MEDISINA

2020
Gynecology: Endometriosis
Lecturer: Julie del Rosario-Lim, M.D. (January 7, 2019)

ENDOMETRIOSIS
DEFINITION
" Presence and growth of the glands and stroma of the lining of
the uterus in an aberrant or heterotopic location
o Normally, glands should only be found inside the
uterus, particularly in the endometrial lining which are
responsive to hormones
" Overall prevalence in reproductive aged women has been
suggested to be as high as 11%
o Present in 5% to 15% of laparotomies performed on
reproductive-age females
o Present in approximately 33% in women with chronic
pelvic pain
o Incidence of endometriosis is 30% to 45% in women
with infertility
" Natural course of endometriosis has been reported to increase
or progress 31% of the time, to remain the same 32% of the
time and to regress in 38%
o Clinically, it is most difficult to predict the natural
course of endometriosis in any individual
" Benign but, in many women, a progressive and aggressive
disease
o Recall, the endometrium is highly responsive to
estrogen and progesterone
o Every time the patient undergoes menstruation,
endometriosis is aggravated
" Disease not only of great individual variability but also of
contrasting pathophysiologic processes
o It is a benign disease, yet it has the characteristics of a
malignancy (locally infiltrative, invasive, and widely
disseminating)
" Physiologic levels of estrogen stimulate the growth of ectopic
endometrium
o Use of contraceptive steroids of various doses is usually
beneficial for treatment.
THEORIES ON ITS ETIOLOGY
" Exact cause is unknown
" Involves many mechanisms:
o Retrograde menstruation
o Vascular dissemination
o Metaplasia
o Genetic predisposition
o Immunologic changes
o Hormonal influences
" There is increasing evidence that environmental factors may
also play a role, including exposure to dioxin and other
endocrine disruptors
RETROGRADE MENSTRUATION
" Most popular theory
" Secondary to implantation of endometrial-based stem cells and
mesenchymal cells shed during menstruation
o These cells attach to the pelvic peritoneum and under
hormonal influence grow as homologous grafts
" Endometriosis is
discovered most
frequently in areas
immediately
adjacent to the
tubal ostia or in the
dependent areas of
the pelvis
" Frequently found in
women with outflow
obstruction of the
genital tract
o The
attachment
of the shed endometrial cells involves the expression of
adhesion molecules and their receptors
METAPLASIA
" Endometriosis arises from metaplasia of the coelomic
epithelium or proliferation of embryonic rests
o The Müllerian ducts and nearby mesenchymal tissue
form the majority of the female reproductive tract
o The Müllerian duct is derived from the coelomic
epithelium during fetal development
o The metaplasia hypothesis postulates that the coelomic
epithelium retains the ability for multipotential
development
" The decidual reaction of isolated areas of peritoneum during
pregnancy is an example of this process
" Endometriosis has been discovered in prepubertal girls,
women with congenital absence of the uterus, and rarely in
men
o Supports that even endometriosis can occur in men as
well
LYMPHATIC AND VASCULAR METASTASIS
" Helps to explain rare and remote sites of endometriosis, such
as the spinal column and nose
o Hematogenous dissemination of endometrium is the
best theory to explain endometriosis of the forearm
and thigh, as well as multiple lesions in the lung
" Endometriosis has been observed in the pelvic lymph nodes of
approximately 30% of women with the disease
IATROGENIC DISSEMINATION
" Endometriosis of the anterior abdominal wall is sometimes
discovered in women after a cesarean delivery
o The hypothesis is that endometrial glands and stroma
are implanted during the procedure
o The aberrant tissue is found subcutaneously at the
abdominal incision
" Rarely, iatrogenic endometriosis may be discovered in an
episiotomy scar

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DISCLAIMER: I only placed what was emphasized in the lecture. Use at your own risk!
 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)
IMMUNOLOGIC CHANGES
" Considered as the latest theory secondary to activity of cytokines
and growth factors in the peritoneal fluid
" Multiple investigations have suggested that changes in the
immune system, especially altered function of immune-related
cells, are directly related to the pathogenesis of endometriosis
" Whether endometriosis is an autoimmune disease has been
intensely debated for many years
" Most likely the primary immunologic change involves an
alteration in the function of the peritoneal macrophages so
prevalent in the peritoneal fluid of patients with endometriosis
o It has been hypothesized that women who do not
develop endometriosis have monocytic-type
macrophages in their peritoneal fluid that have a short
life span and limited function
o Conversely, women who develop endometriosis have
more peritoneal macrophages that are larger
" Another attractive theory is the finding of a protein similar to
haptoglobin in endometriosis epithelial cells called Endo 1
o This chemoattractant protein-enhanced local production
of interleukin- 6 (IL-6) self-perpetuates lesion/cytokine
interactions
" Further compounding the proliferative activity of endometriosis
lesions are angiogenic factors that are increased in lesions
o The expression of basic fibroblast factor, IL-6, IL-8,
platelet derived growth factor (PDGF), and vascular
endothelial growth factor (VEGF) are all increased
" Steroid interactions also enhance the progression of disease
o Estrogen production is enhanced locally, and there is
evidence for upregulation of aromatase activity,
increased COX-2 expression, and dysregulation of 17β -
dehydrogenase activity
REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)
" There is evidence for progesterone “resistance”
o This is occasioned by a dysregulation of the isoform B of
the progesterone receptor in most endometriotic
lesions where levels may be undetectable
o Without progesterone, estradiol cannot be converted
to estrone (less potent)
" Autoimmunity may well exist in women with endometriosisand
o Although the findings of abnormalities of the
histocompatibility locus antigen (HLA) system have not
been consistent, there are reports of increased B and T
cells, and serum immunoglobulin (IgG, IgA, and IgM)
autoantibodies in endometriosis
GENETIC PREDISPOSITION
" Several studies have documented a familial predisposition to
endometriosis with grouping of cases of endometriosis in
mothers and their daughters
" The incidence of endometriosis in first-degree relatives,
women with severe endometriosis, has been thought to be 7%
" Women who have a family history of endometriosis are likely
to develop the disease earlier in life and to have more
advanced disease than women whose first-degree relatives are
free of the disease
" Studies have identified deletions of genes, most specifically
increased heterogenicity of chromosome 17 and aneuploidy,
in women with endometriosis compared with controls
o Loci on 7p and 10q have also been found to increase the
susceptibility for endometriosis
" Genetic predisposition or exposure to environmental factors
may program fetal progenitor cells in an epigenetic way to
overexpress SP1 and estrogen receptor β, which increase the
risk of developing endometriosis
" Certain ethnic groups have an increased risk of having
endometriosis.
o This is particularly striking in Asian women, in whom a
ninefold increase has been suggested
PATHOLOGY
" The majority of endometrial implants are located in the
dependent portions of the female pelvis
" The ovaries are the most common site, being involved in two
of three women with endometriosis
o In most of these women the involvement is bilateral
" Endometriosis may appear in various progressive forms
o Deep lesions, penetrations of greater than 5 mm,
represent a more progressive form of the disease
o Deep endometriotic ovarian cysts and cul-de-sac
nodules are important for therapy and may require a
surgical approach
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 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)
o Approximately 10% to 15% of women with advanced
disease have lesions involving the rectosigmoid
" Gross pathologic changes exhibit wide variability in color,
shape, size, and associated inflammatory and fibrotic
changes
" The gross appearance of the implant depends on the site,
activity, relationship to the day of the menstrual cycle, and
chronicity of the area involved.
" The color of the lesion varies widely and may be red, brown,
black, white, yellow, pink, clear, or a red vesicle
o The predominant color depends on the blood supply
and the amount of hemorrhage and fibrosis
o The color also appears related to the size of the lesion,
the degree of edema, and the amount of inspissated
material
o New lesions are small, bleblike implants that are less
than 1 cm in diameter
o Red, blood-filled lesions have been shown, by
histologic and biochemical studies, to be the most
active phase of the disease
- With time, the areas of endometriosis become
larger and assume a light or dark brown color,
and they may be described as “powder burn”
areas or “chocolate cysts”
REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)
NOTE: THREE CARDINAL HISTOLOGIC FEATURES
§ Ectopic endometrial glands
§ Ectopic endometrial stroma
§ Hemorrhage into adjacent tissue
" Previous hemorrhage can be discovered by identifying large
macrophages filled with hemosiderin near the periphery of
the lesion
" Aberrant endometrial glands and stroma respond in cyclic
fashion to estrogen and progesterone
CLINICAL PRESENTATION
§ Aged mid-30s
§ Nulliparous
§ Involuntarily infertile
§ Has symptoms of secondary dysmenorrhea and pelvic pain
o It must be stressed that symptoms and signs may be
extremely variable
NOTE: CLASSIC SYMPTOMS OF ENDOMETRIOSIS
§ Cyclic pelvic pain
§ Infertility
SYMPTOMS
CYCLIC PELVIC PAIN
" Classic symptom of endometriosis
o However, in clinical practice the majority of cases are not
“classic.”
o Aberrant endometrial tissue grows under the cyclic
influence of ovarian hormones and is particularly
estrogen dependent
o However, 5% of women with endometriosis are
diagnosed following menopause
- Postmenopausal endometriosis is usually
stimulated by exogenous estrogen
o Endometriosis in teenagers should be investigated for
obstructive reproductive tract abnormalities that
increase the amount of retrograde menstruation.
- Although previously thought to be rare in
adolescents, in teens with pelvic pain,
endometriosis has been found in approximately
half the cases
" Studies have shown that there is an inverse relationship between
the extent of pelvic endometriosis and the severity of pelvic pain
o Women with extensive endometriosis may be
asymptomatic, whereas other patients with minimal
implants may have incapacitating chronic pelvic pain
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 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)
" Usually presents as secondary dysmenorrhea or dyspareunia (or
both)
o Secondary dysmenorrhea
- Usually begins 36 to 48 hours prior to the onset
of menses
- Varies from a dull ache to severe pelvic pain
- May be unilateral or bilateral
- May radiate to the lower back, legs, and groin
- Patients often complain of pelvic heaviness or a
perception of their internal organs being swollen
- Pain may last for many days, including several
days before and after the menstrual flow
o Dyspareunia
- Described as pain deep in the pelvis
- The cause of this symptom seems to be
immobility of the pelvic organs during coital
activity or direct pressure on areas of
endometriosis in the uterosacral ligaments or the
cul-de-sac
- The acute pain, experienced during deep
penetration, may continue for several hours
following intercourse
" Related to the sequential swelling and the extravasation of
blood and menstrual debris into the surrounding tissue
" The chemical mediators of this intense sterile inflammation and
pain are believed to be prostaglandins and cytokines
ABNORMAL BLEEDING
" Noted by 15% to 20% of women with endometriosis
" Most frequent complaints are premenstrual spotting and
menorrhagia.
" May be related to abnormalities of the endometrium
INFERTILITY
" Patients with endometriosis frequently have ovulatory
dysfunction
" Approximately 15% of women with endometriosis have
coincidental anovulation or luteal dysfunction
OTHER SYMPTOMS
§ Cyclic abdominal pain
§ Intermittent constipation
§ Diarrhea
§ Dyschezia
§ Urinary frequency
§ Dysuria
§ Hematuria
§ Bowel obstruction
§ Hydronephrosis
§ Catamenial hemothorax – bloody pleural fluid occurring during
menses
§ Massive ascites – Rare but important because the disease
process initially masquerades as ovarian carcinoma
REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)
CLINICAL FINDINGS
PHYSICAL EXAMINATION
" Classic pelvic finding: Fixed retroverted uterus, with scarring and
tenderness posterior to the uterus
o The characteristic nodularity of the uterosacral
ligaments and cul-de-sac may be palpated on
rectovaginal examination
" Advanced cases have extensive scarring and narrowing of the
posterior vaginal fornix
" The ovaries may be enlarged and tender and are often fixed to
the broad ligament or lateral pelvic sidewall
" Speculum examination may demonstrate small areas of
endometriosis on the cervix or upper vagina
" Lateral displacement or deviation of the cervix is visualized or
palpated by digital exam of the vagina and cervix in
approximately 15% of women with moderate or severe
endometriosis
" Pelvic examination during the first or second day of menstrual
flow may aid in the diagnosis as it is the time of maximum
swelling and tenderness in the areas of endometriosis
o Diagnosis can be confirmed in most cases by direct
laparoscopic visualization of endometriosis with its
associated scarring and adhesion formation
IMAGING
" Can be a useful adjunct to the clinical presentation and physical
exam for evaluation of endometriosis, especially with deep
infiltrating endometriosis (DIE)
" Ultrasound examination
- Shows no specific pattern to screen for pelvic
endometriosis
- May be helpful in differentiating solid from cystic lesions
- May help distinguish an endometrioma from other
adnexal abnormalities
- Can only detect endometriosis in the ovaries; Implants in
other areas of the body cannot be detected
" MRI
- Provides the best overall diagnostic tool for
endometriosis but is not always a practical modality for
its diagnosis
- Has a reported sensitivity and specificity of
approximately 91% to 95%
DIAGNOSTIC LAPAROSCOPY
" Gold standard for diagnosis
" Involves direct visualization of implants
" The American Society for Reproductive Medicine developed a
point-scoring system in 1996, designed primarily to record the
extent of the disease in fertility patients
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 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)
" More recently, a proposed scoring system by Adamson focuses MONITORING
on the fertility potential of patients with endometriosis, the
" Use of serum markers:
Endometriosis Fertility Index (EFI)
v Serum levels of cancer antigen-125 (CA-125)
o For example, a low score of 0.3 was shown to have a 3-
- Have been used as a marker for
year cumulative pregnancy rate of only 10% to 11%
endometriosis
STAGING: REVISED AFS SYSTEM - Elevated in most patients with
" Ranges from Stage I (Minimal) to Stage IV (Severe) endometriosis and increases incrementally
o Location and Depth of Disease with advanced stages
o Extent of Adhesions - Have a low specificity because they also
Endometriosis < 1 cm 1-3 cm > 3cm increase with other pelvic conditions such as
Superficial 1 2 4 leiomyomas, acute pelvic inflammatory
Deep 2 4 6 disease, and the first trimester of pregnancy
R Superficial 1 2 4 - Have a low sensitivity for the diagnosis of
Deep 4 16 20 early or minimal endometriosis
L Superficial 1 2 4 v Glycodelin
Deep 4 16 20 - Previously known as placental protein 14
Posterior cul-de- Partial 4 Complete 40 - Has been shown to be elevated in
sac obliteration endometriosis and is produced in
endometriotic lesions
Adhesions < 1/3 1/3-2/3 > 2/3 - Levels also fall with removal of the disease
enclosure enclosure enclosure - However, because of great variability in
R Filmy 1 2 4 levels, glycodelin has not proved to be useful
Dense 4 8 16 clinically
F Filmy 1 2 4 v Interleukins (Il-1, chemoattractant protein-1 and
Dense 4 8 16 interferon gamma)
R Filmy 1 2 4 - Most predictive markers with Il-1 being the
Dense 4 8 16 most useful
L Filmy 1 2 4 - Not usually done to patients
" Although it is generally thought that endometriosis
Dense 4 8 16
improves during pregnancy, this is not always the case, and
an increase in lesions has been documented, although
NOTE: STAGING
primarily in the first trimester
§ Stage I (Minimal): 1 – 5
§ Stage II (Mild): 6 – 15 o Ovarian endometriomas, which may have a
§ Stage III (Moderate): 16 – 40 different pathogenetic origin, from surface implants
§ Stage IV (Severe): > 40 of endometriosis on the ovary may persist during
pregnancy
o Ovarian endometriosis rupture during pregnancy
may occur
" Endometriosis may be associated with ovarian cancer
o The risk of developing ovarian cancer may increase
fourfold in women with endometriosis
o Loss of heterozygosity and mutations in suppressor
genes, for example, p53, may explain this
association
o These findings warrant caution in the long-term
follow-up of women who have extensive disease
and ovarian endometriomas, particularly with large
masses and those that increase in size
" Cervical endometriosis is a particular condition that can
produce abnormalities in cervical cytology
" With natural menopause, there is a gradual relief of
symptoms as endometriosis is dependent on ovarian
hormones to stimulate growth
" Following surgical menopause, areas of endometriosis
rapidly disappear
o 5% of symptomatic cases of endometriosis present
after menopause
" Majority of cases in women in their late 50s or early 60s
are related to the use of exogenous estrogen

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REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)
 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)
TREATMENT
" Primary short-term goals
o Relief of pain
o Promotion of fertility
" Primary long-term goal: Attempting to prevent progression
or recurrence of the disease process
o Treatment plan must be individualized
o Choice of therapy, for women whose primary
symptom is pelvic pain, depends on multiple
variables, including the:
§ Patient’s age
§ Future reproductive plans
§ Location and extent of her disease
§ Severity of her symptoms
§ Associated pelvic pathology
" If other gynecologic conditions such as chronic pelvic
inflammatory disease or neoplasia have been ruled out,
empiric medical therapy for 3 months is a reasonable option
" Forms of Treatment:
o Medical
o Surgical
o Combination of both
MEDICAL
" Optimal regression is observed in small endometriomas that
are less than 1 to 2 cm in diameter
" Response in larger areas of endometriosis may be minimal
with medical therapy
" A poor therapeutic result may be governed by the reduction
of blood supply to the mass caused by surrounding scar tissue
" Some data have suggested that with certain suppressive
therapies, such as the use of dienogest, there is a decrease in
nerve fiber density in endometriosis lesions
" Aimed at suppression of lesions and associated symptoms,
particularly pain
o Best achieved by menstrual suppression
(amenorrhea), ideally without inducing
hypoestrogenism (causes early menopause; increases
risk for cardiovascular disease, osteoporosis, early
dementia)
NOTE: MANAGEMENT OF PATIENTS
§ If you have a patient who is in the reproductive age but
does not have a partner, menstruation may be
suppressed à ü Amenorrhea
§ If you have a patient who is in the reproductive age and
desires to get pregnant, medical treatment cannot be
given because hormones are suppressed à No ovulation
- Ovarian stimulation must be of utmost priority
§ Surgery should not always be performed because
operation decreases the ovarian reserves
- For small endometriomas, proceed to ovulation
induction
- For large endometriomas (ex. Bilateral 6 cm),
proceed to laparoscopy then ovulation induction
(due to risk of rupture)
- If patient has already completed her reproductive
career, with large endometrioma & severe pelvic
endometriosis à Hysterectomy
REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)
" The recurrence rate is 5% to 15% in the first year and
increases to 40% to 50% in 5 years
o Chance of recurrence is directly related to the extent
of initial disease
o Recurrence rate in women who initially had minimal
disease is approximately 35%, whereas in those
women whose initial disease was severe the rate is
approximately 75%
" In summary, medical therapy usually suppresses
symptomatology and prevents progression of endometriosis,
but it does not provide a long-lasting cure of the disease
o Unfortunately, once suppressive therapy is stopped,
symptoms tend to recur at variable rates
o Treatment must be continued until she reaches
menopause
" Agents used:
o Danazol
o Gonadotropin-releasing hormone (GnRH) agonists
o Traditional oral contraceptives (OCs)
- Given continuously (21 or 28-day tablets)
o NSAIDs
o Novel progestogens (eg. gestinone and dienogest, an
oral GnRH antagonist)
- Common side effect: Spotting
o Levonorgestrel-releasing intrauterine system (IUS)
- Best for patients who do not want to get
pregnant
- Good for 4-5 years
o Aromatase inhibitor (eg. letrozole)
- Also used for patients with breast CA
o Selective progesterone receptor modulators
DANAZOL
" Although approved for use in the 1970s, clinicians rarely
prescribe danazol (because of lack of familiarity, its side
effect profile, and the availability of other agents)
" Also prescribed for women with benign cystic mastitis,
menorrhagia, and hereditary angioneurotic edema
" An attenuated androgen that is active when given orally
o Produces a hypoestrogenic and hyperandrogenic
effect on steroid-sensitive end organs
o Mildly androgenic and anabolic leading to its side-
effect profile
o Mild elevation in serum liver enzyme levels has been
reported
o Women who take danazol for longer than 6 months
should have serum liver enzyme determinations
o An androgenic effect on lipids occurs, with reduction
in HDL and triglycerides and an increase in LDL
" Induces atrophic changes in the endometrium of the uterus
and similar changes in endometrial implants
" Standard length of treatment: 600-800 mg daily for 6 to 9
months
" Unfortunately, symptoms will recur in 15% to 30% of women
within 2 years following therapy
" Studies do not show significant differences between the
efficacies between GnRH agonists
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 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)

GONADOTROPIN-RELEASING HORMONE AGONISTS NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

" Given for a maximum duration of 6 months " Beneficial for pain relief and as concomitant therapy may
" Mechanism of action: Downregulation and desensitization of improve the bleeding control of patients on oral
the pituitary gland to produce extremely low levels of contraceptives
circulating estrogen, which renders the patient amenorrheic OTHER HORMONAL TREATMENTS
" Side effects (similar to menopause):
v Progestogens
o Hot flushes
" For women who cannot tolerate the high dosage of
o Vaginal dryness
estrogen in an oral contraceptive or who have a
o Insomnia
contraindication to estrogen therapy
o Decrease in bone mineral content
" May be given in the form of Medroxyprogesterone
" The clinical response to agonist therapy depends on when the
acetate (Provera) orally or depo-
therapy is initiated in regard to the menstrual cycle
medroxyprogesterone acetate (Depo-Provera)
o If agonist therapy is begun during the follicular phase,
intramuscularly
an agonist phase results in an initial rapid rise in follicle-
" Most appropriate for the older woman who has
stimulating hormone (Amenorrhea is induced within 6
completed childbearing
to 8 weeks)
" Gestrinone
o In contrast, beginning agonist therapy during the luteal
- Progestogen originally developed as a once a
phase or if artificially manipulated by the concurrent
week oral contraceptive
administration of oral progestogen, serum E2 levels are
- Acts as an agonist–antagonist of progesterone
suppressed within 2 weeks (Amenorrhea is induced in
receptors and an agonist of androgen
4 to 5 weeks)
receptors and also binds weakly to estrogen
" Currently, many clinicians “add back” hormone replacement
receptors
therapy with dosages similar to those used in menopausal
" Dienogest
therapy in combination with chronic GnRH agonist regimens
- A selective progestogen that causes
o Add-back medication will reduce or eliminate the
anovulation, has an antiproliferative effect on
vasomotor symptoms and vaginal atrophy and also
diminish or overcome the demineralization of bone endometrial cells, and may inhibit cytokine
secretion
DRUG DOSE v Levonorgestrel IUS
Leuprolide acetate (Lupron, 3.75 mg intramuscularly " Has been shown to be beneficial for pain relief in
injectable) once per month or an 11.25- women with endometriosis compared to expectant
mg depot injection management
every 3 months " Particularly suited for women who have rectocervical
Nafarelin acetate (Synarel, one spray (200 μg) in one and cul-de-sac disease
intranasal) nostril in the morning and one v Aromatase inhibitors
spray (200 μg) in the other " Eg. Anastrozole 1 mg, Letrozole 2.5 and 5 mg
nostril in the evening up to a " Have been found to be beneficial in that not only does
maximum of 800 μg daily estrogen tend to cause proliferation of the disease
Goserelin acetate (Zoladex, 3.6 mg every 28 days but also endometriosis lesions have been found to
subcutaneous contain the aromatase enzyme
implant)
SURGICAL
" Can serve as an adjunct or alternative to medical therapy and
GONADOTROPIN-RELEASING HORMONE ANTAGONISTS
can help prevent or delay further disease progression
" Have also been considered an attractive option in that they
" Main roles:
have no “flare” effect
o Provide symptomatic relief (pain)
ORAL CONTRACEPTIVES o Improve fertility outcomes
" Should be given continuously for 6-12 months to produce a " Minimally invasive surgical approaches such as laparoscopy
pseudopregnancy state and robotic surgery have largely replaced the need for
" One potential risk is that there is some risk of rupture if a large laparotomy due to advantages such as improved
endometrioma is present visualization, shorter recovery period, decreased blood loss,
o Rupture of large endometriomas may result in an acute and decreased risks of complications
surgical abdomen during the first 6 weeks of oral " A survey of the abdomen and pelvis should always be
contraceptive therapy performed while identifying key anatomic structures
" During prolonged therapy, the endometrial glands atrophy and including the ureter
the stroma undergoes a marked decidual reaction " Restoring normal pelvic anatomy, preventing adhesions, and
" Some smaller endometriomas (∼3 cm) can undergo limiting tissue damage is essential for successful
necrobiosis and resorption endometriosis surgery
" Most common side effects:
o Weight gain
o Breast tenderness

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REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)
 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)
" Indications:
o Women with chronic pelvic pain
o Failed conservative medical therapies, especially in
cases with moderate to severe endometriosis
o Women with involvement of non-reproductive
organs
" Postsurgical hormonal suppression with progestins or oral
contraceptives may be considered in order to decrease risks
of recurrence, especially if there is any residual or
unresectable disease at the time of surgery
" Other surgical treatments include:
o Presacral neurectomy
- Usually not effective
o Photodynamic therapy
CONSERVATIVE SURGERY
" Involves the resection or destruction of endometrial implants,
lysis of adhesions, and attempts to restore normal pelvic
anatomy
" Preserves reproductive organs and restores normal pelvic
anatomy while removing all macroscopic endometriotic lesions
or endometriomas
DEFINITIVE SURGERY
" Involves the removal of both ovaries, the uterus, and all visible
ectopic foci of endometriosis
SURGICAL MANAGEMENT OF INFERTILITY
" Improved fertility outcomes with prolonged GnRH agonist use
when administered prior to assisted reproductive treatment
" For stage I/II endometriosis, excision or ablation of
endometriosis has been shown to increase live birth and
ongoing pregnancy rates and is therefore recommended when
visible lesions are present.
" Although there is lack of randomized trials, for stage III/IV,
surgical treatment has also been suggested to increase
pregnancy rates
ENDOMETRIOMAS
" Conservative management has potential risks such as infection
of the endometriomas, interfering with response to infertility
treatments and oocyte retrieval, risks of complications in
pregnancy, and malignancy
o Despite these theoretic risks, surgical removal of
endometriomas is not generally recommended prior
to IVF
" Surgical treatment of endometriomas can be beneficial for
certain cases such as in symptomatic patients (i.e., pelvic pain)
or in those with difficult access to follicles
" Excision of endometriomas is preferable over ablation or
drainage, as this technique has been shown to increase clinical
pregnancy rates
" In patients failing to conceive spontaneously after the initial
surgery, assisted reproductive therapy is recommended
" Although controversial, repeat surgery can be considered after
failed assisted reproductive treatments
REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)
THERAPY FOR SUBFERTILITY
" Medical therapy cannot be first-line treatment for
endometriosis because suppression of ovulation interferes
with the ability to conceive
" Occasionally as an adjunct, more prolonged (than usual)
GnRH agonist therapy may be used before IVF
" For symptomatic women with ovarian endometriomas,
laparoscopic surgical excision should be undertaken, then
proceed to IVF
" If all visible normal ovarian tissue is replaced by
endometriomas (typically endometriomas around 4 cm or
greater), surgical excision may be necessary
" Otherwise for small lesions (∼ 2 cm), follicle aspiration can
be accomplished avoiding the endometriomas
" In general, the presence of endometriomas tends to decrease
the number of oocytes aspirated but may not impair oocyte
or embryo quality
o Surgery for endometriomas does not improve IVF
rates, therefore the consideration for surgery should
only be selected on an individual basis
" For mild endometriotic lesions or implants, remain
untouched
o Controlled ovarian stimulation along with
intrauterine insemination may be performed
" Prior suppressive therapy (before initiation of an IVF cycle)
with GnRH agonists has been shown to be benefit
ENDOMETRIOSIS AT OTHER SITES
GASTROINTESTINAL TRACT ENDOMETRIOSIS
" The incidence of gastrointestinal tract involvement varies
from 3% to 37%
" In the majority of cases, endometriosis of the gastrointestinal
tract involves the sigmoid colon and the anterior wall of the
rectum, accounting for approximately 90% of cases
" Involvement of the appendix is the next common type of
gastrointestinal (GI) tract endometriosis with an incidence
reported to be between 1% and 13%
" Endometriosis of the small bowel is rare
" In most cases, the implants do not produce clinical
symptoms
o Classic symptoms of endometriosis of the large bowel
include:
§ Dysmenorrhea (cyclic pelvic cramping and
lower abdominal pain)
§ Dyschezia (rectal pain with defecation),
especially during the menstrual period
" Early diagnosis of gastrointestinal endometriosis and
differentiation from other GI conditions are important
URINARY TRACT ENDOMETRIOSIS
" Most serious consequence of urinary tract involvement is
ureteral obstruction, which occurs in about 1% of women
with moderate or severe pelvic endometriosis
" Surgical therapy is the preferred treatment for ureteral
obstruction secondary to endometriosis
o The most common surgical approaches include
removal of the uterus and both ovaries and the relief
of urinary obstruction by ureterolysis or by
ureteroneocystostomy
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 GYNECOLOGY: ENDOMETRIOSIS
JULIE DEL ROSARIO-LIM, M.D. (JAN 7, 2019)

EXTRAPELVIC ENDOMETRIOSIS
" Endometriosis can also involve the diaphragm
" This may be an incidental finding at laparoscopy and can be
asymptomatic
o However, if a patient is symptomatic, the most
common presentation of diaphragmatic endometriosis
is right-sided catamenial pneumothorax
ADENOMYOSIS
" Growth of endometrial glands and stroma into the uterine
myometrium to a depth of at least 2.5 mm from the basalis
layer of the endometrium
" Sometimes termed internal endometriosis
o However, this is a semantic misnomer because most
likely they are separate diseases
" On internal examination, you would see the uniform
enlargement of the uterus
" Has a darker cut surface, no distinct cleavage

CLINICAL PRESENTATION:
§ Over 50% are asymptomatic
§ Symptomatic cases are between the ages of 35 and 50

CLASSIC SYMPTOMS:
§ Secondary dysmenorrhea
§ Menorrhagia

DIAGNOSIS:
" Confirmed following histologic examination of
hysterectomy specimen
" Diagnostic tools:
Sensitivity Specificity
Ultrasonography 53-89% 50-89%
MRI 88-93% 66-91%

MANAGEMENT:
" Same with Pelvic endometriosis = Induce amenorrhea
" NO satisfactory medical management
o GnRH agonist
o Cyclic hormones
o Prostaglandin synthetase
" Hysterectomy is the definitive treatment
• Factors to consider:
§ Age
§ Parity
§ Reproductive plans
§ Uterine size
§ Presence of associated pelvic pathology

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REFERENCES: Lecture notes & handouts + Comprehensive Gynecology, 7th ed + Trans by caramelmacchiato (3B)