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Endometriosis
Endometriosis
An Enigma

Edited by
Seema Chopra
CRC Press
Taylor & Francis Group
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© 2020 by Taylor & Francis Group, LLC

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Library of Congress Cataloging-in-Publication Data

Names: Chopra, Seema, editor.

Title: Endometriosis : an enigma / edited by Seema Chopra.
Other titles: Endometriosis (Chopra)
Description: Boca Raton : CRC Press, [2020] | Includes bibliographical references and index. |
Summary: “Endometriosis is a complex gynecological disorder with multifactorial etiology. It is an
estrogen-dependent disorder that occurs in 6-10% of women in the general population and in 35-50% of
women with pain and/or infertility. This book aims to discuss different aspects from basic to advanced
levels, in turn exploring this benign but chronic disease”-- Provided by publisher.
Identifiers: LCCN 2020002845 (print) | LCCN 2020002846 (ebook) | ISBN 9781138327962 (hardback) |
ISBN 9780429448980 (ebook)
Subjects: MESH: Endometriosis--therapy | Endometriosis--complications | Infertility, Female--etiology
Classification: LCC RG483.E53 (print) | LCC RG483.E53 (ebook) | NLM WP 390 | DDC 618.1--dc23
LC record available at https://lccn.loc.gov/2020002845
LC ebook record available at https://lccn.loc.gov/2020002846

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Contents

Preface vii
Acknowledgments ix
Editor xi
Contributors xiii

1 Natural history: Basics of endometriosis 1

Arshi Syal and Seema Chopra
2 Epidemiology 7
Pooja Sikka and Rinnie Brar
3 Etiopathogenesis of endometriosis 9
Pooja Sikka and Rinnie Brar
4 Molecular basis and biomarkers of disease activity 13
Parikshaa Gupta and Nalini Gupta
5 Diagnostic evaluation 23
Neha Aggarwal, Seema Chopra, and Arshi Syal
6 Adolescents and endometriosis 31
Aashima Arora
7 Infertility attributed to endometriosis 37
Shalini Gainder and Neethi Mala Mekala
8 Medical management of endometriosis 47
Bharti Joshi and Neelam Aggarwal
9 Surgical exploration as the primary modality of treatment 57
Sujata Siwatch and Indu Saroha
10 Management of deep infiltrative endometriosis (DIE) causing gynecological morbidity:
A urologist’s perspective 67
Aditya Prakash Sharma and Girdhar Singh Bora
11 Management of deep infiltrative endometriosis (DIE) causing gynecological morbidity: A
colorectal surgeon’s perspective 81
Aditya Kulkarni and Rajesh Gupta
12 Adenomyosis and endometriosis 93
Minakshi Rohilla
13 Helping a woman afflicted with endometriosis to conceive 101
Seema Chopra and Shalini Gainder
14 Alternative medicine for endometriosis: Diet and nutrition 111
Nancy Sahni
15 Novel treatment modalities 119
Seema Chopra

v
vi Contents

16 Long-term complications associated with endometriosis 133

Bharti Joshi
17 Recurrence of endometriosis 139
Rakhi Rai and Seema Chopra
18 Quality of life affected by endometriosis: Lifestyle modification for symptom alleviation 149
Seema Chopra and Arshi Syal
19 Literature review: Guidelines for the management of endometriosis 155
Rashmi Bagga and Japleen Kaur
20 Hormone therapy after total surgery for endometriosis 163
Bharti Sharma
21 Ethical dilemmas in the management of endometriosis 167
Seema Chopra
22 Conclusion 173
Seema Chopra

Index177
Preface

Knowledge and practice in the field of gynecology use of biomarkers, such as CA-125, is not sensitive
is constantly changing. With ongoing research, enough to detect the disease in the early stages.
changes in treatment modalities become neces- Peripheral biomarkers show promise as diag-
sary, as well as appropriate. nostic aids, but further research is necessary before
Endometriosis is a complex gynecological dis- these can be recommended in routine clinical care.
order that can affect women from menarche until Panels of markers may allow increased sensitivity
menopause. It is a benign, estrogen-dependent dis- and specificity of any diagnostic tests.
order with multifactorial etiology. Endometriosis is Management is both medical and surgical,
characterized by the presence of functional endo- depending upon age, fertility preservation, symp-
metrial glands and stroma outside the uterine cav- tomatic relief, and whether or not the disease is extra
ity, resulting in chronic pelvic pain, dysmenorrhea, pelvic/deep endometriosis. The disease is notorious
dyspareunia, and infertility, thus affecting the qual- for recurrence and requires long-term management.
ity of life. Availability of new drugs, alternative medi-
Several theories have been put forth to explain cines, and lifestyle modifications are helpful for
the etiopathogenesis of this disease. There is the women inflicted with the disease. Therefore,
increasing evidence to suggest that endometriosis this book aims to help the readers get a concise
is at least partially a genetic disease. knowledge in the field of endometriosis as a valued
At the time of diagnosis, most patients with resource, with evidence based from literature and
endometriosis have had the disease for an recent guidelines.
unknown period, making it difficult to initiate any The support of the publisher, CRC Press/Taylor
clinical experiments that would definitively deter- & Francis, for completion of this book is highly
mine the etiology or progression of the disease. As appreciated.
of now, the gold standard for diagnosis is laparo-
scopic visualization of endometriotic lesions. The Seema Chopra

vii
Acknowledgments

This book is dedicated to all the courageous I sincerely hope that the resource material
women living with endometriosis who have helped will be able to answer the queries in the minds of
us understand this entity. readers of this book.
I thank my family and friends for their constant
support and encouragement in successful comple-
tion of this responsibility.

ix
Editor

Seema Chopra, MBBS, MD, is a consultant (addi- her institute in collaboration with the Department
tional professor) in the Department of Obstetrics of Microbiology. She has been invited for lectures
and Gynecology at the Postgraduate Institute at various scientific meetings, public forums, and
of Medical Education and Research (PGIMER), panel discussions, as well as for conducting drills
Chandigarh, a well-established and reputed ter- in continuing medical education (CME) and other
tiary care institute in North India. She has more workshops. She has attended/organized live surgi-
than 70 publications to her credit in international cal workshops and has a special inclination toward
as well as national journals and as an author minimally invasive surgery. She has been involved
of book chapters. She is an active participant in the management of gynecological as well as
in national and international conferences and obstetrical emergencies for more than 25 years
research projects. Conducting seminars, teach- in her career. Her areas of interest are related to
ing postgraduate students, and administrative endometriosis: early diagnosis and medical, surgi-
responsibilities are part of her curriculum. She is cal management of this entity to help these women
also designated nodal in-charge of sexually trans- for relief of symptoms, as well as part of infertility
mitted infections (STI)/reproductive tract infec- treatment. She is actively conducting research on
tions (RTI) of the state chapter under the National the recurrence of endometriosis after conservative
AIDS Control Organization (NACO), as well as laparoscopic surgery and suppression with medi-
nodal officer for the STI reference laboratory in cal therapy as part of a postgraduate thesis.

xi
Contributors

Neelam Aggarwal Nalini Gupta

Department of Obstetrics and Gynecology Department of Cytology and Gynecological
PGIMER Pathology
Chandigarh, India PGIMER
Chandigarh, India
Neha Aggarwal
Department of Obstetrics and Gynecology Parikshaa Gupta
Maulana Azad Medical College Department of Cytology and Gynecological
Delhi, India Pathology
PGIMER
Aashima Arora Chandigarh, India
Department of Obstetrics and Gynecology Rajesh Gupta
PGIMER Department of General Surgery
Chandigarh, India PGIMER
Chandigarh, India
Rashmi Bagga
Department of Obstetrics and Gynecology Bharti Joshi
PGIMER Department of Obstetrics and Gynecology
Chandigarh, India PGIMER
Chandigarh, India
Girdhar Singh Bora
PGIMER Japleen Kaur
Chandigarh, India Fellowship Reproductive Endocrinology
PGIMER
Rinnie Brar Chandigarh, India
Department of Obstetrics and Gynecology
PGIMER Aditya Kulkarni
Chandigarh, India Department of General Surgery
PGIMER
Seema Chopra Chandigarh, India
Department of Obstetrics and Gynecology Neethi Mala Mekala
PGIMER PGIMER
Chandigarh, India Chandigarh, India

Shalini Gainder Rakhi Rai

Department of Obstetrics and Gynecology Department of Obstetrics and Gynecology
PGIMER AIIMS
Chandigarh, India Delhi, India

xiii
xiv Contributors

Minakshi Rohilla Bharti Sharma

Department of Obstetrics and Gynecology Department of Obstetrics and Gynecology
PGIMER PGIMER
Chandigarh, India Chandigarh, India

Nancy Sahni Pooja Sikka

Department of Dietetics Department of Obstetrics and Gynecology
PGIMER PGIMER
Chandigarh, India Chandigarh, India

Indu Saroha Sujata Siwatch

Department of Obstetrics and Gynecology Department of Obstetrics and Gynecology
PGIMER PGIMER
Chandigarh, India Chandigarh, India

Aditya Prakash Sharma Arshi Syal

Department of Urology Government Medical College and
PGIMER Hospital
Chandigarh, India Chandigarh, India
 1
Natural history: Basics
of endometriosis

ARSHI SYAL AND SEEMA CHOPRA

Ancient descriptions suggesting the Adenomyosis and endometriosis—The

diagnosis of endometriosis 1 differentiation 3
Ovarian endometriosis 3 References 4
Identification of adenomyoma 3

Endometriosis is a relatively common and poten- Hippocratic doctors believed that endometriosis-
tially debilitating condition affecting women of like symptoms are a result of delaying childbear-
reproductive age. Symptomatic endometriosis can ing, which triggers diseases of the uterus. This may
result in long-term adverse effects on personal rela- be an indirect pointer toward the existence of the
tionships, quality of life, and work productivity. As disease in women with dysmenorrhea, as they were
there is no clarity regarding the etiopathogenesis to encouraged to marry at a young age and produce
date, researchers have shown a keen interest in the children so that the ectopic endometrial tissue
history of endometriosis over the past few decades. remained quiescent. This also implies that the dis-
Although, medical texts older than 4000 years ease prevalence rates were higher than the 5%–15%
have described this entity [1], Karl von Rokitansky that is often reported nowadays. If it is considered
was the first to diagnose endometriosis microscop- plausible that the existence of endometriosis was
ically in 1860 [2]. so common historically, we will have to reconsider
As long as 2500 years ago, the disease with the modern theories that suggest links between
symptomatology of chronic pelvic pain was treated endometriosis and environmental toxins such as
as a true organic disorder. As it was difficult to dif- dioxins, polychlorinated biphenyls (PCBs), and
ferentiate the menstrual pain from the severe pain chemicals [1].
due to endometriosis, during the middle ages,
there was a shift from organic cause into the belief ANCIENT DESCRIPTIONS
that women with pelvic pain were malingering or SUGGESTING THE DIAGNOSIS
immoral, had female weakness, or were misbehav- OF ENDOMETRIOSIS
ing. There was development of an attitude of indif-
ference to the patients’ true pain. Hence, through In 1999, Vincent J. Knapp [3] reported a num-
the ages, the historical diagnosis of hysteria in ber of old dissertations as old as the eighteenth
women with severe pelvic pain may have indeed and even the seventeenth centuries; this started
been endometriosis, thus leading to delays in a cor- a new discussion revolving around the history of
rect diagnosis during the twentieth century. endometriosis, thus focusing our attention to the

1
2 Natural history: Basics of endometriosis

exploration of women’s diseases that had onset endometriosis and select organochlorine pesticides
during the eighteenth century. On evaluation of such as aromatic fungicides and hexachlorocyclo-
these texts, no description of macroscopic features hexane [10], polychlorinated biphenyls [11], per-
of endometriosis could be found. Also, it was not fluorochemicals, and dioxins. Its etiology remains
possible in those early times even to predict the unknown despite investigating a number of prob-
presence of endometrial (or even epithelial) tissue able mechanisms for the same. Bisphenol A (BPA)
in the lesions described by those authors without a has the ability to interact with estrogen receptors
microscope. Therefore, substantiating the presence and stimulate estrogen production, being similar
of the specific features of endometriosis during the to endogenous estrogens, and therefore can alter
seventeenth and eighteenth centuries seems nearly gonadotropin hormone secretion [12]. Similar
impossible. observations between these chemicals and endo-
The Barker hypothesis [4] proposes that early metriosis have not been substantiated by many
exposures, including those arising from unhealthy authors in the literature, underscoring remaining
lifestyles of parents, during sensitive windows of critical data gaps.
human development, such as pregnancy, may per- Another environmental toxin widely used
manently reprogram the developing embryo or in plastics to increase its resilience, namely
fetus for extra-uterine life. Thus, this theory gen- ­phthalate, produces anti-androgenic effects largely
erated considerable interest in the potential early through the reduction in testosterone production
origins of health and disease. This reprogramming and, possibly, reduced estrogen production at high
is speculated to occur largely through epigenetic doses [13].
mechanisms [5]. It was observed that mEHP was the only phthal-
In an attempt to verify the early origins of ate consistently associated with endometriosis
health and disease hypothesis, many investigators across cohorts, though significance was only
have assessed in utero exposures with diagnosis achieved when disease was restricted to compari-
of endometriosis in adult women. It was demon- son women with a normal pelvis in the operative
strated that in utero diethylstilbestrol (DES) was cohort. Also of note is the observation that three
associated with higher odds of an endometriosis of the phthalate metabolites (mono (2-ethyl-
diagnosis in these women and a lesser chance of 5-carboxyphentyl) phthalate [mECPP], mono
having this diagnosis with in utero exposure to (2-ethyl-5-hydroxyhexyl) phthalate [mEHHP],
cigarette smoking and increasing birth weight [6]. mono (2-ethyl-5-oxohexyl) phthalate [mEOHP])
There has been research to document the pos- associated with endometriosis are derived from
sible role for endocrine disrupting chemicals the parent compound di-(2-ethylhexyl)-phthalate
(EDCs), defined as exogenous chemicals that (DEHP), which is the most widely used phthalate
can interfere with hormonal milieu in the body, and is present in cosmetics and other personal care
including alterations in estrogen signaling [7]. The products that are a source of continuous human
Endocrine Society published a statement on EDCs exposure [14]. Despite their relatively short half-
citing strong evidence of adverse reproductive out- lives, ubiquitous occurrence of BPA and phthalates
comes following exposure, including the possibil- may produce prolonged exposures for users, thus
ity of epigenetic changes and transgenerational causing toxic levels and the related effects.
effects with early exposure to these agents [8]. While going through the evolution of this
While speculative, this finding may suggest a entity, an important question often asked is, “Who
role for in utero environmental tobacco smoke identified endometriosis?” To have a plausible
and endometriosis that has not been previously answer, two non-complementary methods were
reported. Irrespective of route of exposure, active used: searching for ancient descriptions of similar
smoking, or passive exposure from environmental symptoms associated with endometriosis or, as an
sources, the biologic dose of tobacco chemicals and alternative evidence, identifying researchers who
metabolites may be the relevant exposure [6]. mentioned various pathological features associ-
The ENDO Study was carried out with the ated with the different phenotypes of endometri-
specific aim to assess the relation between per- osis. Rokitansky, in the middle of the nineteenth
sistent environment chemicals and endometrio- century, suggested the presence of endometrial
sis [9]. There were positive associations between glands and stroma in neoplasias of the ovary and
 Adenomyosis and endometriosis—The differentiation 3

the uterus. However, Cullen was the first scientist Similarly, Sampson described 23 cases of ovar-
to delineate peritoneal endometriosis and named ian hematomas of endometrial type in his pub-
it “adenomyoma” using histological parameters lication “Perforating Hemorrhagic (Chocolate)
of endometrial structure and activity. On the Cysts of the Ovary” [21]. Finally, the term “per-
other hand, Rokitansky was the first to describe forating hemorrhagic cyst” was omitted and,
an adenomatous polyp, a form of adenomyosis. instead, “ovarian endometrioma” was coined,
The description of an “ovary containing uterine which included hematomas or hemorrhagic cysts
mucosa” was first published in 1899 by Russel [15]. of endometrial (Müllerian) type. While rupture of
the endometrial cyst was considered as the cause
What is the natural course of peritoneal endometriosis by Sampson [22], sev-
of endometriosis? eral authors proposed that endometriotic lesions
on the cortex invaded the ovary, or lymphatic
As there are no set diagnostic criteria for endome- spread of endometrial cells led to endometriosis
triosis without invasive testing for the presumptive [23]. Finally, it was histological evidence given by
diagnosis of this pathology for chronic pelvic pain Hughesdon in 1957, demonstrated on a surgical
as seen in almost all adolescent girls who report specimen of 27 ovaries with chocolate cyst in situ
painful periods, the natural course of symptomatic that ovarian cortex formed the wall of the cyst in
endometriosis is difficult to delineate. Also, it is not 90% of the cases. This also confirmed the find-
possible to exclude a diagnosis of endometriosis ings of Sampson’s original article “Perforating
clinically; hence, follow-up is not stringent so as to Hemorrhagic Cysts of the Ovary” [21] or Halban’s
know the natural evolution of endometriosis [16]. [23] hypothesis of l­ ymphatic theory that the pres-
The definition of the expression “discovering ence of an inner ­cortex in the cyst is indicative
endometriosis” is the starting point for our his- that relation of the cyst to the surface is primary.
torical journey. The word “discovery” may imply This was further confirmed objectively on endos-
imagining its existence in the susceptible group, copy by Brosens et al. [24]. They showed that
naming it as endometriosis, giving details clinical chocolate cysts were lined by the ovarian cortex,
symptoms, sometimes describing it as a separate which was partially covered by a thin lining of
pathophysiological entity, or confirming it on his- endometrial tissue.
tological examination. In the early days, the term
“adenomyoma” was used to describe peritoneal, IDENTIFICATION
extraperitoneal (scar), and deep-infiltrating endo- OF ADENOMYOMA
metriosis, ovarian endometrioma, and adenomyo-
sis, as all these varieties were considered together. Initially, Rokitansky, in the middle of the nine-
In the 1920s, these two entities were described as teenth century [19], described three cases of
separate entities [17,18]. fibrous polyps of the uterus with additional glan-
dular tubes in some of them. These also contained
OVARIAN ENDOMETRIOSIS a smooth muscle component in addition to the
usual features of endometrial polyps. On histologi-
The work of Carl Rokitansky was not recognized cal examination, they were composed of “endome-
initially as endometriosis, probably because he trial glands intimately mixed with smooth muscle
had described these lesions as sarcomas [19]. It was and thick-walled blood vessels.” Later on, the term
realized later, as reported by Batt, that Rokitansky “adenomyoma” was coined by both Cullen and
had utilized a “personal” definition of these tumors Von Recklinghausen [25], followed by Pick and
as described in his opus magnum A Manual of Rolly around the end of the nineteenth century.
Pathological Anatomy.
Further, in 1920, cases of “ovarian hematomas” ADENOMYOSIS AND
described by Smith [20] could have been endome- ENDOMETRIOSIS—THE
triosis, as one such case, in particular, had all the DIFFERENTIATION
characteristics of ovarian endometriosis; clinically
the patient had severe dysmenorrhea, which was With ongoing research, Sampson, in 1925 [26],
markedly relieved after its surgical removal. postulated that endometrial tissue that sloughs
4 Natural history: Basics of endometriosis

into uterine veins, the theory of retrograde 7. Crews D, McLachlan JA. Epigenetics, evolu-
menstruation, could be the cause of adenomyo- tion, endocrine disruption, health and dis-
sis and spread of disease beyond the pelvis in ease. Endocrinology 2006;147:S4–10.
menstruating women. In an attempt to redefine 8. Zoeller RT, Brown TR, Doan LL, Gore AC,
the terminology, Sampson first introduced the Skakkebaek NE, Soto AM, Woodruff TJ, Vom
term “endometriosis” interchangeably with the Saal FS. Endocrine-disrupting chemicals
term “implantation adenomyoma.” It was the and public health protection: A statement
exact description of the anatomical picture for of principles from The Endocrine Society.
the mucosal invasion of the myometrium by the Endocrinology 2012;153(9):4097–110.
endometrial glands by Frankl [18] as “adenomyo- 9. Buck Louis GM, Peterson CM, Chen Z et al.
sis uteri.” He also enumerated the criteria to dif- Bisphenol A and phthalates and endome-
ferentiate it from endometriosis, stating, “In an triosis: The Endometriosis: Natural History,
adenomyoma the glands originate independently Diagnosis and Outcomes Study. Fertil Steril
within the myoma as an autochthonous (indig- 2013;100(1):162–9.e2.
enous) growth, while in adenomyosis, even when 10. Buck Louis GM, Chen Z, Peterson CM et al.
localized, the direct connection of the endome- Persistent lipophilic environmental chemi-
trium with the islands of mucosa located in the cals and endometriosis: The LIFE Study.
musculature can be established in serial sec- Environ Health Perspect 2012;120:811–6.
tions. In the majority of cases of genuine adeno- 11. Porpora MG, Medda E, Abballe A et al.
myoma, which are extremely rare, the glands are Endometriosis and organochlorine environ-
not accompanied by stroma.” Thus, at this point, mental pollutants: A case control study on
“adenomyoma” was subdivided into two separate Italian women of reproductive age. Environ
entities, endometriosis and adenomyosis. Health Perspect 2009;1117:1070–5.
12. Takeuchi T, Tsutsumi O, Ikezuk Y et al.
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Endometriosis, Natural History, Disease, endometriosis? Fertil Steril 2011;95:13–6.
Outcome (ENDO) Study. Fertil Steril 18. Frankl O. Adenomyosis uteri. Am J Obstet
2013;99(3):790–5, Copyright © 2013. Gynecol 1925;10:680–4.
 References 5

19. Rokitansky C. A Manual of Pathological 23. Halban J. (The lymphatic origin of the so-
Anatomy (transl by W.E. Swaine). called heterotopic adenofibromatosis.) Arch
Philadelphia: Blanchard & Lea, 1855, vol I: Gynäkol 1925;124:457–82.
General pathological anatomy, pp. 189–190. 24. Brosens IA, Puttemans PJ, Deprest J. The
20. Smith RR. Hemorrhage into the pelvic cav- endoscopic localization of endometrial
ity other that of ectopic pregnancy. Am J implants in the ovarian chocolate cyst. Fertil
Obstet Gynaecol 1920;1:240–2. Steril 1994;61:1034–8.
21. Sampson JA. Perforating hemorrhagic (choc- 25. Cullen T. Adenomyoma of the round liga-
olate) cysts of the ovary. Arch Surg 1921;3:​ ment. Johns Hopkins Hosp Bull 1896;7:112–3.
245–323. 26. Sampson JA. Heterotopic or misplaced
22. Sampson JA. Peritoneal endometriosis due endometrial tissue. Am J Obstet Gynecol
to the menstrual dissemination of endome- 1925;10:649–64.
trial tissue into the peritoneal cavity. Am J
Obstet Gynecol 1927;14:422–69.
 2
Epidemiology

POOJA SIKKA AND RINNIE BRAR

Introduction 7 References 8
Epidemiology 7

Endometriosis remains a disease marred with con- undergoing tubal ligation to 50% of teenagers
fusion due to the absence of an easy, noninvasive with intractable dysmenorrhea. The prevalence of
diagnosis; changing definitions; and the absence of endometriosis is undoubtedly higher in women
a validated classification system. Endometriosis is with infertility. However, there is great variation in
one of the most common diagnoses in women with the published estimates (as much as 30–40 times).
pelvic pain. Prevalence estimates vary from about This is primarily because studies on endometriosis
a 4% occurrence of largely asymptomatic endome- focus on women who have a higher probability of
triosis found in women undergoing tubal ligation having the disease, such as women with pelvic pain
to 50% of teenagers with intractable dysmenor- and infertility.
rhea. It is important to clearly distinguish among
subtle, typical, cystic, and deep endometriosis and EPIDEMIOLOGY
to understand the shifts that have occurred, mainly
in the recognition of subtle endometriosis and Advances in understanding the epidemiology
deep endometriosis. Estimations of subtle endo- of endometriosis have lagged behind other dis-
metriosis range from 5% to 50% and from 50% eases because of methodologic problems related
to 80% in asymptomatic or symptomatic women, to the disease definition. It was first described in
respectively. 1860. The definition of endometriosis has changed
over time, contributing to bias in the literature
INTRODUCTION and clinical practice. Initially in the mid-1980s,
nonpigmented or subtle endometriosis was intro-
To describe the incidence and prevalence of endo- duced, and later, the recognition of deep endome-
metriosis is as difficult as is managing it. Over the triosis progressively increased. The concept arose
past few years, endometriosis has become one of when it was seen that even after surgery, symptom-
the most common diagnoses in women with pelvic atic relief in pain did not happen. Taken together,
pain. Whether managed medically or surgically, the absence of an easy, noninvasive diagnosis; the
it constitutes a significant burden on the quality changing definitions; the absence of a clear under-
of life of women, their families, their healthcare standing of the pathophysiology; and the absence
providers, and healthcare facilities. Prevalence of a validated classification system, endometriosis
estimates of the disease in populations that visit a remains a disease marred with confusion.
doctor vary from about a 4% occurrence of largely Nevertheless, a better picture of the epidemiol-
asymptomatic endometriosis found in women ogy of endometriosis has emerged over the past
7
8 Epidemiology

few decades [1,2]. This is because of wider use or a manifestation of outflow obstruction. There is
of computed tomography (CT) scans, magnetic an established hereditary basis for endometriosis.
resonance imaging (MRI), and laparoscopy [3]. The role of nutrition, of lifestyle, of personal-
General awareness among women and gynecolo- ity traits, of the immune system, of the peritoneal
gists about the disease has led to using these tests. fluid, and other variables is not well understood.
To correctly define the epidemiology of endome- Various speculations have been made. For most of
triosis, it is important to clearly distinguish among these factors, indirect evidence strongly suggests
subtle, typical, cystic, and deep endometriosis and a modulating role. The key question that remains,
to understand the shifts that have occurred, mainly however, is to find an answer to the question
in the recognition of subtle endometriosis and whether endometriosis is a normal endometrial cell
deep endometriosis. Estimations of subtle endo- or an abnormal endometrial cell. This is important
metriosis range from 5% to 50% and from 50% to understanding the prediction, prevention, and
to 80% in asymptomatic or symptomatic women, management of the disease. The etiopathogenesis
respectively [4–6]. For typical lesions, estimations of the disease is discussed in Chapter 3.
are less than half of these figures, but those data
were collected before the 1990s. For severe endo- REFERENCES
metriosis, either cystic or deep, estimations in the
population range between 1% and 10%. 1. Parazzini F, Esposito G, Tozzi L et al.
A poorly addressed problem is the variability of Epidemiology of endometriosis and its
prevalence by region and country. There is a clini- comorbidities. Eur J Obstet Gynecol Reprod
cal impression that African Americans have lower Biol 2017;209:3–7.
rates and Asians have higher rates of endometrio- 2. Cramer DW, Missmer SA. The epidemiol-
sis than Caucasians. No systematic studies are ogy of endometriosis. Ann N Y Acad Sci
available, but it is obvious that the prevalence of 2002;955:11–22.
very severe deep endometriosis must be higher in 3. Janssen EB, Rijkers AC, Hoppenbrouwers K
Europe, from where this type of lesion is reported. et al. Prevalence of endometriosis diag-
In Arab countries, endometriosis is rare. A variety nosed by laparoscopy in adolescents with
of personal risk factors for endometriosis have also dysmenorrhea or chronic pelvic pain: A
been described. Women with endometriosis may systematic review. Hum Reprod Update
be taller and thinner. Menstrual factors reported 2013;19:570–82.
to increase risk include dysmenorrhea, early men- 4. Fuldeore MJ, Soliman AM. Prevalence and
arche, and shorter cycle lengths. There is support symptomatic burden of diagnosed endo-
for the idea that lifestyle exposures that might raise metriosis in the United States: National
or lower estrogen levels could affect risk, including estimates from a cross-sectional survey
a decreased risk associated with smoking and exer- of 59,411 women. Gynecol Obstet Invest
cise and an increased risk associated with caffeine 2017;82:453–61.
or alcohol use. These risk factors appear to be com- 5. Mowers EL, Lim CS, Skinner B et al. Prevalence
patible with the central importance of retrograde of endometriosis during abdominal or lapa-
menstruation influenced by outflow obstruction roscopic hysterectomy for chronic pelvic
that might affect its amount, immune factors that pain. Obstet Gynecol 2016;127:1045–53.
might affect its ability to be cleared, or hormonal 6. Stuparich MA, Donnellan NM, Sanfilippo JS.
stimuli that might affect its growth. In this model, Endometriosis in the adolescent patient.
dysmenorrhea could be either a disease symptom Semin Reprod Med 2017;35:102–9.
 3
Etiopathogenesis of endometriosis

POOJA SIKKA AND RINNIE BRAR

What is endometriosis? 9 Risk factors 10

What is the pathology? 9 Genital tract (Müllerian anomalies) 10
What is adenomyosis? 9 Suggested reading 11
Etiology 10

Endometriosis is a chronic, progressive, and trou- WHAT IS ENDOMETRIOSIS?

blesome disease of women in the reproductive age
group. It was first described in 1860. The disease Endometriosis is defined as the presence of func-
is increasingly being diagnosed over the years. tioning glands and stroma of the uterus outside the
Still, it is one of the most underdiagnosed diseases endometrium. It can manifest in two forms:
and mean time period from onset of symptoms to
definitive diagnosis is around seven to eight years. ●● Presence of endometrium in the extra uterine
The incidence of disease is reported to be 10%–15%. organs
However, in women with chronic pelvic pain and ●● Presence of endometrium in the uterine wall
infertility, endometriosis can be found in almost
50%. In many women, the disease may not present WHAT IS THE PATHOLOGY?
any symptom, so it may go undiagnosed.
The research today is focused mainly on etio- An endometriotic lesion has typical histological
pathogenesis of the disorder so that targeted treat- resemblance to the endometrial glands and stroma.
ment can be provided to the patients. In the past They exhibit cyclical changes characteristic of
several decades, significant progress toward expos- menstruation and decidualize during pregnancy.
ing the enigma associated with this disorder has The process of endometriosis formation is gener-
been made. Still, many aspects of the disease are ally a diffuse one. In the ovary, however, blood and
unclear. For example, can endometriosis be pre- debris get collected, then get encapsulated to form
vented or predicted? What triggers malignancy in a cyst. With progression of the pathology, absorp-
endometriosis? tion of fluid elements causes the blood to become
The answers can only be provided if the mecha- inspissated and give a tarry or chocolate look.
nism of the disease is understood. A thorough As the cyst grows, its endothelial lining becomes
understanding of the etiopathogenesis of endo- thinned, stretched, and ultimately destroyed.
metriosis is essential for the development of newer
diagnostic tests and effective treatments of the WHAT IS ADENOMYOSIS?
disease. Maybe it is a disease with several mecha-
nisms of origin, several symptoms, and several The myometrium is invaded by endometrial
treatments. glands. The invasion, however, has to be at least

9
10 Etiopathogenesis of endometriosis

one high power field from the basal endometrium GENITAL TRACT (MÜLLERIAN
to label it as adenomyosis. ANOMALIES)
Other areas where endometriosis has been
reported include urinary bladder, ureter, bowel, Whenever, in medical science, we are unable to pre-
episiotomy or cesarean section scars, rectovaginal cisely decipher the past, present, and future of any
septum, vulva, cervix, pleura, lungs, and kidneys. disease, we propose several theories. It is because all
facts about the disease cannot be explained by one
ETIOLOGY single mechanism. Endometriosis is one such disor-
der. All proposed mechanisms remain to be conclu-
The disease has a few known and many supposed sively confirmed. Of recent interest are the theories
etiological factors. The precise etiopathogenesis of oxidative stress and immune dysfunction.
of endometriosis is unknown, but several theories Various proposed theories behind the etio-
regarding the phenomena involved in its devel- pathogenesis of endometriosis are presented here.
opment have been proposed. Besides the classic Retrograde menstruation theory: The theory
retrograde menstruation theory, lymphatic and of retrograde menstruation was proposed by
vascular metastases, iatrogenic direct implanta- Sampson. According to this theory: eutopic endo-
tion, coelomic metaplasia, embryonic remnants, metrium is transferred through patent fallopian
and mesenchymal cell differentiation or induc- tubes into the peritoneal cavity during menstrua-
tion, the persistence of a form of embryonic endo- tion every month. It must have been proposed as
metriosis may also be involved, as well as the a mechanism when in women with patent tubes
theory of the possible role of endometrial stem/ undergoing laparoscopy during the perimenstrual
progenitor cells. Genetics also plays a role in time of the cycle, the menstrual blood would have
the development of endometriosis. Recent stud- been seen in the pouch of douglas. When the col-
ies have highlighted the role of oxidative stress, lection of this menstrual blood in the pelvis or, to
defined as an imbalance between reactive oxygen be more precise, over the ovaries becomes signifi-
species (ROS) and antioxidants, which may be cant, it causes symptoms. This theory is supported
implicated in the pathophysiology of endometri- by the fact that the prevalence of endometriosis
osis causing a general inflammatory response in is very high in adolescent girls with congenital
the peritoneal cavity. obstructed or compromised tracts.
Coelomic metaplasia theory: According to this
RISK FACTORS theory, endometriosis originates from the meta-
plasia of cells, which are present in the mesothelial
Family history: The risk of developing endome- lining of the visceral and abdominal peritoneum.
triosis is 10 times higher in women with a family Transformation of normal peritoneal cells into
history of the disease in first-degree relatives. No endometrium-like cells occurs as a result of either
specific gene has been identified and therefore a hormonal or immunological triggers.
multifactorial inheritance is suggested. Theory of abnormal embryogenesis: Ectopic
Early menarche, nulliparity, and polymenor- endometrial tissue has also been detected in female
rhea: Endometriosis is an estrogen-dependent fetuses. This theory postulates that residual cells of
disorder. When we compare ectopic endometri- the Wolffian or Müllerian ducts persist and develop
otic tissue with eutopic, an increased activity of into endometriotic lesions that respond to estro-
the aromatase enzyme and decreased activity of gen. Furthermore, recent theories suggest coelomic
17β-Hydroxysteroid dehydrogenase (17β-HSD) metaplasia to be the origin of the adolescent variant
type 2 is found. Increased aromatase activity is the of a severe and progressive form of endometriosis.
consequence of the higher production of prosta- However, endometriotic lesions can also be found
glandin E2 (PGE2), which is stimulated by higher in areas outside of the course of Müllerian duct.
locally bioavailable E2 concentration. These find- Stem cell theory: The stem cells are supposed
ings support the ability of endometriotic lesions to exist in the basalis layer of the endometrium
for E2 biosynthesis and confirm treatments which since the basalis layer of the endometrium is not
lead to hypoestrogenism. shed with the monthly menstrual shedding of the
 Suggested reading 11

functional layer. Recently, clonogenic cells have activated locally. This inflammatory response may
been identified and proposed to be involved in the have a negative influence, which prevents elimina-
formation of ectopic endometrial lesions. These tion of ectopic endometrial cells that now can grow
cells are thought to represent the stem cell popula- in ectopic sites.
tion in the human endometrium. Stem cells are plu- Many theories have been suggested but none
ripotent cells. This means that they have the ability exclusively explains all facets of the disease. Still,
to differentiate into one or several types of special- we are unclear about its etiopathogenesis. Given
ized cells. The undifferentiated endometrial stem the late stage at time of diagnosis at present, young
cells may be less responsive to ovarian steroids than girls may ask for the availability of screening tests
the terminally differentiated cells due to a lack of for endometriosis in the coming years. Further
expression of hormone receptors. Retrograde men- research is suggested in the form of biomarkers or
struation can lead to the abnormal translocation of other immunological tests for understanding of the
normal endometrial basalis, which can result in the mechanism of development of disease. It would be
involvement of stem cells in the formation of endo- wonderful if we could predict the occurrence of
metriotic deposits. Brosens et al. (2020) postulated endometriosis in women and young girls and pro-
that the uterine bleeding in neonatal girls contains tect them from the morbidity of pain and infertility.
a high amount of endometrial progenitor cells and
that some of these cells may reside and reactivate in SUGGESTED READING
response to ovarian hormones later in life.
Leyendecker et al. (2004) proposed that women 1. Greene AD, Lang SA, Kendziorski JA et al.
with endometriosis abnormally shed the endome- Endometriosis: Where are we and where
trial basalis tissue, which, in combination with are we going? Reproduction, 2016 Sep;
retrograde menstruation, initiates endometriotic 152(3):R63–78. doi: 10.1530/REP-16-0052.
deposits. The evidence that some of the endome- [Epub 2016 May 10. Review].
trial stem cells have a bone marrow origin further 2. Gordts S, Koninckx P, Brosens I et al.
supports the hematogenous dissemination theory Pathogenesis of deep endometriosis. Fertil
of these cells. On the other hand, aberrant stem Steril 2017 Dec;108(6):872–85. e1. doi: 10.1016/​
cells can relocate from the endometrium to an j.fertnstert.2017.08.036. [Epub 2017 Oct 31.
ectopic site and generate endometrium-like lesions. Review].
Endometrial tissue produces several chemokines 3. Gargett CE, Schwab KE, Brosens JJ et al.
and angiogenic cytokines so this lesion can reside Potential role of endometrial stem/progenitor
in the ectopic sites due to neovascularization. cells in the pathogenesis of early-onset endo-
The last possibility of stem cell involvement in metriosis. Mol Hum Reprod 2014;20:591–8.
endometriosis is the differentiation of the peri- 4. Donnez J. Introduction: From pathogenesis to
toneal, hematopoietic, or ovarian stem cells into therapy, deep endometriosis remains a source
endometrium-like tissue. Cytokines flow between of controversy. Fertil Steril 2017;108:869–71.
the uterine cavity and the peritoneal cavity through 5. Donnez J, Donnez O, Dolmans MM et al.
the fallopian tubes. This connection may regulate Introduction: Uterine adenomyosis, another
the endometrium-like differentiation of the resi- enigmatic disease of our time. Fertil Steril
dent stem cell population in the peritoneal cavity. 2018;109:369–70.
Autoimmune disease or immune deficiency 6. Kvaskoff M, Mu F, Terry KL et al. Endometriosis:
theory: Endometriosis can occur when a defec- A high-risk population for major chronic dis-
tive immune response is present. This theory is eases? Hum Reprod Update 2015;21:500–16.
supported by the fact that autoimmune diseases 7. Brosens I, Benagiano G. Endometriosis, a
are found to be more common in women with modern syndrome. Indian J Med Res [serial
endometriosis. Women with endometriosis have online 2011] 2020 Jan 1;133:581–93.
a higher concentration of activated macrophages, 8. Leyendecker G, Kunz G, Herbertz M, Beil D,
decreased cellular immunity, and a repressed nat- Huppert P, Mall G, Kissler S, Noe M, Wildt L.
ural killer (NK) cell function. Ectopic endometrial Uterine peristaltic activity and the develop-
cells in the peritoneum induce an inflammatory ment of endometriosis. Ann N Y Acad Sci.
response, and macrophages and leukocytes are 2004 Dec;1034:338–55. Review.
 4
Molecular basis and biomarkers of
disease activity

PARIKSHAA GUPTA AND NALINI GUPTA

Biomarkers in peripheral blood 14 Proteomic biomarkers 17

Endometrial biomarkers 16 Genetic biomarkers 17
Biomarkers in urine 16 Conclusion 19
Biomarkers in saliva 17 References 19
Biomarkers in peritoneal fluid 17

Endometriosis refers to non-uterine, ectopic local- are associated with a momentous increase in the
ization of endometrial tissue in any other tissue or physical and emotional, as well as psychosocial,
organ of the body [1]. Though the exact incidence stress in these women, simultaneously adding to
is not known, it is estimated that the disease affects an ever-increasing socioeconomic burden on soci-
around 10% of women in the reproductive age ety. To date, the standard approach to establish
group [2]. The clinical symptoms are varied and the diagnosis of endometriosis still involves lapa-
depend upon the location of the ectopic endometri- roscopic exploration of the abdomen and biopsy
otic tissue. The most common presenting symptom of the suspicious lesions for histopathological
is chronic pelvic pain with or without infertility. In demonstration of ectopic endometrial glands and
recent years, with advancements of research in this stroma [3]. Like for many other diseases, there is a
field, considerable insights have been obtained in need for identification of effective biomarkers and
terms of pathogenesis of endometriosis; however, development of rapid, noninvasive or minimally
advancements in terms of rapid and early diagno- invasive, biomarker-based tests, which may be of
sis and therapy are still lagging. help in early diagnosis of the disease, as well as in
Establishing an early diagnosis of this complex predicting disease activity. With the advancements
disease is quintessential for prompt management in in understanding of pathogenetic mechanisms of
women with endometriosis. However, more often endometriosis, several biomarkers have recently
than not, diagnostic delays occur with the majority been proposed for early and relatively noninvasive
of these women having to undergo multiple unnec- diagnosis of endometriosis.
essary tests and treatments until a definite diagno- These can be broadly categorized under the
sis is made. This is because a definite diagnosis of f­ ollowing groups:
endometriosis cannot be established based on the
clinical features alone as these show a significant ●● Biomarkers in peripheral blood
overlap with those seen in a number of other gyne- ●● Endometrial biomarkers
cological conditions. The undue diagnostic delays ●● Biomarkers in urine

13
14 Molecular basis and biomarkers of disease activity

●● Biomarkers in body fluids Other glycoprotein biomarkers include galec-

●● Genetic biomarkers tin-9, glycodelin A, and follistatin. Galectin-9 is
●● Molecular and proteomic biomarkers basically an immunomodulatory protein. Studies
have found its levels to be significantly elevated in
BIOMARKERS IN PERIPHERAL endometriosis as compared with normal healthy
BLOOD women. However, the levels were also found to be
elevated in females with other gynecological dis-
The ease of obtaining a peripheral blood sample eases, thereby suggesting that using high levels of
makes it a useful minimally invasive method for galectin-9 may not be of practical utility to diag-
testing for various endometriosis-related biomark- nose endometriosis [8].
ers. Several authors have conducted studies explor- Glycodelin A is a cell proliferation promo-
ing the role of multiple biomarkers in detection of tor that also promotes neovascularization. It also
endometriosis. However, none of these have been exhibits immunosuppressive properties and acts
found to be of significant utility in diagnosing endo- via inactivation of T and NK (natural killer) cells.
metriosis and hence have not been recommended as Several studies have previously been conducted
an alternative to surgical exploration [4,5]. to explore the diagnostic utility of this marker for
endometriosis; however, they have yielded con-
flicting results, with some suggesting a significant
Markers related to inflammation and association of the elevated levels with endometrio-
oxidative stress sis while the others indicating only a limited clini-
cal utility [4,9].
GLYCOPROTEINS
Cancer antigen 125 (CA-125) is the most com- CYTOKINES AND INFLAMMATORY
monly implicated and studied biomarker for PROTEINS
endometriosis. It is basically a marker indicating Endometriosis is known to thrive in inflamma-
inflammation in the peritoneum. Multiple stud- tory conditions. Foci of endometriosis, similar to
ies have evaluated the diagnostic role of CA-125 in the normal uterine endometrium, undergo cyclical
patients with endometriosis using several different shedding, thereby inducing an ambient inflamma-
cutoff values and have found variable sensitivities tory response [10]. The development of inflamma-
and specificities with each set of values. In a recent tory response has been known to promulgate the
meta-analysis published on the Cochrane data- primary endometriotic lesions [11,12]. Based on
base, the authors evaluated all such studies and this knowledge, several researchers have impli-
found that none of the cutoff values had sufficient cated several cytokines and inflammatory proteins
diagnostic accuracy so as to label this biomarker as biomarkers for minimally invasive diagnosis of
as either a useful replacement test or a triage test endometriosis. The roles of these mediators as bio-
[4]. However, in another recent systematic review markers for endometriosis in peripheral blood has
and meta-analysis, the authors concluded that a been explored in multiple studies; however, many
cutoff value of >30 U/mL for CA-125 may be use- of these have yielded inconsistent and rather con-
ful as a rule-in test for endometriosis [6]. Based on flicting results [5].
analysis of various other studies evaluating the role Of all the cytokines, interleukin-6 (IL-6) is the
of CA-125, the diagnostic utility of this biomarker most widely studied biomarker in the context of
seems to be limited, mainly owing to the lower endometriosis. The authors of a recent meta-anal-
specificity as it is elevated not only in endometrio- ysis found a sensitivity of 63% and a specificity of
sis but a plethora of other gynecological diseases 69% for IL-6, when a cutoff value of >1.90–2.00 pg/
as well. This is compounded by low sensitivity, as mL was chosen [5]. IL-35, which is an inhibitory
this marker has been seen to be elevated mainly cytokine involved in immune tolerance and pro-
in advanced endometriosis and the elevation is duced by regulatory T cells, has been seen to be
much more inconsistent in the early stages [6,7]. elevated in cases of endometriosis as compared
Regardless of its shortcomings, CA-125 is still the with others [13]. Other inflammatory cytokines
most widely used marker in studies evaluating that have been studied in endometriosis include
other diagnostic endometriosis biomarkers. IL-1, IL-8, IL-10, IL-12, IL-17, IL-23, monocyte
 Biomarkers in peripheral blood 15

chemoattractant protein-1 (MCP-1), tumor necro- 3a, anti-tropomyosin 3c, and anti-tropomyosin 3d
sis factor alpha (TNF-α), interferon gamma (IFN- autoantibodies for endometriosis [19]. They found a
γ), and many others. Although some studies in higher sensitivity of detecting endometriosis using
the literature have shown some of these markers this panel of six immunomarkers in comparison
to be significantly elevated in women with endo- with some previously used biomarkers, including
metriosis, there are other studies that have sug- CA-125. However, validation of these results by fur-
gested against or have shown a limited role of ther studies is needed before large-scale diagnostic
cytokine measurements in diagnosing endome- application.
triosis [14–16]. This is mainly because cytokine
measurements, rather than being simple, are com- Markers related to cell survival,
plex owing to variability with circadian rhythms, adhesion, and migration
methods of sample collection, short half-lives, and
methods of assessment [17]. As per the retrograde menstruation theory, after
shedding from the endometrium, the endometrial
MARKERS OF OXIDATIVE STRESS cells enter the peritoneal cavity. In the peritoneal
The cyclical bleeding, besides eliciting inflamma- cavity, the endometrial cells, before attaching onto
tion, also leads to increased oxidative stress in the the peritoneum, need to survive the new environ-
tissues by causing increased accumulation of iron ment by evading apoptosis. Thereafter, the survival
from the damaged and ruptured red blood corpus- depends on the establishment of new vasculature.
cles. It has been demonstrated by several authors Some researchers have demonstrated elevated
that the levels of proteins related to oxidative stress levels of FAS/CD95 in the sera of patients with
are elevated in patients with endometriosis. Levels endometriosis, thereby providing evidence to the
of active as well as total myeloperoxidase have been apoptosis-evasion hypothesis [20]. The authors
found to be elevated in association with endome- also found elevated levels of an angiogenic factor,
triosis as compared to women with other gyneco- hypoxia-inducible factor 1 alpha (HIF-1α). A few
logical diseases [18]. Researchers have also found studies have also demonstrated upregulation of the
significant reduction in serum levels of superoxide mRNA of factors such as survivin, vascular endo-
dismutase, paraoxonase (PON1), and high-density thelial growth factor (VEGF), and vascular cell
lipoproteins in women with endometriosis [14]. adhesion molecule 1 (VCAM-1) in cases of endo-
metriosis compared with controls [21,22]. Studies
AUTOIMMUNE MARKERS comparing the diagnostic utility of biomarker pan-
Abnormalities in the numbers and/or functions of els comprising apoptotic and angiogenic markers
immune cells have been implicated in the develop- with panels comprising inflammatory markers
ment and also the progression of endometriosis. have also been conducted, and the authors have
These abnormalities include increased number of found relatively higher utility of the former than
activated macrophages, increased polyclonal acti- the latter [23].
vation of B cells, defective natural killer (NK) cell
and regulatory T-cell functions, and increased CIRCULATING ENDOMETRIAL CELLS
levels of cytokines involved in regulating autoim- Circulating endometrial cells have previously been
munity including IL-27, IL-6, and transforming identified as circulating cells, which are vimentin
growth factor beta (TGF-β). Some researchers have positive (stromal cells), pan-cytokeratin positive
found increased levels of autoantibodies in patients (epithelial cells), ER/PR (estrogen or progesterone
with endometriosis. In a recent meta-analysis, the receptor) positive, and leucocyte common antigen
authors found the detection of autoantibodies in the (CD45) negative. Researchers have found elevated
sera of these patients to be a useful biomarker; how- numbers of circulating endometrial cells in cases
ever, this test can neither be used as a replacement of endometriosis as compared to controls [24].
to the gold standard nor does it qualify to be a triage
test [4]. Recently, some authors attempted to study CIRCULATING CELL-FREE DNA (cfDNA)
the diagnostic utility of an immunomarker panel A few studies have found elevated levels of circu-
comprising anti-tropomodulin 3b, anti-tropomod- lating cfDNA in cases of endometriosis compared
ulin 3c, anti-tropomodulin 3d, anti-tropomyosin with controls, thereby indicating a potential role
16 Molecular basis and biomarkers of disease activity

for cfDNA in the diagnosis of endometriosis [25]. influence the concentrations, as well as expression
However, this needs to be validated in further of urinary proteins such as intake of certain medica-
large-scale studies. tions like diuretics or dehydration. Various methods
that can be used to study urinary proteins include
Markers related to pain electrophoresis, Western blotting, enzyme-linked
immunosorbent assay (ELISA), matrix-assisted
Pain is one of the most common symptoms in laser desorption/ionization–time of flight (MALDI-
women with endometriosis. Several studies focus- TOF), mass spectrometry, and liquid chromatogra-
ing on the pain pathways have been conducted. A phy tandem mass spectrometry (LQ-MS/MS) [31].
literature review shows that many authors have There are a few studies in the literature wherein the
demonstrated elevated levels of brain-derived authors have evaluated certain urinary biomarkers
neurotropic factor (BDNF) in the plasma of these of endometriosis. Some of the commonly implicated
patients compared with controls. However, the role urinary biomarkers have been described below.
is limited in diagnosis of peritoneal endometriosis Soluble feline McDonough sarcoma (fms)-like
and deeply infiltrative endometriosis [26]. tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor,
downregulates VEGF and hence VEGF-mediated
ENDOMETRIAL BIOMARKERS neovascularization. The overexpression of sFlt-1
leading to pathological neovascularization in
Many previous studies have evaluated the role of breast and colonic cancers has been reported. Some
various endometrial biomarkers in rapid, nonin- researchers have shown significantly high urinary
vasive, or minimally invasive diagnosis of endome- levels of sFlt-1 in patients with confirmed endo-
triosis. A recent systematic review published in the metriosis, corrected for creatinine, compared with
literature included 54 studies on the role of endo- controls [32]. They also observed a much higher ele-
metrial markers. In all, more than 90 endometrial vation during the secretory phase of the menstrual
biomarkers were assessed in these studies; however, cycle in the patients, in contrast to the controls in
around 77 were not found to be associated with whom the levels did not fluctuate significantly dur-
endometriosis. Of the remaining 22, only 2 mark- ing the menstrual cycle. The elevated urinary levels
ers, namely, CYP19 and PGP9.5, could be evaluated also correlated with the stage of the disease, which
in the review as only these had been assessed in suf- means that the levels were elevated significantly in
ficient numbers. However, the authors found that initial stages of the disease but not in the advanced
neither of these can be recommended as a diagnos- stage. An important observation in the study was
tic test that can be used for endometriosis [27]. that though the urinary levels were significantly
It has been seen that the levels of glycodelin elevated in endometriosis patients, the serum levels
and EWI-2 (EWI-2 is also referred to as immuno- did not show any significant variation.
globulin superfamily member 8 [IGSF8].) are sig- Matrix metalloproteinases (MMPs) are endo-
nificantly lower in uterine endometrium of cases of peptidases that play a role in degradation and
endometriosis and endometriomas compared with remodeling of the extracellular matrix, thereby
normal controls [28,29]. facilitating cellular migration. Three MMPs,
including MMP-2, MMP-9, and MMP-9/NGAL,
BIOMARKERS IN URINE have been found to be significantly elevated in
urine in the cases of endometriosis when com-
Urine has been recognized as one of the most use- pared with controls [33]. Additionally, increased
ful and easily available samples to be tested for expression of MMP-2 and MMP-9 has been seen
an early, noninvasive diagnosis of endometriosis. in the uterine as well as ectopic endometrial tissue
Detection of proteins associated with endome- in these patients [34].
triosis is relatively easy in urine samples owing to Vitamin D–binding protein (VDBP) plays a
higher concentrations of plasma proteins in urine role in chemotaxis and migration of monocytes,
due to selective glomerular filtration, and hence, neutrophils, and fibroblasts. The urinary levels of
urine samples are preferred for proteomics [30]. VDBP, corrected for creatinine, are significantly
However, care needs to be taken while evaluating elevated in cases of endometriosis, thereby sup-
these results as there are several factors that might porting the association of inflammation with
 Genetic biomarkers 17

endometriosis [35]. However, serum levels do not BIOMARKERS IN PERITONEAL

show any significant elevation in these patients FLUID
compared with the controls.
Cytokeratin-19 (CK-19), a cytoskeletal protein, Peritoneal fluid (PF) contains many cells, such as
has been found to be elevated in urine, but not mesothelial cells, macrophages, and lymphocytes.
serum, in cases of endometriosis, as opposed to When activated, the resident macrophages, as well
controls [36]. However, more recent studies have as the mesothelial cells, can produce cytokines.
not shown any significance of urinary levels of Peritoneal fluid cytokines play a pivotal role in the
CK-19 in cases of endometriosis [37]. etiopathogenesis. Peritoneal fluid thus serves as a
useful potential sample for diagnostics as well as
BIOMARKERS IN SALIVA disease monitoring. The major disadvantage asso-
ciated with PF testing is the fact that it has to be
Like urine, saliva is also a convenient, noninvasive, collected at the time of surgery, thereby making the
easily available sample that can be tested for biomark- entire procedure more invasive than other samples
ers of endometriosis. Some researchers have used such as urine and peripheral blood. As is the case
saliva for studying hormonal variations and identify- with other biomarkers, although many mark-
ing various genetic aberrations in patients with endo- ers have been evaluated in the PF, to date there is
metriosis. An important prerequisite to biomarker no single reliable biomarker or biomarker panel
testing in saliva is proper sample collection. that can replace the gold standard. Some of the
In order to ensure uniformity in this process, important peritoneal fluid biomarkers that have
guidelines have been framed by the World Endo­ been extensively studied for their potential role in
metriosis Research Foundation–Endometriosis ­endometriosis have been listed in Table 4.1 [31].
Phenome and Biobanking Harmonization project
(WERF-EPHECT), highlighting the use of properly PROTEOMIC BIOMARKERS
validated collection kits as well as appropriate sam-
ple storage conditions so that the specimen quality Several previous studies in the literature have eval-
is not compromised. uated expression in the endometrial cells among
patients with endometriosis. Researchers have
Hormones shown at least 72 dysregulated genes in women
with endometriosis by sequencing mRNA from
Hormonal levels, including progesterone and cor- the secretory phase endometrial samples. Of these,
tisol, have been estimated in patients with endo- 4 upregulated proteins including MMP-11, Fos
metriosis, and some studies have found significant proto-oncogene, dual specificity phosphatase and
differences in the hormonal levels in patients of serpin family E member 1, and adenosine deami-
endometriosis compared with controls. Some nase 2 were validated using quantitative poly-
authors have found significant morning hypocor- merase chain reaction (PCR). Similarly, several acyl
tisolism in these patients [38]. carnitines were found to be elevated while trimeth-
ylamine-N-oxide was decreased in the cases of
Cell-cycle regulatory factors endometriosis using mass spectrometry methods.
Studies using nuclear magnetic resonance spec-
WNT4 is an important cell-cycle regulatory pro- trometry have revealed that metabolites contain-
tein. Some researchers have conducted genome- ing valine, fucose, and choline, amino acids lysine/
wide association studies (GWAS) using salivary arginine, and lipoproteins were upregulated, while
samples alone and have shown an association of creatinine was downregulated in patients with late
endometriosis with WNT4 in patients with con- stages of the disease [41].
firmed endometriosis [39]. p27 (the cyclin-depen-
dent kinase inhibitor 1B), is an enzyme inhibitor, GENETIC BIOMARKERS
which is encoded by the CDKN1B gene. A study
using buccal swabs has shown a significantly Endometriosis is a complex disorder having a mul-
higher prevalence of a V109G substitution in the tifactorial etiopathogenesis. The disease is not only
p27 gene in patients of endometriosis [40]. regulated by several environmental factors but
18 Molecular basis and biomarkers of disease activity

Table 4.1 Commonly studied biomarkers of endometriosis in peritoneal fluid

Biomarkers Basic action Role in endometriosis

Tumor necrosis factor-α • Activates helper T cells and other Significantly elevated PF levels
cytokines in patients with
• Proinflammatory endometriosis
• Promotes angiogenesis
RANTES • Regulates inflammation by Elevated PF levels correlate with
recruiting NK cells, histiocytes, and disease severity
granulocytes
Interferon-γ • Induces expression of MHC class II Controversial, decreased PF
molecules levels have been seen in
• Proinflammatory patients with endometriosis
• Macrophage activation
Interleukin-6 • Anti-inflammatory Significantly elevated levels in
• Stimulates of antibody production moderate to severe
• Development of effector T cells endometriosis, no significance
in mild disease
Interleukin-8 • Neutrophil chemotactic factor Controversial, significantly
• Proinflammatory elevated PF levels in mainly
• Promotes angiogenesis early stages of the disease
Interleukin-10 • Human cytokine synthesis Significantly elevated PF levels
inhibitory factor in all stages of the disease
• Anti-inflammatory
Interleukin-13 • Anti-inflammatory Significantly reduced PF levels
• Inhibits macrophage and in endometriosis
lymphocyte activation
Interleukin-18 • Stimulates Th1 and Th2 immune Controversial, some studies
responses showing significantly higher
• Induces the production of PF levels in endometriosis
interferon-γ, IL-4, TNF-α, IL-5, and while others demonstrating
IL-13 lower PF levels in these
patients compared with
controls
TGF-β-1 • Inhibits natural killer cells Significantly higher PF levels in
• Regulates cell proliferation and endometriosis, correlating
angiogenesis with disease severity
• Inhibits macrophages
FAS ligand • Regulates apoptosis Significantly higher PF levels in
• Stimulates secretion of IL-8 moderate to severe
endometriosis, no significance
in early disease
Leptin • Hormone of energy expenditure Significantly elevated PF levels
• Anti-inflammatory in early-stage endometriosis
• Regulates angiogenesis compared with late-stage
disease
Abbreviations: 
PF, peritoneal fluid; MHC, major histocompatibility complex; TGF, transforming growth factor;
RANTES, regulated on activation, normal T cell expressed and secreted.
 References 19

multiple genetic factors as well. This is supported disease, type 2 diabetes, glioma, and nevi [42]. A
by the fact that the relatives of these patients carry few other loci that have been linked to increased
a much higher risk for the disease as compared to susceptibility for endometriosis include 7p15.2 (a
general population. Moreover, several twin studies region between NFE2L3 and HOXA10) and 10q26.
have also demonstrated an increased concordance However, the clinical significance of these genetic
in monozygotic twins as compared to dizygotic variants in predicting the risk of the disease is still
twins [31,42]. Several researchers have tried to unclear. Recently, some researchers have demon-
identify the genes associated with endometriosis strated an increased prevalence of an inherited
using linkage and GWAS. However, the success polymorphism of a let-7 miRNA-binding site in the
rates have been low, probably because the disease KRAS gene in patients with endometriosis as the
is regulated by interplay of multiple genes. first described genetic marker for endometriosis
GWAS have identified several candidate genes risk and also a potential therapeutic target [45].
associated with endometriosis. Some studies have
shown an association of the disease with a single CONCLUSION
nucleotide polymorphism (SNP) PvuII in the
estrogen receptor 1 gene; however, the same could Advances in research have led to identification of a
not be validated by subsequent studies. A study number of noninvasive and/or minimally invasive
evaluating the association of ten estrogen-metab- biomarkers for early diagnosis of endometriosis.
olizing SNPs in cases of endometriosis showed However, despite a large number of biomarkers being
significant association of vIV A→C variant in the available, promising results are sparse, and to date,
hydroxysteroid (17-β) dehydrogenase 1 (HSD17B1) no single biomarker is capable of accurately diagnos-
gene with endometriosis [43]. Similarly, PROGINS ing endometriosis and replacing histopathological
polymorphism in the progesterone receptor gene diagnosis. The major reason for this is the complex
has also been found to be positively associated with etiopathogenesis of the disease. To conclude, endo-
endometriosis; however, the association has not metriosis can most likely be diagnosed using a panel
been found to be statistically significant [42]. of biomarkers rather than a single biomarker alone.
Given the role of cytokines, including TNF-α and
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 5
Diagnostic evaluation

NEHA AGGARWAL, SEEMA CHOPRA, AND ARSHI SYAL

Pain 23 Diagnostic evaluation 25

Infertility 24 References 27
Symptoms from specific sites 24

Endometriosis may have different clinical presen- ●● Infiltration or invasion of the nerves by the
tations depending on the primary location. Pelvic endometriotic implants [6,7]. The inflammatory
pain and infertility are the two most common mediators further sensitize the nociceptors,
symptoms associated with it. which in turn initiate the central neurons [8].

PAIN Infiltration of the uterosacral ligament, recto-

vaginal septum, and posterior cul-de-sac result in
Dysmenorrhea typically developing after years of dyspareunia. Dyspareunia is present due to trac-
pain-free menstrual cycles is suggestive of endome- tion of fixed uterosacral ligaments during inter-
triosis. The pain most often begins 48 hours prior to course. There are mixed opinions regarding the
the onset of menses and persists throughout the men- correlation between the extent of the endometri-
strual period. The pain may be unilateral or bilateral otic implants and intensity of the pain.
and is perceived as a sensation of swelling of the inter- There are various methods of grading the pain
nal organs or pelvic heaviness [1]. Endometriosis- experienced by patients suffering from endome-
associated pain tends to be more severe and responds triosis. Though not used much in clinical prac-
to a lesser degree to conventional treatment with tice, below are some examples for quantifying the
nonsteroidal anti-inflammatory agents and com- pain:
bined oral contraceptive pills [2,3]. Cyclical pain soon
progresses to noncyclical, chronic pelvic pain severe
enough to cause functional disability and compro-
●● Visual Analogue Scale (VAS): Rating the pain
mise day-to-day activities [4]. from none to worst imaginable [9]
There are primarily three main mechanisms for
●● Numerical Rating Scale: Grading the pain at a
the underlying cause of pain in endometriosis: score from 1 to 10
●● McGill Pain Questionnaire [10]
●● Focal bleeding from the endometriotic implants.
●● Macrophages present in the peritoneal fluid of Although endometriosis usually presents as
the women with endometriosis produce various chronic pain, in some instances, the ovarian
cytokines, growth factors, and prostaglandins, endometrioma might rupture and give a clinical
which in turn promote pain and expansion of picture very similar to that of a ruptured hemor-
the ectopic endometrium [5]. rhagic cyst.

23
24 Diagnostic evaluation

INFERTILITY Decreased endometrial receptivity

The overall incidence of endometriosis is greater in For the transition of endometrium from prolif-
infertile women (13%–33%) than in fertile women erative to luteal phase, progesterone is required.
(4%–8%) [11,12]. The fecundity rate of women with However, in women with endometriosis, there will
endometriosis is quite similar to the fecundity rate be increased activation of steroidogenic factor 1
caused by unexplained infertility (i.e., 0.02–0.10) (SF1) and aromatase activity leading to increased
[13]. In addition, there is increased prevalence production of estradiol. Highly potent estradiol
of infertility with severe forms of endometriosis downregulates the expression of progesterone
when compared with women with mild endome- receptors leading to progesterone resistance and
triosis [14–16]. further increasing the level of estradiol by lowering
No definite mechanism has yet been identi- the activity of 17β-hydroxysteroid dehydrogenase
fied to establish an association between endome- (17β-HSD) [23].
triosis and infertility; however, several biological
mechanisms have been suggested. We have briefly SYMPTOMS FROM SPECIFIC SITES
­discussed these mechanisms below.
Rectosigmoid lesions
Distorted adnexal anatomy
Chronic or cyclical constipation, diarrhea, or
Adhesions as a result of endometriosis can hin- hematochezia may arise due to inflammation of
der the normal ovum pickup after ovulation and the rectal wall or adherence of the rectum to the
transport by the uterine tubes [17]. adjacent structures [24]. Deep infiltrating endo-
metriosis (DIE) is defined as endometriotic lesions
Altered peritoneal fluid volume and penetrating into the retroperitoneal space or the
wall of the pelvic organs to a depth of at least
composition 5 mm. DIE complicates around 5%–12% of cases
Women with endometriosis have increased of endometriosis and commonly involves the rec-
peritoneal fluid volume and high levels of pros- tosigmoid colon and, to a lesser extent, the ileum,
taglandin production (PGE2). This induces a the appendix, and the sigmoid colon. Lesions usu-
classic inflammatory response characterized by ally involve the serosa and muscularis propria but
increased production of cytokines, such as IL-1, in rare cases can induce transmural inflammation
IL-6, and TNF-α. Angiogenic cytokines, such leading to intestinal obstruction. Endometriosis of
as VEGF and IL-8, production by macrophages the ileum could result in partial bowel obstruction,
is also increased in the peritoneal fluid [18,19]. typically during menses; however, endometriosis
These inflammatory mediators together contrib- of the colon rarely results in obstruction owing to
ute in peritoneal adhesion formation and subse- the colon’s larger diameter.
quent local angiogenesis. Studies have shown that
the inflammatory milieu present in the peritoneal Urinary tract lesions
fluid of patients with endometriosis contributes to
fragmentation of DNA of sperm [20]. The oxida- Superficial endometriotic lesions involving blad-
tive stress induced by this chronic inflammation der peritoneum are not symptomatic. DIE involv-
may interfere with sperm–oocyte interaction, ing the urinary tract have been found in 2.6% of
impairs the development of embryo, and makes the cases [25]. Endometriotic nodules involving
implantation difficult [21]. the uterosacral ligaments can cause irritation of
the pelvic plexus, leading to voiding symptoms,
Impaired implantation urgency, and dysuria. Cyclical hematuria is an
uncommon finding because the non-involvement
Decreased expression of the cell adhesion molecule of the bladder mucosa.
αvβ3 integrin has been held responsible for the Ureteral endometriosis can result in hydrone-
implantation failure in endometriosis [22]. phrosis, flank pain, and decline of renal function.
 Diagnostic evaluation 25

Anterior abdominal wall lesions epithelium derivatives. Its utility in monitoring

the disease remission and recurrence has been well
Scar endometriosis is a very rare entity reported established in epithelial ovarian cancer. Chronic
in patients who have undergone any previous inflammation in endometriosis can cause irritation
­abdominal or pelvic surgery. The symptoms are of the peritoneum, leading to increased production
usually of cyclical pain and increase in the size of of CA-125 [27]. A study was done by Mol et al. to
the endometriotic implants during menses. assess the utility of CA-125 as a noninvasive diag-
nostic marker for endometriosis. The assay seems
Thoracic–diaphragmatic to be a poor marker for stage I/II endometriosis but
endometriosis has a better sensitivity in diagnosing stage III/IV
disease. Despite having limited utility in diagnos-
Endometriotic implants, when they involve the ing endometriosis, Mol continued to advocate for
thoracic cavity, can lead to cyclical chest or shoul- the routine measurements of CA-125 in patients
der pain with right-sided predominance, hemopty- who present with infertility, as this could identify
sis, and pneumothorax. the subgroup of patients who will benefit from
early laparoscopy [28].
DIAGNOSTIC EVALUATION Serum CA-125 may have a role in differenti-
ating endometriomas from other benign cysts,
Physical examination especially when coupled with the transvaginal
ultrasonography.
In the majority of the cases, the endometriosis A recent study done by Othman and colleagues
remains confined to the pelvic cavity except the few has found elevated levels of IL-6 in the serum of the
exceptions of scar and thoracic endometriosis. In the patients with endometriosis when compared with
order of decreasing frequency, the primary location infertile patients with no evidence of endometrio-
of endometriosis are as follows: ovaries, uterine liga- sis [29]. The discovery of new biomarkers may be of
ments, pouch of Douglas, and peritoneal surfaces. particular advantage in diagnosing endometriosis.
On pelvic examination, external genitalia is
typically normal. The exception may be the rare
cases of episiotomy scars. Diagnostic imaging
On per speculum examination, blue-colored
implants or red powder burn lesions are seen on ULTRASONOGRAPHY
the cervix and the posterior vaginal fornix. These Transvaginal ultrasonography (TVS) is simple,
lesions are usually tender and bleed on contact. widely available, and cost effective, and hence, it is
On bimanual examination, there may be lat- the first imaging modality in evaluation for endo-
eral displacement of the cervix due to unilateral metriosis. Ovaries are the most common site of
involvement of the uterosacral ligaments. The endometriotic implants. The classical finding of an
uterus may be retroverted and exhibit tenderness, ovarian endometrioma on ultrasound is the pres-
decreased mobility, or fixation. Ovarian endome- ence of a “chocolate cyst” caused by the presence of
triomas can present as fixed, immobile, and ten- thick, degenerated blood products that result from
der adnexal masses. Ovarian endometriomas are cyclical bleeding during the menses; it is a homog-
bilateral in 30%–50% of cases [26]. Tender nodules enous hypoechoic lesion with the ovary, with low
can be palpated along the uterosacral ligaments or to medium echoes (ground glass appearance),
posterior cul-de-sac, especially if done before the and no internal vascularity [30–34]. Occasionally,
onset of menses. endometriomas may have thickened walls, a fluid–
Digital rectal examination reveals the nodular- fluid level, an avascular mural nodule (a retract-
ity and tenderness of the rectovaginal septum. ing clot), and solid masses (due to the presence of
older product and fibrosis). A thick, dense fibrous
Serum markers of endometriosis capsule is invariably present at the periphery of
the endometrioma. Traditionally, endometriomas
CA-125 is a transmembrane glycoprotein and are uniloculated but up to 4 thin septations can
is synthesized and secreted by the coelomic be found. Use of power Doppler may show only
26 Diagnostic evaluation

pericystic vascularity with absence of blood flow uniloculated and do not exhibit shading sign on
within it. T2-weighted images.
Endometriosis, when it involves both the ova- Fat-saturated, T1-weighted sequences show per-
ries, the ovaries adhere to one another in the mid- sistence of high signal intensity on T1-weighted
line, giving the appearance of “kissing ovaries.” images in cases of endometriomas. There is loss of
Ovarian endometriosis is usually present in asso- signal intensity on fat-saturated images in cases of
ciation with advanced endometriosis. dermoid cysts [40].
TVS has 88% sensitivity in differentiating endo- MRI confers benefits in the evaluation of
metriomas from other masses and a specificity of deep infiltrating endometriosis and cul-de-sac
90% [35]. obliteration, which are often difficult to visu-
TVS should be performed during menses alize laparoscopically. In these cases, MRI may
or at the time of maximum pain as during this help in preoperative planning. According to one
time endometrial implants grow and are easily study, the sensitivity and specificity of diagnos-
visualized. ing endometriosis is 69% and 75%, respectively
Bladder endometriosis can be accurately diag- [41]. DIE involving the rectosigmoid colon
nosed using transvaginal ultrasonography. The may need resection. MRI can give valuable
endometriotic implants appear as solid hypoechoic ­information on number and location of lesions,
nodules that adhere to the posterior aspect of the depth of i­nfiltration, and distance between
bladder dome. the inferior margin of the nodule and the anal
To diagnose rectal endometriosis in ultraso- border [42].
nography, paramount experience is required. So,
if the patient presents with symptoms suggesting
rectal endometriosis, transvaginal ultrasound can OTHER MODALITIES
be done to diagnose or rule it out [36]. ●● Computed tomography (CT): CT offers limited
TVS is a powerful tool for diagnosing ovarian value in the evaluation of endometriosis. It may
endometrioma and endometriosis of the bladder, reveal endometriomas as nonspecific masses
but its value in evaluating the superficial peritoneal and does not offer diagnostic images as pro-
lesions and deep infiltrating lesions is questionable vided by TVS or MRI. This is because of the fact
[35,37]. that CT has poor sensitivity for small implants
and plaques.
MAGNETIC RESONANCE IMAGING (MRI)   Thoracic lesions of endometriosis can be
The use of MRI comes into the play when ultraso- detected by chest CT. Also, their role has
nography is inconclusive. MRI can be used as an been defined in bowel and ureteral endome-
adjunct to differentiate endometriomas from hem- triosis [43].
orrhagic cysts or dermoid cysts. Endometriomas ●● Cystoscopy: Cystoscopy may aid in diagnosing

are hyperintense on T1-weighted images and show the bladder endometriosis and in providing a
gradual loss of signal with low signal intensity tissue sample for histological confirmation.
on T2-weighted images. This decrease in signal ●● Double-contrast barium enema: It is used to

intensity has been termed as “shading sign” [38]. make a diagnosis of endometriosis and also
It reflects the presence of blood products of vary- allows the evaluation of length and degree of
ing age within the cyst. Another typical finding is bowel occlusion. It is an important presurgical
the presence of the black peripheral rim containing imaging tool.
accumulated hemosiderin-laden macrophages as a   Clinical symptoms when combined with
result of cyclical bleeding [39]. characteristic imaging features can facilitate in
Hemorrhagic cysts are often confused with making a diagnosis of endometriosis by use of
endometriomas. The hemorrhagic cysts appear noninvasive techniques.
 References 27

Stepwise algorithm for the diagnosis of 4. American College of Obstetricians and

endometriosis Gynecologists: Chronic pelvic pain. Practice
Bulletin No. 51, March 2004, Reaffirmed May
Suspect endometriosis if the following symp- 2010.
toms are reported: 5. Bulun SE. Endometriosis. N Engl J Med
2009;360(3):268.
●● Secondary dysmenorrhea 6. Barcena de Arellano ML, Arnold J, Vercellino
●● Chronic pelvic pain F et al. Overexpression of nerve growth
●● Dyspareunia factor in peritoneal fluid from women with
●● Chronic/cyclical bowel symptoms endometriosis may promote neurite out-
●● Chronic/cyclical bladder symptoms growth in endometriotic lesions. Fertil Steril
●● Infertility 2011;95(3):1123.
7. McKinnon B, Bersinger NA, Wotzkow C et al.
Endometriosis-associated nerve fibers, peri-
toneal fluid cytokine concentrations, and
pain in endometriotic lesions from different
locations. Fertil Steril 2012;97(2):373.
8. Evans S, Moalem-Taylor G, Tracey DJ. Pain and
endometriosis. Pain 2007;132(Suppl 1):S22–5.
Physical examination: 9. Jensen MP, Karoly P. Self-report scales and
procedures for assessing pain in adults. In:
●● Blue-colored/red powder burn lesion on Turk DC, Malzack R, editors. Handbook of
cervix/posterior fornix Pain Assessment. New York: Guilford Press;
●● Lateral displacement of cervix 1992, p. 135.
●● Uterus retroverted, fixed, tender 10. Melzack R. The McGill Pain Questionaire:
●● Immobile, tender adnexal mass Major properties and Scoring methods. Pain
●● Nodules palpable on posterior cul-de-sac 1975;1:277.
11. D’Hooghe M, Debrock S, Hill JA et al.
Endometriosis and subfertility: Is the rela-
tionship resolved? Semin Reprod Med
2003;21:243.
12. Strathy JH, Molgaard CA, Coulam CB et al.
Endometriosis and Infertility: A laparoscopic
study of endometriosis among fertile and
Presumptive diagnosis of endometriosis infertile women. Fertil Steril 1982;38:667.
13. Hughes EG, Fedorkow DM, Collins JA. A
quantitative overview of controlled trials in
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Steril 1993;59:963–70.
1. Bieber E. Clinical Gynaecology, 2nd ed. 14. Matorras R, Rodriguez F, Pijoan JI et al.
Cambridge: Cambridge University Press; Women who are not exposed to spermatozoa
2015. and infertile women have similar rates of stage
2. Opoku-Anane J, Lauer MR. Prevalence I endometriosis. Fertil Steril 2001;76:923.
of endometriosis in adolescent girls with 15. D’Hooghe M, Bambra CS, Raeymaekers
chronic pelvic pain not responding to con- BM et al. The cycle pregnancy rate is nor-
ventional therapy. Have we underestimated? mal in baboons with stage I endometriosis
J Pediatr Adolesc Gynecol 2012;25(2):e50. but decreased in primates with stage II and
3. Allen C, Hopewell S, Prentice A et al. stage III–IV disease. Fertil Steril 1996;66:809.
Nonsteroidal anti-inflammatory drugs or 16. Schenken RS, Asch RH. Surgical induc-
pain in women with endometriosis. Cochrane tion of endometriosis in the rabbit:
Database Syst Rev 209;2:CD004753. Effects on fertility and concentrations of
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1980;34:581. metriosis: A meta-analysis. Fertil Steril
17. Practice Committee of the ASRM. Endome- 1998;70:1101–8.
triosis & infertility. Fertil Steril 2006;86(4):​ 29. Othman EE, Hornung D, Salem HT et al.
S156–60. Serum cytokines as biomarkers for nonsurgi-
18. Bedaiwy MA, Falcone T, Sharma RK et al. cal prediction of endometriosis. Eur J Obstet
Prediction of endometriosis with serum and Gynecol Reprod Biol 2007;137:240–6.
peritoneal fluid markers: A prospective con- 30. Bhatt S, Kocakoc E, Dogra VS. Endometriosis:
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19. Pizzo A, Salmeri FM, Ardita FV, Sofo V, 2006;22:273–80.
Tripepi M, Marsico S. Behaviour of cyto- 31. Asch E, Levine D. Variations in appear-
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Invest 2002;54:82–7. Switzerland: S. Karger 32. Kupfer MC, Schwimmer SR, Lebovic J.
AG, Basel; 2003. Transvaginal sonographic appearance of
20. Mansour G, Aziz N, Sharma R et al. The impact endometriomata: Spectrum and findings. J
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from women with endometriosis on sperm 33. Patel MD, Feldstein VA, Chen DC et al.
DNA and its relationship to the sperm defor- Endometriomas: Diagnostic performance of
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Simon C. Exploring the mechanism (s) of Hecht EM. Unusual manifestations and com-
endometriosis- related infertility: An analy- plications of endometriosis—spectrum of
sis of embryo development and implanta- imaging findings: Pictorial review. AJR Am J
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1995;10(Suppl 2):91–7. 35. Mais V, Guerriero S, Ajossa S, Angiolucci
22. Lessey BA, Castelbaum AJ, Sawin SW et al. M, Paoletti AM, Melis GB. The efficiency
Aberrant integrin expression in the endome- of transvaginal ultrasonography in the
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Endocrinol Metab 1994;79:643–9. 1993;60:776–80.
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Sussex: Wiley-Blackwell; 2012. accuracy of transvaginal ultrasound for
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function before and after surgery or endome- triosis: Systematic review and meta-analysis.
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aspects and surgical treatment of urinary Pre-operative assessment of bladder endo-
tract endometriosis: Our experience with 31 metriosis. Hum Reprod 1997;12:2519–522.
cases. Eur Urol 2006;49:1093. 38. Glastonbury CM. The shading sign.
26. Carbognin G, Guarise A, Minelli L et al. Pelvic Radiology 2002;224:199.
endometriosis: US and MRI features. Abdom 39. Outwater E, Schiebler ML, Owen RS et al.
Imaging 2004;29:609. Characterization of hemorrhagic adnexal
27. Barbieri RL, Niloff JM, Bast RC Jr et al. lesions with MR imaging: Blinded reader
Elevated serum concentration of CA-125 in study. Radiology 1993;186:489.
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28. Mol BW, Bayram N, Lijmer JG, Wiegerinck in distinguishing between blood and lipid
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Bossuyt PM. The performance of CA-125 1992;58:321.
 References 29

41. Stratton P, Winkel C, Premkumar A et al. imaging, and laparoscopy. Radiographics

Diagnostic accuracy of Laparoscopy, mag- 2011;31(4):E77–100.
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examination for the detection of endometri- et al. Ultrasound mapping system or the sur-
osis. Fertil Steril 2003;79(5):1078–85. gical management of deep infiltrating endo-
42. Chamie LP, Blasbalg R, Pereira RM, metriosis. Fertil Steril 2014a;102(1):143.
Warmbrand G, Serafini PC. Findings of pel-
vic endometriosis at transvaginal US, MR
 6
Adolescents and endometriosis

AASHIMA ARORA

Prevalence 31 Postoperative treatment 33

Clinical presentation 31 Conclusion 34
Diagnosis 32 References 34
Management 32

Endometriosis refers to the presence of endome- requiring an average of 4.2 physician visits, and
trial glands and stroma outside the endometrial this time is the longest in the adolescent age group
cavity. These ectopic implants may occur anywhere [4]. This is mainly because the pelvic pain of endo-
in the body, but are mostly located in the pelvis. metriosis in adolescents may be noncyclic in com-
The clinical spectrum may vary from a completely parison with adults, who typically present with
asymptomatic nature to a most debilitating pelvic more specific complaints such as cyclical pain,
pain. Endometriosis in adolescents will be dis- dyspareunia, and infertility, making the diagno-
cussed in detail in this chapter. sis easier [3]. Also, dysmenorrhea in adolescents is
more often considered “physiological” and hence
PREVALENCE rarely evaluated seriously. Bowel symptoms such
as rectal pain, constipation, cyclic painful defeca-
The exact prevalence of endometriosis among ado-
tion, rectal bleeding, and bladder symptoms (e.g.,
lescents is not known. The estimated prevalence
dysuria, urgency, and hematuria) are also common
depends upon whether a symptomatic or an asymp-
among adolescents.
tomatic population is being studied and upon the
It may be difficult to diagnose endometriosis in
method used for diagnosis. Around 20%–30% of
adolescents with pelvic pain merely on the basis
adolescents with chronic pelvic pain and around half
of history as similar symptoms occur in patients
of those undergoing laparoscopy for this pain will
evaluated laparoscopically for pelvic pain with and
be diagnosed to have this condition [1]. However,
without endometriosis. It must be remembered
laparoscopy for the sole purpose of diagnosing
that cases of histologically proven endometriosis
endometriosis is not warranted in all adolescents
have been documented even prior to menarche in
with dysmenorrhea. However, pelvic pain not con-
girls who have breast development and in many
trolled with nonsteroidal anti-inflammatory drugs
others soon after menarche. Also, around 60% of
(NSAIDs) or combined oral contraceptive pills
adult women with endometriosis report symp-
(OCPs) strongly points toward endometriosis [2,3].
toms beginning at 20 years of age or earlier [5]. It
CLINICAL PRESENTATION is a common misbelief that endometriosis presents
only after many years of menstruation. Hence,
The average time taken to diagnose endometrio- during evaluation of an adolescent with signifi-
sis from onset of clinical symptoms is 9 years, cant pelvic pain, whether it is cyclic or acyclic,
31
32 Adolescents and endometriosis

endometriosis must be kept as a differential to focus on all characteristics of pain: location (dif-
avoid delay in diagnosis and management. fuse/localized), onset (sudden/gradual), constant/
intermittent, magnitude, quality, duration, radia-
DIAGNOSIS tion, relationship to various activities (such as
menstruation and sexual, physiologic, or physical
Though the gold standard of diagnosis of endo- activities). The bowel and bladder symptoms must
metriosis is histological proof of disease by lapa- be asked for, in addition to menstrual, sexual, and
roscopically taken biopsy, detailed history and contraceptive history. It should be assessed how
age-appropriate examination may clinch the much pain interferes with daily activities and
diagnosis in most adolescents and save an inva- whether or not any treatment for the same has
sive procedure (Figure 6.1). The history must been taken in the past by the adolescent.
General physical examination and abdominal
examination are usually normal and a complete
Adolescent with pelvic examination may not be possible in all ado-
pelvic pain lescents. Even if bimanual examination is done, it
is rare to appreciate fixed retroverted uterus, pel-
vic nodularity, or large ovarian endometrioma in
adolescents. A thorough attempt must be made,
Detailed history and
age-appropriate either clinically or with help of imaging in case of
clinical examination suspicion, to rule out Müllerian anomalies, as they
predispose girls to severe and early onset endome-
triosis, which can resolve with timely treatment.
Clinical suspicion Congenital anomalies of the genital tract are found
No clinical
of endometriosis in around 10% of adolescents with endometriosis,
suspicion
present and endometriosis is present in more than two-
thirds of girls with Müllerian anomalies [6,7].
A complete blood count with erythrocyte sedi-
USG to rule out Rule out other
Müllerian anomalies/ causes like UTI, PID,
mentation rate (ESR) and a urine routine and
gross ovarian pregnancy-related microscopy examination are usually performed
endometriomas events to rule out chronic inflammatory process and uri-
nary tract infection (UTI), respectively. Though
If found (MRI if No gross disease CA-125 is commonly elevated in endometriosis,
needed), treat found but suspicion it is not recommended as a screening test due to
surgically of endometriosis its high false-positive rate. It is commonly used
accordingly present by clinicians to follow the progress of disease in
confirmed cases, though follow-up based on clini-
cal symptomatology seems more reliable. Imaging
3-month trial of is less useful in adolescents compared with adults
OCPs and NSAIDs
since endometriomas rarely occurs in this age
group. However, imaging may be useful in exclud-
ing other causes of pelvic pain such as ovarian
torsion/hemorrhage, Müllerian anomalies, appen-
No significant
Significant relief
relief in symptoms
dicitis, and so on. MRI is not recommended as a
first-line imaging test; however, it may be of use to
better define an abnormality suspected on ultra-
sound or when Müllerian anomaly is suspected.
Continue
symptomatic Laparoscopy
treatment MANAGEMENT
All adolescents with pelvic pain should not be
Figure 6.1 Diagnosis of endometriosis. subjected to invasive diagnosis by laparoscopy.
 Postoperative treatment 33

When initial evaluation suggests endometriosis, a with adults [11]. Also, peritoneal defects must be
3-month trial with NSAIDs/OCPs is a reasonable taken to be suggestive of endometriosis. Though
first-line approach [8]. Literature does not suggest controversial, some authors suggest random biop-
benefit of any specific contraceptive pill formula- sies, including one from the posterior cul-de-sac, if
tion. Hormonal therapy leads to decidualization no evidence of endometriosis is found grossly dur-
and subsequent atrophy of ectopic as well as eutopic ing laparoscopy.
endometrial tissue, thereby reducing bleeding and The revised American Society for Reproductive
bleeding-related pain. Empirical use of GnRH Medicine (ASRM) classification must be used for
analogues is not recommended in adolescents staging the disease during laparoscopy. Overall,
due to concern about bone mass accumulation minimal to mild endometriosis (stage I and II
during these years [9,10]. The American College rASRM classification) is most commonly found
of Obstetricians and Gynecologists (ACOG) also in adolescents [12]. It should, however, be remem-
does not recommend use of empirical GnRH ther- bered that the stage of disease or the location of
apy for treatment of presumed endometriosis in lesions does not correlate with symptoms and,
girls <18 years. However, this may be considered hence, does not dictate further treatment.
as an option after informed consent in adolescents As in adults, treatment of stage I and II dis-
>18 years of age. ease may be excisional or ablative. Electrocautery,
Laparoscopy must be considered if an adoles- endocoagulation, laser ablation, or resection of
cent with chronic pelvic pain does not respond implants must be done during the initial laparos-
to NSAIDs/OCPs since endometriosis is present copy. Although large endometriomas are rare in
in 35%–70% of these female patients, and definite this age group, if found, cysts must be removed
diagnosis must be made before any further treat- with as much preservation of ovarian tissue as pos-
ment is administered. The initial surgical pro- sible [13]. (See Figure 6.2.)
cedure performed must be both diagnostic and
therapeutic. The operating surgeon must be famil- POSTOPERATIVE TREATMENT
iar with the appearance of endometriotic implants
in adolescents. Studies have reported that red- Even though there is no long-term data on the
flame lesions are more common and powder-burn course of adolescents who do not take postoperative
lesions are less common in adolescents compared therapy after laparoscopic treatment of endome-
triosis, there is general consensus that after his-
tological confirmation of the disease, adolescents
must be started on medical treatment. The basic
Laparoscopy rationale of medical therapy is decreasing estro-
gen production from the ovaries and prostaglan-
din synthesis from the endometriotic implants,
Endometriosis No e/o thereby causing decidualization and atrophy of
found endometriosis ectopic endometrial tissue. The goal of therapy is
symptomatic relief and suppression of disease pro-
gression which could later impair fertility.
rASRM staging with Random non
Numerous medical therapeutic options are
ablation/excision directed
of implants biopsies available for endometriosis, with different benefits,
risks, and side effect profiles [9]. The treatment
chosen must depend upon the severity of symp-
Postoperative Histologically Histologically
medical hormonal endometriosis endometriosis toms and compliance. For adolescents <18 years,
therapy present absent OCPs are usually the first line while for older ado-
lescents (>16 years or >18 years according to some
Postoperative Search for other authors), GnRH analogues and OCPs are both con-
medical hormonal causes of pelvic sidered first-line options. OCPS may be used cycli-
therapy pain cally or continuously to retard disease progression
and control remaining pain. No particular OCP
Figure 6.2 Management of endometriosis. formulation has been found to be advantageous
34 Adolescents and endometriosis

over others. Progestins, by themselves, also relieve endometriosis or prior surgery, or any different
symptoms in 80%–100% of patients with endo- disease process and, hence, should be managed as
metriosis by not only causing decidualization of per the cause.
endometrial tissue, but by also inhibiting pituitary
gonadotropin secretion and ovarian hormone REFERENCES
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therapy with GnRH and hence have almost com- starting younger, is more severe. J Pediatr
plete resolution of symptoms. Initial treatment is Adolesc Gynecol 2003;16(3 Suppl):S21–6.
usually continued for 6 months, after which either 5. ACOG Committee Opinion: No. 310. Endo­
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Strong clinical suspicion should warrant a trial of sity in adolescent treated with a GnRH ago-
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The treating gynecologist must adopt a multi­ 11. Vercellini P, Fedele L, Arcaini L, Bianchi S,
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 References 35

13. Marsh EE, Laufer MR. Endometriosis in 15. Wayne PM, Kerr CE, Schnyer RN et al.
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Another random document with
no related content on Scribd:
 It has a certain analogy to the Deposuit. From Christmas to
Epiphany the Psalm Memento was sung at Vespers, and
the anthem De fructu ventris inserted in it. When this
began the ruler of the choir advanced and presented a
bouquet to some canon or bourgeois as a sign that the
choir would sup with him. This was called ‘annonce en
forme d’antienne,’ and the suppers defructus. The C. of
Narbonne (1551), c. 47, forbade ‘parochis ... ne ... ad
commessationes quas defructus appellant, ullo modo
parochianos suos admittant, nec permittant quempiam
canere ut dicunt: Memento, Domine, David sans truffe, &c.
Nec alia huiusmodi ridenda, quae in contemptum divini
officii ac in dedecus et probrum totius cleri et fiunt et
cantantur.’
[1149] When, however, Ducange says that the feast was not
called Subdiaconorum, because the sub-deacons held it,
but rather as being ‘ebriorum Clericorum seu Diaconorum:
id enim evincit vox Soudiacres, id est, ad litteram, Saturi
Diaconi, quasi Diacres Saouls,’ we must take it for a ‘sole
joke of Thucydides.’ I believe there is also a joke
somewhere in Liddell and Scott.
[1150] Cf. p. 60; Gautier, Les Tropaires, i. 186; and C. of
Treves in 1227 (J. F. Schannat, Conc. Germ. iii. 532)
‘praecipimus ut omnes Sacerdotes non permittant
trutannos et alios vagos scolares aut goliardos cantare
versus super Sanctus et Agnus Dei.’
[1151] The ‘abbot’ appears to have been sometimes charged
with choir discipline throughout the year, and at Vienne
and Viviers exists side by side with another dominus festi.
Similarly at St. Omer there was a ‘dean’ as well as a
‘bishop.’ The vicars of Lincoln and Wells also chose two
officers.
[1152] I suppose that ‘portetur in rost’ at Vienne means that
the victims were roasted like the fags in Tom Brown.
[1153] Ducange, s. v. Kalendae.
[1154] Gibbon-Bury, v. 201. The Byzantine authorities are
Genesius, iv. p. 49 B (Corp. Hist. Byz. xi. 2. 102);
Paphlagon (Migne, P. G. cv. 527); Theophanes Continuatus,
iv. 38 (Corp. Hist. Byz. xxii. 200); Symeon Magister, p. 437
 D (Corp. Hist. Byz. xxii. 661), on all of whom see Bury,
App. I to tom. cit.
[1155] C. of Constantinople (869-70), c. 16 (Mansi, xvi. 169,
ex versione Latina, abest in Graeca) ‘fuisse quosdam laicos,
qui secundum diversam imperatoriam dignitatem
videbantur capillorum comam circumplexam involvere
atque reponere, et gradum quasi sacerdotalem per
quaedam inducia et vestimenta sacerdotalia sumere, et, ut
putabatur, episcopos constituere, superhumeralibus, id est,
palliis, circumamictos, et omnem aliam Pontificalem indutos
stolam, qui etiam proprium patriarcham adscribentes eum
qui in adinventionibus risum moventibus praelatus et
princeps erat, et insultabant et illudebant quibusque
divinis, modo quidem electiones, promotiones et
consecrationes, modo autem acute calumnias,
damnationes et depositiones episcoporum quasi ab invicem
et per invicem miserabiliter et praevaricatorie agentes et
patientes. Talis autem actio nec apud gentes a saeculo
unquam audita est.’
[1156] Cedrenus, Historiarum Compendium, p. 639 B (ed.
Bekker, in Corp. Hist. Byz. xxiv. 2. 333), follows verbatim
the still unprinted eleventh-century John Scylitzes (Gibbon-
Bury, v. 508). Theophylactus was Patriarch from 933 to
956.
[1157] Theodorus Balsamon, In Can. lxii Conc. in Trullo (P. G.
cxxxvii. 727) Σημείωσαι τὸν παρόντα κανόνα, καὶ ζήτησον
διόρθωσιν ἐπὶ τοῖς γινομένοις παρὰ τῶν κληρικῶν εἰς τήν
ἑορτὴν ἐπὶ τῆς γεννήσεως τοῦ Χριστοῦ, καὶ τὴν ἑορτὴν τῶν
Φώτων [Luminarium, Candlemas] ὑπεναντίως τούτῳ· καὶ
μᾶλλον εἰς τὴν ἁγιωτάτην Μεγάλην ἐκκλησίαν ... ἀλλὰ καί
τινες κληρικοὶ κατά τινας ἑορτὰς πρὸς διάφορα
μετασχηματίζονται προσωπεῖα. καὶ ποτὲ μὲν ξιφήρεις ἐν τῷ
μεσονάω τῆς ἐκκλησίας μετὰ στρατιωτικῶν ἀμφίων
εἰσέρχονται, ποτὲ δὲ καὶ ὡς μοναχοὶ προοδεύουσιν, ἢ καὶ
ὡς ζῶα τετράποδα. ἐρωτήσας οὖν ὅπως ταῦτα
παρεχωρήθησαν γίνεσθαι, οὐδέν τε ἕτερον ἤκουσα ἀλλ’ ἢ
ἐκ μακρᾶς συνθείας ταῦτα τελεῖσθαι. τοιαῦτά εἰσιν, ὡς ἐμοὶ
δοκεῖ, καὶ τὰ παρά τινων δομεστικευόντων ἐν κλήρῳ
γινόμενα, τὸν ἀέρα τοῖς δακτύλοις κατὰ ἡνιόχους
τυπτόντων, καὶ φύκη ταῖς γνάθοις δῆθεν περιτιθεμένων καὶ
ὑπορρινομένων ἔργα τινὰ γυναικεῖα, καὶ ἕτερα ἀπρεπῆ, ἵνα
 πρὸς γελωτα τοὺς βλέποντας μετακινήσωσι. τὸ δὲ γελᾶν
τοὺς ἀγρότας ἐγχεομένους τοῦ οἴνου τοῖς πίθοις, ὡσεί τι
παρεπόμενον ἐξ ἀνάγκης ἐστὶ τοῖς ληνοβατοισιν· εἰ μήτις
εἴπη τὴν σατανικὴν ταύτην ἐργασίαν καταργεῖσθαι διὰ τοῦ
λέγειν τοὺς ἀγρότας συχνότερον ἐφ’ ἑκάστῳ μέτρῳ σχεδὸν
τό, Κύριε ἐλέησον. τὰ μέντοι ποτὲ γινόμενα ἀπρεπῆ παρὰ
τῶν νοταρίων παιδοδιδασκάλων κατὰ τὴν ἑορτὴν τῶν
ἁγίων νοταρίων, μετὰ προσωπείων σκηνικῶν διερχομένων
τὴν ἀγοράν, πρὸ χρόνων τινῶν κατηργήθησαν, καθ’
ὁρισμὸν τοῦ ἁγιωτάτου ἐκείνου πατριάρχου κυρίου Λουκᾶ.
[1158] Belethus, c. 120, compares the ecclesiastical ball-play
at Easter to the libertas Decembrica. He is not speaking
here of the Feast of Fools.
[1159] e.g. Du Tilliot, 2.
[1160] S. R. Maitland, The Dark Ages, 141, tilts at the
Protestant historian Robertson’s History of Charles V, as do
F. Clément, 159, and A. Walter, Das Eselsfest in Caecilien-
Kalender (1885), 75, at Dulaure, Hist. des Environs de
Paris, iii. 509, and other ‘Voltairiens.’
[1161] Chérest, 81.
[1162] J. Bujeaud, Chants et Chansons populaires des
Provinces de l’Ouest, i. 63. The ronde is known in Poitou,
Aunis, Angoumois. P. Tarbé, Romancero de Champagne (2e
partie), 257, gives a variant. Bujeaud, i. 61, gives another
ronde, the Testament de l’Âne, in which the ass has fallen
into a ditch, and amongst other legacies leaves his tail to
the curé for an aspersoir. This is known in Poitou,
Angoumois, Franche-Comté. He also says that he has
heard children of Poitou and Angoumois go through a mock
catechism, giving an ecclesiastical significance to each part
of the ass. The tail is the goupillon, and so forth. Fournier-
Verneuil, Paris, Tableau moral et philosophique (1826),
522, with the Beauvais Officium in his mind, says ‘Voulez-
vous qu’au lieu de dire, Ite, missa est, le prêtre se mette à
braire trois fois de toute sa force, et que le peuple réponde
en chœur, comme je l’ai vu faire en 1788, dans l’église de
Bellaigues, en Périgord?’
[1163] Cf. ch. xx. Gasté, 20, considers the Rouen Festum
Asinorum ‘l’origine de toutes les Fêtes de l’Âne qui se
célébraient dans d’autres diocèses’: but the Rouen MS. in
 which it occurs is only of the fourteenth century, and the
Balaam episode does not occur at all in the more primitive
forms of the Prophetae, while the Sens Feast of Fools is
called the festa asinaria in the Officium of the early
thirteenth century.
[1164] Tille, D. W. 31. In Madrid an ass was led in procession
on Jan. 17, with anthems on the Balaam legend (Clément,
181).
[1165] Clément, 182; Didron, Annales archéologiques, xv. 384.
[1166] Dulaure, Hist. des Environs de Paris, iii. 509, quotes a
legend to the effect that the very ass ridden by Christ came
ultimately to Verona, died there, was buried in a wooden
effigy at Sta-Maria in Organo, and honoured by a yearly
procession. He guesses at this as the origin of the Beauvais
and other fêtes. Didron, Annales arch. xv. 377, xvi. 33,
found that nothing was known of this legend at Verona,
though such a statue group as is described above
apparently existed in the church named. Dulaure gives as
his authorities F. M. Misson, Nouveau Voyage d’ Italie
(1731), i. 164; Dict. de l’ Italie, i. 56. Misson’s visit to
Verona was in 1687, although the passage was not printed
in the first edition (1691) of his book. It is in the English
translation of 1714 (i. 198). His authority was a French
merchant (M. Montel) living in Verona, who had often seen
the procession. In Cenni intorno all’ origine e descrizione
della Festa che annualmente si celebra in Verona l’ ultimo
Venerdì del Carnovale, comunamente denominata
Gnoccolare (1818), 75, is a mention of the ‘asinello del
vecchio padre Sileno’ which served as a mount for the
‘Capo de’ Maccheroni.’ This is probably Misson’s procession,
but there is no mention of the legend in any of the
eighteenth-century accounts quoted in the pamphlet.
Rienzi was likened to an ‘Abbate Asinino’ (Gibbon, vii. 269).
[1167] Ducange, s. v. Festum Asinorum; cf. Leber, ix. 270;
Molanus, de Hist. SS. Imaginum et Picturarum (1594), iv.
18.
[1168] T. Naogeorgus (Kirchmeyer), The Popish Kingdom, iv.
443 (1553, transl. Barnabe Googe, 1570, in New Shakspere
Society edition of Stubbes, Anatomy of Abuses, i. 332); cf.
Beehive of the Roman Church, 199. The earliest notice is in
 Gerardus, Leben St. Ulrichs von Augsburg (ob. 973), c. 4.
E. Bishop, in Dublin Review, cxxiii. 405, traces the custom
in a Prague fourteenth-century Missal and sixteenth-
century Breviary; also in the modern Greek Church at
Moscow where until recently the Czar held the bridle. But
there is no ass, as he says, in the Palm Sunday ceremony
described in the Peregrinatio Silviae (Duchesne, 486).
[1169] A peeress of the realm lately stated that this custom
had been introduced in recent years into the Anglican
church. Denials were to hand, and an amazing conflict of
evidence resulted. Is there any proof that the Palmesel was
ever an English ceremony at all? The Hereford riding of
1706 (cf. Representations) was not in the church. Brand, i.
73, quotes A Dialogue: the Pilgremage of Pure Devotyon
(1551?), ‘Upon Palme Sondaye they play the foles sadely,
drawynge after them an Asse in a rope, when they be not
moche distante from the Woden Asse that they drawe.’
Clearly this, like Googe’s translation of Naogeorgus, is a
description of contemporary continental Papistry. W. Fulke,
The Text of the New Testament (ed. 1633), 76 (ad Marc.
xi. 8) quotes a note of the Rheims translation to the effect
that in memory of the entry into Jerusalem is a procession
on Palm Sunday ‘with the blessed Sacrament reverently
carried as it were Christ upon the Asse,’ and comments,
‘But it is pretty sport, that you make the Priest that carrieth
the idoll, to supply the roome of the Asse on which Christ
did ride.... Thus you turn the holy mysterie of Christ’s
riding to Jerusalem to a May-game and Pageant-play.’
Fulke, who lived 1538-89, is evidently unaware that there
was an ass, as well as the priest, in the procession, from
which I infer that the custom was not known in England.
Not that this consideration would weigh with the
mediaevally-minded curate, who is as a rule only too ready
to make up by the ceremonial inaccuracy of his mummeries
for the offence which they cause to his congregation.
[1170] Marquardt-Mommsen, vi. 191; Jevons, Plutarch’s
Romane Questions, 134; Fowler, 304, 322; Ovid, Fasti, ii.
531:

‘stultaque pars populi, quae sit sua curia, nescit;

sed facit extrema sacra relata die.’
[1171] Fowler, 306.
[1172] Schaff, iii. 131.
[1173] Belethus, c. 70 ‘Debent ergo vesperae Natalis primo
integre celebrari, ac postea conveniunt diaconi quasi in
tripudio, cantantque Magnificat cum antiphona de S.
Stephano, sed sacerdos recitat collectam. Nocturnos et
universum officium crastinum celebrant diaconi, quod
Stephanus fuerit diaconus, et ad lectiones concedunt
benedictiones, ita tamen, ut eius diei missam celebret
hebdomarius, hoc est ille cuius tum vices fuerint eam
exsequi. Sic eodem modo omne officium perficient
sacerdotes ipso die B. Ioannis, quod hic sacerdos fuerit, et
pueri in ipso festo Innocentium, quia innocentes pro
Christo occisi sunt, ... in festo itaque Innocentium penitus
subticentur cantica laetitiae, quoniam ii ad inferos
descenderunt.’ Cf. also c. 72, quoted on p. 275. Durandus,
Rat. Div. Off. (1284), vii. 42, De festis SS. Stephani, Ioannis
Evang. et Innocentium, gives a similar account. At Vespers
on Christmas Day, he says, the deacons ‘in tripudio
convenientes cantant antiphonam de sancto Stephano, et
sacerdos collectam. Nocturnos autem et officium in
crastinum celebrant et benedictiones super lectiones dant:
quod tamen facere non debent.’ So too for the priests and
boys on the following days.
[1174] Honorius Augustodunensis, Gemma Animae, iii. 12 (P.
L. clxxii. 646).
[1175] Ioannes Abrincensis (bishop of Rouen †1070), de Eccl.
Offic. (P. L. cxlvii. 41), with fairly full account of the ‘officia.’
[1176] Ekkehardus IV, de Casibus S. Galli, c. 14 (ed. G. Meyer
von Knonau, in Mittheilungen zur vaterländischen Gesch. of
the Hist. Verein in St. Gallen, N. F., v.; M. G. H. Scriptores,
ii. 84) ‘longum est dicere, quibus iocunditatibus dies
exegerit et noctes, maxime in processione infantum;
quibus poma in medio ecclesiae pavimento antesterni
iubens, cum nec unum parvissimorum moveri nec ad ea
adtendere vidisset, miratus est disciplinam.’ Ekkehart was
master of the song-school, and von Knonau mentions some
cantiones written by him and others for the feast, e. g. one
beginning ‘Salve lacteolo decoratum sanguine festum.’ He
has another story (c. 26) of how Solomon who was abbot
of the monastery, as well as bishop of Constance, looking
 into the song-school on the ‘dies scolarium,’ when the boys
had a ‘ius ... ut hospites intrantes capiant, captos, usque
dum se redimant, teneant,’ was duly made prisoner, and
set on the master’s seat. ‘Si in magistri solio sedeo,’ cried
the witty bishop, ‘iure eius uti habeo. Omnes exuimini.’
After his jest, he paid his footing like a man. The ‘Schulabt’
of St. Gall is said to have survived until the council of Trent.
[1177] Frere, Winch. Troper, 6, 8, 10. The deacons sang ‘Eia,
conlevitae in protomartyris Stephani natalicio ex persona
ipsius cum psalmista ouantes concinnamus’; the priests,
‘Hodie candidati sacerdotum chori centeni et milleni
coniubilent Christo dilectoque suo Iohanni’; the boys,
‘Psallite nunc Christo pueri, dicente propheta.’
[1178] Rock, iii. 2. 214; Clément, 118; Grenier, 353; Martene,
iii. 38. These writers add several references for the triduum
or one or other of its feasts to those here given: e. g.
Martene quotes on St. Stephen’s feast Ordinarium of
Langres, ‘finitis vesperis fiunt tripudia’; Ordinarium of
Limoges, ‘vadunt omnes ad capitulum, ubi Episcopus, sive
praesens, sive absens fuerit, dat eis potum ex tribus vinis’;
Ordinarium of Strasburg (†1364), ‘propinatur in refectorio,
sicut in vigilia nativitatis.’
[1179] Martene, iii. 38 ‘tria festa, quae sequuntur, fiunt cum
magna solemnitate et tripudio. Primum faciunt diaconi,
secundum presbiteri, tertium pueri.’
[1180] Grenier, 353 ‘si festa [S. Stephani] fiant, ut consuetum
est, a diaconis in cappis sericis ... fit statio in medio choro,
et ab ipsis regitur chorus ... et fiant festa sicut docent libri’;
and so for the two other feasts.
[1181] Martene, iii. 38 ‘cum in primis vesperis [in festo S.
Stephani] ad illum cantici Magnificat versiculum Deposuit
potentes perventum erat, cantor baculum locumque suum
diacono, qui pro eo chorum regeret, cedebat’; and so on
the other feasts.
[1182] Cf. p. 315.
[1183] Durr, 77. Here the sub-deacons shared in the deacons’
feast.
[1184] The Consuetudinarium of †1210 (Frere, Use of Sarum,
i. 124, 223) mentions the procession of deacons after
 Vespers on Christmas day, but says nothing of the share of
the priests and boys in those of the following days. The
Sarum Breviary gives all three (Fasc. i. cols. cxcv, ccxiii,
ccxxix), and has a note (col. clxxvi) ‘nunquam enim dicitur
Prosa ad Matutinas per totum annum, sed ad Vesperas, et
ad Processionem, excepto die sancti Stephani, cuius
servitium committitur voluntati Diaconorum; et excepto die
sancti Iohannis, cuius servitium committitur voluntati
Sacerdotum; et excepto die sanctorum Innocentium, cuius
servitium committitur voluntati Puerorum.’
[1185] York Missal, i. 20, 22, 23 (from fifteenth-century MS. D
used in the Minster) ‘In die S. Steph. ... finita processione,
si Dominica fuerit, ut in Processionali continetur, Diaconis
et Subdiaconis in choro ordinatim astantibus, unus
Diaconus, cui Praecentor imposuerit, incipiat Officium.... In
die S. Ioann. ... omnibus Personis et Presbyteris civitatis ex
antiqua consuetudine ad Ecclesiam Cathedralem
convenientibus, et omnibus ordinate ex utraque parte Chori
in Capis sericis astantibus, Praecentor incipiat Officium....
In die SS. Innoc. ... omnibus pueris in Capis, Praecentor
illorum incipiat.’ There are responds for the ‘turba
diaconorum,’ ‘presbyterorum’ or ‘puerorum.’
[1186] Lincoln Statutes, i. 290; ii. ccxxx, 552.
[1187] Gasquet, Old English Bible, 250.
[1188] Martene, iii. 40.
[1189] Ibid. iii. 39.
[1190] In his second decree of 1199 as to the feast of the
Circumcision at Paris (cf. p. 276), Bishop Eudes de Sully
says (P. L. ccxii. 73) ‘quoniam festivitas beati protomartyris
Stephani eiusdem fere subiacebat dissolutionis et
temeritatis incommodo, nec ita solemniter, sicut decebat et
martyris merita requirebant, in Ecclesia Parisiensi
consueverat celebrari, nos, qui eidem martyri sumus
specialiter debitores, quoniam in Ecclesia Bituricensi
patronum habuerimus, in cuius gremio ab ineunte aetate
fuimus nutriti; de voluntate et assensu dilectorum
nostrorum Hugonis decani et capituli Parisiensis,
festivitatem ipsam ad statum reducere regularem, eumque
magnis Ecclesiae solemnitatibus adnumerare decrevimus;
statuentes ut in ipso festo tantum celebritatis agatur,
 quantum in ceteris festis annualibus fieri consuevit.’ Eudes
de Sully made a donative to the canons and clerks present
at Matins on the feast, which his successor Petrus de
Nemore confirmed in 1208 (P. L. ccxii. 91). Dean Hugo
Clemens instigated a similar reform of St. John’s day (see
p. 276).
[1191] Martene, iii. 40; Grenier, 353, 412. The Ritual of Bishop
Nivelon, at the end of the twelfth century, orders St.
Stephen’s to be kept as a triple feast, ‘exclusa antiqua
consuetudine diaconorum et ludorum.’
[1192] Schannat, iv. 258 (1316) ‘illud, quod ... causa
devotionis ordinatum fuerat ... ut Sacerdotes singulis annis
in festivitate Beati Iohannis Evangelistae unum ex se
eligant, qui more episcopi illa die Missam gloriose celebret
et festive, nunc in ludibrium vertitur, et in ecclesia ludi fiunt
theatrales, et non solum in ecclesia introducuntur monstra
larvarum, verum etiam Presbyteri, Diaconi et Subdiaconi
insaniae suae ludibria exercere praesumunt, facientes
prandia sumptuosa, et cum tympanis et cymbalis ducentes
choreas per domos et plateas civitatis.’
[1193] At Rouen in 1445 the feast of St. John, held by the
capellani, was alone in question. The chapter ordered
(Gasté, 46) ‘ut faciant die festi sancti euangelistae Iohannis
servicium divinum bene et honeste, sine derisionibus et
fatuitatibus; et inhibitum fuit eisdem ne habeant vestes
difformes, insuper quod fiat mensa et ponantur boni
cantores, qui bene sciant cantare, omnibus derisionibus
cessantibus.’ But in 1446 the feast of St. Stephen needed
reforming, as well as that of St. John (A. Chéruel, Hist. de
Rouen sous la Domination anglaise, 206); and in 1451 all
three (Gasté, 47) ‘praefati Domini capitulantes ordinaverunt
quod in festis solemnitatis Nativitatis Domini nostri Ihesu
Christi proxime futuris, omnes indecencie et inhonestates
consuete fieri in dedecus ecclesie, tam per presbyteros
dyaconos quam pueros chori et basse forme, cessent
omnino, nec sit aliquis puer in habitu episcopi, sed fiat
servicium devote et honorifice prout in aliis festis similis
gradus.’
[1194] C. of Toledo (1473), c. 19 (Labbé, xiii. 1460) ‘Quia vero
quaedam tam in Metropolitains quam in Cathedralibus et
aliis Ecclesiis nostrae provinciae consuetudo inolevit ut
 videlicet in festis Nativitatis Domini nostri Iesu Christi et
sanctorum Stephani, Ioannis et Innocentium aliisque certis
diebus festivis, etiam in solemnitatibus Missarum novarum
dum divina aguntur, ludi theatrales, larvae, monstra,
spectacula, necnon quamplurima inhonesta et diversa
figmenta in Ecclesiis introducuntur ... huiusmodi larvas,
ludos, monstra, spectacula, figmenta et tumultuationes
fieri ... prohibemus.... Per hoc tam honestas
repraesentationes et devotas, quae populum ad
devotionem movent, tam in praefatis diebus quam in aliis
non intendimus prohibere’; C. of Lyons (1566 and 1577), c.
15 (Du Tilliot, 63) ‘Es jours de Fête des Innocens et autres,
l’on ne doit souffrir ès Églises jouer jeux, tragédies, farces,
&c.’; cf. the Cologne statutes (1662) quoted on p. 352.
[1195] H. E. Reynolds, Wells Cathedral, 75 ‘Quod non sint ludi
contra honestatem Ecclesiae Wellensis. Item a festo
Nativitatis Domini usque ad octavas Innocentium quod
Clerici Subdiaconi Diaconi Presbiteri etiam huius ecclesiae
vicarii ludos faciant theatrales in ecclesia Wellensi et
monstra larvarum introducentes, in ea insaniae suae
ludibria exercere praesumunt contra honestatem clericalem
et sacrorum prohibitionem canonum divinum officium
multipliciter impediendo; quod de cetero in ecclesia
Wellensi et sub pena canonica fieri prohibentes volumus
quod divinum officium in festo dictorum sanctorum
Innocentium sicuti in festis sanctorum consimilibus quiete
ac pacifice absque quocunque tumultu et ludibrio cum
devotione debita celebretur.’
[1196] Reynolds, op. cit. 87 ‘Prohibitio ludorum theatralium et
spectaculorum et ostentationum larvarum in Ecclesia. Item,
cum infra septimanam Pentecostes et etiam in aliis
festivitatibus fiant a laicis ludi theatrales in ecclesia
praedicta et non solum ad ludibriorum spectacula
introducantur in ea monstra larvarum, verum etiam in
sanctorum Innocentium et aliorum sanctorum festivitatibus
quae Natale Christi secuntur, Presbyteri Diaconi et
Subdiaconi dictae Wellensis ecclesiae vicissim insaniae suae
ludibria exercentes per gesticulationem debacchationes
obscenas divinum officium impediant in conspectu populi,
decus faciant clericale vilescere quem potius illo tempore
deberent praedicatione mulcere....’ The statute goes on to
threaten offenders with excommunication.
[1197] F. C. Hingeston Randolph, Bishop Grandison’s Register,
Part iii, p. 1213; Inhibicio Episcopi de ludis inhonestis. The
bishop writes to all four bodies in identical terms. He
wishes them ‘Salutem, et morum clericalium honestatem,’
and adds ‘Ad nostram, non sine gravi cordis displicencia et
stupore, pervenit noticiam quod, annis praeteritis et
quibusdam praecedentibus, in Sanctissimis Dominice
Nativitatis, ac Sanctorum Stephani, Iohannis, Apostoli et
Evangelistae, ac Innocencium Solempniis, quando omnes
Christi Fideles Divinis laudibus et Officiis Ecclesiasticis
devocius ac quiescius insistere tenentur, aliqui praedicte
Ecclesie nostre Ministri, cum pueris, nedum Matutinis et
Vesperis ac Horis aliis, set, quod magis detestandum est,
inter Missarum Sollempnia, ludos ineptos et noxios,
honestatique clericali indecentes, quia verius Cultus Divini
ludibria detestanda, infra Ecclesiam ipsam inmiscendo
committere, Divino timore postposito, pernicioso
quarundam Ecclesiarum exemplo, temere praesumpserunt;
Vestimenta et alia Ornamenta Ecclesie, in non modicum
eiusdem Ecclesie nostre et nostrum dampnum et dedecus,
vilium scilicet scenulentorumque (or scev.) sparsione
multipliciter deturpando. Ex quorum gestis, seu risibus et
cachinnis derisoriis, nedum populus, more Catholico illis
potissime temporibus ad Ecclesiam conveniens, a debita
devocione abstrahitur, set et in risum incompositum ac
oblectamenta illicita dissolvitur; Cultusque Divinus irridetur
et Officium perperam impeditur....’
[1198] On the Pastores cf. ch. xix. Gasté, 33, gives several
Rouen chapter acts from 1449 to 1457 requiring them to
officiate ‘cessantibus stultitiis et insolenciis.’ These orders
and those quoted on p. 341 above were prompted by the
Letter of the Paris theologians against the Feast of Fools
and similar revels. In 1445 (or 1449) a committee was
chosen ‘ad videndum et visitandum ordinationem ecclesiae
pro festis Nativitatis Domini et deliberationes Facultatis
Theologiae super hoc habitas et quod tollantur derisiones
in ipsis fieri solitas.’
[1199] At Sarum a Constitutio of Roger de Mortival in 1324
(Dayman and Jones, Sarum Statutes, 52) forbade drinking
when the antiphon ‘O Sapientia’ was sung after Compline
on Dec. 16. John of Avranches ( † 1070) allowed for the
feast of his ‘O’ at Rouen ‘unum galonem vini de cellario
 archiepiscopi,’ and the ‘vin de l’O’ was still given in 1377
(Gasté, 47). On these ‘Oes,’ sung by the great functionaries
of cathedrals and monasteries, see E. Green, On the words
‘O Sapientia’ in the Kalendar (Archaeologia, xlix. 219);
Cynewulf, Christ (ed. A. S. Cook), xxxv. Payments
‘cantoribus ad ludum suum’ or ‘ad’ or ‘ante natale’ appear
in Durham accounts; cf. Finchale Priory ccccxxviii (Surtees
Soc.,) and Durham Accounts, passim (Surtees Soc.). I do
not feel sure what feast is here referred to.
[1200] Chérest, 49 sqq.
[1201] Ioannes Abrincensis, de Eccl. Offic. (P. L. cxlvii. 42)
‘Licet, ut in morte Domini, Te Deum et Gloria in excelsis et
Alleluia in aliquot ecclesiis, ex more antiquo, omittantur;
quia ut Christus occideretur tot parvuli occidi iubentur; et
illis occisis fit mors Christi secundum aestimationem
Herodis; tamen quia placuit modernis, placet et nobis ut
cantentur’; cf. the passage from Belethus quoted on p.
336; also Honorius Augustodunensis, Gemma Animae, iii.
14 (P. L. clxxii. 646), and Martene, iii. 40.
[1202] Ordinarium of Rouen (fourteenth century) in Ducange,
s.v. Kalendae; P. L. cxlvii. 155; Gasté, 35. On the Rouen
feast cf. also Gasté, 48.
[1203] These chants are taken from Revelation, xiv. 3 ‘nemo
poterat dicere canticum, nisi illa centum quadraginta
quatuor millia, qui empti sunt de terra. Hi sunt, qui cum
mulieribus non sunt coinquinati, virgines enim sunt. Hi
sequuntur Agnum quocumque ierit.’ This passage is still
read in the ‘Epistle’ at Mass on Holy Innocents’ day. Cf. the
use of the same chants at Salisbury (Appendix M).
[1204] ‘Et tamdiu cantetur Deposuit potentes quod baculus
accipiatur ab eo qui accipere voluerit.’
[1205] Ordinarium of Bayeux (undated) in Gasté, 37. On the
Bayeux feast and its parvus episcopus or petit évêque cf. F.
Pluquet, Essai sur Bayeux, 274.
[1206] ‘Dum perventum fuerit ad illum: Deposuit potentes,
vadunt omnes ad medium ecclesiae et ibi qui in
processione stant ordinate eumdem versum, episcopo
inchoante, plures replicantes. Qui dum sic cantatur, offert
ipse episcopus sociis suis de choro baculum pastoralem.
Post multas itaque resumptiones dicti versus, revertuntur in
 chorum, Te Deum laudamus, si habent novum episcopum,
decantantes, et ita canendo deducunt eum ad altare, et
mitra sibi imposita et baculo cum capa serica, revertuntur
in chorum, illo qui fuerat episcopus explente officium
capellani, creato nihilominus novo cantore. Tunc chorus, si
non fuerit ibi novus episcopus, vel novus episcopus qui
baculum duxerit capiendum, cum suis sociis resumit a
capite psalmum Magnificat, et sic cantant vesperas usque
ad finem.’
[1207] Novus Ordinarius of Coutances (undated) in Gasté, 39.
[1208] ‘Post Matutinas conveniant omnes pueri ad suam
tabulam faciendam, quibus licitum est maiores personas
Ecclesiae minoribus officiis deputare. Diaconis et
subdiaconis ordinatis, thuribula imponantur et candelabra
maiora videlicet et minora. Episcopo vero, cantori et aliis
canonicis aquam, manutergium, missale, ignem et
campanam possunt imponere pro suae libito voluntatis.
Nihil tamen inhonestum aut impertinens apponatur;
antiquiores primi ponantur in tabula et ultimi iuniores.’
[1209] ‘Quo facto dicat [Episcopus] Deposuit. Statimque
electus Episcopus, tradito sibi baculo pastorali a pueris ad
altare praesentetur, et osculato altari in domum suam a
dictis pueris deferatur. Et interim, finito tumultu, eat
processio ad altare S. Thomae martyris.’
[1210] Rituale (fourteenth century) of Tours in Martene, iii. 39.
There was a cantor puerorum as well as the episcopus. At
second Vespers ‘quando Magnificat canitur, veniunt clericuli
in choro cum episcopo habentes candelas accensas de
proprio et quando Deposuit canitur, accipit cantor
puerorum baculum, et tunc in stallo ascendunt pueri, et alii
descendunt.’
[1211] Ducange, s. v. Kalendae.
[1212] ‘Omnes pueri et subdiaconi feriati, qui in numero
dictorum Innocentium computantur.’
[1213] ‘Ipsa autem die de mane equitare habet idem
episcopus Innocentium ad monasteria SS. Mansueti et Apri
per civitatem transeundo in comitiva suorum aequalium,
quibus etiam maiores et digniores personae dignitatum
comitantur per se vel suos servitores et equos, et
descendentes ad fores ecclesiarum praedictarum intonat
 unam antiphonam et dicit episcopus orationem, sibique
debentur a quolibet monasteriorum eorundem xviij den.
Tullenses, qui si illico non solvantur, possunt accipere libros
vel vadia.’
[1214] ‘Cantatis eiusdem diei vesperis, episcopus ipse cum
mimis et tubis procedit per civitatem cum sua comitiva, via
qua fiunt generales processiones.’
[1215] ‘In crastino Innocentium, quo omnes vadunt per
civitatem post prandium, faciebus opertis, in diversis
habitibus, et si quae farsae practicari valeant, tempore
tamen sicco, fiunt in aliquibus locis civitatis, omnia cum
honestate.’ Another passage, referring more generally to
the feast, has ‘Fiunt ibi moralitates vel simulacra
miraculorum cum farsis et similibus ioculis, semper tamen
honestis.’
[1216] ‘In octavis Innocentium rursus vadit episcopus cum
omni comitiva sua in habitibus suis ad ecclesiam B.
Genovefae, ubi cantata antiphona de ipsa virgine cum
collecta, itur ad domum parochialem eius ecclesiae vel
alibi, ubi magister et fratres domus Dei, quibus ipsa
ecclesia est unita, paraverint focapam unam, poma, nuces,
&c. ad merendam oportuna; et ibi instituuntur officiarii ad
marencias super defectibus aut excessibus in officio divino
per totum annum commissis.’
[1217] ‘Fit ... assignatio post coenam diei Innocentium; ita
quod is qui illa die festum peregit, gratias refert episcopo
et toti comitivae, ac excusari petit, si in aliquo defecit; et
finaliter pileum romarini vel alterius confectionis floreum
exhibet ipsi episcopo, ut tradat canonico in receptione
sequenti constituto ad futurum annum ipsum festum
agendum.’ Cf. the bouquets at the ‘defructus’ (p. 324).
[1218] ‘Si autem facere contemneret adveniente festo,
suspenderetur cappa nigra in raustro medio chori, et
tamdiu ibi maneret in illius vituperium, quamdiu placeret
subdiaconis feriatis et pueris chori; et in ea re non
tenerentur nobis capitulo obedire.’
[1219] Amiens: Rigollot, 13 and passim; cf. p. 339.
[1220] St. Quentin: Rigollot, 32; Grenier, 360.
[1221] Senlis: Rigollot, 26; Grenier, 360.
[1222] Soissons: Matton, Archives de Soissons, 75.
[1223] Roye: Rigollot, 33; Grenier, 359.
[1224] Peronne: Rigollot, 34; Grenier, 359, 413.
[1225] Rheims: Rigollot, 50; Petit de Julleville, Rép. Com. 348;
Marlot, Hist. de Rheims, ii. 266. In 1479 the chapter
undertook the expense, ‘modo fiat sine larvis et strepitu
tubicinis, ac sine equitatione per villam.’ Martene, iii. 40,
says that there is no trace of any of the triduum
ceremonies in the early thirteenth-century Rheims
Ordinarium.
[1226] Brussels: Laborde, Ducs de Bourgogne, ii. 2. 286
‘[1378] Item xxi decembris episcopo scholarium sanctae
Gudilae profecto Sancti Nycolay quod scholares annuatim
faciunt 1¹⁄₂ mut[ones].’
[1227] Lille: E. Hautcœur, Hist. de Saint-Pierre de Lille, ii. 217,
223. On June 29, 1501, Guillemot de Lespine ‘trépassa
évêque des Innocens.’ His epitaph is in the cloister gallery
(Hautcœur, Doc. liturg. de S. P. de Lille, 342).
[1228] Liège: Rigollot, 42; Dürr, 82. A statute of 1330 laid the
expense on the last admitted canon ‘nisi canonicus
scholaris sub virga existens ipsum exemerit.’
[1229] Laon: Rigollot, 21; Grenier, 356, 413; C. Hidé, Bull. de
la Soc. acad. de Laon, xiii. 122; E. Fleury, Cinquante Ans de
Laon, 52. A chapter act of 1546 states that the custom of
playing a comedy at the election of the Boy Bishop on St.
Eloi’s day (Dec. 1) has ceased. The Mass is not to be
disturbed, but ‘si les escoliers veulent faire un petit
discours, il seroit entendu avec plaisir.’
[1230] Troyes: T. Boutiot, Hist. de Troyes, iii. 20.
[1231] Mans: Gasté, 43; Julleville, Les Com. 38.
[1232] Bourges: Martene, iii. 40.
[1233] Châlons-sur-Saône: Du Tilliot, 20; C. Perry, Hist. de
Châlons (1659), 435.
[1234] Grenoble: Pilot de Thorey, Usages, Fêtes et Coutumes
en Dauphiné, i. 181.
[1235] C. of Cognac (1260), c. 2 (Mansi, xxiii. 1033) ‘cum in
balleatione quae in festo SS. Innocentium in quibusdam
 Ecclesiis fieri inolevit, multae rixae, contentiones et
turbationes, tam in divinis officiis quam aliis consueverint
provenire, praedictas balleationes ulterius sub intimatione
anathematis fieri prohibemus; nec non et Episcopos in
praedicto festo creari; cum hoc in ecclesia Dei ridiculum
existat, et hoc dignitatis episcopalis ludibrio fiat.’ C. of
Salzburg (1274), c. 17 (Labbé, xi. 1004) ‘ludi noxii quos
vulgaris elocutio Eptus puor. appellat’; CC. of Chartres
(1526 and 1575; Bochellus, Decr. Eccl. Gall. iv. 7. 46; Du
Tilliot, 66) ‘stultum aut ridiculum in ecclesia’ on days of SS.
Nicholas and Catharine, and the Innocents; C. of Toledo
(1565), ii. 21 (Labbé, xv. 764) ‘ficta illa et puerilis
episcopatus electio’; C. of Rouen (1581; Hardouin, Concilia,
x. 1217) ‘in festivitate SS. Innocentium theatralia.’
[1236] There are traces of it in the eighteenth century at
Lyons (Martene, iii. 40) and Rheims (Barthélemy, v. 334);
at Sens, in the nineteenth, the choir-boys still play at being
bishops on Innocents’ day, and name the ‘archbishop’ âne
(Chérest, 81).
[1237] Grenier, 358, quoting Le Vasseur, Epistolae, Cent. ii.
Epist. 68; cf. on the Noyon feast, Leach, 135; Du Tilliot, 17;
Rigollot, 27; L. Mazière, Noyon religieux, in Comptes-
Rendus et Mémoires, xi. 91, of The Comité arch. et hist. de
Noyon. Le Vasseur, an ex-Rector of the University of Paris,
writes to François Geuffrin ‘ecce ludunt etiam ante ipsas
aras; internecionem detestamur, execramur carnificem.
Ludunt et placet iste ludus ecclesiae.... Tam grandis est
natu ritus iste, quem viguisse deprehendo iam ante
quadringentos annos in hac aede, magno totius orbis
ordinum et aetatum plausu fructuque.... O miserum
saeculum! ... solo gestu externoque habitu spectabiles,
sola barba et pallio philosophi, caetera pecudes!’
[1238] Chronicon Montis Sereni in Pertz, Scriptores, xxiii. 144.
[1239] Monum. Boic. xiii. 214, quoted by Specht, 228 ‘in festo
nativitatis Dominicae annuatim sibi ludendo constituentes
episcopum.’
[1240] Vitus Arnpekius, Chron. Baioariorum, v. 53, cited by
Martene, iii. 40.
[1241] Specht, 228.
[1242] Ibid. 225; Creizenach, i. 391; both quoting E. Meyer,
Gesch. des hamburgischen Schul-und Unterrichtswesens im
Mittelalter, 197 ‘praeterea scholares nunquam, sive in
electione sive extra, aliquos rhythmos faciant, tam in latino,
quam in teutonico, qui famam alicuius valeant maculare.’ In
the thirteenth century a child-abbot was chosen in
Hamburg on St. Andrew’s day (Nov. 30). On St. Nicholas’
day (Dec. 6) he gave way to a child-bishop, who remained
in office until Dec. 28 (Tille, D. W. 31, citing Beneke,
Hamburgische Geschichte und Sagen, 90).
[1243] Specht, 229.
[1244] Ibid. 228.
[1245] Cf. p. 319.
[1246] Tille, D. W. 31.
[1247] Ibid. 299.
[1248] Dürr, 67, quoting a Ritual of the cathedral (‘tempore
Alberti’).
[1249] It began:

‘Iam tuum festum Nicolae dives

more solemni recolit iuventus,
nec tibi dignus, sacerdotum Caesar,
promere laudes.’

[1250] Tille, D. W. 31, citing Nork, Festkalender, 783. Dürr’s

tract was published at Mainz in 1755.
[1251] Wetzer und Welte, s. v. Feste ‘consuetudo seu potius
detestabilis corruptela, qua pueri a die S. Nicolai usque ad
festum SS. Innocentium personatum Episcopum
colunt ... ea puerilibus levitatibus et ineptiis plena coeperit
esse multumque gravitatis et decoris divinis detrahat
officiis ... ne clerus se pueris die SS. Inn. submittat ac
eorum locum occupet, aut illis functiones aliquas in divinis
officiis permittat, neque praesentes aliquis Episcopus
benedictiones faciat, aliique pueri in cantandis horariis
precibus lectionibus et collectis Sacerdotum, Diaconorum
aut Subdiaconorum officia quaedam usurpent; multo minus
convenit ut Canonici aut Vicarii ex collegarum suorum
 numero aliquem designent Episcopum qui reliquos omnes
magnis impendiis liberali convivio excipiat.’
[1252] W. H. R. Jones, Vetus Registr. Sarisb. (R. S.), ii. 128;
Wordsworth, Proc. 170 ‘Item, annulus unus aureus ad
Festum Puerorum.’
[1253] Constitutiones, § 45 (Jones and Dayman, Sarum
Statutes, 75; cf. Jones, Fasti, 295) ‘Electus puer chorista in
episcopum modo solito puerili officium in ecclesia, prout
fieri consuevit, licenter exequatur, convivium aliquod de
caetero, vel visitationem exterius seu interius nullatenus
faciendo, sed in domo communi cum sociis conversetur, nisi
cum ut choristam ad domum canonici causa solatii ad
mensam contigerit evocari, ecclesiam et scholas cum
caeteris choristis statim post festum Innocentium
frequentando. Et quia in processione quam ad altare
Sanctae Trinitatis faciunt annuatim pueri supradicti per
concurrentium pressuras et alias dissolutiones multiplices
nonnulla damna personis et ecclesiae gravia intelleximus
priscis temporibus pervenisse, ex parte Dei omnipotentis et
sub poena maioris excommunicationis, quam
contravenientes utpote libertates dictae ecclesiae nostrae
infringentes et illius pacem et quietem temerarie
perturbantes declaramus incurrere ipso facto, inhibemus ne
quis pueros illos in praefata processione vel alias in suo
ministerio premat vel impediat quoquomodo, quominus
pacifice valeant facere et exequi quod illis imminet
faciendum; sed qui eidem processioni devotionis causa
voluerint interesse, ita modo maturo se habeant et honeste
sicut et in aliis processionibus dictae ecclesiae se habent
qui ad honorem Dei frequentant quando que ecclesiam
supradictam.’
[1254] Appendix M.
[1255] Jones, Fasti, 299.
[1256] Wordsworth, Proc. 259. The oblationes vary from lvis.
viiid. in 1448 to as much as lxxxixs. xid. in 1456.
[1257] Jones, Fasti, 300; Rimbault, xxviii; Planché, in Journal
of Brit. Archaeol. Assoc. xv. 123. Gregory, 93, gives a cut of
the statue.
[1258] Ordinale secundum Usum Exon. (ed. H. E. Reynolds), f.
30.
[1259] Archaeologia, l. 446, 472 sqq. (Invent. of 1245) ‘mitra
alia alba addubbata aurifrigio, plana est; quam dedit J.
Belemains episcopo innocentum.... Mitra episcopi
innocentum, nullius precii.... Capa et mantella puerorum ad
festum Innocentum et Stultorum [cf. p. 323] sunt xxviij
debiles et contritae.’ In 1402 there were two little staves
for the Boy Bishop (Simpson, St. Paul’s Cathedral and Old
City Life, 40).
[1260] Statutes, bk. i, pars vi. c. 9, De officio puerorum in
festo Sanctorum Innocencium (W. S. Simpson, Registrum
Statutorum et Consuetudinum Ecclesiae Cathedralis Sancti
Pauli Londinensis, 91).
[1261] ‘Memorandum, quod Anno Domini Millesimo cc lxiij.
tempore G. de fferring, Decani, ordinatum fuit de officio
Puerorum die Sanctorum Innocencium, prout sequitur.
Provida fuit ab antiquis patribus predecessoribus nostris
deliberacione statutum, ut in sollennitate Sanctorum
Innocencium, qui pro Innocente Christo sanguinem suum
fuderunt, innocens puer Presulatus officio fungeretur, ut sic
puer pueris preesset, et innocens innocentibus imperaret,
illius tipum tenens in Ecclesia, quem sequuntur iuvenes,
quocumque ierit. Cum igitur quod ad laudem lactencium
fuit adinventum, conversum sit in dedecus, et in derisum
decoris Domus Dei, propter insolenciam effrenatae
multitudinis subsequentis eundem, et affluentis
improborum turbae pacem Praesulis exturbantis,
statuendum duximus ut praedicti pueri, tam in eligendo
suo Pontifice et personis dignitatum Decani,
Archidiaconorum, et aliorum, necnon et Stacionariorum,
antiquum suum ritum observent, tabulam suam faciant, et
legant in Capitulo. Hoc tamen adhibito moderamine, ut
nullum decetero de Canonicis Maioribus vel Minoribus ad
candelabra, vel turribulum, vel ad aliqua obsequia eiusdem
Ecclesiae, vel ipsius Pontificis deputent in futurum, set suos
eligant ministeriales de illis qui sunt in secunda forma vel in
tercia. Processionem suam habeant honestam, tam in
incessu, quam habitu et cantu, competenti; ita vero se
gerant in omnibus in Ecclesia, quod clerus et populus illos
habeant recommendatos.’
[1262] ‘Die vero solemnitatis post prandium ad mandatum
personae Decani convenient omnes in atrio Ecclesiae,
 ibidem equos ascendant ituri ad populum benedicendum.
Tenetur autem Decanus Presuli presentare equum, et
quilibet Stacionarius sua personae in equo providere.’
[1263] Statutes, bk. i, pars vii. c. 6 (Simpson, op. cit. 129), a
statute made in the time of Dean Ralph de Diceto (1181-
†1204) ‘Debet eciam novus Residenciarius post cenam die
Sanctorum Innocencium ducere puerum suum cum daunsa
et chorea et torchiis ad Elemosinariam, et ibi cum torticiis
potum et species singulis ministrare, et liberatam vini
cervisiae et specierum et candellarum facere, et ibidem
ministri sui expectare, quousque alius puer Canonici
senioris veniat. Et secundam cenam in octavis Innocencium
tenebit, Episcopum cum pueris et eorum comitiva
pascendo, et in recessu dona dando, et, si diu expectat
adventum illorum nocte illa, ad matutinos non teneatur
venire.’
[1264] Rimbault, xxxii.
[1265] Printed in Rimbault, 1. Duff, Handlists, ii. 5, notes also
a Sermo pro episcopo puerorum by J. Alcock, printed in the
fifteenth century by R. Pynson.
[1266] Concio de puero Iesu pronunciata a puero in nova
schola Iohannis Coleti per eum instituta Londini in qua
praesidet imago Pueri Iesu docentis specie (Erasmi Opera
(1704), v. 599). The English version was printed by W.
Redman (Lupton, Life of Colet, 176). It is not clear that this
Concio was preached by a boy bishop, for Colet’s school
(cf. next note) attended the ‘bishop’ of St. Paul’s song-
school.
[1267] Lupton, op. cit. 175 ‘Alle these Chyldren shall every
Chyldremasse day come to paulis Church and here the
Chylde Bisshoppis sermon, and after be at the hye masse,
and eche of them offre a 1d. to the Childe Bisshopp; and
with theme the Maisters and surveyours of the scole.’
[1268] Lincoln Statutes, ii. 98 ‘Inveniet [thesaurarius] Stellas
cum omnibus ad illas pertinentibus, preter cirpos, quos
inveniet Episcopus Puerorum futurorum [?fatuorum], vnam
in nocte Natalis Domini pro pastoribus et ·ijas in nocte
Epiphanie, si debeat fieri presentacio ·iijum regum.’
[1269] Warton, iv. 224 ‘Ioannes de Quixly confirmatur
Episcopus Puerorum, et Capitulum ordinavit, quod electio
Episcopi Puerorum in ecclesia Eboracensi de cetero fieret
de eo, qui diutius et magis in dicta ecclesia laboraverit, et
magis idoneus repertus fuerit, dum tamen competenter sit
corpore formosus, et quod aliter facta electio non valebit.’
[1270] Warton, iv. 237 ‘nisi habuerit claram vocem puerilem.’
[1271] Warton, iv. 224.
[1272] Appendix M. Cf. Rimbault, xi, for further elucidations of
the Computus.
[1273] Percy, North. H. B. 340.
[1274] York Missal, i. 23. The rubric at the beginning of Mass
is ‘Omnibus pueris in Capis, Praecentor illorum incipiat.’
There are some responds for the ‘Praecentor’ and the
‘turba puerorum.’ After the Kyrie, ‘omnibus pueris in medio
Chori stantibus et ibi omnia cantantibus, Episcopo eorum
interim in cathedra sedente; et si Dominica fuerit, dicitur
ab Episcopo stante in cathedra Gloria in excelsis Deo: aliter
non.’ The Sequentia for the day is

‘Celsa pueri concrepent melodia,

eia, Innocentum colentes tripudia, &c.’

[1275] Rimbault, xvi. The dates are between 1416 and 1537.
[1276] Raine, Fabric Rolls of York Minster (Surtees Soc.), 213
sqq. ( † 1500, the additions in brackets being † 1510) ‘una
mitra parva cum petris pro episcopo puerorum ... [unus
annulus pro episcopo puerorum et duo owchys, unus in
medio ad modum crucis cum lapidibus in circumferenciis
cum alio parvo cum uno lapide in medio vocato turchas]....
Capae Rubiae.... Una capa de tyssue pro Episcopo
puerili ... [duae capae veteres olim pro Episcopo
puerorum].’ Leach, 132, says ‘At York, in 1321, the Master
of the Works gave “a gold ring with a great stone for the
Bishop of the Innocents.” In 1491 the Boy Bishop’s
pontifical was mended with silver-gilt.’
[1277] Lincoln Statutes, i. 290 (Black Book, †1300); ii. ccxxxi.
[1278] Archaeologia, liii. 25, 50; Monasticon, viii. 1282 ‘Item,
a coope of Rede velvett wt Rolles & clowdes ordenyd for
 the barne busshop wt this scriptur “the hye wey ys best”.’
The entry is repeated in a later inventory of 1548.
[1279] Hereford, Consuetudines of thirteenth century (Lincoln
Statutes, ii. 67) ‘Thesaurarius debet invenire ... in festo
Innocencium pueris candelas et ·ijos cereos coram parvo
Episcopo.’
[1280] Lichfield—J. C. Cox, Sports in Churches, in W. Andrews,
Curious Church Customs, 3, quoting inventories of 1345
and of the fifteenth century. The latter uses the term
‘Nicholas Bishop.’
[1281] Gloucester—Rimbault, 14, prints from Cotton MSS.
Vesp. A. xxv, f. 173, a Sermon of the Child Bishop,
Pronownysed by John Stubs, Querester, on Childermas Day,
at Gloceter, 1558.
[1282] Norwich—a fourteenth-century antiphonal of Sarum
Use, probably of Norwich provenance (Lansd. MS. 463, f.
16v), provides for the giving of the baculus to the
Episcopus Puerorum at Vespers on St. John’s Day.
[1283] Beverley—the fifth earl of Northumberland about 1522
gave xxs. at Christmas to the ‘Barne Bishop’ of Beverley, as
well as to him of York (Percy, North. H. B. 340); cf. p. 357.
[1284] Wordsworth, Proc. 52; cf. Appendix M (1).
[1285] Ottery—Statutes of Bishop Grandisson (1337), quoted
by Warton, ii. 229 ‘Item statuimus, quod nullus canonicus,
vicarius, vel secundarius, pueros choristas in festo
sanctorum Innocentium extra parochiam de Otery trahant,
aut eis licentiam vagandi concedant.’
[1286] Magdalen—see Appendix E.
[1287] All Souls—An inventory has ‘j chem. j cap et mitra pro
Episcopo Nicholao’ (Rock, iii. 2. 217).
[1288] In 1299 Edward I heard vespers said ‘de Sancto
Nicholao ... in Capella sua apud Heton iuxta Novum
Castrum super Tynam’ (Wardrobe Account, ed. Soc. of
Antiq., 25). In 1306 a Boy Bishop officiated before Edward
II on St. Nicholas’ Day in the king’s chapel at Scroby
(Wardrobe Account in Archaeologia, xxvi. 342). In 1339
Edward III gave a gift ‘Episcopo puerorum ecclesiae de
Andeworp cantanti coram domino rege in camera sua in
 festo sanctorum Innocentium’ (Warton, ii. 229). There was
a yearly payment of £1 to the Boy Bishop at St. Stephen’s,
Westminster, in 1382 (Devon, Issues of Exchequer, 222),
and about 1528-32 (Brewer, iv. 1939).
[1289] The fifth earl of Northumberland (†1512) was wont to
‘gyfe yerly upon Saynt Nicolas-Even if he kepe Chapell for
Saynt Nicolas to the Master of his Childeren of his Chapell
for one of the Childeren of his Chapell yerely vjs. viijd. And
if Saynt Nicolas com owt of the Towne wher my Lord lyeth
and my Lord kepe no Chapell than to have yerely iijs. iiijd.’
(Percy, North. H. B. 343). An elaborate Contenta de
Ornamentis Ep., puer., of uncertain provenance, is printed
by Percy, op. cit. 439.
[1290] St. Mary at Hill (Brand, i. 233); St. Mary de Prees
(Monasticon, iii. 360); St. Peter Cheap (Journal of Brit.
Arch. Ass. xxiv. 156); Hospital of St. Katharine by the
Tower (Reliquary, iv. 153); Lambeth (Lysons, Environs of
London, i. 310); cf. p. 367.
[1291] Louth (E. Hewlett, Boy Bishops, in W. Andrews, Curious
Church Gleanings, 241)—the payments for the Chyld
Bishop include some for ‘making his See’ (sedes);
Nottingham (Archaeologia, xxvi. 342); Sandwich (Boys,
Hist. of S. 376); New Romney (Hist. MSS. v. 517-28),
Yorkshire, Derbyshire, Somersetshire (J. C. Cox, Sports in
Churches, in W. Andrews, Curious Church Customs); Bristol
—L. T. Smith, Ricart’s Kalendar, 80 (1479-1506, Camden
Soc.). On Nov. 24, the Mayor, Sheriff, and ‘worshipfull men’
are to ‘receyue at theire dores Seynt Kateryn’s pleyers,
making them to drynk at their dores and rewardyng theym
for theire playes.’ On Dec. 5 they are ‘to walke to Seynt
Nicholas churche, there to hire theire even-song: and on
the morowe to hire theire masse, and offre, and hire the
bishop’s sermon, and have his blissyng.’ After dinner they
are to play dice at the mayor’s counter, ‘and when the
Bishope is come thedir, his chapell there to synge, and the
bishope to geve them his blissyng, and then he and all his
chapell to be serued there with brede and wyne.’ And so to
even-song in St. Nicholas’ church.
[1292] L. T. Accounts, i. ccxlvi record annual payments by
James IV (†1473-98) to Boy Bishops from Holyrood Abbey
and St. Giles’s, Edinburgh.
[1293] Wilkins, ii. 38 ‘Puerilia autem solemnia, quae in festo
solent fieri Innocentum post vesperas S. Iohannis, tantum
inchoari permittimus, et in crastino in ipsa die Innocentum
totaliter terminentur.’
[1294] Archaeologia, lii. 221 sqq.
[1295] Transactions of London and Middlesex Arch. Soc. vols.
iv, v.
[1296] Athenæum (1900), ii. 655, 692 ‘data Pueris de
Elemosinaria ludentibus coram Domino apud
Westmonasterium, iijs. iiijd.’ Dr. E. J. L. Scott and Dr.
Rutherford found in this entry a proof of the existence of
the Westminster Latin play at ‘a period anterior to the
foundation of Eton’!
[1297] Rimbault, xviii; Finchale Priory (Surtees Soc.),
ccccxxviii; Durham Accounts (Surtees Soc.), iii. xliii, and
passim.
[1298] Hist. MSS. xiv. 8. 124, 157.
[1299] Computi of Cellarer (Warton, ii. 232, iii. 300) ‘1397, pro
epulis Pueri celebrantis in festo S. Nicholai ... 1490, in larvis
et aliis indumentis Puerorum visentium Dominum apud
Wulsey, et Constabularium Castri Winton, in apparatu suo,
necnon subintrantium omnia monasteria civitatis Winton, in
festo sancti Nicholai.’
[1300] G. W. Kitchin, Computus Rolls of St. Swithin’s
(Hampshire Rec. Soc.), passim; G. W. Kitchin and F. T.
Madge, Winchester Chapter Documents (H. R. Soc.), 24.
[1301] Warton, ii. 231 ‘1441, pro pueris Eleemosynariae una
cum pueris Capellae sanctae Elizabethae, ornatis more
puellarum, et saltantibus, cantantibus, et ludentibus, coram
domina Abbatissa et monialibus Abbathiae beatae Mariae
virginis, in aula ibidem in die sanctorum Innocentium.’
[1302] Harpsfield, Hist. Eccl. Angl. (1622), 441, citing
Peckham’s Register. He says the mandate was in French.
[1303] Visitations of Diocese of Norwich (Camden Soc.), 209
‘Domina Iohanna Botulphe dicit ... quod ... habent in festo
Natalis Domini iuniorem monialem in abbatissam
assumptam, vocandi [? iocandi] gratia; cuius occasione
ipsa consumere et dissipare cogitur quae vel elemosina vel
 aliorum amicorum largitione acquisierit ... Iniunctum
est ... quod de cetero non observetur assumptio abbatissae
vocandi causa.’
[1304] Gregory of Tours, x. 16 (M. G. H. Script. Rerum
Meroving. i. 427), mentions among the complaints laid
before the visitors of the convent of St. Radegund in
Poitou, that the abbess ‘vittam de auro exornatam idem
neptae suae superflue fecerit, barbaturias intus eo quod
celebraverit.’ Ducange, s. v. Barbatoriae, finds here a
reference to some kind of masquing, and Peter of Blois,
Epist. 14, certainly uses barbatores as a synonym for mimi.
The M. G. H. editors of Gregory, however, explain
‘barbatoria’ as ‘primam barbam ponere’ the sense borne by
the term in Petronius, Sat. lxxiii. 6. The abbess’s niece had
probably no beard, but may not the reference be to the
cutting of the hair of a novice when she takes the vows?
[1305] Ducange, s. v. Kalendae (‘de monialibus Villae-Arcelli’),
‘Item inhibemus ne de caetero in festis Innocentum et B.
M. Magdalenae ludibria exerceatis consueta, induendo vos
scilicet vestibus saecularium aut inter vos seu cum
secularibus choreas ducendo’; and again ‘in festo S.
Iohannis et Innocentium mimia iocositate et scurrilibus
cantibus utebantur, ut pote farsis, conductis, motulis;
praecepimus quod honestius et cum maiori devotione alias
se haberent’; Gasté, 36 (on Caen) ‘iuniores in festo
Innocentium cantant lectiones suas cum farsis. Hoc
inhibuimus.’ In 1423, the real abbess gave place to the
little abbess at the Deposuit. Gasté, 44, describes a survival
of the election of an ‘abbess’ from amongst the
pensionnaires on the days of St. Catherine and the
Innocents in the Abbaye aux Bois, Faubourg St. Germain,
from the Mémoires of Hélène Massalska. This was about
1773.
[1306] Howlett, Monumenta Franciscana (R. S.), ii. 93
‘Caveant fratres in festo Sancti Nicolai seu Innocentium, vel
quibuscunque aliis festis vestes extraneas religiosas seu
seculares aut clericales vel muliebres sub specie devotionis
induere; nec habitus fratrum secularibus pro ludis faciendis
accommodentur sub poena amotionis confusibilis de
conventu.’
[1307] Denifle, i. 532. It was forbidden ‘in eisdem festis vel
aliis paramenta nec coreas duci in vico de die nec de nocte
cum torticiis vel sine.’ But it was on Innocents’ Day that the
béjaunes or ‘freshmen’ of the Sorbonne were subjected to
rites bearing a close analogy to the feast of fools; cf.
Rigollot, 172 ‘1476 ... condemnatus fuit in crastino
Innocentium capellanus abbas beiannorum ad octo solidos
parisienses, eo quod non explevisset officium suum die
Innocentium post prandium, in mundationem beiannorum
per aspersionem aquae ut moris est, quanquam solemniter
incoepisset exercere suum officium ante prandium
inducendo beiannos per vicum super asinum.’
[1308] Denifle, iii. 166.
[1309] ‘Verbis nedum gallicis sed eciam latinis, ut ipsi qui de
partibus alienis oriundi linguam gallicam nequaquam
intelligebant plenarie.’
[1310] S. F. Hulton, Rixae Oxonienses, 68. There had been
many earlier brawls.
[1311] Statute xxix (T. F. Kirby, Annals of Winchester College,
503) ‘Permittimus tamen quod in festo Innocencium pueri
vesperas matutinas et alia divina officia legenda et
cantanda dicere et exsequi valeant secundum usum et
consuetudinem ecclesiae Sarum.’ The same formula is used
in New College Statute xlii (Statutes of the Colleges of
Oxford, vol. i).
[1312] Cf. Appendix E. Kirby, op. cit. 90, quotes an inventory
of 1406 ‘Baculus pastoralis de cupro deaurato pro Epõ
puerorum in die Innocencium ... Mitra de panno aureo ex
dono Dñi. Fundatoris hernesiat (mounted) cum argento
deaurato ex dono unius socii coll. [Robert Heete] pro Epõ
puerorum.’
[1313] The Charter of King’s College (1443), c. 42 (Documents
relating to the Univ. of Camb. ii. 569; Heywood and Wright,
Ancient Laws of the Fifteenth Century for King’s Coll.
Camb. and Eton Coll. 112), closely follows Wykeham’s
formula: ‘excepto festo Sti Nicholai praedicto, in quo festo
et nullatenus in festo Innocentium, permittimus quod
pueri ... secundum usum in dicto Regali Collegio hactenus
usitatum.’ The Eton formula (c. 31) in 1444 is slightly
different (Heywood and Wright op. cit. 560) ‘excepto in
 festo Sancti Nicholai, in quo, et nullatenus in festo
Sanctorum Innocentium, divina officia praeter missae
secreta exequi et dici permittimus per episcopum puerorum
scholarium, ad hoc de eisdem annis singulis eligendum.’
[1314] Warton, ii. 228; Leach, 133. The passage from the
Consuetudinarium is given from Harl. MS. 7044 f. 167
(apparently a transcript from a C. C. C. C. MS.) by
Heywood and Wright, op. cit. 632; E. S. Creasy, Eminent
Etonians, 91 ‘in die Sti Hugonis pontificis solebat Aetonae
fieri electio Episcopi Nihilensis, sed consuetudo obsolevit.
Olim episcopus ille puerorum habebatur nobilis, in cuius
electione et literata et laudatissima exercitatio, ad
ingeniorum vires et motus excitandos, Aetonae celebris
erat.’
[1315] Eton Audit Book, 1507-8, quoted by H. C. Maxwell-
Lyte, Hist. of Eton (ed. 1899), 149 ‘Pro reparatione le
rochet pro episcopo puerorum, xjd.’ An inventory of Henry
VIII’s reign says that this rochet was given by James
Denton (K. S. 1486) for use at St. Nicholas’ time.
[1316] Maxwell-Lyte, op. cit. 450.
[1317] Hearne, Liber Niger Scaccarii, 674 ‘Item, unam Mitram
de Cloth of goold habentem 2 knoppes arḡ. enameld, dat.
ad occupand. per Barnebishop.’
[1318] John Stone, a monk of Canterbury, records in his De
Obitibus et aliis Memorabilibus sui Coenobii (MS. C. C. C.
C., Q. 8, quoted Warton, ii. 230) ‘Hoc anno, 1464, in festo
Sancti Nicolai non erat episcopus puerorum in schola
grammatica in civitate Cantuariae ex defectu Magistrorum,
viz. I. Sidney et T. Hikson.’
[1319] J. Stuart, Extracts from Council Registers of Aberdeen
(Spalding Club), i. 186. The council ordered on Nov. 27,
1542, ‘that the maister of thair grammar scuyll sell haf iiijs
Scottis, of the sobirest persoun that resauis him and the
bischop at Sanct Nicolace day.’ This is to be held a legal
fee, ‘he hes na uder fee to leif on.’
[1320] Wilkins, Concilia, iii. 860 ‘And whereas heretofore
dyverse and many superstitious and childysshe
observations have been usid, and yet to this day are
observed and kept in many and sondry parties of this
 realm, as upon sainte Nicolas, sainte Catheryne, sainte
Clement, the holye Innocentes, and such like; children be
strangelye decked and apparelid to counterfaite priestes,
bysshopps, and women; and so ledde with songes and
daunces from house to house, bleasing the people, and
gatherynge of monye; and boyes doo singe masse, and
preache in the pulpitt, with suche other unfittinge and
inconvenyent usages, rather to the derision than to any
true glory of God, or honour of his saints; the kyng’s
majestie therefore mynding nothing so moche, as to
avaunce the true glorye of God without vayne superstition,
willith and commaundeth, that from henceforth all suche
superstitions be loste and clyerlye extinguisshed
throughowte all this his realmes and dominions,
forasmoche as the same doo resemble rather the unlawfull
superstition of gentilitie, than the pure and sincere religion
of Christe.’ Brand, i. 236, suggests that there was an earlier
proclamation of July 22, 1540, to the same effect. Johan
Bale in his Yet a Course at the Romyshe Foxe (1542), says
that if Bonner’s censure of those who lay aside certain
‘auncyent rytes’ is justified, ‘then ought my Lorde also to
suffer the same selfe ponnyshment, for not goynge
abought with Saynt Nycolas clarkes.’ Thomas Becon,
Catechism, 320 (ed. Parker Soc.), compares a bishop who
does not preach, a ‘dumb dog,’ to a ‘Nicholas bishop.’ The
Articles put to bishop Gardiner in 1550 required him to
declare ‘that the counterfeiting St. Nicholas, St. Clement,
St. Catherine and St. Edmund, by children, heretofore
brought into the church, was a mockery and foolishness’
(Froude, iv. 550).
[1321] Machyn’s Diary, 75 ‘The xij day of November [1554]
was commondyd by the bysshope of London to all clarkes
in the dyoses of London for to have Sant Necolas and to go
a-brod, as mony as wold have ytt ... [the v day of
December, the which was Saint Nicholas’ eve, at even-song
time, came a commandment that St. Nicholas should not
go abroad, nor about. But, notwithstanding, there went
about these Saint Nicholases in divers parishes, as St.
Andrew’s, Holborn, and St.] Nicolas Olyffe in Bredstret.’
Warton, iv. 237, says that during Mary’s reign Hugh
Rhodes, a gentleman or musician of the Chapel royal,
printed in black letter quarto a poem of thirty-six octave
 stanzas, entitled The Song of the Chyldbysshop, as it was
songe before the queenes maiestie in her privie chamber at
her manour of saynt James in the Feeldes on Saynt
Nicholas day and Innocents day this yeare nowe present,
by the chylde bysshope of Poules churche with his
company.’ Warton apparently saw the poem, for he
describes it as ‘a fulsome panegyric on the queen’s
devotion, in which she is compared to Judith, Esther, the
Queen of Sheba, and the Virgin Mary,’ but no copy of it is
now known; cf. F. J. Furnivall, The Babees Book (E. E. T.
S.), lxxxv.
[1322] Machyn’s Diary, 121 ‘The v day of Desember [1556]
was Sant Necolas evyn, and Sant Necolas whentt a-brod in
most partt in London syngyng after the old fassyon, and
was reseyvyd with mony good pepulle in-to ther howses,
and had myche good chere as ever they had, in mony
plasses.’ Foxe, Acts and Monuments, viii. 726, celebrates
the wit of a ‘godly matron,’ Mrs. Gertrude Crockhay, who
shut ‘the foolish popish Saint Nicholas’ out of her house in
this year, and told her brother-in-law, Dr. Mallet, when he
remonstrated, that she had heard of men robbed by ‘Saint
Nicholas’s clerks.’ This was a slang term for thieves, of
whom, as of children, St. Nicholas was the patron; for the
reason of which cf. Golden Legend, ii. 119. Another
procession forbidden by the proclamation of 1541 was also
revived in 1556; cf. Machyn’s Diary, 119 ‘[The xxiv day of
November, being the eve of Saint Katharine, at six of the
clock at night] sant Katheryn(’s) lyght [went about the
battlements of Saint Paul’s with singing,] and Sant
Katheryn gohying a prossessyon.’
[1323] At Exton in Rutlandshire, children were allowed at the
beginning of the nineteenth century to play in the church
on Innocents’ Day (Leicester and Rutland Folk-Lore, 96).
Probably a few other examples could be collected.
[1324] At Mainz, not only the pueri, but also the diaconi and
the sacerdotes, had their episcopus (Dürr, 71). On the
other hand at Vienne the term used at all the feasts, of the
triduum and on January 1 and 6, was rex (Pilot de Thorey,
Usages, Fêtes et Coutumes en Dauphiné, i. 179). The Boy
Bishops received, for their brief day, all the external marks
of honour paid to real bishops. They are alleged to have
occasionally enjoyed more solid privileges. Louvet (Hist. et
Ant. de Beauvais, cited Rigollot, 142), says that at Beauvais
the right of presentation to chapter benefices falling vacant
on Innocents’ Day fell to the pueri. Jean Van der Muelen or
Molanus (De Canonicis (1587), ii. 43) makes a similar
statement as to Cambrai: ‘Immo personatus hic episcopus
in quibusdam locis reditus, census et capones, annue
percipit: alibi mitram habet, multis episcoporum mitris
sumptuosiorem. In Cameracensi ecclesia visus est
vacantem, in mense episcopi, praebendam, quasi iure ad
se devoluto, conferre; quam collationem beneficii vere
magnifici, reverendissimus praesul, cum puer grato animo,
magistrum suum, bene de ecclesia meritum, nominasset,
gratam et raram habuit.’ At Mainz lost tradition had it that if
an Elector died during the tenure of office by a Boy Bishop,
the revenues sede vacante would fall to him. Unfortunately
the chapter and verse of history disprove this (Dürr, 67,
79). On the other hand it is certain that the Boy Bishops
assumed the episcopal privilege of coinage. Rigollot, 52
sqq., describes and figures a long series of fifteenth-and
sixteenth-century coins or medals mostly struck by
‘bishops’ of the various churches and monastic houses of
Amiens. They are the more interesting, because some of
them bear ‘fools’ as devices, and thus afford another proof
of the relations between the feasts of Boys and Fools. Lille
monetae of the sixteenth century are figured by Vanhende,
Numismatique Lilloise, 256, and others from Laon by C.
Hidé, in Bull. de la Soc. acad. de Laon, xiii. 126. Some of
Rigollot’s specimens seem to have belonged, not to Boy
Bishops, but to confréries, who struck them as ‘jetons de
présence’ (Chartier, L’ancien Chapitre de N.-D. de Paris,