Endometriosis

Endometriosis

• Presence and growth

of endometrial
glands and stroma
in an aberrant or
heterotopic location
• Benign yet it has the
characteristic of a
malignancy- locally
infiltrative, invasive,
widely disseminating
 ANATOMIC DISTRIBUTION OF ENDOMETRIOSIS
COMMON SITES RARE SITES
Ovaries (most common) Umbilicus
Pelvic peritoneum Episiotomy scar
Ligaments of the uterus Bladder
Sigmoid colon Kidney
Appendix Lungs
Pelvic lymph nodes Arms
Cervix Legs
Vagina Nasal mucosa
Fallopian tubes Spinal column
3 types of lesions:

•Superficial (peritoneal)
•Endometriomas
•Deep infiltrating endometriosis
(DIE)
Superficial (peritoneal) lesions
Spectrum of lesions with black and white
lesions reflecting older lesions with
inflammatory and fibrotic changes
Endometriomas
(Chocolate cysts)

• Ovarian cysts may range

from <1 -8 cm
• The associated
adhesions may be filmy
or dense
• Larger cysts are usually
densely adherent to the
surrounding pelvic
sidewall or broad
ligament
Deep infiltrating
endometriosis (DIE)

•Penetration of
>5 mm,
represent a
more
progressive
form of the
disease
Theories of Pathogenesis

1. Retrograde menstruation / Sampson’s theory

2. Coelomic metaplasia (Meyer’s)
3. Benign metastases (lymphatic and vascular)
4. Iatrogenic dissemination
5. Immunologic changes
6. Genetic predisposition
 1. Retrograde menstruation/
Sampson’s theory
• Most popular theory
Pathogenesis of peritoneal endometriotic • Reflux of endometrial cells shed during
implants via retrograde menstruation
menstruation
• Cells attach/implant to the pelvic peritoneum
and under hormonal influence grow as
homologous grafts

• Evidence:
1. Endometriosis is discovered most frequently in
areas immediately adjacent to the tubal ostia
or in the dependent areas of the pelvis
2. Endometriosis is frequently found in women
with outflow obstruction of the genital tract
2. Coelomic
Metaplasia

• Multipotent cells of the visceral and abdominal peritoneum

transforms into endometrial cells after an “induction
phenomenon”
• Induction substance may be a combination of menstrual
debris and the influence of estrogen and progesterone
• Ovarian endometriosis- from metaplasia of the coelomic
epithelium that invaginates into the ovarian cortex
• Also proposes that residual embryonic cells of the Wolffian
or Mullerian ducts may persist and develop into
endometriotic lesions that respond to estrogen
2. Coelomic
Metaplasia

Evidence: Endometriosis in
1. prepubertal girls
2. women with congenital
absence of uterus
3. very rarely in men
4. Decidual reaction of
isolated areas of
peritoneum during
pregnancy
3. Lymphatic and Vascular
metastasis

• Explain rare and remotes sites of

endometriosis,much as the spinal column and
nose
• Hematogenous dissemination best explains
endometriosis of the forearm, thigh, and multiple
lesions of the lung (catamenial hemothorax-
bloody pleural fluid during menses)
4. Iatrogenic dissemination

•Endometriosis of
the anterior
abdominal wall
after CS
•Episiotomy scar
5. Immunologic changes

• Changes in the immune system, esp altered

function of immune-related cells

• Theory of different populations of macrophages

• Monocytic type of macrophages with short life
span and limited function (no endometriosis) vs.
Larger macrophages which secrete multiple
growth factors and cytokines (with
endometriosis)
5. Immunologic changes

• Endo1 protein (chemoattractant protein) found in

endometriotic tissues enhance local production of
Interleukin-6 (IL-6) and self-perpetuates lesion/ cytokine
interactions
• Increased angiogenic factors (basic fibroblast factor, IL-6,
IL-8, and platelet-derived growth factor, vascular
endothelial growth factor/VEGF) which further increase
the proliferative activity of endometriosis lesions
6. Genetic predisposition

• 7-fold increase if with relatives with the disease

• Women with family history are likely to develop

the disease earlier in life and to have more
advanced disease
Diagnosis: History

• Dysmenorrhea, Dyspareunia (Classic)

• Infertility (25-50%)
• Dyschezia, Hematochezia
• Abnormal uterine bleeding (15-20%)
• Chronic pelvic pain (20%)
• Asymptomatic (1/3)
Diagnosis: PE
• Timing- Do exam on D1 Or D2 of menses to
aid in the Dx as this is the time for
maximum swelling and tenderness in the
areas of endometriosis
• Classic findings:
• Fixed/immobile retroverted
(secondary to adhesions) uterus, with
scarring and tenderness posterior to
the uterus
• Adnexae: Ovaries may be enlarged and
tender and often fixed to the broad
ligament or lateral pelvic sidewall
• Nodularities of the uterosacrals and
cul de sac on RVE
• Extensive scarring and narrowing of
the posterior vaginal fornix (advance
cases)
Diagnosis:
PE

• Small areas of
endometriosis on the
cervix or upper vagina on
speculum exam
• Lateral displacement or
deviation of the cervix
• Some with normal PE
findings
Diagnosis: PE

A diffusely or
symmetrically
enlarged, tender,
“boggy” uterus is
suggestive
of adenomyosis.
Diagnosis: Transvaginal
Ultrasound
TVS
• first line in diagnostic imaging
• has the highest sensitivity and specificity in
identifying ovarian endometriomas
• helpful in differentiating solid from cystic lesions
and may help distinguish an endometrioma from
other adnexal abnormalities
• Because the lesions are vascular, doppler flow
may be demonstrated in endometriosis
Endometrioma: unilocular , “ground glass”
appearance; (+) diffuse low-level internal echoes
Diagnosis: Transvaginal
Ultrasound

Normal Endometrioma
Diagnosis: Transvaginal
Ultrasound
The sonographic findings of adenomyosis, best obtained by transvaginal
sonography:

Uterine enlargement—Globular uterine enlargement that is generally up to

12 cm in uterine length and that is not explained by the presence of
leiomyomata is a characteristic finding
Cystic anechoic spaces or lakes in the myometrium— The cystic anechoic
spaces within the myometrium are variable in size and can occur throughout
the myometrium (Figure 4). The cystic changes in the outer myometrium may
on occasion represent small arcuate veins rather than adenomyomas. The
application of color Doppler imaging at low velocity scales may help in this
differentiation.
Uterine wall thickening—The uterine wall thickening can show
anteroposterior asymmetry, especially when the disease is focal
Diagnosis: Transvaginal
Ultrasound
Subendometrial echogenic linear striations—Invasion of the endometrial
glands into the subendometrial tissue induces a hyperplastic reaction, which
appear as echogenic linear striations fanning out from the endometrial layer

Heterogeneous echo texture—There is a lack of homogeneity within the

myometrium with evidence of architectural disturbance. This finding has
been shown to be the most predictive of adenomyosis.

Obscure endometrial/myometrial border—Invasion of the myometrium by

the glands also obscures the normally distinct endometrial/myometrial
border

Thickening of the transition zone—This zone is a layer that appears as a

hypoechoic halo surrounding the endometrial layer. A thickness of 12 mm or
greater has been shown to be associated with adenomyosis
Diagnosis:
Laparoscopy
Diagnosis: Laparoscopy
 ASRM scoring system
for severity of Pelvic Endometriosis

Score: < 15 = minimal to mild (stage I-II)

> 15 = moderate to severe (stage III- IV)
 • Adenomyosis
• Chronic PID
• Myoma with degeneration
• Ovarian cyst with complication
Differentials (hemorrhage or torsion)
• Ovarian malignancy
• Primary dysmenorrhea
• Functional bowel disease
 • Medical
• Surgical

Short-term goals
• Pain relief
Management
of • Promotion of fertility
endometriosis
Long-term goal
• prevent progression or
recurrence of the the disease
process
 • Patient age
• Patient preference
• Reproductive plans
• Pain severity
Management of• Degree of disease
endometriosis• Treatment cost and
intended duration
• Treatment risks/side effect
profiles
• Accessibility
 • Aimed at suppression of lesions
and addressing pain
• Does not provide a long-lasting
cure of the disease
• Recurrence rate following
medical therapy
Medical • 5-15% (1st year)
• 40-50% (5th year)
• Chance of recurrence is directly
related to the extent of initial
disease (35% if mild, 75% if
severe)
 • Continuous or cyclic, low
–dose, monophasic COC
for 6-12 months
COC :
Pseudopregnancy • Decrease in
symptomatology in 80%
of cases
• Smaller endometriomas
(~3 cm) undergo
necrobiosis and
resorption
• Reduces postoperative
endometriomas
• Side effects: weight gain,
breast tenderness
 • For women who cannot
tolerate high dosage of
estrogen in OCP or who have
contraindication to OCP
Progestin • Suitable for older women
who has completed
childbearing
• MPA( Provera) 20-30 mg
daily
• DMPA 150 mg IM every 3
months to a max of 200 mg
monthly
• Norethindrone acetate 5
mg daily (2.5-15 mg)
• Gestrinone (Dimetrose,
Nemestran)- 2.5-7.5 mg
once weekly
 Dienogest (Visanne)
• New hybrid progestin-nortestosterone
• As effective as GnRH agonist
• Oral actively
• Lipid-friendly; less androgenic side effects
• Contraindicated in patients with thromboembolism or cardiovascular disease

Lowers E2 Inhibits
Inhibition levels vascular
of PGE2 proliferation
and Inhibits Promotes
aromatase angiogenesis apoptosis
LNG-IUD
• Treatment of choice for chronic
pelvic pain- associated
endometriosis in women who
do not wish to conceive
• Suited for rectovaginal and cul
de sac disease
• Delivers significant amounts of
levonorgestrel into the
peritoneal fluid: clearing up the
local effect on the
endometriotic implants
GnRH agonist: Pseudomenopause

Induce an initial
gonadotrophin
hypersecretion (flare effect)
followed by pituitary
desensitization and
profound suppression of LH
and FSH
GnRH agonist : Pseudomenopause
• “Medical oophorectomy” with chronic use
• Growth of endometriosis is arrested, diminished or
eliminated (esp in endometriomas < 1 cm)
• Improves symptoms in 75-90% of cases
• Ovarian function returns to normal in 6-12 weeks
after 6 months of therapy
GnRH agonist
• Types:
o Leuprolide acetate (Lupron, injectable)- 3.75 mg IM once
monthly or 11.25 mg IM once q 3 months
o Nafarelin acetate (Synarel, intranasal)- 1 spray ( 200 ug) in
one nostril (am and pm), max of 800 ug daily
oGoserelin acetate (Zoladex, subcutaneous implant)- 3.6 mg
every 28 days
• Side effects: hot flushes, vaginal dryness, insomnia,
decrease bone density in the trabecular bone of the
lumbar spine (by 2-7% during a 6- month course therapy)
 • To reduce or eliminate the
vasomotor symptoms and
vaginal atrophy
• To diminish or overcome
“Add back” the demineralization of
bone
hormone • Allow longer duration of
replacement GnRH therapy for up to
12 months
• Additional add back
therapy: Tibolone,
Raloxifene
Estradiol therapeutic window
NSAIDs
• Most common first intervention to address pain
• Used for temporary relief of pain especially in adolescents
 • Synthetic steroid, 17a-
ethinyltestosterone
• Hypoestrogenic- induces atrophic
changes in the endometrium of the
uterus and similar changes in
endometrial implants
• No longer recommended because of the
side effects
Danazol • Side effects: hirsutism, acne, deepening
of voice, liver enzyme elevation,
decrease HDL and triglycerides and
increase LDL
• 400-800 mg to 100-200 mg daily on D1-
5 of cycle for 6-9 mos
 Aromatase inhibitors

• Recently proposed to be effective (still experimental)

• Anastrozole 1 mg
• Letrozole 2.5 and 5 mg
• May inhibit growth of implants and relieve pain

X
 • Comparable with
Leuprolide in efficacy
• Direct reversible
GnRH suppression (no “flare”
effect)
antagonist • Less bone loss
• Elagolix (oral) 150 or 250
mg oral OD or BID for up
to 6-24 months
 •Conservative or
definitive
•Goals:
•to provide
Surgical symptomatic relief
(pain)
•to improve fertility
outcomes
 • Failure of empiric
therapy
• Intolerance to medical
management
• For purpose of diagnosis
Surgical: and immediate
Indications management
• For diagnosis and
treatment of an adnexal
mass
• For treatment of
infertility
 • Preservation of
reproductive organs
• Restoration of normal
pelvic anatomy
• Removal of all
Conservative macroscopic
endometriotic lesions or
endometriomas ( by
ablation or resection)
• Performing lysis of
adhesions (adhesiolysis)
Definitive

• TAH +/- BSO

•Excision/Resection
of implants
 •Post surgical hormonal
suppression with
progestins or OCPs
may be considered in
Surgical order to decrease
recurrence esp if there
is any residual or
unresectable disease
at the time of surgery
Endometriosis