ENDOMETRIOSIS

 Is the presence and growth of the plands and stroma of the lining of the uterus in an aberrant or heterotropic location
 A benign but progressive disease which frustrated pynecologists, fascinated pathologists, and burdened patients for years

 The prevalence in the general female population is suggested to be 6% to 10%

 Diagnosed incidently during surgery performed for a variety of other indications
 The prevalence of active endometritis is approximately 33% in women with chronic pelvic pain
 The incidence of endometriosis is 30% to 45% in women with infertility
 5% of women with endometriosis are diagnosed following menopause

 The typical patient with endometriosis is in her mid-30s, is nulliparous and involuntarily infertile, and has symptoms of secondary
dysmenorrheal and pelvic pain
 Retrograde menstruation, vascular dissemination, metaplasia, genetic predisposition, immunologic changes, and hormonal influences,
environmental factors

Retrograde menstruation
 Pelvic endometriosis was secondary to implantation of endometrial cells shed during menstruation
 These cells attach to the pelvic peritoneum and i\under hormonal influence grow as homologous grafts
 Endometriosis is frequently found in women with outflow obstruction of the genital tract
 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
 The mullerian duct is derived from the coelomic epithelium during fetal development
 It postulates that the surface epithelium of the ovary can differentiate into several different histologic cell types

Lymphatic and vascular metastasis

 Endometriosis has been observed in the pelvic lymph nodes of approximately 30% of women
 Hematogenous dissemination of the endometrium explains endometriosis of the forearm, thigh and multiple lesions in the lung

Iatrogenic dissemination
 Endometrial glands and stroma are implanted during the performance of cesarean section ezplains endometriosis found in the
subcutaneous tissue at the anterior abdominal wall after cesarean delivery
 Rarely, iatrogenic endometriosis may be discovered in an episiotomy scar

Immunologic changes
 Abnormalities in cell-mediated humoral components of the immune system in both peripheral blood and peritoneal fluid involves an
alteration in the function of the peritoneal macrophages prevalent in the peritoneal cavity
 Women who do not devlop endometriosis have monocytic-type macrophages in their peritoneal fluid that have a short life span and
limited function
 These hyperactive cells secrete multiple growth factors and cytokines that enhance the development of endometriosis
 The attraction of leukocytes to specific areas is controlled by chemokines, which are chemotactic cytokines
 Endometriosis epithelial cells called endo1 is a chemoattractant protein which enhanced local production of interleukin-6 (IL-6)
 Compounding the proliferative activity of endometriosis lesions are angiogenic factors such as basic fibroblast factor, IL-6, IL-8, platelet-
derived growth factor (PGDF), and vascular endothelial growth factor (VEGF) are all increased
 Steroid interactions also enhance the progression of disease
 Enhanced aromatose activity which is a result of overexpression of the orphan nuclear receptor steroidogenic factor-1 (SF-1) in lesions
explains why progression of lesions may occur even with ovarian suppression

Genetic predisposition
 Increased heterogenecity of chromosome 17 and aneuploidy, in women with endometriosis
 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
 7x increase incidence of endometriosis in relatives
 1/10 with severe endometriosis will have sister or mother with symptoms
 Increased heterogenecity of chromosome 17 & aneuploidy

Pathology
Common sites Rare sites
Ovaries Umbilicus

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 pelvic peritoneum Episiotomy scar
Ligaments of the uterus Bladder
Pelvic lymph nodes – 30% Kidney
Rectosigmoid – 10-15% Lungs
Appendix Arms and legs
Vagina Nasal mucosa
Cervix Spinal column
Fallopian tubes

Terminology used to describe peritoneal endometriosis

 Powder burn, puckered black lesions
 Vascularized glandular papules
 Vesicular lesions
 Red, flamelike
 Petechiae peritoneum
 Discolored areas
 Deep penetrating lesions, >5mm, are more progressive form of the disease
 Approximately 10%-15% of women with advanced disease have lesions involving the rectosigmoid
 Can be found in umbilicus, areas of previous surgical incisions of the anterior abdominal wall or perineum, bladder, ureter, kidney, lung,
arms, legs, and even the male urinary tract
 Gross pathologic changes of endometriosis exhibit wide variability in color, shape, sixe, and associated inflammatory and fobrotic 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 variea widely and may be red, brown, black, white, yellow, pink, clear, or a red visicle
 The predominant color depends on the blood supply and the amount of hemorrhage and fibrosis
 The color is also related to the size of the lesion, degree of edema, and the amount of inspissated material
 Small, bleblike implants that are raised above the surrounding tissues <1cm in dm are new lesions
 Red, blood-filled lesions are the most active phase of the disease
 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”
 The older lesions are white, have more intense scarring, and usually puckered or retracted form the surrounding tissue
 White or mixed colored lesions are more likely to provide histologic confirmation of endomeriosis
 The progression from red to white lesions also seems to correlate with age
 Individual areas range from 1mm to large chocolate cysts >8cm in dm
 The associate adhesions may be minimal or extensive, filmy or dense, and avascular or vascular
 Larger cysts are usually densely adherent to the surrounding pelvic sidewalls or broad ligament

3 cardinal histologic features of endometriosis

 Ectopic endometrial glands
 Ectopic endometrial stroma
 Hemorrhage into the adjacent tissue

 The ectopic endometrial stroma undergo classic decidual changes similar to pregnancy when exposed to high physiologic or
pharmacologic levels of progesterone

ENDOMETRIOSIS: a disease of clinical contrast

Characteristics Contrasts
Benign disease Locally invasive
Widespread disseminated foci
Proliferates in pelvic lymph nodes
Minimal disease Severe pain
Many large endometriomas Asymptomatic patient
Cyclic hormones cause growth Continuous hormones reverse the growth pattern

CLINICAL DIAGNOSIS

Symptoms:
- Cyclic pelvic pain
o Usually presents as secondary dysmenorrheal or dyspareunia (or both)
o Related to the sequential swelling and the extravasation of blood and menstrual debris into the surrounding tissue

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 o Chemical mediators of this intense sterile inflammation and pain are believed to be prostaglandins and cytokines
- Infertility
- Secondary dysmenorrhea
o Usually begins 36 to 48 hours prior to the onset of menses
o Varies from a dull ache to severe pelvic pain
o May be unilateral or bilateral radiating to the lower back, legs, and groin
o Pelvic heaviness or a perception of their internal organs being swollen
o Pain may last for many days, including several days before and after the menstrual flow
- Dyspareunia
o Described as pain deep in the pelvis cause by immobility of the pelvic organs during coital activity or direct pressure on areas of
endometriosis in the uterosacral ligaments or the cul-de-sac
o Acute pain may continue for several hours following intercourse
- Abnormal bleeding
o Noted by 15% to 20% of women with endometriosis
o Most frequent complaints: premenstrual spotting and menorrhagia
o Usually it is not associated with an anovulatory pattern
o But, approximately 15% of women with endometriosis have coincidental anovulation
- Approximately one third of patients with endometriosis are asymptomatic
- Patients with only a few small foci with deep infiltration may experience moderate to severe chronic pain
- Less common yet troublesome are the symptoms resulting from endometriosis influencing the gastrointestinal and urinary tracts
o Cyclic abdominal pain
o Intermittent constipation
o Diarrhea
o Dyschezia
o Urinary frequency
o Dysuria
o Hematuria
o Bowel obstruction
o Hydronephrosis

Signs
Classic signs:
- Fixed, retroverted uterus with scarring and tenderness at the posterior
- Nodularity of uterosacral ligament and cul de sac
o May be palpated on rectovaginal examination in approximately one third of women with the disease
- Ovaries may be enlarged and tender
o And are often fixed to the broad ligament or lateral pelvic sidewall
o Adnexal enlargement is rarely symmetrical
o Bilateral ovarian endometriomas were observed in 28%
o 63% of unilateral endometriomas were found in the left ovary

- Advanced cases have extensive scarring and narrowing of the posterior vaginal fornix
- 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

Diagnostics
- Transvaginal ultrasound
- CT scan or MRI
- CA 125
- Laparoscopy

MANAGEMENT
Two primary short term goals
 Relief of pain
 Promotion of fertility

Primary long term goal

 Prevent progression or recurrence of disease

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  Choice of therapy, depends on multiple variables, including the patient’s age, her future reproductive plans, the location and extent of her
disease, the severity of her symptoms, and associated pelvic pathology
 Most patients should undergo a diagnostic evaluation, such as diagnostic laparoscopy to establish the nature and extent of endometriosis
before embarking on prolonged therapy

Medical Therapy
 Induction of amenorrhea
o The primary goal of hormonal treatment
 Recurrent bleeding in the ectopic implants is one of the most important pathophysiologic processes to interrupt
 The choice of medical therapy depends on the clinician’s evaluation of adverse effects, side effects, cost of therapy, and expected patient
compliance

 Recurrence rate: 5-15% in 5 yrs

40-50% in 5 yrs

1. NSAIDS – 1st line

2. Danazol
 Hypoestrogenic and hyperandrogenic
 Dosage: 400-800 mg/d for 6 months
 MOA: binds to androgen and progesterone receptors and sex hormone-binding globulin
 Adverse reactions
o Menopausal hot flushes
o Atrophic vaginitis
o Emotional lability
o Weight gain
o Fluid retention
o Migraine headaches
o Deepening of voice

3. GnRH agonists
 Leuprolide acetate (Lupron, injectable)
o 3.75 mg intramuscularly once/month or 11.25 mg depot injection q 3 months
 Nafarelin acetate (Synerel, intranasal)
o One spray (200 mg) in one nostril in the morning and one spray (200 mg) in the other nostril in the
evening up to a maximum of 800 mg daily
 Goserelin acetate (Zoladex, subcutaneous implant)
o 3.6 mg q 28 days in a biodegradable subcutaneous implant
 Chronic use ------ “medical oopherectomy”
 No effect on sex-hormone binding globulin
 Side effects: hot flushes, vaginal dryness and insomnia
 Advantage: better patient compliance
 Add back hormone replacement therapy
o Dosages similar to menopausal therapy in combination with GNRH agonist regimen
 Reduce or eliminate side effects
4. Oral contraceptive
 Single monophasic OCP for 6-12 months
 “pseudopregnancy”
 Others:
o Medroxyprogesterone 30 mg/d
o Depomedroxyprogesterone 150 mg IM q 3 months
 To produce amenorrhea
 Low-estrogen monophasic combination pills, with a relatively high progestin potency
 Continous daily oral contraceptives for 6-12 months
 Beginning on the 3rd day of the patient’s period

 Treatment
o Medical
o Surgical
 Conservative surgery

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  resection or destruction of endometrial of implants, lysis of adhesion, and attempts to restore normal pelvic
anatomy
 Definitive surgery
 Removal of both arteries, the uterus, and all visible ectopic foci of endometriosis
 A combination of both

Surgical therapy
 Mandatory:
o Acute rupture endometriosis
o Urethral obstruction
o Compromise bowel’s function
o Endometriosis >2cm or adnexal enlargement >8cm
 Conservative:
o Resection or destruction of endometrial implants, adhesiolysis and restoration of normal anatomy
 Definitive:
o THBSO

ADENOMYOSIS
 Endometriosis interna
 Growth of endometrial glands and stroma into the myometrium to a depth of 2.5 mm from the basalis layer
 Pathogenesis:
o Barrier between the endometrium and myometrium is broken
 Two distinct pathologic presentation
o Diffuse adenomyosis
 The most common, involvement of both anterior and posterior walls of the uterus
 Posterior wall is usually involved more than the anterior wall
 Not encapsulated
 2/3 cases
o Focal area or ademyoma
 Results in an asymmetrical uterus, and this special area of adenomyosis may have a pseudocapsule
 Cut surface protrudes convexly nand has a spongy appearance
 Diagnosis: finding of endometrial glands and stroma more than one low-powered field (2.5 mm) from the basalis layer of the
endometrium
 Histologically the glands exhibit an inactive or proliferative pattern
 Manifestations:
o Asymptomatic
o Parous, more than 35 y/o
o Symptoms: secondary dysmenorrheal & menorrhea
o Sign: diffusely enlarges uterus, 2-3x normal size
 Diagnosis: usually confirmed following histologic examination of the hysterectomy specimen
 Management:
o GnRH agonists
o Cyclic hormones
o Prostaglandin inhibitors
o Hysterectomy; Bilateral oopherectomy
 Definitive treatment if this therapy is appropriate for the woman’s age, parity, and plans for future reproduction

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