abnormal uterine bleeding sorting it all out · • distinguish the etiology of abnormal uterine...

Abnormal Uterine Bleeding-Sorting It All OutPatricia Geraghty MSN, FNP-BC, WHNP

Disclosures• Abbvie Inc. Speakers Bureau, Advisory Board• Therapeutics MD Speaker, Advisory Board• Sharecare Inc. Advisory Board

• No commercial material is included in this presentation. All citations are from peer-reviewed academic sources. The speaker has not been paid by any outside entity for this presentation or any presentation on this topic.

Objectives• Define the variation in normal uterine bleeding.• Distinguish the etiology of abnormal uterine bleeding

according to the PALM-COEIN classification system.• Determine age appropriate approach to the diagnostic work-

up of abnormal uterine bleeding.• Select the management strategies for specific abnormal

bleeding etiology utilizing an understanding of structural and hormonal interventions.

• Differentiate the interventions for acute heavy uterine bleeding.

Defining Normal• Normal menses (95% of population)1

• Frequency every 24 to 38 days• Duration 4 to 6 days• Blood volume 20-80 cc; requires change of protection every 3 to 6

hours on heaviest day(s)• Tapers over following days• 50% volume loss is vaginal and cervical secretions

• Regular -difference between longest and shortest interval < 20 days in 12 month period

1Fraser I, et al. Fertil Steril. 2007;87(3):466-476. ACOG Committee Practice Bulletin. Ob Gyn. 2012; 120(1):197-206. Sharp HT, Johnson JV et al. Obstet Gynecol. 2017 Apr;129(4):603-607

Updating Terminology Dimension < 5th Percentile 5th-95th Percentile >95th Percentile

Regularity cycle-to-cycle over 12 mos

AbsentAmenorrhea

Regular (variation2 ± 20d)

Irregular (typical variation >20d between longest/shortest interval)Intermenstrual

Frequency Infrequent (>38d)Oligomenorrhea

Normal Frequent (<24d)Polymenorrhea

Duration Shortened (< 4.5d)Hypomenorrhea

Normal Prolonged (> 8d)Hypermenorrhea

Volume Light (< 5 cc)Hypomenorrhea

Normal Heavy (> 80 cc)Menorrhagia

Combination Irregular and HeavyMenometrorrhagia

Sharp HT, Johnson JV et al. Obstet Gynecol. 2017 Apr;129(4):603-607

Abnormal Uterine Bleeding Etiology & Pattern: PALM-COEIN

Abnormal Uterine Bleeding (AUB)

PolypAdenomyosisLeiomyomaMalignancy & hyperplasia

CoagulopathyOvulatory dysfunctionEndometrialIatrogenicNot yet classified

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Munro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13.

FIGO Classification System

Definitions• Polyp- endometrial or endocervical

• Typically asymptomatic but may contribute to AUB• Typically histology benign w/only small fraction malignant• Detected via ultrasound and hysteroscopic imaging

• Adenomyosis- endometrial cells w/in the myometrium• Link to AUB unclear w/increasingly heavy bleeding and pain• Traditional dx histopathology s/p hysterectomy but now diagnostic

criteria through ultrasound or MRI• Leiomyoma- benign fibromuscular tumor of myometrium

• Location, number and size• Relationship to endometrium and serosa affects AUB

• Malignancy and HyperplasiaMunro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13.

• Coagulopathy- systemic disorders of hemostasis• Etiology of 13% of heavy menstrual bleeding (HMB)• Include anticoagulation therapy HMB here

• Ovulatory dysfunction- unpredictable timing, variable flow of which some are HMB• Many r/t endocrinopathies (PCOS, hypothyroid, hyperprolactinemia,

mental stress, obesity, anorexia, weight loss, extreme exercise)• Endometrial- HMB in presence of regular ovulatory cycles and no

other identifiable etiology• Documented deficiencies vasoconstrictors (endothelin-1,

prostaglandin F2α), accelerated endometrial clot lysis (excess plasminogen activator)or excess local production vasodilators.

• No clinical tests available; dx of exclusionMunro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13.

• Iatrogenic- caused by medical intervention or device• Direct impact on endometrium, blood coagulation or systemic

control of ovulation• Unscheduled bleeding aka break through bleeding (BTB) while on

gonadal steriods• Effect both the HPO axis and the endometrium directly• Missed/delayed doses

• Drug effect: anticonvulsants, rifampin & griseofulvin, cigarettes• Dopamine metabolism effects (tricyclic antidepressants,

phenothiazines) reduce serotonin uptake and inhibit prolactin release.

• Any SSRI can cause ovulatory dysfunction w/amenorrhea or irregular• Not yet classified- connection unclear or not yet identified

• Ovarian follicular phase- follicle develops in response to FSH from the pituitary and secretes estrogen. Estrogen stimulates growth, or proliferation of the endometrium.

• Ovulation- High levels of estrogen trigger LH from the pituitary, which causes ovulation. The follicular structure becomes the corpus luteum, and secretes progesterone.

• Ovarian luteal phase- Progesterone halts growth and causes maturation of the endometrium.The endometrium becomes secretory. The corpus luteum degenerates over 14 days. Estrogen and progesterone levels fall, triggering increase in FSH.

The Menstrual

Cycle

Managment Acute Heavy Menstrual Bleeding• Estrogen/Progesterone Sequential

• Conjugated estrogen 10 mg (2.5mg po q 6h) to cause rapid growth of endometrium over denuded basalis

• Controls bleeding within 24 hours• May need antiemetic• Alternate IV estrogen 20-25 mg every 3-4 hours x 24 hours

• After bleeding slows dramatically (12-24 hours), add progestin MPA 5-10 mg to stabilize endometrium

• Continue both estrogen and progestin for 7 to 10 days• Close follow up

Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott, Williams & Wilkins. 2011.

Alternate Protocol Acute HMB• Estrogen/Progesterone Combined

• High dose birth control pill (Norgestrel 0.5mg/EE 50 mcg; Ovral®)• 1 Tablet PO Q 12h x 5-7 days, then 1 tablet QD to finish pill pack.

• May taper sooner if bleeding is controlled, and if patient complains of side effects

• One study found this protocol less effective than sequential but compliance was better

• Follow up 7-21 days• Continue Norgestrel 0.5 mg/EE 50 mcg or Conjugated estrogen

2.5mg PO with MPA 5-10 mg• Begin diagnostic work up

Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott, Williams & Wilkins. 2011.

Management Acute Heavy Bleeding With Concerns About Estrogen Use

High Dose Progestin Treatments for Acute Uterine Bleeding (n=40)

MPA 20 mg 3 times daily x 7 days, then

once daily x 3 weeks

Norethindrone 1 mg/EE 35 mcg 3 times daily x 7 days, then once daily x 3

weeksNo Surgery 100% 95%Cessation of Bleeding 76% 88%Days to Cessation 3 3Patient Satisfaction 0-40 = unsatisfied

3 3

Munro MG, et al. Obstet Gynecol. 2006; 108(4): 924-29.

Acute Bleeding Tranexamic Acid• Anti-fibrinolytic

• Data from CRASH-2 (trauma) and WOMAN (obstetrical hemorrhage) extrapolated to other acute bleeding

• 1 g (100 mg/ml) at 1 ml/min IV• Only effective if initiated within first 3 hours of bleeding in PP

hemorrhage• Meets ACOG guidelines for therapy

CRASH-2 Collaborators. Lancet. 2010;376:23–32. WOMAN Trial Collaborators. Lancet. 2017 May 27; 389(10084): 2105–2116. ACOG Committee Opinion 557. Obstet Gynecol. 2013 Apr;121(4):891-6. ACOG Committee Opinion 785. Obstet Gynecol. 2019; 134(3)e71-83.

OFF LABEL

https://www.ncbi.nlm.nih.gov/pubmed/23635706

Approach to Work-up




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Parameters for Evaluation• Evaluate any woman with

• Cycles < 24 days or > 38 days• Duration > 7 days• Volume > 80 ml

• Evaluate any woman whose perception of her cycles is that of interfering with typical daily activities or of causing concern• Deviations from individual’s established pattern

• AAP and ACOG call the menstrual cycle a “vital sign” in adolescents• Cycles established within 3 years of menarche; evaluate any change,

evaluate any pattern of cycles > 90 daysACOG Committee on Adolescent Medicine Opinion No. 349. Obstet Gynecol. 2006:180(5):1323-28. AAP Committee on Adolescence , et al. Pediatrics. 2006; 118(5): 2245050.

19 y with HMB and Irregularity• She reports irregular cycle length of 14 to 60 days• Both flow and duration vary from 5-10 days of light spotting to

4 days heavy bleeding followed by spotting.• The heavy flow days require changing protection every 2 hours

• There are no temporal associations (post-coital, post-pill, weight gain or loss)

• She has associated symptoms of cystic acne and complains it is harder for her to maintain her weight than for her friends

• She is not on any medications and denies tobacco use.• She is not sexually active and STD screen is up to date.




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19 y with HMB and Irregularity

Ovulatory Dysfunction• Physiologic unopposed estrogen causes heavy but

unstable endometrium• Irregular heavy bleeding w/o typical moliminal

symptoms mixed with spotting d/t partial endometrial sloughing

• Life stage is most common contributing factor• Menarche followed by 2 to 3 years of infrequent cycles• Early perimenopause (age 40-42) frequent and heavy cycles• Late perimenopause cycles infrequent, flow is variable

Polycystic Ovarian Syndrome (PCOS)

• Increased peripheral aromatization of androgens to estrogen

• Decreased SHBG increased free testosterone and estrogen

• Peripheral insulin resistance Increased insulin increased ovarian production of androgens

PCOS Diagnostic Criteria• 4 phenotypes with menstrual irregularity as the hallmark

symptom• Phenotype A (75%):

• Clinical and/or biochemical hyperandrogenism (HA) +• Oligo-/anovulation (OA) +• Polycystic ovarian morphology (PCOM)

• Phenotype B: HA + OA• Phenotype C: HA + PCOM• Phenotype D: OA + PCOM

• Phenotype B incorporates into Type A if elevated serum anti-Mullerian Hormone (AMH) used v. PCOM

Goodwin NF, Cobin RH, Futterweit W, et al. Endocr Pract. 2015 Nov;21(11):1291-300.Fraissinet A, Robin G, Pigney P, et al. Hum Reprod. 2017 Aug 1;32(8):1716-1722.

• Polycystic ovary morphology present in 75% of anovulatory women and 8-25% normally menstruating women

• 14% women on hormonal contraceptives meet PCOS sonography criteria.

• Obesity present in 30-60%

Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed.Lippincott, Williams & Wilkins. 2011.

Laboratory Testing & Imaging“For the majority of women with true anovulatory bleeding, the menstrual

history alone can establish the diagnosis with sufficient confidence that treatment can begin without additional laboratory evaluation or imaging.”1

• Labs• Pregnancy• CBC• Ferritin• TSH• Free testosterone• AMH• FSH• Progesterone day 22-24• Coagulation Studies

• Imaging• Transvaginal Ultrasound

including endometrial stripe measure

• PCOM > 25 small follicles per ovary

1. Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott, Williams & Wilkins. 2011;p.602. Goodwin NF, Cobin RH, Futterweit W, et al. Endocr Pract. 2015 Nov;21(11):1291-300.




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What if 19 y HMB & Regular?

Coagulopathy• Bleeding Disorders

• 47% prevalence hemostatic disorder in 115 women presenting with heavy bleeding:1

• Platelet aggregaton 44%• Von Willebrand Disease (VWD) 7%• Coagulation factors 5%• Defects seen in all age groups <20, 21-44, >44

• Platelet defects affect 1-3% of US population2

• Adolescents presenting with heavy bleeding had 33% incidence VWD3

1Phillip CS, et al. Obstet Gynecol. 2005; 105:61-6. 2Boshert S. Ob Gyn News. 2008; 11:19. 3Mikhail S, et al. Haemophilia. 2007; 13:627-32.

Coagulopathy Clinical Screen• Screen Positive indicates laboratory work up

• Heavy menses since menarche• One Of:

• Postpartum Hemorrhage• Surgery-related bleeding• Bleeding associated w/dental work

• Two or more of:• Bruising 1-2 times/month• Epistaxis 1-2 times/month• Frequent gum bleeding• Family history of bleeding symptoms

Kouides PA, Conard J, Peyvandi F, et al. Fertil Steril. 2005;84(5):1345–1351

Identifies 90% of AUB-C

Laboratory Evaluation Coagulopathy• First Level Studies

• CBC with platelets, Ferritin• Partial Thromboplastin Time• Prothrombin Time• Ristocetine cofactor activity and antigen (VWF)*• FVIII*• Fibrinogen and thrombin time optional

• Second Level Studies• Platelet aggregation• Platelet release

*repeat during menses if low normal

ACOG Committee Opinion 785. Obstet Gynecol. 2019; 134(3)e71-83

Labs of Pregnancy, CBC, TSH still apply

AUB-E: Controlling Menstrual Volume & The Role of Prostaglandins

PGE2 yields vasodilationProstacyclin inhibits

platelet aggregation

PGF2α yields vasoconstrictionThromboxane promotes

platelet aggregation

• Both PGE2 and PGF2α increase with menses

• Ratio PGF2α :PGE2 increases near menses

• Women with HMB have higher levels of prostaglandins and prostacyclinin menstrual flow, and more PG receptors in endometrium

• PGE2 > PGF2α ratio is reversed

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19 y With Light or Absent Menses?

Central Nervous System Induced• Hyperprolactinemia (typically associated galactorhhea)• Hypothalamic Amenorrhea

• Stress, Malnutrition• Excessive hypothalamic activity of corticotropin

releasing hormone (CRH) disrupts GnRH pulsatility• Hypoestrogenic• Continuum from inadequate luteal phase anovulation absent menses

• Infrequent and light bleeding to no bleeding


Female Athlete Triad• First described 1993• Combination of one or all of following symptoms

• Disordered eating• Infrequent menses/Absent menses• Low bone mass

• Enter care typically because of amenorrhea• Focus of treatment is on malnutrition

Nattiv A, Loucks AB, Manore MM, et al. The American College of Sports Physicians Position Statement Female Athlete Triad. J ACSM. 2007:1867-1882. Doi:DOI: 10.1249/mss.0b013e318149f111

Premature Ovarian Insufficiency• Cessation of ovarian function ≤ 40 y

• Spontaneous• Iatrogenic – surgery, chemotherapy, radiation

• Long term health consequences• Decreased bone mineral density and increase fracture

risk 1.5• Cardiovascular disease risk increase• Overall mortality increase

Podfigurna-Stopa A, Czyzyk A, Grymowicz M, et al. J Endocrinol Invest. 2016; 39: 983–990.

Laboratory Testing & Imaging• Labs

• Pregnancy• TSH• Prolactin• Estradiol (fluctuates)• FSH (fluctuates)• Progesterone withdrawal• Genetics POI spontaneous

• Imaging• Transvaginal Ultrasound

including endometrial stripe measure

• MRI with contrast with prolactinemia

1. Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed.Lippincott, Williams & Wilkins. 2011;p.602.

OR




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What if 46 y HMB & Regular?

Adenomyosis• Regular painful menses gradual worsening +/- HMB; Painful intercourse• Enlarged uterus +/- tender• Heterogenous myometrium on ultrasound

Wikipedia.org

Uterine Leiomyoma (Fibroid)• Pelvic pressure,

painful intercourse, +/- HMB 2° location

• Irregular +/- enlarged uterus

• Ultrasound imaging diagnostic

commons.wikipedia.org




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What if 46 y HMB & Irregular?

Ovulatory Dysfunction: Perimenopause• Primordial follicular depletion d/t aging

• Follicular development w/inconsistent ovulation

• Hormone levels rarely contribute to diagnosis or management• Perimenopause characterized by fluctuating hormone

• Cycles closer and bleeding heavier

Harvard Women’s Health Watch. Perimenopause. September 1999. used with permission

(180 days)

Evaluation Ovulatory Dysfunction > 45 y

• Labs• Pregnancy• CBC• TSH• AMH

• Labs NOT useful• FSH• Estradiol

• Imaging• Transvaginal

Ultrasound including endometrial stripe measure

• Endometrial biopsy

Burger HG. Menopause Int. 2011 Dec;17(4):153-4.

Co-morbidities common

When Endometrial Biopsy?• All women over 45 years and younger women with high risk1

• Nulliparous, obesity, family history of endometrial cancer • ACOG Practice Bulletin 136; 2013

• Sensitivity of Transvaginal Ultrasound Endometrial Stripe• Endometrial stripe <5 mm is 99%+ negative predictive value • Reasonable first approach• ACOG Committee Opinion 734; 2018

• Persistent bleeding, even with negative pipelle sampling biopsy, needs further testing s/a hysteroscopy with D&C.

ACOG. Obstet Gynecol 2018;131:e124–9.




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What if 55 y Postmenopause?

Endometrial Neoplasia or Atrophy?• Postmenopause bleeding risk endometrial cancer 4.9-

11.5% with peak over 60 y (13%) • 90% endometrial cancer first presented as postmenopause

bleeding• Associated risk factors obesity, delayed menopause, diabetes,

family hx, tamoxifen

• Benign neoplasms polyps• Endometrial atrophy can also cause bleeding

Munro MG. Perm J. 2014 Winter; 18(1): 55–70. ACOG Comm Opin No. 440. Obstet Gynecol 2009 (reaffirmed 2013);114:409–11

Evaluation Perimenopause Bleeding• First line transvaginal ultrasound (TVS) perimenopausal women

with long cycles and all postmenopausal bleeding• Endometrial thickness regular and ≤ 4 mm is 96% sensitive to rule

out cancer and 92% sensitive for other endometrial pathology.• Endometrial thickness > 4 mm should have endometrial biopsy

• Pipelle endometrial sampling (ES)• Hysteroscopic directed biopsy (HDB)• HDB if ES insufficient

• Relative sensitivity TVS .88, ES .90, HDB .91• Hysteroscopic sampling any woman with negative TVS or ES with

continued bleeding

ACOG Comm Opin No. 734. Obstet Gynecol 2018;131:e124-9. Deuholm MM, Marinovskij E, Hansen E, et al. Menopause. 2015;22(6):616–626




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Management

Surgical ExcisionHysterectomyLNG-IUD

HysterectomyUterine Artery Embolization

Hysterectomy/ D&C, Progestin

Modify offending agent

AUB Management Strategy• Treat organic pathology• Control ongoing blood loss and restore

hematologic status• Coordinate endometrial sloughing• Normalize prostaglandins• Suppress endometrium

• Protect against hypoestrogenic sequellae

Medical Management• Combined Oral Contraceptive (COC)/Patch/Ring• Progestin Only: Continuous or cyclic*, injectable• NSAID• GnRH agonist/antagonist• Antifibrinolytics/ Tranexamic acid*• LNG-IUS (Mirena®)*

*Cyclic progestin, tranexamic acid and LNG-IUS are the only FDA approved therapies for heavy menstrual bleeding. All other therapeutics are off label.

Combined Oral ContraceptivePill/Patch/Ring• Provide contraception while maintaining future fertility• Increase regularity and reduce duration &volume of

bleeding • Consider extended cycles• Only one study of COC on women with HMB, 43%

volume reduction1

• Provide estrogen in premature ovarian insufficiency1Fraser IS, McCarron G. Aust N A J Obstet Gynaecol. 1991; 31(1):66-70.

OFF LABEL

Progestin Only: Continuous or Cyclic, Long-acting Injectable• In anovulatory women, restores normal sequence of endometrial

steroid hormone stimulation• Estrogen Estrogen plus Progesterone Withdrawal Bleed

• DMPA IM or SQ suppresses gonadotropins thinned endometrium• Does not provide contraception• Anti-estrogenic activity reduces blood volume but increases

irregularity• Less effective to treat HMB than other pharmacological treatments

(danazol, tranexamic acid, NSAIDs, and LNG-IUS)• May have bloating, breast tenderness, reversible bone density loss

Lethaby A, et al. Cochrane Database Syst Rev. 2008; (1):CD001016. Pinkerton JV. Menopause. 2011;18( 4 ):459-467

Progestin Regimens• Cyclic MPA 10 mg daily days 15 to 26 of cycle.

• FDA approved• Equivalent dose micronized progesterone 200mg

• Alternate regimens • Norethindrone 5 mg days 19-26• MPA 5 mg daily• DMPA 150 mg IM every 11 to 13 weeks• Progestin only contraceptive pills

NSAID• Reduce prostaglandin production when used in higher doses.

• Good choice for women with associated painful menses or who desire conception

• 30% reduction menstrual blood loss• No single NSAID regimen superior to any other NSAID• Less effective to treat HMB than tranexamic acid, danazol, or

LNG-IUS

Lethaby A, et al. Cochrane Database Syst Rev. 2007; (4): CD00040040

NSAID Regimens• Mefenamic acid

• 500 mg TID day one of menses x 4 to 5 days• 500 mg TID starting 4 to 5 days before menses through cessation• 500 mg initially, 250 mg QID for 3 to 5 days

• Naproxen• 500 mg onset menses. Repeat dose in 3 to 5 hours, then 500 mg BID for

5 days• 500 mg AM/250 mg PM for 2 days, then 250 mg BID for 7 days• 500 mg initially, then 250 mg QID for 4 days• 500 mg initially, then 275 mg QID for 5 days

• Ibuprofen• 600 mg daily or 1200 mg daily • 800 mg TID for 5 days

Lethaby A, et al. Cochrane Database Syst Rev. 2007; (4): CD00040040

GnRH Agonists/Antagonists*• Down regulate* GnRH receptors leading to FSH and LH with

subsequent estrogen and progesterone• Hypoestrogenic effects hot flashes, vaginal dryness, loss of

bone mass limit duration of treatment• Extend agonist treatment beyond 6 months with add back

progestin• More effective to treat HMB d/t endometriosis than placebo,

progestins, NSAID, and COC

Pinkerton JV. Menopause. 2011;18( 4 ):459-467

Anti-fibrinolytics: Tranexamic Acid• Blocks conversion of plasminogen to clot dissolving plasmin• Approved by FDA for treatment HMB

• 2 tablets of 650 mg TID for 5 days during menses• Contraindicated with history of or increased risk for VTE• Should not be used in conjunction with combined hormonal

contraception• Cochrane Review TXA

• More effective than placebo, NSAIDS, herbals in blood loss and likelihood of improvement

• Equal efficacy progestins, higher likelihood of improvement• Less effective LNG-IUD

Pinkerton JV. Menopause. 2011;18( 4 ):459-467. Bryant-Smith AC, et al Cochrane Data Base SytemicRev. 2018 Apr 15;4:CD000249.

LNG-IUS • Local progestin effect cause insensitivity to estrogen and

endometrial atrophy• FDA approved for women with HMB who chose intrauterine

contraception (Mirena©)• Provides highly reliable contraception

• Reduction blood loss 86% at 3 months and 97% at 6 months• 20-50% women achieve amenorrhea within one year use

• Patient satisfaction superior to any other medical treatment, equal to endometrial ablation.

Pinkerton JV. Menopause. 2011;18( 4 ):459-467

Endometrial Ablation• Indicated for HMB

• women who may have failed medical therapy• have no desire for future fertility; must have highly

reliable contraception• have a normal endometrial cavity

• Outcome is normalization of menstrual flow, not amenorrhea

• Must rule out malignancy and endometrial hyperplasia• Identify location of any leimoyoma

Post Ablation Satisfaction• Satisfaction > medical therapies; = LNG-IUS

• 5 years RCT only 10% continued medical tx• 77% of medical had undergone surgery compared ablation 27% further

surgeries (18% hysterectomies)1

• Equal decrease in bleeding and improvement in quality of life over 2 years after LNG-IUS and both first and second generation endometrial ablation techniques.2

• No difference between rates of treatment failures (21.2% LNG-IUS vs17.9% ablation)

• 8 Year follow up of 3,681 women post endometrial ablation3

• 21% has subsequent hysterectomy; 3.9% had uterine-conserving procedures - 2.1 x hysterectomy if ≤ 45 years3

1ACOG. Obstet Gynecol. 2007; 109:1233-48. 2Neuwirth RS, et al. J Am Assoc Gynecol Laparosc. 2004; 11(4):492-4. 3Valle RF, Baggish MS. Obstet Gynecol. 1998; 179(3): 569-572.

Non-uterine Sources of Bleeding• Infection

• Cervicitis• Endometritis

• Vaginal• Trauma• Foreign body

• Systemic Disease• Liver cirrhosis or active hepatitis• Renal failure

abnormal uterine bleeding sorting it all out · • distinguish the etiology of abnormal uterine...

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