Endometriosis

Subrat Behera 06.13.2012

Introduction
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

Epidemiology
Major gynecologic surgery 1% Teenagers undergoing laparascopy for pelvic pain or dysmenorrhea 50% Sterilization 1-7%

Endometriosis

Women undergoing laparoscopy for infertility 9-50%

Women of reproductive age undergoing laparoscopy to diagnose pelvic pain 12-32%

 Growth of endometriotic implants is dependent upon ovarian steroid production.

Typically occurs in the reproductive years and is rare in prepubertal girls and post menopausal women. Delayed pregnancy is believed to increase the risk of endometriosis Higher socio-economic strata. Also, have access to better health care increasing incidence in the group. Caucasians = Afro-americans.

Pathogenesis
Implantation theory Endometrial tissue shed from the uterus during menstruation enters the pelvis
through the fallopian tubes and implants on pelvic structures

Direct transplantation Explains the development of endometriosis at episiotomy, laparotomy, and theory other surgical sites
Hematogenous or lymphatic spread
Endometriosis at extrapelvic sites

Coelomic metaplasia Coelomic or peritoneal cavity contains undifferentiated cells or cells capable of theory transforming into endometrial tissue Retrograde menstruation Altered immunity theory Genetic factors
Reflux of menstrual blood through the fimbriated end of the fallopian tubes, this blood carrying viable endometrial cells that could thereby attach to and proliferate on peritoneal surfaces
Deficient CMI and reduced NK cell activity may permit the growth of autologous endometrium in abnormal locations Also secrete cytokines (including IL-1, 6, and 8; tumor necrosis factor, RANTES) and growth factors promoting implants.

7 times more common in first-degree relatives than in the general population.

Twin concordance has also been observed

Pathology and surgical findings

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, and umbilicus. 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.

 Implants -> Classic dark blue or brown "powder burn" lesions, white or red opacifications, yellow-brown discolorations, clear vesicles, or a 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.

Clinical features - symptoms

Cyclic pelvic pain (more severe during menses), dysmenorrhea, dyspareunia, abnormal menses, and infertility. Sometimes dysuria and painful defecation.
Many are completely asymptomatic. Pain attributed to bleeding, production of cytokines, and irritation of pelvic nerves. Related more to peritoneal inflammatory reaction than to the volume of implants.

Clinical features - signs

The most common physical finding is tenderness on palpating the posterior 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

Diagnosis
Gold standard is by direct visualization - Laparoscopy (the preferred less invasive technique) or laparotomy w or w/o biopsy and histologic analysis. Staging by site and severity of pelvic involvement : minimal, mild, moderate, or severe : American Society of Reproductive Medicine in 1979, revised in 1996. Pelvic ultrasonography and MRI to differentiate from other adnexal masses, but cannot detect implants. Elevated serum CA125 or CA19-9 level : Not very sensitive : Also elevated with ovarian tumors and other disorders.

Treatment
Dependent on the severity of symptoms, the extent and location of disease, the age of the patient, and the patient's desire for pregnancy. Medical management - considered for women with very little disease or for perimenopausal women Medical management - Expectant management, analgesia with non-steroidal antiinflammatory drugs (NSAIDs), oral contraceptives, other medical therapies including progestins, 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 also benefit from cyclic oral contraceptives to retard disease progression

Medical treatment
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.

Oral Contraceptives
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

Progestins
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 to 150 mg) Side effects include irregular bleeding, nausea, breast tenderness, fluid retention, and depression.

GnRH analogs
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 definitive diagnosis 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 without reducing their effect on pain.

Danazol
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.

Surgical treatment
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 - Conservative

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 percent at 10 years.

Surgical treatment - Definitive

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 low even with residual implants, except if there is bowel involvement.

Combination medical and surgical treatment

Pre-operative medical therapy : To reduce the amount of surgical resection required.

Post-operative medical therapy : To treat residual implants or pain.

Endometriosis and Infertility

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

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