, due to most of the
respondents coming from the Kamloops, British Columbia, TRU student population, this was not
a representative sample of women across Canada. Therefore, the results found would only apply
to the TRU female student population, though it is unclear if this sample consisted of an even mix
of domestic and international students, which could have also had an impact on the results due to
differences in ethnic backgrounds and socioeconomic status, among other things. In addition, since
there is very little data on many of the variables studied, it was unclear if some questions should
have held more weight than others when condensing related questions into a single variable. For
instance, we considered the amount of alcohol consumed to have just as much weight as the age
at which a participant started to consume alcohol when calculating the alcohol consumption score,
when one of these might have played a greater role in the dysmenorrhea and/or menorrhagia
experienced by the participant than the other.

4.2

Menorrhagia
In our study, we found that eight or more days of menstrual bleeding, cycle irregularity,

moderate stress, moderate to high drug use, and moderate alcohol consumption were all correlated
with menorrhagia experienced in the study population.
Moderate alcohol consumption seemed to decrease an individual’s risk of experiencing
menorrhagia compared to those who had low or high alcohol consumption. Though not significant,
it is worth noting that high alcohol consumption exhibited a trend towards significant correlation
(p=0.052, OR=0.310). In our study, risk of experiencing menorrhagia decreased from 20% to 2%
with moderate alcohol consumption in our study population. Alcohol metabolism increases
estrogen levels143 and decreases progesterone levels144 in the body, which disrupts the bodies
regular hormonal fluctuations, depending on when drinking occurs during the menstrual cycle.
49

This disruption can lead to anovulation,114,115 which cause also cause hypomenorrhea, or light
periods.145
Moderate to high drug use seemed to decrease an individual’s risk of experiencing
menorrhagia compared to those who had low or no drug use. In our study, risk of experiencing
menorrhagia decreased from 20% to 4% with moderate to high drug use in our study population.
Though drug use was not an original part of our literature review due to the lack of research done
on drug use and its effects on menstruation, we had decided to include questions on drug use in
our survey due to Canada’s current opioid crisis146 and the recent legalization of marijuana by the
Canadian Government in 2018.147 Despite a lack of research in terms of recreational drug use and
menorrhagia, there has been research that shows drug use can cause other cycle irregularities, such
as anovular menstruation.148,149 We did not specify the types of drugs used in our study and only
defined drug use in general terms, including the use of prescription drugs recreationally. As such,
further research should be done in this area.
Moderate stress seems to decrease an individual’s risk of experiencing menorrhagia compared
to those who had low or high stress. Though not significant, it is worth noting that the high stress
variable had a small sample size (n=19) compared to moderate stress (n=122) and the control, low
stress (n=37), which is likely the cause for high stress not being significantly correlated. In our
study, risk of experiencing menorrhagia decreased from 20% to 4% with moderate stress in our
study population. Previous researchers have found that stress levels can cause anovulation and
changes in menstrual cycle length.118 The most likely cause of the reduction in bleeding is the
stress hormone cortisol, which has already been shown to cause irregular or missed periods,150
although the affect of cortisol is dependent on when during the menstrual cycle stress occurs.151
For instance, the timing of the stress might cause a delay in ovulation as well as the menstrual
cycle, it may cause a disruption in flow, or, in prolonged cases of stress, may lead to the absence
of a period all together.151
Cycle irregularity seemed to increase an individual’s risk of experiencing menorrhagia, where
those who have more irregular cycles have a higher risk of menorrhagia. In our study, risk of
experiencing menorrhagia increased from 20% to 90% with irregular cycles in our study
50

population. One of the most common causes of menorrhagia is irregular ovulation, which in turn
causes cycle irregularity.152 Both cycle irregularity and menorrhagia are often treated using
hormone therapy.152 So it is likely that cycle irregularity and menorrhagia seen in our participants
is a result of hormone imbalances. 40,47-50
Menstruation that lasts 8 or more days seems to increase an individual’s risk of experiencing
menorrhagia, where those that menstruate for 8 or more days have a higher risk of menorrhagia
than those who menstruate for less than 8 days. In our study, risk of experiencing menorrhagia
increased from 20% to certainty with menstruation that lasts 8 or more days in our study
population. This variable was used as a control, where we expected to see an increase in bleeding
experienced the more days a woman experienced menstrual bleeding.
Of the significant variables, it seems moderate alcohol consumption has the biggest impact
on reducing menstrual bleeding, followed by moderate to high drug use and moderate stress. It is
important to note that there may be a link between alcohol consumption and the stress levels
reported, as alcohol consumption has been shown to dampen the stress response.153 This may be
one reason why alcohol consumption has a greater impact on reducing menstrual bleeding in our
participants, as a lower stress level may have been reported in those who moderately consumed
alcohol, though further analysis would be needed to confirm this. Alcohol may also have a more
disruptive effect on the endocrine system than the stress response does. Long menstruation events
that last eight or more days had the greatest impact on increasing menstrual bleeding, followed by
cycle irregularity.
Many variables tested were not significantly correlated with menorrhagia in our study
population, although other researchers mentioned in chapter 1 have found contradictory results.
These differences may be due to small sample sizes, small control sizes (or heavily skewed
compared to sample size), not having a representative sample population, and counting each
normalized question as just as powerful as any other for a variable, all of which were discussed in
the previous section on dysmenorrhea.

51

4.3

Strengths and Limitations
Our greatest limitation in this research study was our broad topic coverage, which did not

allow us to go in depth in the variables that were found to be significant. Future research would be
required to look at significant variables in more depth to determine exact causes for our results. In
addition, some of the survey questions were on topics regarding the participants past experiences
or family history (such as if they had been exposed to chemicals at a young age, if there is a history
of dysmenorrhea in the family, etc.), where a majority of participants were unsure, and thus some
questions had to be cut from our analysis. Other questions were on sensitive topics, where, even
in an anonymous study, participants might not have felt comfortable sharing information and there
is a chance answers are not completely accurate. Besides this, self-reporting also could impact the
accuracy of information collected. Our study design was also a limitation, where we were only
able to consider correlations and not causation. Our correlational study was limited by the use of
non-validated measures and a limited sample size that was required for logistic regression without
collapsing categories. Despite these limitations, our study considered many different variables that
have not been considered in a single study, which may help encourage further research in a field
where women’s studies are limited.

4.4

Future Directions
Our study is the first study, to our knowledge, that looks at the effects of various factors in

addition to chemical exposure.
We hoped to collect information on whether there were known chemical exposures during
childhood or at work, home, or school, but many participants were unsure of their exposures in
these areas. This could be due to a lack of knowledge of an individual’s own upbringing but is
most likely due to the fact individuals are exposed to chemicals they are not even aware of in daily
life through seemingly insignificant means, such as touching or handling receipt paper.142 Prenatal
and early childhood exposure can have long lasting effects on health later in life, so not tracking
this information left a gap in our research. The timing of chemical exposures is extremely
important when looking at their effects on the body, where the human reproductive system is
52

especially vulnerable to chemicals during critical windows of development,3 including infancy,
childhood, and adolescence, due to the many developmental changes that occur during this time.11
As it is possible for long term health effects to arise even after harmful chemical exposure as a
zygote,1 further research is required that takes a more in depth look at prenatal and early childhood
exposure to determine the true effects on the female reproductive system, including the menstrual
cycle.
We hope this study can act as a steppingstone for future research that looks at this topic in
more detail.

53

Chapter 5: Conclusion
5

Conclusion
In our study, we found that high chemical exposure does have an impact on the female

reproductive system, where high chemical exposure decreased the risk of experiencing
dysmenorrhea. We also found that, of the additional factors that were significant, moderate alcohol
consumption had the biggest impact on reducing menstrual bleeding, followed by moderate to high
drug use and moderate stress. Other factors that played a role in menstrual irregularities included
increasing age decreases the risk of dysmenorrhea, long menstruation events lasting eight or more
days increase the risk of dysmenorrhea and menorrhagia, and irregular cycles increase the risk of
menorrhagia.
Our study aims to encourage future research in the field of women’s health, where research in
this area is often limited, especially regarding research looking at women’s health under a more
holistic lens.

54

Chapter 6: References
6

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Chapter 7: Appendix
7

Appendix

A1. Recruitment email.
Hello,
My name is Kyley Drach and I am a Master’s student at Thompson Rivers University in
Kamloops, British Columbia. I am doing research of chemical exposure and its effects on the
female reproductive system. My study is looking at various areas of potential chemical exposure
in a woman’s life and how this can impact her reproductive health. If it is found that chemical
exposure can influence female reproductive health, we will aim to determine which routes of
chemical exposure seem to have the greatest effect.
I am seeking female participants for this study between the ages of 18 to 35 who still
currently experience a menstrual cycle. The study consists of a one-time survey, which will take
between 45-60 minutes to complete. The survey does not need to be completed in one sitting and
responses can be edited until the survey is submitted. Questions include the areas of reproductive
health, product use, and general health.
I am wondering if you would be able to share this information within your institution to
assist in recruitment of women across Canada. I have provided the link to the survey below, where
more information will also be provided regarding the study.
https://www.surveymonkey.ca/r/chemical_exposure
If you have any questions about this study, please feel free to contact me at:
Kyley-drach@mytru.ca
Thank you for your time and assistance,
Kyley Drach

67

A2. Consent form.

Consent Form
This study is entitled Chemical Exposure and Female Reproductive Health and will be
conducted by Kyley Drach (email: kyley-drach@mytru.ca). This study examines various areas of
potential chemical exposure in a woman’s life and how this can impact her reproductive health. If
it is found that chemical exposure can influence reproductive health, we will aim to determine
which routes of chemical exposure seem to have the greatest effect. There is no direct benefit to
you by partaking in this study, but the data collected will provide researchers with a better
understanding of whether chemical exposure is related to women's reproductive health. This
information can help to shape future research projects related to this topic.
As a participant in this study, you will be asked to complete the following one-time survey,
which will take between 45-60 minutes to complete. You are not required to complete the entire
survey in one sitting, and you may come back later to edit your questions or continue the survey.
There are a total of 6 pages with various numbers of questions per page, where one full page is
submitted at a time. If you do not submit a full page of responses at a time, some of your responses
might not be saved. After you have submitted your survey in full you will not be able to go back
and edit your responses. Questions include the areas of reproductive health, product use, and
general health. There are no known risks associated with participating in this study. However,
there are questions in this survey that may cause emotional distress in certain individuals
including questions on alcohol consumption, drug use, and mental health. If these questions are
at all distressing to you, please feel free to withdraw at any point within the study. You can also
reach out to the counselling service that are listed below for help.
Mental Health:
Crisis Services Canada
https://www.crisisservicescanada.ca/en/looking-for-local-resources-support/

Alcohol and Drug Use:
68

Canadian Centre on Substance Use and Addiction
https://www.ccsa.ca/addictions-treatment-helplines-canada
Data will be recorded in a secure online database and subjects will be identified only by
an assigned number.
The data collected will be summarized and used for the researcher’s master’s thesis, which
will be submitted to the faculty supervisor and master’s committee for review. If applicable, this
research may be published in a scientific journal. The only individuals who will have access to the
raw data will be the students who conduct this research and her faculty supervisor and master’s
committee. All data collected will be archived anonymously for potential further study.
This initial agreement does not obligate you in any way to fully complete the online survey
if you later decide you do not wish to participate. If the study is not fully completed, your data will
be removed from the study. You can withdraw from the study at any time without any negative
repercussions.
If you have any questions about this study or need clarification on any questions, please
contact Kyley Drach (researcher) at kyley-drach@mytru.ca. If you have any concerns about this
study, please contact Dr. Gregory Anderson (TRU Dean of Science) at ganderson@tru.ca or
250.852.7137, or the Chair of the Research Ethics Board (REB) at TRU-REB@tru.ca or
250.828.5000.

69

A3. Survey.

Chemical Exposure & Female Reproductive Health

1. Study Information and Consent

This study is entitled Chemical Exposure and Female Reproductive Health and
will be conducted by Kyley Drach (email: kyley-drach@mytru.ca), a Master's student
at Thompson Rivers University, under the supervision of Dr. Heidi HuttunenHennelly, Dr. Kingsley Donkor, and Dr. Mark Rakobowchuk. This study examines
various areas of potential chemical exposure in a woman’s life and how this can
impact her reproductive health. If it is found that chemical exposure can influence
reproductive health, we will aim to determine which routes of chemical exposure
seem to have the greatest effect. There is no direct benefit to you by partaking in this
study, but the data collected will provide researchers with a better understanding of
whether chemical exposure is related to women's reproductive health. This
information can help to shape future research projects related to this topic.
As a participant in this study, you will be asked to complete the following one-time
survey, which will take between 45-60 minutes to complete. You are not required to
complete the entire survey in one sitting and you may come back later to edit your
questions or continue the survey. There are a total of 6 pages with various numbers
of questions per page, where one full page is submitted at a time. If you do not submit
a full page of responses at a time, some of your responses might not be saved. After
you have submitted your survey in full you will not be able to go back and edit your
responses. The questions in this survey are divided into the following sections:
General Personal Information, Socioeconomic Status, Reproductive Health, Product
Use, General Health, and Mental Health. There are no known risks associated with
participating in this study. However, there are questions in this survey that may cause
emotional distress in certain individuals including questions on alcohol
consumption, drug use, and mental health. Sensitive questions will have an option of
“prefer not to say” if you are uncomfortable answering these questions. If these
70

questions are at all distressing to you, please feel free to withdraw at any point within
the study. You can also reach out to the counselling services that are listed below for
help.

Mental Health:
Crisis Services Canada
https://www.crisisservicescanada.ca/en/looking-for-local-resources-support/
Alcohol and Drug Use:
Canadian Centre on Substance Use and Addiction
https://www.ccsa.ca/addictions-treatment-helplinescanada
(Click "Next" to continue to the second page of Study Information and
Consent)

71

Chemical Exposure & Female Reproductive Health

2. Study Information and Consent

Data will be recorded in a secure online database and subjects will be identified
only by an assigned number.
The data collected will be summarized and used for the researcher’s master’s
thesis, which will be submitted to the faculty supervisor and master’s committee for
review. If applicable, this research may be published in a scientific journal. The only
individuals who will have access to the raw data will be the students who conduct this
research and her faculty supervisor and master’s committee. All data collected will be
archived anonymously for potential further study.
This initial agreement does not obligate you in any way to fully complete the
online survey if you later decide you do not wish to participate. If the study is not fully
completed, your data will be removed from the study. You can withdraw from the
study at any time without any negative repercussions.
If you have any questions about this study or need clarification on any questions,
please contact Kyley Drach (researcher) at kyley-drach@mytru.ca or Dr. Mark
Rakobowchuk (secondary investigator) at mrakobowchuk@tru.ca. If you have any
concerns about this study, please contact Dr. Gregory Anderson (TRU Dean of
Science) at ganderson@tru.ca or 250.852.7137, or the Chair of the Research Ethics
Board (REB) at TRU-REB@tru.ca or 250.828.5000.

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Chemical Exposure & Female Reproductive Health

3. Participant Eligibility

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Chemical Exposure & Female Reproductive Health

4. General

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5. Reproductive Health

77

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6. Product Use

82

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7. General Health

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8. Mental Health

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9. Available Resources

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A4. Perceived Stress Scale (PSS).

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A5. Tables
Table 1A. Andersch and Milson Pain Scale.

Grade

Description

0

I do not experience pain during menstruation and my daily
activities are unaffected.

1

I experience mild pain during menstruation but it rarely
stops me from participating in my normal daily activities.

2

I experience moderate pain during menstruation and
require analgesics to relieve my pain; my daily activities
are affected but my pain rarely causes me to miss work,
school, or other activities.

3

I experience severe pain during menstruation and
analgesics do not fully relieve my pain; my daily activities
are inhibited and my pain stops me from participating in
work, school, and other activities.

(modified from Parra-Fernandez et al. 2020)

Table 2A. Reasons for exclusion of potential participants.
Outside of age range
Taking medications that influence hormones (besides IUD or
birth control) or reproductive system
Has a diagnosed gynecological disorder
Does not have a period
Contradicting responses to questions
Has a hormonal issue
Has a chronic disease

7
48
17
3
4
7
33

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Table 3A. Questions excluded due to insufficient data.

What is the highest level of education you have completed

What is your approximate household income

How many people currently live in your household
Do you have a family or extended family history of any
gynecological or blood disorders?
Do you have a family history of painful periods?
Do you have a family or extended family history of irregularly
heavy or light menstrual bleeding
Are you exposed to chemicals at work, home, or school?
How frequently are you exposed to chemicals at work, home, or
school?
From the below list, check all that apply regarding where you
experience chemical exposure (work, home, school)
Were you ever exposed to chemicals during key development
windows, such as while you were still in the womb, during
childhood, or during puberty?
Do you currently or have you ever smoked marijuana?
How long have you smoked marijuana for if you still currently
smoke marijuana?
How often do you smoke marijuana?
Within the last year, have you gained or lost a significant amount of
weight?

Too few questions to
adequately measure
socioeconomic status
Too few questions to
adequately measure
socioeconomic status
Too few questions to
adequately measure
socioeconomic status
Too many unsure
responses
Too many unsure
responses
Too many unsure
responses
Too many unsure
responses
Too many unsure
responses
Too many unsure
responses
Too many unsure
responses
Outside study scope
Outside study scope
Outside study scope
Outside study scope

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