DYSFUNCTIONAL UTERINE DYSFUNCTIONAL UTERINE BLEEDINGBLEEDING

Ozgul Muneyyirci-DelaleOzgul Muneyyirci-Delale

Dysfunctional Uterine BleedingDysfunctional Uterine Bleeding

Dysfunctional uterine bleeding is a diagnosis of Dysfunctional uterine bleeding is a diagnosis of exclusion, and will apply in 40-60% of cases of exclusion, and will apply in 40-60% of cases of excessive menstrual bleeding.excessive menstrual bleeding.

Patterns of Abnormal BleedingPatterns of Abnormal Bleeding

OligomenorrheaOligomenorrhea

Infrequent, irregular episodes of bleeding, Infrequent, irregular episodes of bleeding, usually occurring at intervals greater than 35 usually occurring at intervals greater than 35 daysdays

PolymenorrheaPolymenorrhea

Frequent, but regular episodes of uterine Frequent, but regular episodes of uterine bleeding, usually occurring at intervals of 21 bleeding, usually occurring at intervals of 21 days or lessdays or less

Hypermenorrhea (Menorrhagia)Hypermenorrhea (Menorrhagia)

Uterine bleeding, prolonged or excessive Uterine bleeding, prolonged or excessive occurring at regular intervals (80 ml or more)occurring at regular intervals (80 ml or more)

• MetrorrhagiaMetrorrhagia• Uterine bleeding, usually not excessive, occurring at Uterine bleeding, usually not excessive, occurring at

irregular intervalsirregular intervals• MenometrorrhagiaMenometrorrhagia• Uterine bleeding, usually excessive and prolonged, Uterine bleeding, usually excessive and prolonged,

occurring at frequent and irregular intervalsoccurring at frequent and irregular intervals• HypomenorrheaHypomenorrhea• Uterine bleeding that is regular but decreased in amountUterine bleeding that is regular but decreased in amount• Intermenstrual bleedingIntermenstrual bleeding• Uterine bleeding, usually not excessive, occurring between Uterine bleeding, usually not excessive, occurring between

otherwise regular menstrual periodsotherwise regular menstrual periods

• MetrostaxisMetrostaxis• Continuous bleedingContinuous bleeding• Ovulation bleeding (pseudopolymenorrhea)Ovulation bleeding (pseudopolymenorrhea)• Spotting or light flow at time of midcycle Spotting or light flow at time of midcycle

estrogen nadirestrogen nadir• Premenstrual stainingPremenstrual staining• Spotting or light flow up to 7 days prior to Spotting or light flow up to 7 days prior to

menstruation in ovulatory cyclemenstruation in ovulatory cycle

The Major Categories of The Major Categories of Dysfunctional Uterine BleedingDysfunctional Uterine Bleeding

•Estrogen breakthrough bleedingEstrogen breakthrough bleeding•Estrogen withdrawal bleedingEstrogen withdrawal bleeding•Progestin breakthrough bleedingProgestin breakthrough bleeding•Progestin withdrawal bleedingProgestin withdrawal bleeding

Physiologic Causes of AnovulationPhysiologic Causes of Anovulation

• AdolescenceAdolescence• PerimenopausePerimenopause• LactationLactation• PregnancyPregnancy

Etiologies of Dysfunctional Uterine BleedingEtiologies of Dysfunctional Uterine Bleeding

• EndocrinologicEndocrinologic

ThyroidThyroid

HyperthyroidHyperthyroid

HypothyroidHypothyroid

AdrenalAdrenal

HyperplasiaHyperplasia

Benign/malignant tumorBenign/malignant tumor

Hypothalamic-pituitaryHypothalamic-pituitary

FailureFailure

NeoplasiaNeoplasia

HyperprolactinemiaHyperprolactinemia

Diabetes mellitusDiabetes mellitus

OvarianOvarian

Polycystic ovarian syndromePolycystic ovarian syndrome

Functioning ovarian tumorsFunctioning ovarian tumors

Sertoli-Leydig cell tumorSertoli-Leydig cell tumor

Granulosa or theca cell tumorsGranulosa or theca cell tumors

Hilus cell tumorHilus cell tumor

Chronic pelvic inflammatory diseaseChronic pelvic inflammatory disease

EndometriosisEndometriosis

Premature menopausePremature menopause

• Gonadal steroidsGonadal steroidsProgesteroneProgesteroneTestosteroneTestosteroneAdrenal androgensAdrenal androgensEstrogensEstrogensOral contraceptivesOral contraceptives

• StressStressEmotionalEmotionalExcessive exerciseExcessive exercise

• NutritionalNutritionalMarked obesityMarked obesityMalnutritionMalnutrition Anorexia nervosaAnorexia nervosa Malabsorption syndromesMalabsorption syndromes

• DrugsDrugs

Nonsteroidal hypothalamic depressantsNonsteroidal hypothalamic depressants

MorphineMorphine

ReserpineReserpine

PhenothiazinePhenothiazine

Monoamine oxidase inhibitorsMonoamine oxidase inhibitors

Anticholinergic drugsAnticholinergic drugs

ChlorpromazineChlorpromazine

Etiologic Classification of Abnormal Uterine Etiologic Classification of Abnormal Uterine Bleeding Associate with AnovulationBleeding Associate with Anovulation

Central causesCentral causes

Functional and organic diseaseFunctional and organic disease

Traumatic, toxic, and infectious lesionsTraumatic, toxic, and infectious lesions

Polycystic Ovary SyndromePolycystic Ovary Syndrome

Immaturity of the hypothalamo-pituitary axisImmaturity of the hypothalamo-pituitary axis

Psychogenic factorsPsychogenic factors

Stress, anxiety, emotional traumaStress, anxiety, emotional trauma

Neurogenic factorsNeurogenic factors

Psychotropic drugs, drug addictionPsychotropic drugs, drug addiction

Exogenous steroid administrationExogenous steroid administration

Intermediate causesIntermediate causesChronic illnessChronic illnessMetabolic or endocrine diseaseMetabolic or endocrine diseaseNutritional disturbancesNutritional disturbances

Peripheral causesPeripheral causesOvarianOvarian

Functional or inflammatory cystsFunctional or inflammatory cystsFunctional tumors, especially estrogenicFunctional tumors, especially estrogenic

Premature ovarian failurePremature ovarian failure

PhysiologicPhysiologicPerimenarchealPerimenarchealPerimenopausalPerimenopausal

Anatomic Factors Causing Nonuterine BleedingAnatomic Factors Causing Nonuterine Bleeding

• Cervical lesionsCervical lesions

Neoplasia, benign and malignantNeoplasia, benign and malignant

PolypsPolyps

CarcinomaCarcinoma

Cervical eversionCervical eversion

CervicitisCervicitis

Cervical condylomataCervical condylomata

• Vaginal lesionsVaginal lesionsCarcinoma, sarcoma, or adenosisCarcinoma, sarcoma, or adenosisLaceration or traumaLaceration or trauma

Abortion attemptsAbortion attemptsCoital injuryCoital injury

InfectionsInfectionsForeign bodiesForeign bodies

PessariesPessariesTampons, chronic usageTampons, chronic usage

Vaginal adhesionsVaginal adhesionsAtrophic vaginitisAtrophic vaginitis

• Bleeding from other sitesBleeding from other sitesUrinary tract and urethraUrinary tract and urethra Urethral caruncle, infected Urethral caruncle, infected

diverticulumdiverticulum Gastrointestinal tract and rectumGastrointestinal tract and rectum

• External genitaliaExternal genitaliaLabial varices, condylomataLabial varices, condylomataLabial traumas, inflammationLabial traumas, inflammationNeoplasia, benign and malignantNeoplasia, benign and malignantInfectionsInfectionsAtrophic conditionsAtrophic conditions

Abnormal Uterine Bleeding Associated with Abnormal Uterine Bleeding Associated with Ovulatory CyclesOvulatory Cycles

Complications of a past pregnancyComplications of a past pregnancy

Retained secundines, placental polypsRetained secundines, placental polyps

Ectopic pregnancyEctopic pregnancy

Organic pelvic diseaseOrganic pelvic disease

Neoplastic disease (benign or malignant)Neoplastic disease (benign or malignant)

Sarcoma, carcinoma, or myomata of Sarcoma, carcinoma, or myomata of uterineuterine

fundus, Fallopian tube, and/or ovaryfundus, Fallopian tube, and/or ovary

Infectious diseasesInfectious diseases

TuberculosisTuberculosis

Pelvic inflammatory diseasePelvic inflammatory disease

OtherOtherEndometriosisEndometriosis

Bleeding at ovulation (Kleine Regel)Bleeding at ovulation (Kleine Regel)Polymenorrhea due toPolymenorrhea due to

Follicular shorteningFollicular shorteningLuteal shorteningLuteal shortening

Irregular endometrial sheddingIrregular endometrial sheddingPremenstrual stainingPremenstrual stainingProlonged mensesProlonged menses

Persistent corpus luteum (Halban’s disease)Persistent corpus luteum (Halban’s disease)Blood dyscrasiasBlood dyscrasias

ITP, von Willebrand’s diseaseITP, von Willebrand’s diseaseLeukemiaLeukemia

IatrogenicIatrogenic Drugs - anticoagulants, progestational agentsDrugs - anticoagulants, progestational agents

Intrauterine deviceIntrauterine device

Systemic Bleeding Disorders Associated with Systemic Bleeding Disorders Associated with Abnormal Uterine BleedingAbnormal Uterine Bleeding

Abnormalities in primary hemostasisAbnormalities in primary hemostasis

ThrombocytopeniaThrombocytopenia

Bone marrow failureBone marrow failure

Immune: AITP, drug related, HIVImmune: AITP, drug related, HIV

Nonimmune: TTP, HUS, HELLPNonimmune: TTP, HUS, HELLP

Qualitative platelet abnormalitiesQualitative platelet abnormalities

vWDvWD

Abnormalities in secondary hemostasisAbnormalities in secondary hemostasisCongenital factor deficienciesCongenital factor deficienciesOral anticoagulantsOral anticoagulantsAcquired factor VIII inhibitorsAcquired factor VIII inhibitors

Hyperfibrinolytic statesHyperfibrinolytic states2-antiplasmin deficiency2-antiplasmin deficiency?PAI-1 deficiency?PAI-1 deficiency

Complex coagulopathiesComplex coagulopathiesDICDICLiver diseaseLiver disease

The Incidence of Endometrial Cancer in 1995The Incidence of Endometrial Cancer in 1995

Age 15 – 19 years:Age 15 – 19 years: 0.1 / 100,0000.1 / 100,000

Age 30 – 34 years:Age 30 – 34 years: 2.3 / 100,0002.3 / 100,000

Age 35-39 years:Age 35-39 years: 6.1 / 100,0006.1 / 100,000

Age 40 – 49 years:Age 40 – 49 years: 36.2 / 36.2 / 100,000100,000

Medical Option for the Management of DUBMedical Option for the Management of DUB

• IronIron• Antifibrionolytics (transexamic acid)Antifibrionolytics (transexamic acid)• Cyclo-oxygenase inhibitorsCyclo-oxygenase inhibitors• ProgestinsProgestins

Cyclic administrationCyclic administration

Continuous systemic administrationContinuous systemic administration

Local administration (IUD)Local administration (IUD)

EstrogensEstrogens

Estrogens plus progestinsEstrogens plus progestins

Androgens (Danazol)Androgens (Danazol)

Gonadotropin-releasing hormone agonist and antiagonistsGonadotropin-releasing hormone agonist and antiagonists

Surgery for Dysfunctional Uterine BleedingSurgery for Dysfunctional Uterine Bleeding

• HysterectomyHysterectomy• Endometrial ablationEndometrial ablation

HysteroscopicHysteroscopic

neodymium:yttrium aluminum garnet (Nd:YAG) laserneodymium:yttrium aluminum garnet (Nd:YAG) laser

electrocoagulationelectrocoagulation

Non hysteroscopic endometrial ablationNon hysteroscopic endometrial ablation

radio frequency electrosurgical ablationradio frequency electrosurgical ablation

location hyperthermialocation hyperthermia

cryotherapycryotherapy

microwavemicrowave

other (low-power Nd:YAG laser and photodynamic other (low-power Nd:YAG laser and photodynamic therapytherapy

Follow-up Studies of Endometrial AblationFollow-up Studies of Endometrial Ablation

• 8.5% needed repeat ablation in 3 years8.5% needed repeat ablation in 3 years

• 8.5% had undergone hysterectomy in 3 years8.5% had undergone hysterectomy in 3 yearsAccording to Chulloprem et al According to Chulloprem et al

19961996

• 34% of women had hysterectomy in 5 years34% of women had hysterectomy in 5 yearsAccording to Unger et al 1996According to Unger et al 1996

Dysfunctional Uterine Bleeding (DUB)Dysfunctional Uterine Bleeding (DUB)

Hormonal TherapyHormonal Therapy

2.5 mg Premarin po TID x 7 days, then OCP’s x 3 2.5 mg Premarin po TID x 7 days, then OCP’s x 3 weeks orweeks or

OCP’s QID x 7 days, then q day x 3 weeks orOCP’s QID x 7 days, then q day x 3 weeks or

OCP’s TID x 3 days, then BID x 3 days then q dayOCP’s TID x 3 days, then BID x 3 days then q day

Persistent BleedingPersistent Bleeding

I.V. Premarin 25 mg q 4 hr for 24 hr or until I.V. Premarin 25 mg q 4 hr for 24 hr or until bleeding stopsbleeding stops

Surgical Evaluation (Hysteroscopy, D&C)Surgical Evaluation (Hysteroscopy, D&C)

If bleeding persists in spite of hormonal therapy If bleeding persists in spite of hormonal therapy will provide tissue for pathologic diagnosiswill provide tissue for pathologic diagnosis

The initial choice of therapy should be estrogen in The initial choice of therapy should be estrogen in the following situation:the following situation:

• When bleeding has been heavy for many days When bleeding has been heavy for many days and it is likely that the uterine cavity is now lined and it is likely that the uterine cavity is now lined only by a raw basalis layer.only by a raw basalis layer.

• When the endometrial curet yields minimal When the endometrial curet yields minimal tissue.tissue.

When the patient has been on progestin When the patient has been on progestin medication (oral contraceptives, intramuscular medication (oral contraceptives, intramuscular progestins) and the endometrial is shallow and progestins) and the endometrial is shallow and atrophic.atrophic.

• When follow-up is uncertain, because estrogen When follow-up is uncertain, because estrogen therapy will temporarily stop all categories of therapy will temporarily stop all categories of dysfunctional bleeding.dysfunctional bleeding.