In the Name of GodIn the Name of God

Abnormal perimenopausal and Abnormal perimenopausal and Postmenopausal BleedingPostmenopausal Bleeding

F.BehnamfarF.BehnamfarGYNECOLOGY ONCOLOGY FELLOWSHIPGYNECOLOGY ONCOLOGY FELLOWSHIPKASHAN UNIVERSITY OF MEDICAL SCIENCESKASHAN UNIVERSITY OF MEDICAL SCIENCES

Abnormal perimenopausal Abnormal perimenopausal BleedingBleeding

► After adolescence, menstrual cycle length After adolescence, menstrual cycle length normally is 21-35 days with fewer than seven normally is 21-35 days with fewer than seven days menstrual flowdays menstrual flow

► As a woman approaches menopause, cycle As a woman approaches menopause, cycle length becomes irregular as fewer cycles are length becomes irregular as fewer cycles are ovulatory ovulatory

► The avarage blood loss is 35cc per cycle, The avarage blood loss is 35cc per cycle, recurrent bleeding in excess of 80cc results in recurrent bleeding in excess of 80cc results in anemiaanemia

► Although pregnancy related bleeding should be Although pregnancy related bleeding should be considered, most frequent cause of irregular considered, most frequent cause of irregular bleeding in reproductive age is hormonalbleeding in reproductive age is hormonal

Anovulatory Uterine Anovulatory Uterine Bleeding Bleeding

► Anovulatory uterine bleeding (dysfunctional Anovulatory uterine bleeding (dysfunctional bleeding) is a result of estrogen bleeding) is a result of estrogen breakthrough, endometrial growth without breakthrough, endometrial growth without periodic shedding and breakdown of fragile periodic shedding and breakdown of fragile endometrial tissue with irregular bleedingendometrial tissue with irregular bleeding

► Episodes of amenorrhea followed by acute Episodes of amenorrhea followed by acute heavy bleedingheavy bleeding

► Endogenous estradiol level is higher in Endogenous estradiol level is higher in perimenopausal women presenting with perimenopausal women presenting with menorrhagia than those with normal cyclemenorrhagia than those with normal cycle

M.H.Moen M.H.Moen Maturitas Maturitas 47(2004)151-15547(2004)151-155

Differential DiagnosisDifferential Diagnosis

► Pregnancy related bleedingPregnancy related bleeding50% of pregnancies in USA are unintended50% of pregnancies in USA are unintendedand these are more likely to occur among and these are more likely to occur among

adolescentsadolescents and and women older than 40women older than 40

► Exogenous hormonesExogenous hormonesBreakthrough bleeding during OCP use and other Breakthrough bleeding during OCP use and other

estrogen and progestin systems, progestin only estrogen and progestin systems, progestin only regimensregimens

Clamydia Trachomatis infections more common in Clamydia Trachomatis infections more common in these individualsthese individuals

Endocrine CausesEndocrine Causes

Hypo and hyperthyroidismHypo and hyperthyroidism► Graves disease 4-5 times more often in Graves disease 4-5 times more often in

women than in men,especially women than in men,especially perimenopausal.perimenopausal.

► Can result in oligomenorrhea and elevated Can result in oligomenorrhea and elevated plasma estrogenplasma estrogen

Diabetes MellitusDiabetes Mellitus► Anovulatoin, obesity, insulin Anovulatoin, obesity, insulin

resistance ,androgen excess, more immediate resistance ,androgen excess, more immediate concern in older women of reproductive age concern in older women of reproductive age

► Management with OCP or insulin sensitizing Management with OCP or insulin sensitizing agents plus dietary exercise modificationagents plus dietary exercise modification

Anatomic CausesAnatomic Causes

Uterine leiomyomasUterine leiomyomas►50% of all women 35 years and more50% of all women 35 years and more►Most common tumor of genital tractMost common tumor of genital tract►Asymptomatic in at least 50% of womenAsymptomatic in at least 50% of women►Most common symptoms abnormal Most common symptoms abnormal

bleeding (30%) blaoting and pelvic bleeding (30%) blaoting and pelvic discomfortdiscomfort

Gupta Gupta Best Practice &Research Clinical Obs.Gyn 2008.1.008Best Practice &Research Clinical Obs.Gyn 2008.1.008

Anatomic CausesAnatomic Causes

Endometrial PolypsEndometrial Polyps► Intermenstrual ,irregular bleedingIntermenstrual ,irregular bleeding

menorrhagia and dysmenorrheamenorrhagia and dysmenorrhea► Increasing incidence with ageIncreasing incidence with age► diagnosis based on visualization with diagnosis based on visualization with

hysteroscopy, sonohysterography or hysteroscopy, sonohysterography or microscopic assessment of tissue obtained microscopic assessment of tissue obtained by biopsyby biopsy

► 0.5% chance of malignancy0.5% chance of malignancy

Anatomic CausesAnatomic Causes

Cervical lesionsCervical lesions ► endocervical polypsendocervical polyps► clamydia infection,herpes simplex clamydia infection,herpes simplex

ulceration,condylomataulceration,condylomata► Cervical cancer, abnormal bleeding the most Cervical cancer, abnormal bleeding the most

common symptomcommon symptom

Abnormal intermenstrual or post coital bleedingAbnormal intermenstrual or post coital bleeding► Wide ectropion, nabothian cysts rarely cause Wide ectropion, nabothian cysts rarely cause

bleedingbleeding

Coagulopathies and Coagulopathies and Hematologic disordersHematologic disorders

Excessive heavy mensesExcessive heavy menses►Check CBC to detect anemia, Check CBC to detect anemia,

leukemia,thrombocytopenialeukemia,thrombocytopenia►Abnormal liver function , decreased Abnormal liver function , decreased

production of clotting factoresproduction of clotting factores►von willebrand disease occuring in up von willebrand disease occuring in up

to 1% of population ,OCP to 1% of population ,OCP increasing increasing factor VIIIfactor VIII and Desmopressin acetate and Desmopressin acetate may be necessarymay be necessary

Infectious Causes

► Women with cervicitis especially clamydial

can experience AUB and PCB

► Endometritis may cause menorrhagia with dysmenorhea

NeoplasiaNeoplasia

►Abnormal B is the most frequent Abnormal B is the most frequent symptom of invasive cervical cancersymptom of invasive cervical cancer

►Biopsy of any obvious cervical lesion Biopsy of any obvious cervical lesion should be done should be done

► Negative cytology results may be due to Negative cytology results may be due to tumor necrosistumor necrosis

►Unoppsed estrogen(Obesity, anovulation,Unoppsed estrogen(Obesity, anovulation,…) may cause variety of abnormalities …) may cause variety of abnormalities from from

endometrial hyperplasia to cancer endometrial hyperplasia to cancer

DiagnosisDiagnosis

►Medical and gynecologic historyMedical and gynecologic history►Exclusion of pregnancyExclusion of pregnancy►Consideration of possible malignancyConsideration of possible malignancy►Careful gynecologic examinationCareful gynecologic examination►Additional lab and imaging studies for:Additional lab and imaging studies for: Women>35yWomen>35y risk factors for STDsrisk factors for STDs signs of androgen excesssigns of androgen excess

Lab Studies

►CBC,hCG,PT,PTT,Platelet function

Imaging StudiesImaging Studies

► Pelvic ultrasound if exam results is Pelvic ultrasound if exam results is suboptimal or ovarian mass suspected, TVS suboptimal or ovarian mass suspected, TVS particularly for obese womenparticularly for obese women

►Measurement of endometrial strip thickness Measurement of endometrial strip thickness significantly less useful in premenopausalsignificantly less useful in premenopausal

than post menopausal womenthan post menopausal women► Sonohysterography especially helpful in Sonohysterography especially helpful in

visualizing intrauterine visualizing intrauterine problems(polyp,myoma)problems(polyp,myoma)

Histologic evaluation is required to rule out Histologic evaluation is required to rule out malignancymalignancy

Endometrial SamplingEndometrial Sampling

►Should be performed to evaluate Should be performed to evaluate abnormal bleeding in women who are abnormal bleeding in women who are at risk for endometrial at risk for endometrial polyps ,hyperplasia or carcinomapolyps ,hyperplasia or carcinoma

►Sampling is Sampling is mandatory mandatory in evaluation of in evaluation of anovulatory bleeding in women older anovulatory bleeding in women older than 35-40 years, in younger women than 35-40 years, in younger women who are obese and in those with who are obese and in those with history of prolonged anovulationhistory of prolonged anovulation

Endometrial SamplingEndometrial Sampling

►D&C has been replaced largely by D&C has been replaced largely by office endometrial biopsy office endometrial biopsy

►Studies have showed comparable Studies have showed comparable ability to detect anomaliesability to detect anomalies

►D&C for cervical stenosis, suspected D&C for cervical stenosis, suspected polyp, persistent AUBpolyp, persistent AUB

►Hysteroscopy may be done in office or Hysteroscopy may be done in office or operating room operating room

ManagementManagement

► In most cases medical therapy is effective In most cases medical therapy is effective and should be attempted before surgical and should be attempted before surgical managementmanagement

► In women with anovulatory bleeding and In women with anovulatory bleeding and failed medical therapy endometrial ablation failed medical therapy endometrial ablation is an efficient alternative to hysterectomyis an efficient alternative to hysterectomy

► In women with liomyomas ,hysterectomy is In women with liomyomas ,hysterectomy is a definitive cure (Alternatives :UAE, a definitive cure (Alternatives :UAE, Myomectomy) Myomectomy)

None surgical managementNone surgical management

►NSAIDS (30-50% decrease in NSAIDS (30-50% decrease in menstrual flow)menstrual flow)

►Antifibrinolytics, Tranexamic acid (FDA Antifibrinolytics, Tranexamic acid (FDA not approved)not approved)

►Levonorgestrel IUDs, significant Levonorgestrel IUDs, significant reduce in blood loss(80-90%), reduce in blood loss(80-90%), improved quality of life, may be improved quality of life, may be comparable to hysterectomycomparable to hysterectomy

Hormonal ManagementHormonal Management

►Treatment of choice for anovulatory Treatment of choice for anovulatory bleeding, LD OCP for premenopausalsbleeding, LD OCP for premenopausals

If healthy nonsmoker, and no major If healthy nonsmoker, and no major cardiovascular risk factorcardiovascular risk factor

Benefits of menstrual regulation in such Benefits of menstrual regulation in such women often overrides potential riskswomen often overrides potential risks

If estrogen use If estrogen use contraindicated ,contraindicated ,Progestins Progestins oral, oral, parenteral can be usedparenteral can be used

Hormonal ManagementHormonal Management

►Cyclic oral medroxyprogestrone acetate►Depot formulations of

medroxyprogestrone acetate►Parenteral /intrauterine delivery of

progestins►Danazol,rarely for ongoing management

of AUB►GnRH agonists

Surgical TherapySurgical Therapy► Should be reserved for situations in which medical Should be reserved for situations in which medical

therapy fails or is contraindicatedtherapy fails or is contraindicated► D&C ,diagnostic technique, questionable as a D&C ,diagnostic technique, questionable as a

therapeutic modalitytherapeutic modality► Variety of techniques of endometrial ablation or Variety of techniques of endometrial ablation or

resection to hysterectomyresection to hysterectomy► Myoma:hysteroscopic resection,laparoscopicMyoma:hysteroscopic resection,laparoscopic myomectomy,Uterine artry embolization,MR guided myomectomy,Uterine artry embolization,MR guided

ultrasonographic ablationultrasonographic ablationChoice of Procedures: Cause, patient preference,Choice of Procedures: Cause, patient preference,Physicians experience and skillsPhysicians experience and skillsIn the absence of preexisting psycopathology,indicated In the absence of preexisting psycopathology,indicated

but elective hysterectomy have few if any sequelaebut elective hysterectomy have few if any sequelae

Abnormal Bleeding in Abnormal Bleeding in Postmenopuasal Age GroupPostmenopuasal Age Group

►Exogenous estrogens 30%Exogenous estrogens 30%►Athrophic vaginitis,endometritis 30%Athrophic vaginitis,endometritis 30%►Endometrial cancer 15%Endometrial cancer 15%►Endometrial/cervical Polyps 10%Endometrial/cervical Polyps 10%►Endometrial Hyperplasia 5%Endometrial Hyperplasia 5%►Miscellaneous 10%Miscellaneous 10%

Benign DisordersBenign Disorders

► Women who are taking HRT during Women who are taking HRT during menopause ,endometrial sampling is indicated for menopause ,endometrial sampling is indicated for any unexpected bleeding that occurs with hormone any unexpected bleeding that occurs with hormone therapytherapy

► A significant change in withdrawal bleeding or A significant change in withdrawal bleeding or breakthrough bleedingbreakthrough bleeding

► Other benign causes: polyps,athrophic vaginitisOther benign causes: polyps,athrophic vaginitis► Postmenopausal women may attempt toPostmenopausal women may attempt to minimize minimize

the extent of problemthe extent of problemIn the absence of HRT any bleeding after In the absence of HRT any bleeding after

menopause should prompt evaluationmenopause should prompt evaluation with with endometrial samplingendometrial sampling

NeoplasiaNeoplasia

► At least one forth of postmanopausal women At least one forth of postmanopausal women with bleeding have a neoplastic lesionwith bleeding have a neoplastic lesion

► Endometrial polyps are more likely to be Endometrial polyps are more likely to be malignant in postmenopausalsmalignant in postmenopausals

► In the study by In the study by AntunesAntunes in women over 60y,5.3 in women over 60y,5.3 times more prevalence of malignancy in polypstimes more prevalence of malignancy in polyps

► Cervical malignancy grossly visible lesion Cervical malignancy grossly visible lesion biopsy, Colposcopy biopsy for abnormal pap biopsy, Colposcopy biopsy for abnormal pap results results

Maturitas 2007 415-421Maturitas 2007 415-421

DiagnosisDiagnosis

Cervical endometrial and ovarian Cervical endometrial and ovarian malignancy should be ruled outmalignancy should be ruled out

► Pelvic examination (local lesions,Pap test)Pelvic examination (local lesions,Pap test)► Pelvic ultrasound and in particular vaginal Pelvic ultrasound and in particular vaginal

ultrasoundultrasound► Endometrial sampling essentialEndometrial sampling essential► Initial biopsy done in the office is more cost Initial biopsy done in the office is more cost

effective than D&Ceffective than D&C► An endometrial thickness of less than 6 mm An endometrial thickness of less than 6 mm

essentially excludes malignancyessentially excludes malignancy

ManagementManagement

► Athrophic vaginitis,topical or systemic steroidAthrophic vaginitis,topical or systemic steroid► Polyps,removalPolyps,removal► Benign hyperplasia of endometrium is Benign hyperplasia of endometrium is

resolved with D&C or progestin therapyresolved with D&C or progestin therapy

,repeat biopsy is needed,repeat biopsy is needed

HysterectomyHysterectomy for those who do not respond for those who do not respond and for atypical hyperplasiaand for atypical hyperplasia

Progestin therapy for atypical hyperplasia only Progestin therapy for atypical hyperplasia only if poor candidates for hysterectomyif poor candidates for hysterectomy

Thank YouThank You