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Endometriosis II ( Treatment ) Somkiat Sitavarin MD. Asso. Prof. Kamthorn Pruksananonda MD. ( Advisor ) Medical treatment of endometriosis Indication for treatment of endometriosis • Pain : pelvic pain, dysmenorrhea, or dyspareunia • Abnormal bleeding • Pelvic pathology : ovarian cyst • Infertility • ? Prophylaxis Modality of medical treatment for endometriosis • • • • • • • Nonsteroidal anti-inflammatory drug Estrogen-progestogen combination : cyclic, continuous Progestogen : injectable, oral Danazol GnRH-a Antiprogestin Others Therapeutic options Analgesic • NSAIDS inhibit biosynthesis of PGs and alleviate symptoms • Well tolerated, safe and inexpensive and are recommended as a first-line of treatment in mild symtoms Therapeutic options Combination of estrogen and progestin ( pseudopregnancy ) • anovulation, amenorrhea and progressive decidualization then necrobiosis and resorption of ectopic endometrium • Use of OC. ( .020-.035 mg EE ) continuously 6-9 mos. • Lowest dose to produce amenorrhea • Side effects - abdominal swelling, depression,breast pain and tenderness, increase appetite, weight gain, edema to breakthrough bleeding. Combination of estrogen and progestin ( pseudopregnancy ) • Superficial varicosity occasionally appear, and there is an increase risk of DVT. • Symptomatic relieve 75-100 %; Pregnancy rate ranged from 10-58 % • Today, this regimen is not commonly used and initial treatment Progestogens Progestogens used for management of endometriosis Parenteral • MPA ( Provera ) Oral • MPA ( Provera ) • Megase • Gestrinone • Lyestrenol • CPA MPA • 100 mg DMPA every 2 wks. 4 doses followed by 200 mg monthly 4 mos. • When breakthrough bleeding occurred, EE .02 mg daily 25 days each month was added • Other regimen consists of 150 mg every 3 mos. For 1 year • Adequate data to document the effectiveness of MPA to soppress endometriosis and enhance fertility are not available • Spotting, depression, breakthrough bleeding, weight gain Other Progestogen Gestinone ( R2323 ) • Unsaturated 19-norsteroid • Is a weak progestin and androgen agonist/ antagonist • Suppress midcycle LH surgh and FSH and folliculogenesis • Amenorrhea and symtomatic relieve in 85-90 % within 2 mos • Side effects were moderate, transient and primarily related to androgenic and anabolic activities Megestrol acetate • Antiandrogenic effect and suppressive action on gonadotropin • In retrospective study, using 40 mg/day for upto 24 weeks - 86% relieve symtoms Dydrogesterone ( Duphaston ) • 20-30 mg/day • 60 mg in luteal phase • shown to relieve pain, neither regimen seem to improve pregnancy rates CPA • 17-OH progesterone derivatives • In combination with EE. may be as effective as danazol to alleviate pain • Antiandrogenic, antigonadotropic and progestational activities • Side effects were fatigue, loss of libido, depression and weightgain Antiprogestins ( RU 486 ) • Bind to progesterone receptors and exert antiprogesterone and antiglucocorticoid activities • Inhibit ovulation and disrupt endometrial integrity • 100 mg/day for 3 mos. induce amenorrhea and decrease pelvic pain • 50 mg/day for 6 mos. alsoso has been report • Side effects were atypical flushes, anorexia and fatique Danazol • Isoxazole derivatives of 17-alpha-ethinyl testosterone • Androgen and glucocorticoid agonist, suppression of Gn, inhibit ovarian steroidogenesis and alter immune response • 400-800 mg/dy for 6 mos. with pregnancy be excluded • Symtomatic relieve 60-100 %, dyspareunia relieve 80 % • 0n second look assesment, almost 100 % resolute in minimalmild, 50-70 % in advanced disease Danazol • Side effects were weight gain, acne, hirsutism, oily skin and decrease in breast size, muscle cramp, flushing, mood changes, depression and edema • HDL decrease, LDL increase, VLDL not changed ,