Leiomyomas (1 of 6)

1 Patient presents w/ symptoms suggesting leiomyoma or asymptomatic leiomyoma is discovered upon pelvic exam or imaging

2 DIAGNOSIS No ALTERNATIVE Do pelvic exam & diagnostic DIAGNOSIS tests confirm leiomyoma?

Yes

CLINICAL DECISION Is the leiomyoma Yes growing rapidly? Should patient be managed medically or surgically?

No

CLINICAL DECISION Is uterine size <16 weeks & other causes of pelvic mass have been excluded? MIMSMedically Surgically No Yes

A EXPERT Pharmacological therapy REFERRAL C Patient observation MEDICAL SURGICAL MANAGEMENT MANAGEMENT © See next page See next page

© MIMS 2019 LEIOMYOMAS 3 2 1 A Patient uterus toretain whowishes Patient fertility toretain whowishes &uterus fertility toretain Patient notwish whodoes • TestLaboratory • • • Exam Physical • • • • • • &Symptoms Signs • • • • • • MEDICAL MANAGEMENT MANAGEMENT MEDICAL Pharmacological therapy Pharmacological A CBC to evaluate hemoglobin (Hb) will detect iron-defi detect hemoglobin (Hb)will toevaluate A CBC bleeding anemia menstrual inpatients w/heavy ciency diffi be can Diagnosis women cult inobese exam onabdominal palpated may be of>12to20weeks Size - isapregnantuterus as week inmenstrual Myomatous isreported size uterus’ that w/the issuggestive offi uterus mass moves Apelvic broids - Pelvic apalpable enlarged, may exam fi reveal uterus &irregular rm, birthweight low presentation, cesarean section, delivery, infants preterm primary of the complications: Rapidfi growth Obstetric breech degenerationbroid, red miscarriage, & pain, spontaneous Infertility, &dysmenorrhea pain,dyspareunia pelvic non-cyclic back pressure, low pain constipation, rectal incontinence hydronephrosis, tenesmus, orretention, dysuria, &urgency, frequency urinary urinary girth, abdominal Increased pressure symptoms: Pelvic &pelvic mass toiron-defi leading menorrhagia as manifests clinically bleeding uterine Abnormal anemia ciency number, onsize, depending Symptoms vary ofthe fi &location broids 50%offiAbout broids are asymptomatic fi ofuterine history obesity,broids, nulliparity, alcohol &caff descent), race genetic factors, (African eine intake Factors fi theofuterine that risk increase broids include age menarche old,early >40years old,family <10years women Fibroids descent orAsian than inwomen occur more ofAfrican inCaucasian often isstimulated estrogen Development by & - Tend menopause during &usuallyregress years reproductive during togrow - the uterus) outside (protruding the orsubserosal myometrium), fi onlocation, Based submucosal be broids into can (protruding the intramural cavity), uterine (foundwithin tumors &oneofthe common frequent conditionsMost pelvic clinical most practice solid encountered ingynecologic transformation isextremely Malignant rare - - collagen &elastin fi called Also tumors ofthe that are uterus benign these consist muscle ofsmooth &extracellularbroids, matrix • • &/or intramural extension are taken into account classifi (FIGO) Federation and Obstetrics ofGynecology distortion cation wherein cavity of uterine the degree Fibroid classifi (ESGE)orthe Endoscopy International forGynecological cation may the European use Society pseudocapsule muscle cell’s the by transformationformation of a followed connective tissue component neoplastic & a  oughpathogenesis well isnotyet defi fined, broids are thought asmooth the from after myometrium todevelop receptor modulator (SPRM) (SPRM) modulator receptor progesterone Selective therapy add-back estrogen-w/ orwithout agonist (GnRH) hormone releasing Gonadotropin © LEIOMYOMA OF Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing A Surgical Surgical Leiomyomas (2of6) 1 • • pretreatment 2 3 months acetateUlipristal x 2-4 months agonist x GnRH LEIOMYOMAS DIAGNOSIS MIMS Yes SURGICAL MANAGEMENT MANAGEMENT SURGICAL surgical pharmacological pharmacological surgical OF LEIOMYOMA OF patient receive pre- patient receive therapy? B Should Should • • therapies: interventional Other • • • • Surgery ultrasound surgery (MRgFUS) surgery ultrasound focused resonance-guided Magnetic (UAE) embolization Uterine artery ablationEndometrial Myolysis Myomectomy Hysterectomy 3 2, 3 1 3 No © MIMS 2019 3 3 LEIOMYOMAS • • • toSurgery Pretreatment • • • • • (SPRMs) Modulators Receptor Progesterone Selective • • • • • • • • Agonists (GnRH) Hormone Releasing Gonadotropin • • • • • • • Treatment forMedical Indications • Alternative Diagnosis • • • TestsDiagnostic - Should also be considered inanemic be Should patients also tosurgery prior - acetateUlipristal preoperatively for3months isgiven duration ofoperation &complication decreased rates are also Eff ects: incombination given May be w/oraliron therapy - orpre-op anemia size) (>18 weeks' months for uterine Pretreatmentfi agonist w/ GnRH for 2-4 broids is recommended for patients w/ large uterus ofamenorrhea higher risk &menopausal loss sideeff agonist bone w/less are toGnRH non-inferior SPRMs Data showed butw/ ects changes (PAEC)]endometrial therapy w/SPRM changes occur tissue in [progesteronethe & reversible endometrial associated modulator receptor Benign - Signifi &volumeofleiomyomacantly bleeding reduces - acetateUlipristal for managementpreoperative is used of ofuterine womenfi symptoms w/ moderate to severe broids &leiomyoma &uterine volume bleeding menstrual heavy reduces acetate Ulipristal Eg Mifepristone, tocompromise shown Add-back the effi therapy notbeen has - agonists ofGnRH cacy may limitthehormones eff intreating myomaectiveness Side eff add-back by therapy using estrogen, however,progestin, or both; alleviated be can ects addition of demineralization &bone depression dryness, vaginal Significant sideeff a clinically manifesting the stem from state ofhypoestrogenism ects Treatment nomore duration than shouldbe 6months treatment cessation Approximately months experience after afew halfofthe leiomyoma within will women treated regrowth onthe May induce duration women depending ofuse insome amenorrhea - inthe 1st2months are usuallyrelieved Pressure symptoms - orrelated Menorrhagia anemia iscontrolled the 1stmonth after oftreatment - oftherapy the within 1st12weeks diminution &myoma ofuterine isachieved size Maximal - Eff ects: state thus ahypoestrogenic producing , &ovarian stimulating (LH) (FSH), hormone hormone luteinizing insignifi resulting level at receptors the GnRH pituitary Down-regulate Actions: infollicle cant reductions timeare reduced both operative &recovery Given towomen periods; inthe orpreoperative perimenopausal Triptorelin LeuprorelinEg (Leuprolide), Goserelin, adjunct toreduce apreoperative the offi size as given be Can control &improve Hblevels broids, bleeding relief symptom stand-alonetreatment as Option fortemporary indications fordelayingPersonal surgery ormedical Women contraindications w/medical tosurgery Treatment menopause ofwomen inaneff near toavoid ort surgery the uterus Symptomatic butwant topreserve patients fertility future whodonotwish - inwomen fertility w/large toattempting leiomyomas prior Preserve conception polyp endometrial sarcoma, uterine , neoplasm, ovarian Pregnancy, pregnancy, ectopic adenomyosis, - toavoid ofTVSH whowish discomfort inthose used be May also - &TVSH TVS remain after unclear considered May inwomen be & nature resonance (MRI): inwhomthe imaging location Magnetic ofthe fibroids - Transvaginal considered Should ifsubmucosal be sonohysterography fi (TVSH): are suspected broids &polyps ofmyoma the &growth adnexae inassessing Helpful Transvaginal (TVS): ultrasound Ulipristal acetateUlipristal ifw/fi of≤102g/L broids &Hblevel of≥3cmindiameter off may be bleeding menstrual Patients w/heavy intermittent (long-term upto4courses ered therapy) of their buthave fertility forpregnancy desire noimmediate age topreserve whowish toconceive ageMay include women whowish ofreproductive infertile women orsymptomatic ofreproductive presence ofintratumoral heterogeneity signal &T2-weighted hemorrhage, origin, nonmyometrial thickening menopausal status, ofthe include endometrium, age >45years, ofmalignancy predictors MRI operative hysteroscopyto planned may hysteroscopy avoid for diagnostic TVSH the in approximately need 47% of women then who can proceed Preoperative Hb is increased, &fi Hbisincreased, Preoperative inhysterectomy, loss, broid volume isdecreased; &uterine blood © &myoma uterine volume&improve menorrhagia Decrease Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing A PHARMACOLOGICAL THERAPY 2 DIAGNOSIS (CONT’D) MIMS Leiomyomas (3of6) s hotfl headaches, ushes, © MIMS 2019 LEIOMYOMAS • Other Options erapeutic • • (SERM) Modulator Receptor Estrogen Selective • Anti-InflNonsteroidal (NSAIDs) Drugs ammatory • • • Contraceptives Hormonal • • Inhibitors Aromatase • • Antifi Drug brinolytic • • Agonists Androgenic • • • • Antagonists GnRH Treatments Medical Other ofLeiomyomas • • Hysterectomy Laparoscopic • • Hysterectomy Abdominal • • • • • Hysterectomy • • • • • • • • Treatment forSurgical Indications surgery. need donotusually leiomyomas Asymptomatic potential. reproduction patient’s retain to desire offi &number size, position, &preference, onpatient’s symptoms depend age, will Type ofsurgery & broids curcumin, & vitamin D curcumin, &vitamin Telapristone, , Relugolix, gallate,Tranilast, Pirfenidone, Elagolix, of leiomyomas: epigallocatechin  investigations their are todetermine role undergoing inthe efollowing management &laboratory trials clinical towomen periods given inthe orpreoperative May perimenopausal be Eg fi from loss totreat pain,reduceUsed blood butdonotreduce volumeoffibroids, broids eff tobe notappear Do bulksymptoms inreducing ective related toleiomyoma contraceptionReduce bleeding &provide intrauterineEg exogenous -releasing system, progestins cost eff its to determine &duration ofresponse ectiveness though additional studies are needed of leiomyomas, & symptoms in size reduction have trials shown Clinical Eg including related menorrhagia tofi bleeding, uterine Decreases notreduce volumeoffi butdoes broids, broids Eg offi treat symptoms Can broids butare related tofrequent sideeffects Eg , : eff t agonist stimulation w/GnRH observed ect c ffe E gonadotropin suppressing bindingsites release Directly competeAction: w/endogenous forpituitary GnRH 3monthsat least mg twice dailyfor 0.8 by days followed mg twice daily forthe initial2 of5 usuallyat doses injectables, as Used Ganirelix Cetrorelix, Eg Abarelix, Benefi recovery pain&faster postoperative include less ts laparotomy over Preferred forfi onimaging typical broids appearing stay hospital w/prolonged Associated complications ofreduced because are removed) &cervix uterus (both is a potential alternative to total hysterectomy preserved) Subtotal hysterectomy & cervix removed (uterus toprevent premature therapyHormone menopause isneeded incontinence stress prolapse theforurinary &pelvic risk Increases  approach undergoing invasive forpatients chosen must be hysterectomy eleast whowill be women w/symptomatic fibroids uncontrolled symptoms other considered perimenopausal by May therapies inwomen be w/severe &informed orwhenfertility leiomyosarcoma isdetected Treatment ofchoice their forpatients toretain & &donotwish uterus whohave completed childbearing forleiomyosarcoma factors Other risk radiation age, &Tamoxifen are pelvic increasing use - of leiomyosarcoma rare though itremains even very Rapidly enlarging fibroids inthe premenopausal patient menopause; enlarging orafter the myoma risk raises (hydronephrosis complete symptoms after evaluation) Urinary enlarged from ordiscomfort uterus Compression symptoms Treatment ofinterstitial orintramural fi notimprove fertility broids does - w/fiInfertility thebroids onlyabnormal fi as nding Acute pain(prolapsing submucosal leiomyoma) leiomyoma ortorsionofpedunculated pressure/pain) abdominal orlower dyspareunia dysmenorrhea, Chronic pain(severe Worsening bleeding oranemia abnormal uterine from bleeding vaginal treatment tomedical Unresponsiveness Raloxifene Letrozole, Anastrozole, Fadrozole Tranexamic acid © inmyoma volumew/minorsideeff &uterine inarapid Result decrease the initial“fl lacks ects; are” A Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing PHARMACOLOGICAL THERAPY (CONT’D) Leiomyomas (4of6) B MIMS SURGERY © MIMS 2019 LEIOMYOMAS leiomyomas, which may eventually require hysterectomy which require may eventually leiomyomas, ofpreexisting &rapid growth leiomyomas ofnew allow the formation hysterectomy to alternatives All surgical • • • • (MRgFUS) Surgery Ultrasound Focused Resonance-Guided Magnetic • • • • • (UAE) Embolization Uterine Artery  Interventional Other erapies • • • Ablation Endometrial • • • &Cryomyolysis Myolysis • • Myomectomy Hysteroscopic • • • • Myomectomy Laparoscopic • • Myomectomy Abdominal • • • • Myomectomy • • Vaginal Hysterectomy • (Cont’d) Hysterectomy Laparoscopic • • • • • May be considered in symptomatic women who do not wish preservation of fertility but want to preserve the uterus the uterus but want topreserve offertility considered preservation May insymptomaticwomen be whodonotwish Volume myomectomy both after &UAE seen than isless the levels reduction mean time approachA noninvasive recovery w/shorter fi todestroy waves high-energy ultrasound focused Uses broid tissue - w/surgery complications associated &lengthy recovery Eff ects: supplytofi the blood disrupts OcclusionAction: arteries of uterine toinfarction broids leading offMay be optiontohysterectomy topatients avalidated ered &myomectomy as the &/oravoid uterus surgery topreserve butwish age women forsymptomatic whoare ofreproductive notinterestedOption inchildbearing Percutaneous that procedure involves nogeneral incision orsurgical anesthesia is nolonger desired fi w/uterine isthe mainsymptom when employed bleeding abnormal uterine May be broids <3cm,&fertility totreat generation submucosalSecond used may fi techniques be broids priming surgical needs energy; theSurgical todestroy entire procedure liningw/electricity, uterine orradiofrequency microwaves laser, freezing, ifleiomyomas are >10cmor<3 performed be Cannot myolysis formyoma treatment radiofrequency Recent development isthe ultrasound-guided - supply tothe fibroids extreme cold uses the current todestroy blood electric while cryomyolysis Myolysis employs ahigh-frequency who do notyears desire future fertility alternative a uterine-sparing to myomectomyConsidered patients in select ≥40 time recovery the shortest &has invasive Least or submucosal fi their fertility broids <4cminlength inwomen whowant topreserve therapyPreferred toremove symptomatic fibroids into that the from wall the uterine cavity have uterine grown are compared No significant diff erence outcomes inthe when reproductive laparoscopic isnoted myomectomy &abdominal complications postoperative &less more rapid recovery Provides their potential Preferable reproductive myomectomy abdominal over topreserve inwomen whowish fi toremove isolated used May be broids that ≤8cmindiameter ofthe onthe uterus outside have grown time the stay hospital longest Requires &recovery toremove largeUsed ormultiple fi intobroids that the wall deep uterine have grown w/complications related Exception pregnancy tofi are women whohave hadaprevious broids - are notanindication formyomectomy Leiomyomas inpregnancy Approximately w/myomectomy 10%ofwomen treated wouldeventually undergo hysterectomy 5-10years within offi &location Size the appropriatebroids most determine approach the uterus butwant topreserve offertility preservation orsymptomatic women fertility whodonotwish topreserve insymptomatic womenRecommended whowish the ofthe by size myomatousUse islimited uterus hysterectomy vaginal ortotallaparoscopic hysterectomyassisted compared as w/laparoscopically time&hospitalization ileus time,paralytic surgery &shorter loss blood less Has - resection uterine bloc undergoUse women oflaparoscopic morcellation whocannot toreproductive-aged power en limited shouldbe As most fi most As patients menopause, asymptomatic may during insize management have expectant broids decrease required may notbe inthe ofthe size fi therapy regression preoperative causes Medical surgery muchbroids so that cases, so insome toensure rapidly exams tumors are repeat notgrowing Periodically occur symptoms ifnew Re-assess ofpalpableRecord leiomyomas location quality oflife that haveyears shown UAE durable relief symptom provides &improves 5-7 Studies after w/patient follow-up morcellation container wherein doneinsideanenclosed tissuefragmentation be can fi malignancy, though therebroid w/an unexpected containment are now &manual forpower systems patient &complicationsInform the about risks ofthe including procedure ofcancer spread arare from © Improvement in fi of of thethe & obviation potentialuterus preservation symptoms, broid-associated C B PATIENT OBSERVATION SURGERY (CONT’D) SURGERY MIMS Leiomyomas (5of6) © MIMS 2019 LEIOMYOMAS every inj SC/IMevery 3.75mgdepot Triptorelin Leuprorelin Goserelin Analogues Hormone Releasing Gonadotropin acetate Ulipristal All dosage recommendations are for non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults non-elderly for are recommendations dosage All Drug Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed Up mth to6 Duration: of the cycle menstrual therapyStart the during 1st5days inj/day 0.1 mgSC by followed 7-10 days, 28 days or0.5mgSCinj/day for upto3mth tosurgery prior used Duration: Administer w/ Fe supplement of the cycle menstrual therapyStart the during 1st5days 3mth every a singledose mthly inj IMas or11.25mgdepot inj SC/IMonce3.75 mgdepot 1.88 mginj SC/IMonce mthly or surgery Up to3mthDuration: to prior Administer w/Fe supplement 28 days every anterior wall abdominal inj SCinto3.6 mgdepot the 4courses dose: Max course treatmentcompletion ofprevious the 2ndmenstruation following at the the during 1stwkof earliest Re-treatment shouldstart courses cycle theduring 1stwkofthe menstrual Treatment started shouldbe surgery before 24hrly forupto3mth5 mgPO © TROPHIC HORMONES&RELATED SYNTHETICDRUGS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Up to6mth may be Please see the end of this section for the reference list. reference the for section this of end the see Please Dosage Dosage DRUGS ACTINGONTHEUTERUS Dosage Guidelines MIMS Leiomyomas (6of6) • • • Instructions Special • Reactions Adverse • • • Instructions Special • Reactions Adverse acetate progestin 12days within ofstopping Ulipristal Patients acetate onUlipristal shouldavoid any cancer,breast etiology ofunknown genital bleeding - In later stages of treatment, pregnancy is Inlater stages oftreatment, pregnancy - used should be control ofbirth other methods non-hormonal discontinued totherapy shouldbe prior & OCs eliminate sideeff ofthese most ects w/estrogen/progesteroneAdd-back strategy can reactions) hypersensitivity lipids&hepatic effchanges inserum ects, inglucose tolerance reduction develop, can eff bleeding, inmenstrual (transient increase ects eff Other discomfort); abdominal (nausea, ects wkoftreatment); several GI after osteoporosis ofthe elasticity skin,headache, decreased fatigue, & irritability depression, insomnia, tenderness, breast fllibido, dryness,decreased ushes, vaginal bleeding,hot Hypoestrogenism (transientvaginal oral Avoid uncontrolled asthma in patients by w/severe hepatic impairment Use renal w/caution inpatients or w/severe treatment Monitor LFTs stopping &after during before, thickening) endometrial amenorrhea, tenderness, hotfl pain,skinreactions, (pelvic breast ushes, Other eff fatigue); myalgia, dizziness, (headache, ects GI effects eff (abdominal CNS pain,nausea); ects administered are doses recommended longas unlikely as Remarks Remarks , uterine, cervical, ovarian or or ovarian cervical, , uterine, © MIMS 2019