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7/31/2019 Endometriosis - Subrat
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Endometriosis
Subrat Behera
06.13.2012
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Chronic condition
Defined as the presence of endometrial glands
and stroma outside the endometrial cavity
and musculature
Severe pain, but it is most often silent
Introduction
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Epidemiology
Endometriosis
Majorgynecologicsurgery 1%
Sterilization1-7%
Women of reproductiveage undergoing
laparoscopy to diagnosepelvic pain 12-32%
Women undergoinglaparoscopy forinfertility 9-50%
Teenagers undergoinglaparascopy for pelvic
pain or dysmenorrhea50%
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Growth of endometriotic implants is dependent upon ovarian
steroid production.
Typically occurs in the reproductive years and is rare in pre-
pubertal girls and post menopausal women.
Delayed pregnancy is believed to increase the risk ofendometriosis Higher socio-economic strata.
Also, have access to better health care increasing incidence in
the group.
Caucasians = Afro-americans.
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Pathogenesis
Endometrial tissue shed from the uterus during menstruation enters the pelvisthrough the fallopian tubes and implants on pelvic structures
Implantation theory
Explains the development of endometriosis at episiotomy, laparotomy, andother surgical sites
Direct transplantationtheory
Endometriosis at extrapelvic sitesHematogenous orlymphatic spread
Coelomic or peritoneal cavity contains undifferentiated cells or cells capable oftransforming into endometrial tissue
Coelomic metaplasiatheory
Reflux of menstrual blood through the fimbriated end of the fallopian tubes,
this blood carrying viable endometrial cells that could thereby attach to andproliferate on peritoneal surfaces
Retrogrademenstruation
Deficient CMI and reduced NK cell activity may permit the growth of autologousendometrium in abnormal locations Also secrete cytokines (including IL-1, 6, and 8;tumor necrosis factor, RANTES) and growth factors promoting implants.
Altered immunitytheory
7 times more common in first-degree relatives than in the general population.
Twin concordance has also been observedGenetic factors
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Most common site of endometriosis is the ovary; 50% cases bilateral
Other sites - Posterior and anterior cul-de-sac, posterior broad ligament,
uterosacral ligaments, uterus, fallopian tubes, sigmoid colon and appendix,
and round ligaments
Myometrium involvement is termed adenomyosis
Less commonly, vagina, cervix, rectovaginal septum, small intestine, inguinal
canals, abdominal and perineal scars, ureters, bladder mucosa, andumbilicus.
Has been reported to occur in the breast, pancreas, liver, gallbladder,
kidney, urethra, arm, leg, vertebrae, bone, diaphragm, lung, and peripheral
and central nervous systems.
Pathology and surgical findings
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Implants -> Classic dark blue or brown "powder burn" lesions, white
or red opacifications, yellow-brown discolorations, clear vesicles, ora scarred or puckered area of peritoneum.
Ovary -> superficial implants or as pelvic masses containing cysts
(endometriomas) filled with thick chocolate syrup-like material.
Microscopically -> Endometrial glands and stroma. May also contain
fibrous tissue, blood, and cysts.
Decidual reaction or a "naked nuclei" cellular pattern surrounded by
a delicate reticulum or spiral arterioles with adjacent predecidua,
with or without hemorrhage.
Malignancy is rare.
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Cyclic pelvic pain (more severe during menses), dysmenorrhea,dyspareunia, abnormal menses, and infertility. Sometimesdysuria and painful defecation.
Many are completely asymptomatic.
Pain attributed to bleeding, production of cytokines, andirritation of pelvic nerves.
Related more to peritoneal inflammatory reaction than to thevolume of implants.
Clinical features - symptoms
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The most common physical finding is tenderness on palpating theposterior fornix
Localized tenderness and nodularity in the cul-de-sac, utero-sacral
ligaments, or recto-vaginal septum
Pain on uterine movement
Tender and enlarged adnexal masses
Deviation of the cervix
Fixation of the adnexa or uterus in a retroverted position
Clinical features - signs
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Gold standard is by direct visualization - Laparoscopy (the preferredless invasive technique) or laparotomy w or w/o biopsy andhistologic analysis.
Staging by site and severity of pelvic involvement : minimal, mild,moderate, or severe : American Society of Reproductive Medicinein 1979, revised in 1996.
Pelvic ultrasonography and MRI to differentiate from other adnexalmasses, but cannot detect implants.
Elevated serum CA125 or CA19-9 level : Not very sensitive : Alsoelevated with ovarian tumors and other disorders.
Diagnosis
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Dependent on the severity of symptoms, the extent and location of disease, the ageof the patient, and the patient's desire for pregnancy.
Medical management - considered for women with very little disease or forperimenopausal women
Medical management - Expectant management, analgesia with non-steroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, other medical therapies includingprogestins, danazol, or gonadotropin-releasing hormone (GnRH) analogs
Surgical therapy with laparoscopy or laparotomy (conservative or definitive)
Combination of medical and surgical therapy
Endometriosis detected incidentally on physical examination or at surgery may alsobenefit from cyclic oral contraceptives to retard disease progression
Treatment
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Types of treatment:
Minimal pelvic pain - NSAIDs, other analgesics, and cyclic oral contraceptives
(OCs).
Refractory pain - Progestins, danazol, and GnRH agonists.
MoA:
Progestins alone or in combination with estrogen (as in continuous OCs) mimic
the hormonal state of pregnancy.
Danazol and GnRH analogs induce pseudomenopause.
When not suitable:
Advanced endometriosis with adhesions or for women desiring pregnancy.
Medical treatment
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Administered cyclically or continuously
Induce decidualization and subsequent atrophy of endometrial
tissue
Good choice for women with minimal or mild symptoms
Low rate of side effects and provide contraception
Randomized trial gave significant relief of pain with both, goserelin,
a GnRH analog, and OC pills, but goserelin was superior for treating
dyspareunia
Oral Contraceptives
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Cause initial decidualization, then atrophy
Also inhibit gonadotropin secretion and ovarian hormone
production
Excellent pain relief : Effective in 80% women
Oral medroxyprogesterone acetate (10 mg three times OD) or
norethindrone acetate (5 mg OD) x 6 months.
Depot medroxyprogesterone acetate as monthly injection (100 to150 mg)
Side effects include irregular bleeding, nausea, breast tenderness,
fluid retention, and depression.
Progestins
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Inhibit pituitary gonadotropin secretion -> Near-complete suppression of ovarian
hormone production Side effects -> Hypoestrogenic state (hot flushing, vaginal dryness, transient
menstruation, decreased libido, insomnia, breast tenderness, depression, and
headaches).
Loss of bone density when administered for 6 months or longer
Due to these significant side effects, usually administered only after a definitivediagnosis is made at surgery.
Usual dose is
400 to 800 mg daily for nafarelin nasal spray
3.6 mg subcutaneous goserelin monthly
3.75 mg monthly intramuscular leuprolide
Duration of therapy : 3-6 months usually.
Extended therapy of 12 months requires add-back low dose estrogen therapy to
protect the bone. Add-back therapy -> Estrogen and/or progestins -> Decrease loss
in bone mineral density and vasomotor symptoms with GnRH agonists withoutreducing their effect on pain.
GnRH analogs
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19-nortestosterone derivative with progestin-like effects.
Mechanisms of action ->
Inhibition of pituitary gonadotropin secretion
Suppression of endometriotic implant growth
Direct inhibition of ovarian enzymes used in estrogen production
Mild to moderate disease
Orally in divided doses ranging from 400 to 800 mg daily, generally for six
months.
Side effects are dose-dependent -> weight gain, edema, decreased breast
size, acne, oily skin, hirsutism, voice deepening, headache, hot flushes, and
muscle cramps. HDL levels decrease.
Pregnancy should be avoided due to pseudohermaphroditism in female
offsprings.
Danazol
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Indicated :
When the symptoms of endometriosis are severe, incapacitating, or acute
When symptoms have failed to improve with medical therapy
When the disease is advanced
Conservative surgery preserves the uterus and the maximal amount of
ovarian tissue possible
Definitive surgery involves hysterectomy with or without oophorectomy.
Surgical treatment
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Laparoscopy (Implants are excised, fulgurated, or vaporized with
laser ; adhesions are lysed)
Extensive and invasive disease may require laparotomy
Pain relief is obtained in 80 to 90 percent of patients
However risk of recurrence is estimated to be as high as 40 percentat 10 years.
Surgical treatment - Conservative
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When significant disease is present and childbearing is completed
When incapacitating symptoms persist after medical therapy or
conservative surgery.
Bilateral oophorectomy only when the ovaries are extensively
damaged by endometriosis or when the woman is approaching
menopause.
Risk of symptom recurrence with hormone replacement therapy is loweven with residual implants, except if there is bowel involvement.
Surgical treatment - Definitive
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Pre-operative medical therapy : To reduce the amount of surgical
resection required.
Post-operative medical therapy : To treat residual implants or pain.
Combination medical and surgicaltreatment
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Common cause of female infertility
Mechanisms :
Anatomic distortion from pelvic adhesions
Endometriomas
Secretion of cytokines etc. that interfere with normal
ovulation, fertilization, and implantation
When pregnancy does occur, regression or complete resolution of
endometriosis is common
Endometriosis and Infertility
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Thanks!