Menstrual Menstrual DisordersDisorders

Geetha Kamath, M.D.Geetha Kamath, M.D.

Dept. of MedicineDept. of Medicine

West Virginia UniversityWest Virginia University

DefinitionDefinition Normal menstrual cycle involves Normal menstrual cycle involves

hypothalamus-pituitary-ovary and uterus hypothalamus-pituitary-ovary and uterus and is 28 daysand is 28 days

Vaginal bleeding is abnormal (Abnormal Vaginal bleeding is abnormal (Abnormal Uterine Bleeding--AUB) when:Uterine Bleeding--AUB) when: Volume is excessive or Volume is excessive or Occurs at times other than expected, Occurs at times other than expected,

including during pregnancy or menopauseincluding during pregnancy or menopause Known as dysfunctional uterine bleeding Known as dysfunctional uterine bleeding

(DUB) when organic causes are (DUB) when organic causes are excludedexcluded

AUBAUB

Duration >7 days or Duration >7 days or Flow >80ml/cycle or Flow >80ml/cycle or Occurs more frequently than 21 days Occurs more frequently than 21 days

or or Occurs more than 90 days apart or Occurs more than 90 days apart or Intermenstrual or postcoital Intermenstrual or postcoital

bleedingbleeding

TerminologyTerminology

Menorrhagia: excessive flowMenorrhagia: excessive flow Menometrorrhagia: excessive Menometrorrhagia: excessive

volumevolume Oligomenorrhea: scanty flowOligomenorrhea: scanty flow Dysmenorrhea: painful menstrual Dysmenorrhea: painful menstrual

cyclescycles

Causes of Menstrual Causes of Menstrual DisordersDisorders

StructuralStructural Pregnancy associatedPregnancy associated Hormonal and endocrineHormonal and endocrine Hematologic and coagulation Hematologic and coagulation

disordersdisorders OtherOther

Causes--structuralCauses--structural

Endometrial polypsEndometrial polyps Endometrial hyperplasiaEndometrial hyperplasia EndometritisEndometritis FibroidsFibroids Intrauterine devicesIntrauterine devices Uterine arterio-venous malformation Uterine arterio-venous malformation

(AVM)(AVM) Uterine sarcomaUterine sarcoma

Pregnancy relatedPregnancy related

Implantational bleedingImplantational bleeding Ectopic pregnancyEctopic pregnancy Spontaneous abortion [incomplete, Spontaneous abortion [incomplete,

missed, septic, threatened]missed, septic, threatened] Therapeutic abortionTherapeutic abortion Gestational trophoblastic diseaseGestational trophoblastic disease

Hormonal and Endocrine Hormonal and Endocrine causescauses

Anovulatory (including polycystic Anovulatory (including polycystic ovary syndrome)ovary syndrome)

Ovarian cystOvarian cyst Estrogen-producing ovarian tumorEstrogen-producing ovarian tumor PerimenopausePerimenopause Hormonal contraceptivesHormonal contraceptives Hormone Replacement TherapyHormone Replacement Therapy HypothyroidismHypothyroidism

HematologicHematologic

Von Willebrand’s disease (most Von Willebrand’s disease (most common inherited bleeding disorder common inherited bleeding disorder with frequency 1/800-1000)with frequency 1/800-1000)

HemophiliaHemophilia ThrombocytopeniaThrombocytopenia Hematologic malignancies Hematologic malignancies

(leukemia)(leukemia) Liver diseaseLiver disease

Other Other

DUB (dysfunctional uterine bleeding): non-DUB (dysfunctional uterine bleeding): non-organic causes, either ovulatory or anovulatoryorganic causes, either ovulatory or anovulatory

Fallopian tube cancerFallopian tube cancer TraumaTrauma Foreign bodyForeign body Cervical bleeding--mets, cervicitis, cervical Cervical bleeding--mets, cervicitis, cervical

cancercancer Vaginitis--atrophic, cancer of vaginaVaginitis--atrophic, cancer of vagina Endometrial cancer (10% of post-menopausal Endometrial cancer (10% of post-menopausal

bleeding)bleeding)

Evaluation of Abnormal Evaluation of Abnormal Uterine Bleeding (AUB)Uterine Bleeding (AUB)

AcuteAcute

History suggestive of:History suggestive of: Pregnancy and Pregnancy and

related complicationsrelated complications Recent and Heavy Recent and Heavy

bleeding bleeding Pelvic painPelvic pain Medications Medications

contributing to abovecontributing to above

ChronicChronic

History:History: Long standing Long standing

abnormal menstrual abnormal menstrual historyhistory

Symptoms of anemia, Symptoms of anemia, hypothyroidism, hypothyroidism, perimenopauseperimenopause

Personal or family Personal or family history of excessive history of excessive bleedingbleeding

AUB Examination AUB Examination

Assess vitals/hemodynamic stabilityAssess vitals/hemodynamic stability Look for features of anemia (pallor, Look for features of anemia (pallor,

tachycardia, syncope)tachycardia, syncope) Look for features of hypothyroidismLook for features of hypothyroidism Look for metabolic syndrome (obesity, Look for metabolic syndrome (obesity,

hirsutism, acne)hirsutism, acne) Pelvic exam for structural Pelvic exam for structural

abnormalities: fibroids, pregnancy, abnormalities: fibroids, pregnancy, active bleeding—uterine vs. cervical active bleeding—uterine vs. cervical bleedingbleeding

AUB Lab StudiesAUB Lab Studies Serum HCG to rule out pregnancySerum HCG to rule out pregnancy CBC and iron studies to assess severity of anemiaCBC and iron studies to assess severity of anemia TSH for thyroid disordersTSH for thyroid disorders Coagulation studies (PT, PTT, platelet count, VWF) Coagulation studies (PT, PTT, platelet count, VWF)

(primarily for adolescents)(primarily for adolescents) Transvaginal ultrasound to look for fibroids and other Transvaginal ultrasound to look for fibroids and other

masses/lesionsmasses/lesions Endometrial biopsy to rule out endometrial cancer in Endometrial biopsy to rule out endometrial cancer in

perimenopausal and chronic anovulatory cycles perimenopausal and chronic anovulatory cycles (primarily for women >35 years with AUB and (primarily for women >35 years with AUB and postmenopausal women)postmenopausal women)

Sonohysterography is useful in diagnosis of Sonohysterography is useful in diagnosis of anatomical lesions which might even be missed with anatomical lesions which might even be missed with transvaginal ultrasoundtransvaginal ultrasound

Treatment of Chronic Treatment of Chronic Menorrhagia for Most Menorrhagia for Most

Causes (including DUB)Causes (including DUB) Combined hormonal contraceptives Combined hormonal contraceptives

(cyclical or continuous)(cyclical or continuous) DMPA (depot medroxyprogesterone)DMPA (depot medroxyprogesterone) IUD (Intrauterine devices)IUD (Intrauterine devices)

Treatment options Treatment options continuedcontinued

After excluding coagulopathy, pregnancy, After excluding coagulopathy, pregnancy, or malignancy:or malignancy:

ProgestinsProgestins Estrogens including oral contraceptivesEstrogens including oral contraceptives Cyclic NSAIDSCyclic NSAIDS Dilatation and curettage (surgical)Dilatation and curettage (surgical) Endometrial ablation (surgical)Endometrial ablation (surgical) Hysteroscopic endometrial resection Hysteroscopic endometrial resection

(surgical)(surgical)

Treatment for FibroidsTreatment for Fibroids

Surgical: Surgical: Hysterectomy/myomectomy, uterine Hysterectomy/myomectomy, uterine artery ablationartery ablation

Medical: Suppression of Medical: Suppression of gonadotropins (danazol and gonadotropins (danazol and leuprolide) leuprolide)

Treatment: progestins Treatment: progestins

Inhibits endometrial growth by Inhibits endometrial growth by inhibiting synthesis of estrogen inhibiting synthesis of estrogen receptors, promotes conversion of receptors, promotes conversion of estradiol to estrone, inhibits LHestradiol to estrone, inhibits LH

Organized slough to basalis layerOrganized slough to basalis layer Stimulates arachidonic acid Stimulates arachidonic acid

productionproduction Progestins preferred for those women Progestins preferred for those women

with anovulatory AUBwith anovulatory AUB

Progestational AgentsProgestational Agents

Cyclic medroxyprogesterone 2.5-Cyclic medroxyprogesterone 2.5-10mg daily for 10-14 days10mg daily for 10-14 days

Continuous medroxyprogesterone Continuous medroxyprogesterone 2.5-5mg daily2.5-5mg daily

DMPA 150 mg IM every 3 monthsDMPA 150 mg IM every 3 months Levonorgestrel IUD (5 years)Levonorgestrel IUD (5 years)

EstrogensEstrogens

Conjugated estrogens given IV every Conjugated estrogens given IV every 6 hours effective in controlling heavy 6 hours effective in controlling heavy bleeding followed by oral estrogenbleeding followed by oral estrogen

For less severe bleeding, oral For less severe bleeding, oral conjugated estrogens 1.25 mg, 2 conjugated estrogens 1.25 mg, 2 tabs qid--until bleeding stopstabs qid--until bleeding stops

NSAIDSNSAIDS

Cyclooxygenase pathway is blockedCyclooxygenase pathway is blocked Arachidonic acid conversion from Arachidonic acid conversion from

prostaglandins to thromboxane and prostaglandins to thromboxane and prostacyclin (which promotes prostacyclin (which promotes bleeding by causing vasodilation and bleeding by causing vasodilation and platelet aggregation) is blockedplatelet aggregation) is blocked

Clinical HighlightsClinical Highlights

Most common cause of AUB in Most common cause of AUB in reproductive age is pregnancy reproductive age is pregnancy related--so initial evaluation must related--so initial evaluation must include pregnancy test.include pregnancy test.

Pregnancy must be ruled out before Pregnancy must be ruled out before initiating invasive testes or medical initiating invasive testes or medical therapytherapy

Clinical HighlightsClinical Highlights

Endometrial biopsy is recommended Endometrial biopsy is recommended for post menopausal women for post menopausal women

OrOr Younger women with history of Younger women with history of

chronic anovulation >35 years of chronic anovulation >35 years of ageage

Clinical HighlightsClinical Highlights

Uterine cancer and endometrial Uterine cancer and endometrial hyperplasia must be ruled out before hyperplasia must be ruled out before medical therapy is initiated in medical therapy is initiated in postmenopausal/perimenopausal postmenopausal/perimenopausal bleedingbleeding

NSAIDS may reduce menstrual flow by NSAIDS may reduce menstrual flow by 20-60% in women with chronic 20-60% in women with chronic menorrhagiamenorrhagia

Coagulopathy workup must be initiated Coagulopathy workup must be initiated in menorrhagia in adolescentsin menorrhagia in adolescents

ReferencesReferences

ACOG Practice Bulletin #14, 2000ACOG Practice Bulletin #14, 2000 American Journal Obstetrics and American Journal Obstetrics and

Gynecol 2005;193:1361Gynecol 2005;193:1361 Clinical Obstetrics & Gynecology Clinical Obstetrics & Gynecology

50(2):324-353, June 200750(2):324-353, June 2007 Comprehensive Gynecology, 4Comprehensive Gynecology, 4thth edition edition Harrison’s Principles of Internal Harrison’s Principles of Internal

Medicine, 14Medicine, 14thth edition edition Karlsson, et al, 1995Karlsson, et al, 1995