Abnormal Uterine Abnormal Uterine BleedingBleeding: :

Pathophysiology and Pathophysiology and Clinical ManagementClinical Management

Abnormal Uterine BleedingAbnormal Uterine Bleeding

1/3 of all outpatient gynecologic 1/3 of all outpatient gynecologic visitsvisits#1 reason for urgent hospital #1 reason for urgent hospital admission for adolescentsadmission for adolescentsAffects 50% of menstruating women Affects 50% of menstruating women worldwide at some timeworldwide at some time4 out of 5 women with AUB have no 4 out of 5 women with AUB have no anatomic pathologic conditionanatomic pathologic conditionAccounts for 50% of hysterectomies Accounts for 50% of hysterectomies in USin US

Pathophysiology of Pathophysiology of menstruationmenstruation

Normal duration 4Normal duration 4--6 days6 days , , Abnormal if <2 or >7Abnormal if <2 or >7

Normal volume 30cc (10Normal volume 30cc (10--80)80)Abnormal if >80ccAbnormal if >80cc

Normal cycle length 24Normal cycle length 24--35 days35 daysLonger for 5Longer for 5--7 years after 7 years after

menarchemenarche At least 20% of At least 20% of women have irregular women have irregular cycles. cycles. Be sure they are answering the questions you Be sure they are answering the questions you asked re: LMP and regularity.asked re: LMP and regularity.

DefinitionsDefinitions

Amenorrhea Amenorrhea -- absence of flow for 3 usual absence of flow for 3 usual cycle lengthscycle lengthsOligomenorrhea Oligomenorrhea -- cycle length >35 dayscycle length >35 daysPolymenorrhea Polymenorrhea -- cycle length <24 dayscycle length <24 daysMenorrhagia Menorrhagia -- regular cycle with heavy regular cycle with heavy volume or duration of flowvolume or duration of flowMetrorrhagia Metrorrhagia -- irregular intervals of irregular intervals of bleeding but light or normal volume and bleeding but light or normal volume and durationdurationMenometrorrhagia Menometrorrhagia -- irregular interval and irregular interval and excessive volume and durationexcessive volume and duration

Causes of AUBCauses of AUB

Vary with age of patientVary with age of patientChildhoodChildhoodPubertyPubertyReproductive YearsReproductive YearsPerimenopausePerimenopausePostmenopausePostmenopause

Case Case -- childhoodchildhood

Consulted by NICU for 1 week old Consulted by NICU for 1 week old infant with vaginal bleedinginfant with vaginal bleeding

6 year old with vaginal bleeding6 year old with vaginal bleeding

12 yo with heavy bleeding, soaking 12 yo with heavy bleeding, soaking pads in one hour for 2 dayspads in one hour for 2 days

Infant Infant

Estrogen withdrawal bleedEstrogen withdrawal bleedSarcoma botryoides (very rare)Sarcoma botryoides (very rare)

6 year old with vaginal bleeding6 year old with vaginal bleedingForeign bodyForeign bodyInfectionInfectionSarcoma botryoidesSarcoma botryoidesTraumaTraumaUrethral Urethral prolapseprolapsePrecocious pubertyPrecocious pubertyOvarian tumor Ovarian tumor -- embryonalembryonal tumor, tumor, choriocarcinomachoriocarcinoma, , polyembryomapolyembryoma, sex cord , sex cord stromalstromal tumors, etc tumors, etc –– any hormonally any hormonally active tumoractive tumor

12 year old with menorrhagia12 year old with menorrhagia

CoagulopathyCoagulopathyHypothalamic immaturityHypothalamic immaturityInadequate luteal functionInadequate luteal functionPsychogenic Psychogenic -- including anorexia and including anorexia and bulimiabulimiaOvarian tumors as beforeOvarian tumors as before

HPO axisHPO axis

Cases Cases -- Reproductive AgeReproductive Age

24 yo with oligomenorrhea q 224 yo with oligomenorrhea q 2--3 3 months, with menometrorrhagiamonths, with menometrorrhagia

30 yo with menorrhagia for 6 months 30 yo with menorrhagia for 6 months associated with new dysmenorrheaassociated with new dysmenorrhea

38 yo 2 weeks after a D&C for a 38 yo 2 weeks after a D&C for a missed AB with persistent heavy missed AB with persistent heavy bleedingbleeding

Reproductive Age Reproductive Age

Anovulation Anovulation -- #1#1Functional Functional -- coagulopathy, coagulopathy, hypothyroid, luteal phase hypothyroid, luteal phase dysfunctiondysfunctionIatrogenic Iatrogenic -- anticoagulants, anticoagulants, hormonal contraception, hormonal contraception, hemodialysishemodialysis

Reproductive AgeReproductive Age

Pregnancy related Pregnancy related –– Abortion Abortion (spontaneous, elective), retained (spontaneous, elective), retained POC, etc.POC, etc.Structural Structural -- fibroids, polyps, fibroids, polyps, hyperplasia, hyperplasia, neoplasianeoplasia, infection, infection

Case Case -- PerimenopausePerimenopause

49 yo with irregular cycles, 49 yo with irregular cycles, intermittently heavy or light with intermittently heavy or light with bleeding q 15bleeding q 15--35 days35 days

PerimenopausePerimenopause

Anovulation Anovulation -- depleted store of depleted store of oocytesoocytesStructural Structural -- fibroids, polyps, fibroids, polyps, hyperplasia, cancerhyperplasia, cancer

Case Case -- PostmenopausePostmenopause

59 yo s/p menopause age 51 with 59 yo s/p menopause age 51 with new onset bleeding new onset bleeding -- light bleeding light bleeding for 4 days, now stoppedfor 4 days, now stopped

PostmenopausalPostmenopausal

AtrophyAtrophyHRT relatedHRT relatedHyperplasia, polyps, submucous Hyperplasia, polyps, submucous myomamyomaCancer Cancer -- 10%10%One study showed 80% have One study showed 80% have structural cause structural cause

EvaluationEvaluation

History, detailedHistory, detailedExamExamPregnancy testPregnancy testLab tests Lab tests -- CBC, coagulation profileCBC, coagulation profileUS US -- SIS vs traditional vaginal USSIS vs traditional vaginal USEndometrial biopsyEndometrial biopsyHysteroscopyHysteroscopyD&C (evaluation and treatment)D&C (evaluation and treatment)

OvulatoryOvulatory vsvs AnovulatoryAnovulatory

OvulatoryOvulatory –– menorrhagiamenorrhagia with regular, with regular, cyclic bleeding, PMS symptoms, often cyclic bleeding, PMS symptoms, often have structural abnormality. Abnormal PG have structural abnormality. Abnormal PG ratios.ratios.AnovulatoryAnovulatory –– erratic bleeding , both in erratic bleeding , both in timing and volume, may have times of timing and volume, may have times of amenorrhea. Absence of cyclic progestin amenorrhea. Absence of cyclic progestin causes fragile unstructured causes fragile unstructured endometriumendometriumprone to breakage and bleedingprone to breakage and bleeding

TreatmentTreatment

Goals Goals -- control acute bleeding, control acute bleeding, prevent future abnormal bleeding prevent future abnormal bleeding and minimize the risk of endometrial and minimize the risk of endometrial cancercancerMedical Medical -- Iron, antifibrinolytics, Iron, antifibrinolytics, cyclooxygenase inhibitors, cyclooxygenase inhibitors, progestins, progestins, OCsOCs, GnRH , GnRH agonists/antagonists, agonists/antagonists, antiprogestationalantiprogestational agentsagents

TreatmentTreatment

Surgical Surgical -- hysterectomy, hysterectomy, hysteroscopichysteroscopic resection of lesions, resection of lesions, endometrial ablationendometrial ablation

Treatment OverviewTreatment Overview

OVULATORY AUBOVULATORY AUB

OCPsOCPsProgestinsProgestins, IUD, IUDTranexamic AcidTranexamic AcidNSAIDsNSAIDsGnRH with GnRH with addbackaddbackDanazolDanazol

ANOVULATORY ANOVULATORY AUBAUB

OCsOCsCyclic Cyclic progestinsprogestinsGnRHGnRH agonistsagonists

OCsOCs

#1 treatment in US#1 treatment in USRegulates cycles especially with Regulates cycles especially with anovulatory bleedinganovulatory bleedingThins lining in Thins lining in anovanov. and . and ovov. bleeders. bleedersCan use high dose (BID Can use high dose (BID -- QID) for QID) for acute bleeding, with dose reduction acute bleeding, with dose reduction as bleeding improvesas bleeding improvesNot very effective if structural Not very effective if structural problemproblem

IV PremarinIV Premarin

Useful for acute bleedingUseful for acute bleeding25 mg IV q 4 hours until bleeding 25 mg IV q 4 hours until bleeding slowsslowsCauses nausea, breast tenderness. Causes nausea, breast tenderness. Give slowly or can cause vasovagal Give slowly or can cause vasovagal reaction or LOCreaction or LOCMust give progestins for 7Must give progestins for 7--10 days 10 days after and then will have withdrawal after and then will have withdrawal bleed or start continuous bleed or start continuous OCPsOCPs

ProgestinsProgestins

Commonly used Commonly used -- norethindronenorethindrone or or medroxyprogesteronemedroxyprogesteroneCyclic vs continuous Cyclic vs continuous -- orally or via orally or via IUDIUDOne study of cyclic use in One study of cyclic use in ovulatoryovulatorywomen showed increased menstrual women showed increased menstrual flow by 20%!!flow by 20%!!MirenaMirena -- very well tolerated, reduce very well tolerated, reduce bleeding 79bleeding 79--94% 94% -- best of all best of all txtxoptionsoptions

AntifibrinolyticsAntifibrinolytics

Tranexamic acid Tranexamic acid -- reduces menstrual reduces menstrual flow by 50% 1gm QID days 1flow by 50% 1gm QID days 1--4 of 4 of periodperiodReduces flow better than Reduces flow better than NSAIDsNSAIDs, , progestinsprogestins. 45. 45--54% reduction in 54% reduction in flowflow#1 treatment in world#1 treatment in world?Concern for thromboembolic events ?Concern for thromboembolic events -- large Swedish study shows no large Swedish study shows no increase in riskincrease in risk

COX inhibitorsCOX inhibitors

NSAIDsNSAIDs -- many typesmany typesReduce menstrual bleeding by about Reduce menstrual bleeding by about 25%25%Start day prior to menses if possibleStart day prior to menses if possibleIbuprofen easy, cheap 800 TIDIbuprofen easy, cheap 800 TID

GnRHGnRH agonistsagonists

Very effective at achieving Very effective at achieving amenorrheaamenorrheaLimited by side effects (hot flashes, Limited by side effects (hot flashes, depression, depression, osteopeniaosteopenia) and cost) and costAdd back with low dose progestin Add back with low dose progestin reduces side effects significantlyreduces side effects significantlyStudy of Study of ovulatoryovulatory menorrhagiamenorrhagiapatients with add back showed 90% patients with add back showed 90% wanted to continue >12 monthswanted to continue >12 months

DanazolDanazol

Androgen Androgen –– 200200--400mg/day400mg/dayReduces flow by about halfReduces flow by about halfMore effective than More effective than NSAIDsNSAIDs or or progestinsprogestinsSide effects bothersome Side effects bothersome –– weight weight gain, acne, deepening of voicegain, acne, deepening of voice

Surgical TreatmentSurgical Treatment

Hysterectomy Hysterectomy -- definitive therapydefinitive therapyHysteroscopy Hysteroscopy -- good for structural good for structural causes, myomectomy, polypectomy causes, myomectomy, polypectomy etc.etc.Endometrial ablation Endometrial ablation -- hysteroscopic hysteroscopic or or nonhysteroscopicnonhysteroscopic techniquestechniques

HysterectomyHysterectomy

DefinitiveDefinitiveAbdominal, vaginal, laparoscopic or Abdominal, vaginal, laparoscopic or laparoscopically assisted vaginallaparoscopically assisted vaginalSupracervical also an optionSupracervical also an option550,000/year in US 550,000/year in US -- 40% done for 40% done for AUB, 50% show no pathologic AUB, 50% show no pathologic abnormalityabnormality

HysteroscopyHysteroscopy

Myomectomy, polypectomyMyomectomy, polypectomyEndometrial ablation Endometrial ablation -- laser, laser, rollerball coagulation, loop resection, rollerball coagulation, loop resection, vaporizationvaporization

NonhysteroscopicNonhysteroscopic AblationAblation

Thermal balloonThermal balloonCryoablationCryoablationRadiofrequency probeRadiofrequency probeUnipolar or bipolar electrodesUnipolar or bipolar electrodesDiode laserDiode laserPhotodynamic therapyPhotodynamic therapySuccess rates 68Success rates 68--80%, patient 80%, patient satisfaction 86satisfaction 86--96%96%

Abnormal Uterine Bleeding Abnormal Uterine Bleeding

Approach possible causes as related Approach possible causes as related to reproductive statusto reproductive statusConsider anatomic causesConsider anatomic causesConsider hormonal causesConsider hormonal causes