Endometriosis子宮內(nèi)膜異位精講.ppt

1、Endometriosis,Sun-Wei Guo Shanghai OB/GYN Hospital Fudan University Shanghai College of Medicine ,Learning objectives,To know Definition of endometriosis Its signs and symptoms Some notable features of endometriosis Its diagnosis Epidemiology Its treatedment,Definition of endometriosis,“endo”: insid

2、e E.g. endoscopy, endocrinology, “metra”: womb, uterus A gynecological condition in which endometrial cells appear and grow outside the uterine cavity Endometrial cells: Both stromal and epithelial cells If appeared in the myometrium, its called adenomyosis (once called “endometriosis in interna”) L

3、esions: ectopic endometrium, endometriotic lesion, (ectopic) endometrial implant,Signs and Symptoms,Recurring pelvic pain (rarely, pain in other body parts) Chronic pelvic pain Dysmenorrhea (painful menstruation) Dyspareunia (painful sex) Dysuria (painful voiding) Infertility Menstrual disturbances,

4、Some notable characteristics,Estrogen-dependence Invasiveness Like tumors, endometriotic cells are invasive Adhesion Tough to treat, let alone cure Quite common gynecological surgeries are endometriosis-related A debilitating disease Loss of productivity Reduction in life quality Emotional and relat

5、iontional burden Quite expensive to treat $2800/yr for Tx, then $1000/yr for loss of productivity In China, 15000 Yuan for surgery+medication+hospitalization,Epidemiology: prevalence,Incidence Unknown Mostly women of reproductive age Prevalence 1-22%, depending on screening method and the population

6、; precise number unknown Often 10% is used 26.1% in women with infertility 17.7% in women with pelvic pain 5.7% in women undergoing sterilization,Epidemiology: risk factors,Consistently identified (“incessant menstruation”) Earlier age of menarche Shorter menstrual cycle Lower parity Controversial D

7、ioxin exposure Heavier menses Alcohol consumption Red hair Protective factors Regular exercise Smoking,Subtypes of endometriosis,Depending mostly on location Ovarian endometriosis (ovarian endometriomas) Unilateral or bilateral Mostly 5 cm in size Peritoneal endometriosis Deep infiltrating endometri

8、osis (DIE) Rectovaginal Ovarian endometriomas is the most common (40-80%, depending on hospital),Extraperitoneal endometriosis,Lung, brain, nose, eyelid, Very rarely, in men with prostate cancer after receiving estrogen therapy,Pathogenesis,Formal description by Von Rokitansky (1860) Largely unknown

9、 (“An enigma”) Many theories, yet none proven Retrograde menstruation Coelomic metaplasia (peritoneum and endometrium are both derived from the coelomic cells) Mllerianosis Neoclassic theories Dioxin exposure Prenatal exposure Genetic predisposition Immune deficiency,13,Laparoscopic photographs,Ovar

10、ian endometrioma: chocolate cyst,Ovarian endometrioma: “kissing ovaries”,Peritoneal endometriosis,The most popular theory,John A. Sampsons retrograde menstruation theory Viable menstrual debris is regurgitated into the pelvic cavity through the fallopian tubes, attatches itself to ectopic sites, inv

11、ades the tissue and grows Evidence Human experimentation (innoculation of menstrual debris did cause endometriosis) Uterine dysperistalsis and hyperperistalsis in endometriosis Animal experiment (in baboons) Anatomic anomaly (closure of cervical os and endometriosis) Yet retrograde menstruation occu

12、rs in 95% of women with patent fallopian tubes; why not all of them develop endometriosis?,Diagnosis,Gold standard: Direct visualizationof endometriotic lesions usu. by laparoscopy or laparotomy Imaging: Ultrasonography MRI CT Signs and symptoms Secondary dysmenorrhea Dyspareunia Infertility Gynecol

13、ogical examination Histological confirmation The presence of both endometrial stroma and epithelium Blood biochemistry,Laparoscopy/laparotomy,Pros: “Gold standard” Can also remove lesions Cons Invasive procedure Has its own risk of morbility and, rarely, mortality Costly Still difficult to detect mi

14、croscopic and/or subperitoneal lesions Accuracy depends on the skill levels of surgeons,Staging of endometriosis,The revised American Fertility Society (rAFS) scoring system is the most widely used (1995) Could be used for determining treatment modalities A score is assigned to lesions based on Loca

15、tion Number of lesions Size Infiltration depth Presence of adhesion 0140 rAFS stage: I: 1-5 II: 6-15 III: 16-40 IV: 40 Problems It does not correlate with either the severity of pain or infertility It has no predictive value in prognosis,Serum markers,Over 200 different serum biomarkers have been pr

16、oposed, yet none stands the test of time The most used: CA125 30 U/ml CA125 level can be elevated in moderate/severe cases Pros Non-invasive Cheap Fast Cons Low sensitivity/specificity,Symptomology,Pains Secondary dysmenorrhea Dyspareunia Progressive Infertility Other factors ruled out Difficulty in

17、 conceiving Problems in implantation Cyclic pains/bleedings (or bloody cough) Caution: the signs and symptoms are not specific,Gynecological examination,Pelvic exam Appearance (for cutaneous lesions) Test for uterus size Palpation of any nodules or tenderness on or near the posterior wall of the ute

18、rus (Douglas pouch, cul de sac) Palpation of adnexal mass Limited value,Radiologic imaging,Pros Non-invasive Cheaper than surgery Cons Lacks sufficient sensitivity and specificity Somewhat expensive Lower availability MRI Performed after day 8 of the cycle Anti-peristaltic i.m. T1 or T2-weighted ima

19、ges, before/after taking contrast Good for peritoneal and ovarian endometriosis CT Only good for endometriosis in the lung,Ultrasound,Excellent for ovarian endometriomas “Chocolate cyst” is filled with old blood, giving a typical ground-glass appearance with low-level echoes Not good for other types

20、 of endometriosis,Differential diagnosis,Ovarian malignancy Adenomyosis Pelvic Inflammatory Disease (PID),Treatment goals,To alleviate pains To delay recurrence as long as possible To help patients get pregnant,Treatment options,Thoughts before deciding the treatment Symptoms Pain or infertility or

21、both Patient characteristics Age Severity of disease Severity of pain Prior treatment history Reproductive needs Other wishes,Some rough guidelines,First-line medical treatment: patients with mild symptoms or adolascent girls Medical treatment: Patients with endometriosis who wish to get pregnant Fe

22、rtility-preserving surgery: Young patients with severe endometriosis who wishes to have children Ovary-preserving surgery+medication: young patients with severe endometriosis who does not wish to have children Radical surgery: Older patients with severe endometriosis who do not wish to have children

23、,Treatment options,Surgery Laparoscopy or laparotomy Radical or conservative Non-surgical treatment (medication) First-line medication Progestins Gonadotropin-releasing hormone (GnRH) agonists Danazol (androgenic) Oral contraceptives Controlled ovarian hyperstimulation (fertility treatment),Surgery,

24、Indications Medical treatment ineffective Size of the adnexal mass 5 cm Wishing to get pregnant Purposes Accurate diagnosis Removal of endometriotic lesions as much as possible Removal of adhesion and restoration of normal anatomy,Surgery: Pros and cons,Pros Proven efficacy Cons Invasive Costly Cert

25、ain risks Due to high recurrence risk (50% 5 yrs), 2nd surgery may be needed Increases the risk of damaging ovaries, and the risk of premature ovarian failure,Medical treatment: Expectant treatment,Use NSAIDs Asprin Other analgesics such as ibuproten Selective COX-2 inhibitors Little impact, if any,

26、 on endometriotic lesions Follow-up,Medical treatment,Principles (for current treatment modalities) To suppress ovarian estrogen production (GnRH-a and danazol) necessary for the development and maintenance of ectopic endometrium To induce a pseudo-pregnency (progestins and OC), which suppresses ovu

27、lation and estrogen production With reduced estrogen production, endometriotic lesions may shrink in size or may be eliminated All are short-term; recurrence after termination All have various side-effects 10% simply do not respond to pregestin therapy,Progestin treatment,Based on a serendipitous fi

28、nding that pregnancy relieves the sysmptoms of endometriosis Mechanism of action (MOA) Suppresses ovulation Suppress the growth of endometriotic lesions Reduce inflammation Progestins Oral Norethisterone acetate Cyproterone acetate Dienogest Intramuscular route Medroxiprogesterone acetate Intrauteri

29、ne route Levonorgestrel-releasing IUD Side-effects Spotting, hot-flashes, breakthrough bleeding,GnRH agonists treatment,MOA Negative feedback control of ovarian estrogen production Method of administration Injection Side-effects Hot-flashes loss of libido vaginal dryness, decreased bone density Quite expensive,Danazol treatment,Danazol is a modified androgen 2.5-3.5% of activity of methyl testosterone MOA Antagonizes estrogen at the tissue level Blocks estrogen receptor sites Suppresses ovulati