DYSFUNCTIONAL UTERINE BLEEDING. Betty Anne Johnson, M.D., Ph.D. Professor of Medicine Director, University Student Health Services March, 2001

Transcription

1 DYSFUNCTIONAL UTERINE BLEEDING DEFINITIONS: Betty Anne Jhnsn, M.D., Ph.D. Prfessr f Medicine Directr, University Student Health Services March, 2001 Dysfunctinal Uterine Bleeding (DUB): excessive, prlnged, r irregular uterine bleeding in a reprductive aged wman wh lacks pelvic rgan disease r a systemic disrder. Menrrhagia: excessive uterine bleeding ccurring at the regular intervals f menstruatin, the perid f flw being greater than usual in duratin Metrrrhagia: uterine bleeding f a nrmal amunt, ccurring at cmpletely irregular intervals Menmetrrrhagia: excessive uterine bleeding ccurring bth during the menses and at irregular intervals Oligmenrrhea: markedly diminished menstrual flw; relative amenrrhea; infrequent menstruatin Hypermenrrhea: excessive uterine bleeding ccurring at regular intervals, the perid f flw being f usual duratin Hypmenrrhea: uterine bleeding f less than nrmal amunt ccurring at regular intervals, the perid f flw being f the same r less than usual duratin GENERAL CONSIDERATIONS 10-15% f pts referred t gyneclgists are treated fr DUB. Half f these are perimenpausal; 20% are perimenarchal and the rest are in the reprductive age grup Mst cases f DUB are assciated with vulatry dysfunctin. Yu MUST make the crrect dx t rx prperly!

2 THE NORMAL MENSTRUAL CYCLE The nrmal menstrual cycle is a result f cmplex interactin between hypthalamus, anterir pituitary, vary and endmetrium. Maturatin f the endmetrium is relatively uncmplicated (cmpared with the maturatin f the cyte) and is slely dependent upn tw hrmnes, estrgen and prgesterne. The first half f the menstrual cycle (prliferative phase) is estrgen dependent resulting in grwth f the endmetrium frm 1 t 5 mm at the time f vulatin. The secnd half f the menstrual cycle (secretry phase) is prgesterne dminant. Prgesterne halts the grwth f the endmetrium and stimulates secretry activity in the endmetrium. Menstruatin ccurs when bth prgesterne and estrgen levels fall after the failure f cnceptin. Synchrnus shedding f the endmetrial lining ccurs. **Nte** Randm breakdwn f the endmetrial lining (DUB) des NOT ccur when the endmetrium has been adequately primed with estrgen and stabilized with prgesterne. Nrmal menses: Last 2-7 days Bld lss ranges frm ml (average 30-35ml) Mean cycle length is 29 days (range days) EVALUATION OF ABNORMAL UTERINE BLEEDING 1. First decide if this is really abnrmal bleeding and is an evaluatin justfied? Islated events may nt be wrth pursuing. 2. It is nearly impssible t estimate bld lss frm histry. Cltting r bleeding > 7 days suggest substantial bld lss but the nly bjective way t quantitate bld lss is by checking a CBC. Hct < 30 implies significant bld lss. ** Bleeding at a rate f saking a tampn r pad in an hur fr at least 2 cnsecutive hurs implies PROFUSE bleeding. Orthstatic hyptensin implies hemdynamic instability. Urgent evaluatin is imperative!!

3 3. The clratin f the bld can ften give clues t the etilgy f the abnrmal bleeding. Brwn r prune-clred discharge superimpsed upn regular red menstrual bleeding is mst cmmnly caused by an bstructed genital tract. It may be heavy, initially cntinuus, and mst ften will be nted immediately after a menstrual perid. Endmetrisis als causes brwn discharge but this is usually premenstrual. Cervical endmetrisis and stensis trap bld within the endmetrial cavity. As the cervix dilates late in the cycle, the trapped ld bld and by-prducts are allwed t empty frm the cavity. 4. Next decide if the bleeding is vulatry r anvulatry. Ovulatry bleeding: Bleeding which ccurs at regular intervals and is preceded by premenstrual symptms: Breast tenderness Water weight gain Md swings Abdminal cramping Anvulatry bleeding: prlnged bleeding ccurring at irregular intervals fllwed by mnths f amenrrhea 5. T determine if the wman is vulating, it may help t: D Basal Bdy Temperature determinatins (vulatin shuld increase bdy temperature by half a degree r s during the last 2 weeks f the cycle). Perfrm vulatin predictr tests Measure prgesterne levels (>9.5 nml/li r > 3 ng/ml is evidence that vulatin has taken place) Endmetrial bipsy shwing secretry changes cnfirms vulatin OVULATORY DUB Ovulatry bleeding is mre likely t be assciated with an anatmic r rganic cause such as fibrids, infectins, laceratins, r plyps. Pregnancy-related causes f DUB: Ectpic pregnancy Spntaneus abrtin Incmplete abrtin Threatened abrtin

4 Retained prducts f cnceptin Placental prducts Trauma at delivery Trphblastic disease Inflammatry causes f DUB: Endmetritis: prlngatin f nrmally timed menses r irregular sptting Cervicitis: prlngatin f nrmally timed menses r irregular sptting Vaginitis: infectin with Trichmnas can cause persistent sptting superimpsed upn nrmal cyclic bleeding IUD: prlnged heavy bleeding during nrmally timed menses Freign bdy: retained tampn r diaphragm results in irregular sptting usually f ld bld Laceratins Systemic Diseases which cause DUB: Bld dyscrasias (ITP, Vn Willebrand s): Pts with Vn Willebrand s may have nrmal PT, PTT but abnrmal bleeding times. Vn Willebrand s disease is the mst cmmn inherited cltting disrder that can present at menarche as severe menrrhagia. Malnutritin Anticagulant therapy Thyrid disease Tumrs which cause DUB: Fibrids: submucus mymata are ntrius fr causing prlnged heavy bleeding; cmmn in lder wmen and in African Americans. Submucus fibrids are nt bvius n exam (try endvaginal ultrasund) Adenmysis Endmetrisis: mst cmmnly presents with luteal phase sptting characterized by dark brwn r prune clred discharge Plyps Cervical: ften pst-cital sptting Uterine: may present with prlnged trail-ff sptting at the cnclusin f a nrmally timed menses r persistent sptting thrughut the cycle Endmetrial hyperplasia Cervical hemangimas: very heavy bleeding, ften after trauma Cancer f the cervix, endmetrium, r fallpian tubes

5 ANOVULATORY DUB Anvulatry DUB can be secndary t chrnic unppsed estrgen r estrgen withdrawal In chrnic unppsed estrgen states, the endmetrium is cntinuusly stimulated by estrgen which causes prliferatin withut the stabilizatin frm prgesterne. The endmetrium slughs in an irregular and incmplete manner. Areas that have shed begin t heal under the influence f cntinuus estrgen. This randm, nn-unifrm shedding/healing can cause prfuse and prlnged bleeding. In estrgen withdrawal states, estrgen levels may rise but insufficiently t trigger an LH surge. Bleeding ccurs when estrgen levels fall. There are bth physilgic and pathlgic causes f anvulatry bleeding. Physilgic Causes: 1. Puberty: The first cycles after menarche are anvulatry and the bleeding is secndary t estrgen withdrawal. This bleeding is usually light t mderate and ccurs at d intervals. 2. Perimenpausal: The peak estrgen level attained as a wman nears menpause will nt be sufficient t trigger an LH surge and vulatin fails. Bleeding ccurs because f estrgen withdrawal. Pathlgic Causes: Dysfunctin can ccur at any level f the hypthalamic-pituitaryvarian axis. 1. Ovarian Failure: can be premature and assciated with an autimmune prcess 2. Hypthalamic amenrrhea: can be frm weight lss, emtinal stress r chrnic illness 3. Plycystic Ovary Syndrme: assciated with besity, hirsutism, infertility and anvulatry DUB 4. Other causes: hyperprlactinemia

6 EVALUATION OF DUB 1. Histry:?frequency and amunt f bld flw (***Remember** Saking 1 pad r tampn in an hur fr at least 2 hurs cnstitutes wrrisme flw)?dysmenrrhea?bruising?epistaxis?gingival bleeding?perimenpausal symptms?sexual behavirs 2. Physical examinatin: Check rthstatics?pale cnjunctiva?cervical plyp?enlarged uterus 3. Labs: CBC (stat, if indicated) hcg Pap smear Chlamydia Gnrrhea 4. As indicated: Endvaginal ultrasund Peripheral smear Cagulatin prfile (plt, PT, PTT, bleeding time) TFTs, prlactin, LH, FSH Wet preps Endmetrial bipsy: Age 35 Clinical suspicin f prlnged unppsed estrgen state (PCOS, iatrgenic unppsed estrgen)

7 MANAGEMENT OF DUB 1. The apprach t stpping the initial bleeding depends upn the severity. Fr acute prfuse bleeding: 1. Cnsult gyneclgy 2. If the patient is hemdynamically stable: a. ral cntraceptives: 2. 1 tablet qid fr 5-7 days. Flw shuld cease within hurs. Within 2-4 days f stpping therapy, the pt shuld experience heavy, crampy flw. On the fifth day f flw, start a lw dse OC daily fr at least three 28 day cycles alng with FeSO4 supplementatin 3. Alternatively, 1 tablet qid until bleeding stps. Begin FeSO4. Once bleeding stps, taper pills by taking 1 pill q 8 hrs x 3 d; then 1 pill q 12 hrs x 3 d; then 1 pill daily t cmplete the 21 day cycle. Cycle n lw dse OC s fr 3-6 mnths. With each successive cycle, the pt s bleeding shuld becme lighter and shrter. 4. Alternatively, t avid a withdrawal bleed immediately after stpping DUB, use a 21-day mnphasic pill packet r a 28-day pill packet with the 7 placeb pills remved t stp acute bleeding as abve. When the initial packet is empty, immediately begin a new 28-day packet f at least 35 micrgram pills. Warn the pt that the first menses n this packet is likely t be heavy because f endmetrial thickening in respnse t the estrgen. It will lighten ver the subsequent mnths. She shuld stay n the OC s at least anther 3 mnths. 3. If the patient is nt hemdynamically stable: refer t gyn fr IV premarin r D&C. Fr chrnic DUB, the apprach depends upn yur best judgment abut whether the patient is vulatry r anvulatry and the cause f the DUB: Medrxyprgesterne acetate and megestrl acetate are effective ral prgestatinal agents which can be used t stp anvulatry bleeding. Medrxyprgesterne acetate (Prvera) can be given at mg/d in divided dses and cntinued fr 5-10 d. This apprach wrks well in patients in whm there is sufficient endmetrium remaining t allw prgestin induced stabilizatin. Lng-term therapy can be accmplished with cyclical prgestins (10 mg Prvera daily fr 14 days/mnth). Again, fr anvulatry bleeding, since all ral cntraceptives are prgesternedminant, any lw dse mnphasic ral cntraceptive can be administered at a dse f 1-4 pills per day and cntinued fr 1 week and then decreased t ne pill a day. Bleeding shuld slw r stp within hurs f starting the OC; if nt, further investigatin is warranted. The estrgen prvides the benefit f a grwth and healing effect n the endmetrium s that prgesterne will have its maximal effect. OC s may be cntinued fr 3-6 mnths.

8 Prgesterne alne has prven useful in management f DUB assciated with fibrids. DepPrvera injectins cmpletely atrphy the endmetrium and thus stp bleeding. Estrgen alne als has a rle in the treatment f DUB. Lng term treatment with ral cntraceptives r prgestatinal agents such as Nrplant r DepPrvera result in atrphic changes in the endmetrium that make it prne t bleeding. Reslutin f this bleeding can be achieved by adding ug f ethinyl estradil r 1.25 t 2.5 mg cnjugated estrgen fr 10 d t 3 mnths. Cyclic NSAID s will reduce the amunt f flw during regularly timed menses and will als relieve cramps. Advise the patient t begin NSAID 1-2 days befre their menses and cntinue regular dses f the NSAID thrughut the menses. Begin irn therapy and cntinue fr 3-6 mnths while mnitring Hct. INDIVIDUALIZED APPROACH TO TREATMENT OF DUB Adlescent: Anvulatry bleeding after menarche is cmmn. If the bleeding is nt significant, then bservatin alne is sufficient Rule ut pregnancy, even in the adlescent wh denies sexual activity Adlescents wh present with heavy vaginal bleeding after several mnths f amenrrhea are best treated with OC s. Treatment can be stpped after 3-6 mnths t see if a nrmal menstrual cycle has been established. Acute Anvulatin: Mst wmen with nrmal menstrual cycles will ccasinally have an anvulatry cycle that can result in prtracted bleeding. Rule ut pregnancy first and then treat with a single curse f a prgestatinal agent such as 10 mg Prvera fr 5-10 d. If the bleeding des nt reslve in hurs, then yu must rule ut anther cause f the bleeding Chrnic Anvulatin: Mnthly administratin f a prgestatinal agent will result in regular endmetrial shedding which will prtect against endmetrial cancer. A 12 day curse f medrxyprgesterne at 10 mg/d shuld be adequate. If ccasinal vulatin cannt be ruled ut and the wman des nt desire pregnancy, then ral cntraceptives are a better chice. Any wman with at least a 1 year histry f anvulatin shuld be referred t a gyneclgist fr endmetrial bipsy

9 Perimenpausal Wmen: Many perimenpausal wmen fluctuate between vulatry and anvulatry cycles. Lw dse ral cntraceptives can be used t prvide a mnthly withdrawal bleed and prvide cntraceptin as well. The FDA has apprved use f ral cntraceptives in wmen up t the time f menpause as lng as there is n cntraindicatin such as smking, HTN, cltting disrders r hyperlipidemia. T determine that a wman has entered menpause, an FSH > 40 n day 6 r 7 f the placeb pills cnfirms varian failure and the pt can then be switched t hrmne replacement therapy. OTHER MANAGEMENT OPTIONS Mst cases f DUB can be managed medically but ccasinally hysterscpy and/r D & C may be necessary. Endmetrial ablatin is an alternative t hysterectmy and is effective in > 50% f cases. REFERENCES Cullins VE Gyneclgy fr the Practicing Internist. Jhns Hpkins Medical Center, Gyneclgy Curriculum Cmmittee Bayer SR and DeCherney AH. Clinical Manifestatins and Treatment f Dysfunctinal Uterine Bleeding. JAMA 1993; 269: Mitan LAP, Slap GB Adlescent Menstrual Disrders Medical Clinics f Nrth America, 2000; 84: Reindllar, R Dysfunctinal Uterine Bleeding. Gyneclgy fr the NnGyneclgist. Bstn, Rsenfeld, JA. Treatment f Menrrhagia due t Dysfunctinal Uterine Bleeding Amer Fam Physician 1996; 53: