Central Philippine University

College of Medicine

ENDOMETRIOSIS

STECEL M. MANGYAN
Clinical Clerk
 Introduction
• presence and growth of the glands and stroma of the
lining of the uterus in an aberrant or heterotopic
location
• Benign
• Malignancy: locally infiltrative, invasive, and widely
disseminating
• Grows under the cyclic influence of ESTROGEN
• Diagnosed incidentally
 Adenomyosis/Internal
Endometriosis

- 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
 Age Distribution
• Reproductive Age Group: 11%

• Postmenopausal Endometriosis: 5%, exogenous

estrogen

• In Teeenagers: investigated for reproductive tract

abnormalities that increase the amount of retrograde
menstruation
 Prevalence

• 33% in women with chronic pelvic pain

• 30% to 45% in women with infertility

 Introduction

NATURAL COURSE (Taylor, 2014)

▪ increase or progress 31% of the time

▪ remain the same 32% of the time
▪ regress in 38%
 Introduction

TYPICAL PATIENT
• Mid 30s
• Nulliparous
• Involuntarily infertile
• Secondary Dysmenorrhea
• Pelvic Pain
-classic symptom of endometriosis
 Introduction

• Inverse relationship between the extent of pelvic

endometriosis and the severity of pelvic pain

• Pelvic lesions of endometriosis: (+)

immunostaining for smooth muscle and nerve
cells (Medina, 2009)
ETIOLOGY
Retrograde Menstruation

Metaplasia

Lymphatic and Vascular Metastasis

Iatrogenic Dissemination

Immunologic Changes

Genetic Predisposition
RETROGRADE MENSTRUATION

• Reflux of menstrual blood and viable

endometrial cells • Shedding of
• Adjacent to the tubal ostia or in the endometrial-based
dependent areas of the pelvis adult stem cells and
• Outflow obstruction of the genital mesenenchymal cells
tract (Gargett, 2010).
• Peritoneal endometriotic
implants via retrograde
menstruation
• (Flores, 2007)
• Early Invasion of an Endometrial
Implant through the Mesothelium.

• (Witz, 2001)
METAPLASIA

• Coelomic epithelium retains the ability for

multipotential development
• Prepubertal girls, women with congenital absence of
the uterus, and rarely in men.

• Endometriosis arises from metaplasia of the coelomic

epithelium or proliferation of embryonic rests (Meyer, 1924)
• Metaplasia: “induction phenomenon” of
multipotential cell
• Induction substance:menstrual debris and
influence of estrogen and progesterone
LYMPHATIC AND VACULAR METASTASIS

• Endometrium being transplanted via

lymphatic channels and the vascular
system (Halban, 1925)

• spinal column
• nose
• forearm
• thigh
• lung
• pelvic lymph nodes
 IATROGENIC DISSEMINATION

• Endometriosis of the anterior

abdominal wall after a cesarean
delivery

• Episiotomy scar
 IMMUNOLOGIC CHANGES

• Changes in the immune system

and altered function of
immune-related cells
• Pathophysiologic
characteristics of human
peritoneal macrophages in
endometriosis
• (Halme, 1984)
• Natural killer (NK) cells and Endometriosis
-decreased cytotoxicity against endometrial and hematopoietic
cells
-less influence on peritoneal fluid

• Endo 1
-chemoattractant protein-enhanced local production of IL-6 self-perpetuates
lesion/cytokine interactions
-compounding the proliferative activity of endometriosis lesions are angiogenic factors
-basic fibroblast factor, IL-6, IL-8, PDGF, and VEGF are all increased
• Increased
estrogen
• Evidence for progesterone
“resistance” (Bulun, 2009)

• Dysregulation of the isoform B of

the progesterone receptor
• Autoimmunity
• increased B and T cells,
IgG, IgA, and IgM
autoantibodies
 GENETIC PREDISPOSITION

• Sevenfold increase in the incidence of • 7%: Incidence of endometriosis in first-degree

endometriosis in relatives of women with the relatives
disease ( Simpson, 1980)
• Women who have a family history of
• 1 of 10 women with severe endometriosis will endometriosis are likely to develop the disease
have a sister or mother with clinical earlier in life and to have more advanced
manifestations of the disease disease
• increased heterogenicity of
chromosome 17 and aneuploidy
• (Kosugi, 1999)

• Loci on 7p and 10q

• (Painter, 2011; Treloar, 2005)
 • Genetic predisposition or exposure to
environmental factors: fetal progenitor
cells overexpress SP1 and estrogen
• MMPs and integrins receptor β
• attachment and for implantation • (Bulun, 2009).
defects
• infertile women with endometriosis
• Reflux into the peritoneal cavity at
menstruation

• Asian women: ninefold increase

• ( Jacoby, 2010).
PATHOLOGY
• dependent portions of the female pelvis
• Ovaries: most common site; 2 out of 3,
bilateral
• Pelvic lymph nodes: 30%
• superficial and deep
lesions
• Deep lesions:
penetrations of >5 mm,
more progressive
• important for therapy
• 10% to 15% of women with advanced disease have lesions
involving the Rectosigmoid
• Biopsy confirmation

• Gross appearance of the implant

depends:
- site
-activity
-day of the menstrual cycle
-chronicity of the area involved

• COLOR
• red, brown, black, white, yellow, pink, clear, or a red vesicle
• depends on the blood supply and the amount of hemorrhage and fibrosis
• related to the size of the lesion, the degree of edema, and the amount of inspissated material
 Lesions

• New lesions: small, bleblike less

than 1 cm, raised

• Red, blood-filled lesions:most

active phase

• Chocolate cysts: large, light or

dark brown color, powder burn
area
 Lesions

• Older lesions: white, more

intense scarring,puckered or
retracted
• White or mixed colored lesions:
provide histologic confirmation
• Progression from red to white
lesions also seems to correlate
with age.
• OVARIAN ENDOMETRIOSIS

• 1 mm - 8 cm
• associated adhesions
• Larger cysts: densely adherent to the
surrounding pelvic sidewalls or broad
ligament.
3 CARDINAL FEATURES OF
ENDOMETRIOSIS

• ectopic endometrial glands

• ectopic endometrial stroma
• hemorrhage into the adjacent tissue
• Aberrant endometrial glands and stroma respond in cyclic fashion
to estrogen and progesterone.
• Ectopic endometrial stroma: classic decidual changes similar to
pregnancy when exposed to high levels of progesterone
• Previous hemorrhage: large
macrophages filled with
hemosiderin near the periphery of
the lesion

• Presumptive diagnosis:
intense inflammatory reaction and
large macrophages filled with blood
pigment
 CLINICAL
DIAGNOSIS
CHERRY LOU SERAFINO
CLINICAL CLERK
 SYMPTOMS
Classic symptoms:
• Cyclic pelvic pain
• Infertility
Chronic pelvic pain
• Secondary dysmenorrhea
36 to 48 hours prior to the onset
of menses
• Dyspareunia
 SYMPTOMS
Cyclic pelvic pain
• Sequential swelling and the
extravasation of blood and menstrual
debris into the surrounding tissue

Chemical mediators
• Prostaglandin
• Cytokines
SYMPTOMS
SYMPTOMS
Secondary dysmenorrhea
• Dull ache to severe pelvic pain
• Unilateral/ bilateral
• May radiate to the lowerback, legs and groin
• May last for many days

Dyspareunia
• Pain deep in the pelvis
• May continue several hours following intercourse

Abnormal bleeding
• Premenstrual spotting and menorrhagia
Other symptoms
OTHER SYMPTOMS

• Intermittent constipation
• Diarrhea
• Dyschezia
• Urinary frequency
• Dysuria
• Hematuria
• Massive ascites
PHYSICAL EXAM
PHYSICAL EXAM
Classic Finding
• Fixed retroverted
uterus
Speculum
• Demonstrate small areas
• With scaring
• Tenderness to
of endometriosis on cervix
posterior uterus or upper vagina
Rectovaginal exam Digital exam
• Nodularity of the • Lateral displacement or

uterosacral ligaments deviation of cervix

and culde-sac may
be palpated
DIAGNOSTIC IMAGING
DIAGNOSTIC IMAGING

Ultrasound examination
• No specific pattern

• Differentiates solid from cystic lesions

• Distinguish an endometrioma from other adnexal

abnormalities

MRI
• Best overall diagnostic

Diagnostic Laparoscopy
• Confirmatory
LABORATORY

• CBC
• Urinalysis
• Gram stain and Culture
• CA 125
Endometriosis may be associated with ovarian cancer.
• LOSS OF HETEROZYGOSITY
• P53 SUPPRESSOR GENE MUTATION
TREATMENT
TREATMENT

Short term goals • Treatment plan must be

• Relief of pain individualized
• Promotion of fertility
Long term goals
• Prevent progression or • Treatment options:
recurrence of the disease Medical, surgical, or both
process
Medical Therapy
MEDICAL THERAPY

• Optimal regression of small endometriomas of 1-2cm in

diameter

• Suppression of lesion and associated symptoms (pain)

• Menstrual suppression, without inducing

hypoestrogenism
 MEDICAL THERAPY-DANAZOL

• Attenuated androgen
• Orally, 400 to 800 mg for 6-9mos
• Produces a hypoestrogenic and hyperandrogenic effect
• MOA: Induces atrophic changes in the endometrium of the uterus and similar
changes in endometrial implants
Side effects:
• Deepening of voice
• Hot flushing
• Hirsutism
• Mood changes
MEDICAL THERAPY- Gonadotropin-Releasing Hormone Agonist

1. Leuprolide acetate (Lupron, injectable

- 3.75 mg IM once/month
- 11.25-mg depot injection every 3 months.
2. Nafarelin acetate (Synarel, intranasal)
- One spray (200 μg) in one nostril in the morning and one spray (200 μg) in
the other nostril in the evening
- Maximum of 800 μg daily.
3. Goserelin acetate (Zoladex, subcutaneous implant)
- 3.6 mg every 28 days as implant
- Side effects: of GnRH
-Decreased estrogen Similar to menopause
- Decrease in bone mineral
“Add back” Hormone Replacement Therapy

• Reduce or eliminate the vasomotor symptoms and vaginal

atrophy and also diminish or overcome the
demineralization of bone

• Facilitate safe and effective prolongation of GnRH agonist

therapy for up to 12 months.
Oral Contraceptives

•Norethynodrel with mestranol

•Amenorrhea and “pseudopregnancy”

•Low-estrogen monophasic combination pills

•Most economical regimen
•Continuous daily oral use for 6 to 12 months
•Aimed at more complete suppression
Oral Contraceptives

•Potential risk
•Rupture of large endometrioma
•Acute surgical abdomen during first 6 weeks

•Smaller endometriomas (~3cm) can undergo necrobiosis and resorption

NSAIDS

•Pain relief
•Improve bleeding control
•May also have direct therapeutic value

•COX-2 inhibitors
•Lesions of endometriosis express high levels of COX-2
Other Hormonal Treatment

•Medroxyprogesterone Acetate (Provera)

•20 to 30 mg orally per day

•Depo-medroxyprogesterone Acetate (Depo-Provera)

•Produce prolonged amenorrhea
•Women who completed childbearing
•Not prescribed in young women with plans of pregnancy in the near
future
•150 mg IM every 3 months to 200 mg IM/month
Other Hormonal Treatment
•Gestrinone
•Once a week oral contraceptive
•Acts as agonist-antagonist of progesterone receptors
•Agonist of androgen receptors
•Weakly binds to estrogen receptors
•2.5-7.5 mg/week

•Dienogest
•Anovulation, antiproliferation of endometrial cells, & may inhibit
cytokine secretion
•2 mg/d orally
Other Hormonal Treatment
•Levonorgestrel IUS
•Beneficial for pain relief
•Retrocervical and cul-de-sac disease

•Aromatase Inhibitor
•Anastrozole 1 mg and Letrozole 2.5mg
•Endometriosis lesions contain aromatase enzyme
•Premenopausal women: stimulate gonadotropins induce ovulation
•Premenopausal women and postmenopausal women:
•Combination with progestogen/ OCP can be used for treatment
of endometriosis
Surgical Therapies

•Adjunct or alternative to medical therapy

•Prevention or delay in disease progression

•2 main roles:
•Pain relief
•Improve fertility outcome

•Conservative and definitive surgical management

Surgical Therapies

•Conservative Surgery
•Preserve reproductive organs
•Restore normal pelvic anatomy
•Remove all macroscopic lesions
•Lysis of adhesions

•Definitive Surgery
•Removal of uterus and cervix
•Preserving or removing one or both ovaries
Surgical Therapies
•Laparoscopy and robotic surgery
•Improved visualization
•Shorter recovery period
•Decreased blood loss
•Decreased risk of complications

•Successful endometriosis surgery:

•Restoring normal pelvic anatomy
•Prevent adhesions
•Limit tissue damage
Surgical Management for Pain

•Chronic pelvic pain due to endometriosis

•Failed conservative therapy
•Moderate or severe endometriosis with pelvic adhesive disease
•Definitive surgical treatment is effective
•Removal of ovaries should be individualized
•Postsurgical hormonal suppression to decrease risk of recurrence
Surgical Management for Pain

•Presacral Neurectomy
•Short-term improvement of pain
•Bowel and bladder dysfunctions

•Photodynamic Therapy
•IV injection of special dye
•Laser light produces photochemical reaction
Surgical Management for Fertility

•Medical therapy may be given for symptomatic control

•Generally not recommended

•Prolonged GnRH agonist use improve fertility outcomes when

administered prior to ART
•Stage I/II: excision or ablation of endometriosis
•Visible lesions are present
•Stage III/IV: surgical treatment
Surgical Management for Fertility
(Endometriomas)
•Surgical removal of endometriomas is not generally recommended prior
to IVF
•Potential risk for infection
•Interfere with response to infertility treatment and oocyte retrieval
•Risk of complications in pregnancy
•Malignancy
•Does not improve fertility outcome
•Compromise ovarian reserve
•Premature ovarian failure
•Induce early menopause
Therapy for Subfertility

•Medical management
cannot be first-line
management for
endometriosis
•Prolonged GnRH agonist
therapy may be used
prior to IVF
Therapy for Subfertility
•Symptomatic women with ovarian endomtriomas: laparoscopic
surgical excision
•In vitro fertilization/ embryo transfer (IVF-ET) and pelvic pain is
not significant issue
•Endometrioma removal is not beneficial
•May compromise ovarian reserve
•Surgery may be necessary if normal ovarian tissue is replaced by
endometrioma ( >4 cm )
•Presence of endometriomas may not impair oocyte or embryo
quality
Therapy for Subfertility
•Macrophage and cytokine abnormalities
•Oocyte quality
•Fertilization
•Embryo quality
•Endometrial receptivity

•Controlled ovarian stimulation with intrauterine insemination

•Beneficial to women with endometriosis
Therapy for Subfertility

•GnRH agonist for 3 to 6 months prior to IVF-ET improves

pregnancy outcomes

•Surgical therapy is dependent on:

•Clinical presentation of the patient
•Desire for future fertility
ENDOMETRIOSIS
AT OTHER SITES
Gastrointestinal Tract Endometriosis

•Most common extrapelvic site

•Most challenging to manage
•Severity and extent of involvement varies from incidental
finding to obstruction of rectosigmoid

•Majority involves the sigmoid colon and anterior wall of

rectum
Gastrointestinal Tract Endometriosis
•Appendix: 2nd most common site
•Endometriosis of the small bowel is rare
•Classic symptoms:
•Dysmenorrhea
•Dyschezia, especially during menstrual period
•Other Associated symptoms:
•Deep dyspareunia
•Change in bowel function
•Diarrhea or constipation
•Hematochezia
Gastrointestinal Tract Endometriosis
•Dysfunction of the enteric nervous system
•Difficult to differentiate symptoms associated with
endometriosis
•Early diagnosis and differentiation is important
•Diagnosis of deep infiltrating endometriosis
•Palpation of pelvic mass or “rectal shelf”
•Usually unresponsive to medical therapy
•Surgical excision is required
Gastrointestinal Tract Endometriosis

•Complete excision often needs bowel resection

•Symptomatic women
•Lesions >2 cm
•>30% circumference involvement
•Invasion to the inner muscularis layer
Gastrointestinal Tract Endometriosis

•Parameters considered in surgical planning:

•Size
•Number and depth of lesions
•Extent of bowel circumference involvement
•Distance to anal verge
•Lymph node involvement
Urinary Tract Endometriosis
•Commonly involves the peritoneum overlying the ureter or
bladder
•Incidental finding
•Aberrant endometrial glands and stroma
•Ureteral Obstruction: most serious consequence
•History of previous pelvic surgery: 50% of women
•May develop from implanted endometrium
•An extension from adenomyosis
•Hematuria and flank pain
Urinary Tract Endometriosis
•Endometriosis of the bladder
•Region of the trigone
•Anterior wall of the bladder
•Midline, lower abdominal
pain
•Suprapubic pain
•Dysuria
•Cyclic hematuria
Urinary Tract Endometriosis

•Almost always in the distal 1/3 of the ureter

•Ureteral Obstruction
•Intrinsic: active endometriosis
•Extrinsic: long-standing fibrotic reactions to retroperitoneal
inflammation
•3-5x more common than intrinsic
•Danazol or GnRH agonists
•Serial ultrasound imaging or intravenous pyelograms
•Surgical therapy: preferred treatment
Urinary Tract Endometriosis

•TAHBSO and relief of urinary obstruction

•Ureterolysis: peristalsis of involved ureter should be observed
•Ureteroneocystostomy: bypass urinary obstruction
•Easier to resect area of endometriosis and assoc. retroperitoneal fibrosis

•Needed when hydronephrosis is present

Extra Pelvic Endometriosis
•Can also involve diaphragm
•Incidental finding
•Right-sided catamenial pneumothorax
•Dyspnea
•Chest pain
•Shoulder pain
•Hemoptysis
•Pulmonary nodules
•Medical suppressive therapy if first
approach
•Referred to thoracic surgery
REFERENCES:

Lobo, R. A., Gershenson, D. M, Lentz, G. M., & Valea, F. A. Comprehensive

Gynecology. 7th edition
THANK
YOU!