To,

Dr. Blakey,
Professor of Biology 453,
Ball State University.
Dear Professor Blakey,
I, Jessica A. Eddy, am enclosing herewith a research paper entitled The Pain Inside
submitted on November 22, 2013 for evaluation.
I request you to kindly accept my research paper. I am willing to make any changes as you
may feel appropriate. I hereby confirm that all the work mentioned is original and true to the
best of my knowledge.

Thanking you for giving me this opportunity to present my research paper.

Sincerely,
Jessica A. Eddy

Jessica A. Eddy
Endometriosis
November 22, 2013
Dr. Blakey
Biology 453
Ball State University

The Pain Inside

Endometriosis afflicts five million women in the United States and six to seven of all
females,7 and six to ten percent of women in their reproductive years have endometriosis.2,16
Endometriosis is when the cells that are usually inside the womb grow outside the uterine
cavity.1 It seems to be ambiguous as to when a woman may first experience endometriosis;
however, there are some articles that attempt to establish a specific age range. Endometriosis
can range from mild to moderate to severe.4 A pelvic exam or laparoscopy may be used to
identify if the cause of pain is due to endometriosis.4 To date, there is no cure for
endometriosis, only treatments. Currently scientists are uncertain as to the reason for
endometriosis, but a common rationalization is retrograde menstration.14 For some women,
surgery and hormonal treatments are necessary, but there are other alternatives as well. While
there is progress in the formation of clinics and centers to treat endometriosis and inform the
public, there are still many misconceptions, myths, and lies that not only confuse women but
hinder them in achieving relief. This research intends to explore the basis behind
endometriosis, how it can be diagnosed, what treatments are available, possible causes,
progress in the field, and misconceptions.

Menstruation is in part characterized by a degree of pain, which varies on an

individual basis. Usually it involves the female reporting pain, but what if her reports of
pain was due to a more complex causality rather than just a low threshold for pain? What if
there were something actually wrong inside? There is a disease called endometriosis that can
be the cause of more than just the pain some females experience during their menstrual cycle.
This research intends to explore the basis behind endometriosis, how it can be diagnosed,
what treatments are available, possible etiology, research progress, and misconceptions.

Although endometriosis is typically associated with females, there have been reports
of males experiencing the disease. In 1979, a study by Pinkert et al. reported a male with
endometriosis of the urinary bladder.9 For several years, the man had been treated with
estrogen after profound prostatectomy and orchidectomy for prostatic cancer.10 A year later in
1980, Schrodt et al. announced another man had endometriosis.10 This man was 73 years old
and had had adenocarcinoma of the prostate and was treated with estrogen therapy for five
years.10 This line of investigation requires more research, but the studies show that there may
be causality between estrogen and endometriosis.
Endometriosis is when the cells that are usually inside the womb grow outside the
uterine cavity (figure 1).1 Endometriosis is the thickening of the womb lining or other parts of
Figure
1

the body once a month.4 This

excess lining is benign, but
has the potential to grow into
malignant tumors.4 It is
possible for the lining to
grow so large that it effects
other organs.4 There is a cycle

of growing and shedding, but the extra tissues remain in the body and are unable to pass
through the vagina.4 Scar tissue can form and grow together. In addition, inflammation or
cysts may occur.4 Adhesions may also be present in which the abnormal tissue binds organs
together.14 Endometriosis is a disease that capitalizes on the malfunction of the womb lining
of women in varying ages.
It seems to be ambiguous as to when a woman may first experience endometriosis;
however, there are some studies that attempt to establish a specific age range and percentage
of women affected. Endometriosis is thought to be limited in premenarcheal girls and

postmenopausal women.13 An endometriosis fact sheet from PubMed Health says women
between the ages of thirteen and fifty may be affected by endometriosis until the disease stops
after menopause.4 It is believed that forty to sixty of one hundred women who have painful
periods actually have endometriosis.4 Several articles concur on the percentage of women
who have endometriosis. Jennifer Warner from WebMD proclaims that six to ten percent of
women in their reproductive years have endometriosis.16 This disease affects five million
women in the United States and six to seven of all females.7 This disease appears to be fairly
widespread in not only the United States.
Endometriosis can have a range of severity.4,10,12 Generally the surplus tissue goes
unnoticed and has no consequence, and so endometriosis can go untreated due to that lack of
symptoms.4 Mild cases, stages I and II, usually do not affect fertility; however, moderate to
severe, stages III and IV, typically encounter difficulties in becoming pregnant.4 A woman
may have many symptoms but only a small area affected by endometriosis, or a woman may
have no symptoms but have a large affected area.14 Endometriosis does not discriminate
based on symptoms.
Symptoms can vary from woman to woman. Women with endometriosis may
experience excruciating periods, hurting during or after intercourse or with urination or bowel
movements, disproportionate bleeding, and/or infertility.14 Other symptoms can occur such as
fatigue, diarrhea, constipation, bloating or nausea.14 Ovarian cancer is higher than expected
rates in women with endometriosis, but is relatively low in general to begin with, so the
elevation is not substantial.14 Another type of cancer associated with endometriosis is the rare
disorder adenocarcinoma which can develop later in life.14 Adenocarcinoma involves cancer
in mucus-secreting glands. The disease is common in the following cancers: lung, prostate,
pancreatic, esophageal cancer, and colorectal. Symptoms for endometriosis are unlikely to

resolve themselves and vanish without treatment.4 The key to curing endometriosis and its
symptoms, is to correctly identify the etiology.
Due to the similarity between endometriotic symptoms and other diseases,
endometriosis can be misidentified. Some women with endometriosis are misdiagnosed as
having other diseases such as pelvic inflammatory disease (PID), ovarian cysts, or irritable
bowel syndrome (IBS).14 Irritable bowel syndrome can coincide with endometriosis which
complicates the diagnosis.14 A link was created in recent research between other ailments and
endometriosis. Allergies, asthma, chemical sensitivities, and autoimmune diseases such as
hypothyroidism, multiple sclerosis, and lupus, and frequent yeast infections are a few health
problems that have been associated with women with endometriosis.5 More health problems
include ovarian, breast, endocrine, kidney, thyroid, brain, and colon cancers, melanoma and
non-Hodgkins lymphoma, chronic fatigue syndrome (CFS), fibromyalgia, and mitral valve
prolapsed which is where one heart valve does not close as securely as normal.5 With so
much uncertainty, understanding what is plaguing a person can be complex.
How might one diagnose endometriosis? Diagnosis should start with a talk with a
doctor or gynecologist. A pelvic exam and a general check up will be administered.4 A pelvic
exam entails using an instrument called a speculum to feel and look at the organs. The doctor
determines whether pressure to areas or movement of the womb is painful. In addition, the
doctor will search for hard areas or lumps in the pelvic connective tissue. Large cysts and
regions of endometriotic tissue can be established with the use of ultrasound exams.4 To
conclude more definitely whether the patient has endometriosis, laparoscopy, may be
necessary.4 Laparoscopy requires at least two small incisions and a small camera placed in the
abdomen.4 During a laparoscopy, doctors can remove endometriotic tissues or take a biopsy.4
While laparoscopy can more accurately establish a diagnosis to evaluate treatment options,
the surgery is only performed if the symptoms are severe or if close organs are adversely

affected.4 Although there are methods to determine whether endometriosis is the cause of a
womans pain, it is still a fight because there is no cure as of today.
After one ascertains that endometriosis is to blame, one might wonder why this has
happened. Currently scientists are uncertain about the causality of endometriosis, but there
are numerous rationalizations.14 The majority of scientists working with the disease concur
that oestrogen (estrogen) aggravates and intensifies endometriosis.6 An experiment was
conducted by Bianca Bianco et al. in which Brazilian women were studied.9 One hundred and
eight women with endometriosis and incapable of having children were analyzed.9 These
women were compared to 210 fertile women without endometriosis or a history of the
disease.9 The results of the study were that there was a significant difference between the
estrogen receptor , ER, gene frequencies in women with endometriosis and those without.9
Although correlation does not equivocate causation, there is just reason to believe that the
ER may be involved.
One common idea is that menstrual blood with endometrial cells returns through the
fallopian tubes and into the pelvic cavity and not out of the body.13,14 This is called retrograde
menstruation or the transplantation theory.12,13,14 The transplantation theory was first
suggested in the 1920s.12 The relocated endometrial cells attach to the pelvic walls and
exterior of pelvic organs and develop, coagulate, and bleed throughout menstrual cycles.14
This flowing backwards is common in menstruating women, occurring in 75 to 90 percent of
women, but some women go on to develop endometriosis while others do not.12,13 More
factors are likely involved since manifestation of endometriosis is so diminished in
comparison to the widespread occurrence of retrograde menstruation.13
A few other possible causes of endometriosis are embryonic cell growth, surgical scar
implantation, endometrial cells transport, immune system disorder, or metaplasia.5,6,12,13,14 In
1997, even peritoneal fluid was being researched as a possible cause of endometriosis.12

Tissue from when a woman was an embryo may convert to endometriotic tissue.5 When
endometrial tissue is outside of the uterus, the same hormonal changes during menstruation
cause the tissue to react the same way as if the tissue were in the uterus (figure 2).12
Inflammation can cause scarring which can lead to adhesions that alter the typical anatomy in
the pelvis.12 In embryonic cell growth, the inside
coating of cells in the abdominal and pelvic cavities
are embryonic cells and once areas of the abdominal
layer become endometrial tissue, endometriosis can
form.14 In surgical scar implantation, endometrial
cells bind to incisions from surgeries like
hysterectomy or Cesarean Section.14 Endometrial
Figure

cell transport is when endometrial cells are

transplanted to other parts of the body.14 Immune

system disorders can also play a role in that the body does not identify and eliminate
endometrial tissue that is not in the uterus.14 Metaplasia is where a normal type of tissue
transforms into another type of tissue.6, 13 Related to metaplasia, is the induction theory, which
proposes that endogenous biochemical or immunologic factors cause cells to develop into
endometrial tissue.13 There are a number of scientists that believe endometrial tissue is able in
some instances to substitute for other types of tissues outside of the uterus.6 A portion of
researchers think that adults preserve the ability to transform some cells into reproductive
tissue.6 Some researchers are looking outside the body for answers of causation.
There are arguments for and against the possibility that environments may have an
influence on whether a woman develops endometriosis.6 Some believe that endometriosis
may be the result of mutagens that resemble estrogen.11 Radiation and dioxin exposure are
thought to be related to higher frequencies of endometriosis.11 In Belgium, the place with the

highest level of dioxin pollution in the world, there is the highest prevalence of
endometriosis.11 Although there is correlation, this does not equivocate cause.
There has been a large quantity of research completed concerning endometriosis.
From a genetics stand point, researchers have accumulated information regarding
chromosomes seven and five.6 A 2013 article on the causes of endometriosis reports that there
is evidence supporting chromosome 7p13.15 as having at least one susceptible loci with nearMendelian inheritance.6 One gene has been determined to have a decisive responsibility in the
implantation of the embryo.6 Krina Zondervan, a Wellcome Trust Research Career
Development Fellow at the University of Oxford in England among other researchers
compared genes in a study involving 5,586 women with endometriosis and 9,931 healthy
women.16 Chromosomes one and seven are alleged to have genetic variants that accompany
women with endometriosis.16 Chromosome seven is believed to deal with the development of
the uterus and its lining while chromosome five deals with the development of the female
reproductive tract.16 Researchers are hopeful that this new information will aid in diagnosing
and treating endometriosis, but further studies will need to be conducted to establish that
these variants are key players in the development of the disease.16 More research is needed to
establish causality.
Researchers from the University of Oxford, Harvard Medical School, and the
Queensland Institute of Medical Research were involved in a study comparing the genomes
of 10,000 healthy volunteers to that of 5,500 volunteers with endometriosis in the United
Kingdom, the United States, and Australia.2 This article identifies chromosomes one and
seven as central to a woman developing endometriosis.2 It is believed that chromosome one is
near a gene that is imperative for hormone metabolism and the development of the female
reproductive tract.2 Dr. Stephen Kennedy, the senior author of the study as well as the head of
the Nuffield department of obstetrics and gynecology at Oxford believes that the results of

the study will aid in finding less invasive methods of diagnosis and more successful
treatments.2 Helen North from Endometriosis UK says that it takes approximately ten years to
establish that a woman has endometriosis.2 Further research is needed to confirm these
results.
Another study identified chromosomes one and seven as aiding in the development of
endometriosis in a study involving more than 5,000 women.1 Quantities of aspects are
thought to be related to the development of endometriosis including genes and environmental
factors.1 A typical study in genetics is the genome-wide association (GWA) study.1 This type
of study is basically a control study that compares two sets of people and the dissimilarities
found are then related to the disease being studied.1 Research was performed on 3,194
women from the United Kingdom and Australia who were surgically confirmed as having
endometriosis.1 The women were segregated based on the severity of the disease.1 These two
groups were then compared to 7,060 women without endometriosis.1
After this experiment, testing was performed on an independent group to determine
whether the identified genetic variants were still related to the disease.1 Another 2,392 women
with endometriosis and 2,271 women without endometriosis were recruited from the United
States.1 These groups did not have their state determined surgically.1 The researchers
predicted approximately forty percent of the group would have severe disease based upon
their previous sample.1 The study determined that a specific variant on chromosome seven,
rs12700667, was closely linked with endometriosis.1 It is predicted that rs12700667
elucidates approximately 0.69 percent of the 51 percent of the variants estimated to be due to
heretiability.1 Studies of twins, population-based studies, and clinical studies all show an
congregating of endometriosis within families.11 If a family member has endometriosis, there
is an increased risk for other members to have or develop endometriosis.13
More research needs to be conducted to better understand the relationship.

Although endometriosis can affect any woman with a menstrual cycle, women in their
thirties or forties have this disease most commonly.5 An article by Ros Wood, Heather
Guidone, and Lone Hummelshoj seems to have a differing opinion of endometriosis affecting
primarily women in their thirties and forties.17 The article goes on to say that due to a lack of
technology, a major surgery known as laparotomy was the only way to determine whether a
woman had endometriosis.17 This meant that typically only women in their thirties or forties
with the most severe symptoms were operated on since they were past their reproductive
age.17 This generalization mistake occurred again in the 1970s and 1980s when laparoscopy
made it possible to examine women in their twenties and thirties, and doctors failed to take
into account that they found endometriosis in those age ranges because they were looking in
those age ranges.17 Sixteen centers in ten countries were observed and the results show that
two thirds of the women seeking help were below the age of thirty and countless women were
experiencing these symptoms from their first period.17
An increase in the achievements of women and university or career goals, having
children can be put off for years. This means that women in their thirties or forties may be the
ones trying to get pregnant. This can possibly lead to a decline in the number of children born
and possibly a spike in the number of children being adopted. Endometriosis is a chronic
disease that affects not only a womans health but her relationships, choices in life, and her
productivity levels.15 This disease can be grave and crippling.13 Women during the prime of
their lives are generally affected and are then occasionally incapable of completing their
education, working at their job, enjoying or attending social activities, having children, and/or
maintaining normal relationships.17 Women that are unable to perform their duties may
experience feelings of guilt or shame.4
There are some risks that women can take note of in order to reduce their probability
of endometriosis. If a woman has a short menstrual cycle of approximately 27 days or less or

has damaged cells in the pelvis due to an infection, she could have an increased risk
endometriosis.5 An article from the Mayo Clinic lists the following as some factors that may
be associated with the development of endometriosis: never giving birth, one or more
relatives (mother, aunt or sister) with endometriosis, any medical condition that prevents the
normal passage of menstrual flow out of the body, history of pelvic infection, and/or uterine
abnormalities.14
Due to a lack of understanding concerning the cause of endometriosis, a cure is
currently unavailable; therefore, treatments for symptoms are all that can be offered to
patients. As aforementioned, surgery is an option, but the tissue and symptoms frequently
return within a few years.4 This option however can to some extent augment a womans
chance to conceive a child naturally.4 A further step to surgery could be to entirely remove the
womb. This procedure is called a hysterectomy. If the ovaries are not also removed,
endometriosis could still be a problem.4 Removing both the womb and the ovaries at the same
time can lead to issues such as hot flashes like those experienced by women undergoing
menopause.4
An alternative to surgery is hormonal preparations which repress the creation of
hormones in the ovaries.4 The reduction of hormones in the ovaries stems the monthly period
in order to lessen the activity of endometriotic tissue.4 Hormone preparations also go by the
name of hormone therapy.4 There are negative effects to hormonal preparations that should be
considered.4 Long exposure is not always possible, and is not appropriate for women
interested in becoming pregnant.4
Other options exist in place of surgery and hormonal treatments. Some patients utilize
medications or herbs as painkillers.4,11 Vitex agnus castus, also known by the name chaste
tree, is a traditional herb used for hormonal imbalances and reduces the amount of estrogen
available during perimenopausal times.11 This is helpful since estrogen stimulates endometrial

tissue.11 Leonorus cardiac, motherwort, is a mild sedative some women take in order to relax
and rest from painful periods.11 Bioidentical progesterone has been used in conjuncture with
other treatments to help women with endometriosis.11 Progesterone modifies the action of
estradiol by lowering the retention of receptors which then decreases the level of serum
estradiol.11 This helps women avoid an excess of estrogen.11 Progesterone sedates painful
uterine contractions and possibly the entire pelvic region.11 Some examples of
nonprescription anti-inflammatory pain relievers without steroids are ibuprofen-containing
Advil or Motrin IB or naproxen-containing Aleve.14 Birth control pills are utilized to reduce
the amount of menstrual flow and keep tissue that lines the uterus in check.5 BnRH agonists
and antagonists that decrease estrogen levels in the body stop the menstrual cycle.5 Similar to
menopause, side effects can consist of vaginal dryness, hot flashes, and bone loss; therefore,
it is recommended to take a low dose of progestin or estrogen with the drugs in order to avoid
some of the side effects.5
Others have found that exercise or yoga or tai chi is helpful.4 Acupuncture, TENS, or
applying heat such as warm baths or applying heating pads are a few other methods some
patients have found useful to relieve symptoms.4,15 Changes in lifestyle can also better the life
of patients suffering from endometriosis.4 The results are not proven, but increased movement
such as regular exercise, decreased stress, relaxation techniques, and/or eating different foods
can lead to an enhanced life for patients with endometriosis.4,15 An article on
womenshealth.gov suggests to decrease the levels of estrogen in a womans body, exercise be
performed regularly, a low total body fat be maintained, and hefty quantities of alcohol and
caffeinated drinks be avoided.5 Women may miss out on social events and skip school or
work due to endometriosis. In addition, relationships with partners, friends, children, and coworkers can be negatively influenced by endometriosis.5

There is progress in developing centers specialized in treating endometriosis. These

centers have appeared in places such as Germany4, the United States3, and England8. In
Germany, these clinics have multiple specialists of different areas working to give holistic
treatment that is fitted to the womans symptoms and circumstances.4 No research has
determined the effectiveness as of yet.4 The New York center is one of the leaders in
endometriosis treatment and gynecologic surgery.3 The New York center also has an office in
Greenwich.3 Connecticut is the second leader in the USA with its Reproductive Medicine
Associates of Connecticut fertility clinics in Connecticut and New York.3 The next ranking
clinics are the Vital Health Institute in California, the Beach Center for Infertility,
Endocrinology and IVF in Virginia, the St Charles Medical Center in Bend, Oregon, and the
Endometriosis Research Center in Delray Beach, Florida.3 The last ranking clinics in the USA
are the Center for Endometriosis Care in Atlanta, Georgia, the Georgia Reproductive
Specialists, also in Atlanta, the Continuum Reproductive Center of New York, and lastly, the
Cleveland Clinic in Cleveland, Ohio.3
Although there is progress in the formation of clinics and centers to treat
endometriosis and inform the public, there are still many misconceptions, myths, and lies that
not only confuse women but hinder them in achieving relief. Due in part to nineteenth
century doctors, women are viewed as having unstable and delicate psychological
constitutions.17 The treatment of women has seen progress; however, when a woman
complains of period pain, some of the old beliefs still remain unconsciously and my affect the
outlook of medical professions.17 Some women are told that the pain in their pelvis they
experience before, after, or during their period, is normal, part of being a woman, in
their head, or even that they have a low pain threshold or are psychologically
inadequate.17 Too many doctors believe that endometriosis is exceptional in teens and young
women.17 Another myth, that is slowly disappearing according to the article by Ros Wood,

Heather Guidone, and Lone Hummelshoj, is that pregnancy cures endometriosis. Also,
abortion has not been shown to cause endometriosis.17 Thirty to forty percent of patients with
endometriosis are infertile.7 About ten percent of couples that are unable to have a child have
endometriosis.7 The fecundity, chance of getting pregnant, for women affected by
endometriosis lowers by twelve to thirty-six percent, but endometriosis does not equate to
infertility. 7,17
There is progress in the formation of clinics and centers to treat endometriosis and
inform the public, there are still many misconceptions, myths, and lies that not only confuse
women but hinder them in achieving relief. Due to its large presence and impact,
endometriosis deserves more public notice to inform women that if their period is painful and
reduces their productivity, there may be a reason and there may be a treatment option to
reduce their discomfort. Although currently there is a lack of knowledge about the etiology of
endometriosis, there are several centers across the world that are dedicated to endometriosis.
Research is continuing, and once more is understood about the disease, more alternative
treatments can be developed. One day with more information it is possible that even a cure
will be produced.

Resources
1. 2010. Endometriosis genetics explored. NHS. Aug. 26, 2013.
2. 2010. Gene research gives hope for women with endometriosis. BBC news health.
Aug. 26. 2013.
3. 2011. Endometriosis: Top 10 Treatment Centers. Newsmax.com. Oct. 23, 2013.
4. 2011. Fact sheet: Endometriosis. PubMed Health. Institute for Quality and Efficiency
in Health Care. Aug. 26, 2013.
5. 2012. Endometriosis fact sheet. Womenshealth.gov. U.S. Department of Health and
Human Services. Aug. 26. 2013.
6. 2013. Causes of Endometriosis. Endometriosis.org. Aug. 26, 2013.
7. 2013. Causes of Female Infertility. Internet Health Resources. Stanford. Aug. 26,
2013.
8. 2013. Endometriosis. University College London Hospitals and NHS. Oct. 23, 2013.
9. Bianco, B., Christofolini, D., Mafra, F., et al. (2009). +1730 G/A polymorphism of the
estrogen receptor b gene (ERb) may be an important genetic factor predisposing to
endometriosis. Acta Obstetricia et Gynecologica, , 1397-1401.
10. Daniel, O. (1987). Pathology and staging of endometriosis.Endometriosis (pp. 44-6).
New York: Churchill Livingstone.
11. Hudson, Tori. "Endometriosis." Textbook of Natural Medicine. 4th ed. St. Louis:
Elsevier Churchill Livingstone, 2013. 1349-354. Print.
12. Jill, S. (1997). Common Gynecological Problems . Women's Sexual Health (pp. 414416). London: Baillire Tindall.
13. Kerri, S., and Likis, F. (2013). Benign Gynecologic Conditions.Womens Gynecologic
Health (2nd ed., pp. 688-69). Burlington, MA: Jones & Bartlett Learning.
14. Mayo Clinic Staff, 2013. Endometriosis. Mayo Clinic. Aug. 26, 2013.
15. Montgomery, G., Nyholt, D., Zhao, Z., Treloar, S., Painter, J., Missmer, S., Kennedy,
S., and Zondervan, K., 2008. The search for genes contributing to endometriosis risk.
Oxford Journals 14:5 447-457.
16. Warner, J., 2010. New Genes Linked to Endometriosis. WebMD Health News. Aug.
26. 2013.
17. Wood, R., Guidone, H., and Hummelshoj, L., 2013. Myths and misconceptions in
endometriosis. Endometriosis.org. Aug. 26, 2013.