Dysfunctional Uterine BleedingDysfunctional Uterine Bleeding

Janice Bernal-Lacuna, MD, FPOGS, FPSREIJanice Bernal-Lacuna, MD, FPOGS, FPSREI

Abnormal uterine bleedingAbnormal uterine bleeding

Abnormal uterine bleeding encompasses any Abnormal uterine bleeding encompasses any significant deviation from normal frequency, significant deviation from normal frequency, regularity, heaviness and duration of menstrual regularity, heaviness and duration of menstrual bleeding. It is used to describe all abnormal bleeding. It is used to describe all abnormal menstrual signs and symptoms arising from the menstrual signs and symptoms arising from the uterine corpusuterine corpus

Level of Evidence IIILevel of Evidence IIIGrade of Recommendation: CGrade of Recommendation: C

The normal limits for the 4 main clinical The normal limits for the 4 main clinical dimensions of menstruation and the menstrual dimensions of menstruation and the menstrual cycle are regularity, frequency, duration and flow.cycle are regularity, frequency, duration and flow.

AUB may include short or long (but regular) AUB may include short or long (but regular) menstrual cycles, irregular menstrual cycles, heavy menstrual cycles, irregular menstrual cycles, heavy or light menstrual periods, intermenstrual bleeding, or light menstrual periods, intermenstrual bleeding, premenarcheal or postmenopausal bleeding, with premenarcheal or postmenopausal bleeding, with or without any recognizable pathologyor without any recognizable pathology

Abnormal Uterine BleedingAbnormal Uterine Bleeding NormalNormal - 28 +/- 7 days, mean of 4 days duration, not - 28 +/- 7 days, mean of 4 days duration, not

more than 7 daysmore than 7 days Intermenstrual bleedingIntermenstrual bleeding – bleeding of variable – bleeding of variable

amounts in between regular mensesamounts in between regular menses Menorrhagia or hypermenorrheaMenorrhagia or hypermenorrhea– prolonged (>7 days – prolonged (>7 days

or excessive (>80 ml) bleeding at regular intervalsor excessive (>80 ml) bleeding at regular intervals MetrorrhagiaMetrorrhagia – irregular but frequent intervals, – irregular but frequent intervals,

variable amountvariable amount Menometrorrhagia Menometrorrhagia – prolonged bleeding at irregular – prolonged bleeding at irregular

intervalsintervals PolymenorrheaPolymenorrhea – regular intervals < 21 days – regular intervals < 21 days OligomenorrheaOligomenorrhea – regular intervals > 35 days – regular intervals > 35 days

It is recommended that the term menorrhagia be It is recommended that the term menorrhagia be discarded and replaced by the term “heavy discarded and replaced by the term “heavy menstrual bleeding”menstrual bleeding”

Level of Evidence: IIILevel of Evidence: III Grade of Recommendation: CGrade of Recommendation: C

Menstrual blood loss (MBL) - < 80 mlMenstrual blood loss (MBL) - < 80 ml Difficult to measureDifficult to measure Sanitary pad countSanitary pad count Radioisotope labeling of rbcsRadioisotope labeling of rbcs Photometric measurement of hematin in sanitary Photometric measurement of hematin in sanitary

padspads Estimate, reports of change in duration of blood Estimate, reports of change in duration of blood

flowflow

Abnormal Uterine BleedingAbnormal Uterine Bleeding EtiologyEtiology

OrganicOrganic SystemicSystemic reproductivereproductive

Dysfunctional or endocrinologicDysfunctional or endocrinologic

Organic: SystemicOrganic: Systemic Blood coagulatoion defects – von Willebrands, Blood coagulatoion defects – von Willebrands,

prothrombin deficiencyprothrombin deficiency Platelet deficiency: leukemia, DIC, sepsis, ITP, Platelet deficiency: leukemia, DIC, sepsis, ITP,

hypersplenismhypersplenism Hypothyroidism – menorrhagia or intermenstrual Hypothyroidism – menorrhagia or intermenstrual

bleedingbleeding Cirrhosis of the liver – reduced capacity to Cirrhosis of the liver – reduced capacity to

metabolize estrogenmetabolize estrogen

Organic: ReproductiveOrganic: Reproductive Accidents of pregnancyAccidents of pregnancy MalignanciesMalignancies Infection – endometritisInfection – endometritis Uterine abnormalities – myoma, polyp, Uterine abnormalities – myoma, polyp,

adenomyosisadenomyosis Cervical lesions – erosions, polyps, Cervical lesions – erosions, polyps,

cervicitiscervicitis Vagina - Traumatic lesions, foreign Vagina - Traumatic lesions, foreign

bodybody IUDIUD OCPs HRT, TRANQUILIZERS, OCPs HRT, TRANQUILIZERS,

PSYCHOTROPIC DRUGSPSYCHOTROPIC DRUGS

Dysfunctional Uterine BleedingDysfunctional Uterine Bleeding After other causes have been ruled outAfter other causes have been ruled out Excessive uterine bleeding with no Excessive uterine bleeding with no

demonstrable organic cause. demonstrable organic cause. most frequently due to endocrine problem, most frequently due to endocrine problem,

particularly anovulationparticularly anovulation TypesTypes

OvulatoryOvulatory anovulatoryanovulatory

DUBDUB Prostaglandins – regulation of Prostaglandins – regulation of

vasoconstiction and vasodilationvasoconstiction and vasodilation PGEPGE22 – vasodilatation – vasodilatation PGFPGF22αα – vasoconstriction – vasoconstriction Thromboxane – platelet aggregationThromboxane – platelet aggregation Prostacycline – inhibits platelet Prostacycline – inhibits platelet

aggregationaggregation Increasing Increasing PGFPGF22αα to to PGEPGE2 2 ratio ratio

from midcycle to menses in normal from midcycle to menses in normal ovulatory women with normal MBLovulatory women with normal MBL

Dysfunctional Uterine BleedingDysfunctional Uterine Bleeding OvulatoryOvulatory

After adolescent yearsAfter adolescent years Before perimenopausal yearsBefore perimenopausal years 10% of ovulatory women10% of ovulatory women Reduced uterine synthesis of PGFReduced uterine synthesis of PGF22αα and increase in and increase in

synthesis of prostacycline and PGEsynthesis of prostacycline and PGE22

Due to relative deficiency in thromboxaneDue to relative deficiency in thromboxane

DUBDUB AnovulatoryAnovulatory

PostmenarchealPostmenarcheal PremenopausalPremenopausal Continuous estrogen production without corpus Continuous estrogen production without corpus

luteum formation and progesterone productionluteum formation and progesterone production Estrogen – proliferation of endometrium Estrogen – proliferation of endometrium

necrosis necrosis non-uniform slough off of functionalis non-uniform slough off of functionalis layer layer excessive bleeding excessive bleeding

Not secondary to excessive number of arteries and Not secondary to excessive number of arteries and abnormal distribution of endometrial glands abnormal distribution of endometrial glands

DUBDUB Anovulatory DUBAnovulatory DUB

Progesterone is needed to increase arachidonic acid which Progesterone is needed to increase arachidonic acid which is the precursor of is the precursor of PGFPGF22αα Lower PGFLower PGF22αα

Estrogen stimulates synthesis of prostaglandins from Estrogen stimulates synthesis of prostaglandins from arachidonic acid by cyclic peroxidase arachidonic acid by cyclic peroxidase Normal Normal PGEPGE22

PGFPGF22αα binds to receptors in the spiral arteries in the late binds to receptors in the spiral arteries in the late secretory phase secretory phase vasoconstriction vasoconstriction control menstrual control menstrual flow flow

Anovulation - low PGF2Anovulation - low PGF2αα – excessive bleeding – excessive bleeding

DUBDUB DiagnosisDiagnosis

History of bleeding: frequency, duration and History of bleeding: frequency, duration and amount of bleeding, change in menstrual patternamount of bleeding, change in menstrual pattern

Bleeding calendarBleeding calendar Determine menstrual blood lossDetermine menstrual blood loss

Estimate not reliableEstimate not reliable Indirect assessment: hemoglobin, serum ironIndirect assessment: hemoglobin, serum iron Serum ferritin – valid indirect measurement of iron in Serum ferritin – valid indirect measurement of iron in

the bone marrowthe bone marrow

DiagnosisDiagnosis hcG determinationhcG determination TSHTSH Tests for coagulationTests for coagulation Test for ovulation: BBT, Test for ovulation: BBT,

luteal phase serum luteal phase serum progesterone, premenstrual progesterone, premenstrual sampling of endometriumsampling of endometrium

DiagnosisDiagnosis If ovulatory: rule out If ovulatory: rule out

uterine lesions like uterine lesions like submucous myoma, submucous myoma, endometrial polyp and endometrial polyp and CACA

Transvaginal ultrasoundTransvaginal ultrasound D and CD and C Endometrial biopsyEndometrial biopsy HSGHSG HysteroscopyHysteroscopy sonohysterographysonohysterography

DiagnosisDiagnosis Endometrial biopsy is Endometrial biopsy is

recommended to rule recommended to rule out hyperplasia or out hyperplasia or carcinomacarcinoma

Age 40Age 40 Arbitrary cut offArbitrary cut off Age specific cancer Age specific cancer

registry showed that registry showed that endometrial cancer rises endometrial cancer rises exponentially above 40 exponentially above 40

ManagementManagement Medical – preferred treatment especially for Medical – preferred treatment especially for

those desirous of future child-bearingthose desirous of future child-bearing SurgicalSurgical

Acute bleeding or reduce MBL in subsequent Acute bleeding or reduce MBL in subsequent menstrual cyclemenstrual cycle

Medical ManagementMedical Management EstrogensEstrogens

Causes rapid growth of endometrium over the Causes rapid growth of endometrium over the denuded and raw areasdenuded and raw areas

Conjugated equine estrogen 10 mg/ day in 4 Conjugated equine estrogen 10 mg/ day in 4 divided doses highest dose at 20 mg/ daydivided doses highest dose at 20 mg/ day

IV CEE IV CEE Continue with progestin therapy once bleeding Continue with progestin therapy once bleeding

stops for 7 -10 days to induce withdrawal bleedingstops for 7 -10 days to induce withdrawal bleeding Combination oral contraceptive: 4 tabs 50Combination oral contraceptive: 4 tabs 50µg of µg of

estrogen with progestin every 24 hours. Continue estrogen with progestin every 24 hours. Continue tx until 1 week after bleeding stoppedtx until 1 week after bleeding stopped

ProgestinsProgestins Stop endometrial growth Stop endometrial growth Support and organize the endometrium for organized Support and organize the endometrium for organized

slough to the basalis layer after withdrawalslough to the basalis layer after withdrawal Stimulate arachidonic acid formation increasing Stimulate arachidonic acid formation increasing

PGF2PGF2αα/PGE2 ratio /PGE2 ratio Not for acute bleedingNot for acute bleeding Treatment of choice for anovulation for long-term Treatment of choice for anovulation for long-term

treatment after acute episodetreatment after acute episode May also be tried for women who ovulateMay also be tried for women who ovulate

ProgestinsProgestins Anti-estrogenAnti-estrogen Medroxyprogesterone acetate Medroxyprogesterone acetate

10mg daily for 10 days each 10mg daily for 10 days each monthmonth

19-nortestosterone – affects lipid 19-nortestosterone – affects lipid levelslevels

Levonorgestrel-releasing IUDLevonorgestrel-releasing IUD

OCPOCP Can be used to reduce MBL in ovulatory Can be used to reduce MBL in ovulatory

women with heavy menstrual bleedingwomen with heavy menstrual bleeding(regardless of association with other pathology)(regardless of association with other pathology)

In women with unexplained menorrhagia, In women with unexplained menorrhagia, OCP can decrease bleeding by 40%OCP can decrease bleeding by 40%

May regulate menstruation in anovulatory May regulate menstruation in anovulatory DUBDUB

Amenorrhea and delayed fertilityAmenorrhea and delayed fertility Rather than causing oligomenorrhea or Rather than causing oligomenorrhea or

amenorrhea, OCs merely mask it by inducing amenorrhea, OCs merely mask it by inducing cyclic withdrawal bleedingcyclic withdrawal bleeding

The risk of amenorrhea after OC pill The risk of amenorrhea after OC pill discontinuation is less than 1% and appears to be discontinuation is less than 1% and appears to be more common in women who had irregular more common in women who had irregular menses before using OCsmenses before using OCs

Low-dose Combined Oral Low-dose Combined Oral ContraceptivesContraceptives

Effect on heightEffect on height fear that OC use by adolescents will stunt physical growth. fear that OC use by adolescents will stunt physical growth. Oral contraceptives do not cause premature closure of the Oral contraceptives do not cause premature closure of the

epiphyses or inhibit skeletal growth. epiphyses or inhibit skeletal growth. By the time menarche occurs, endogenous estrogen By the time menarche occurs, endogenous estrogen

production has already initiated epiphyseal closure, and production has already initiated epiphyseal closure, and this process cannot be altered by exogenous steroidsthis process cannot be altered by exogenous steroids

Therefore, use of OCs after menarche is appropriate.Therefore, use of OCs after menarche is appropriate.Bolton GC. Adolescent contraception. Clin Obstet Gynecol 1981 Bolton GC. Adolescent contraception. Clin Obstet Gynecol 1981

Low-dose Combined Oral Low-dose Combined Oral ContraceptivesContraceptives

Adolescent anovulationAdolescent anovulation Progestin treatment is idealProgestin treatment is ideal Immaturity of HPO axisImmaturity of HPO axis OCPs may delay maturity (no evidence)OCPs may delay maturity (no evidence)

Medical ManagementMedical Management NSAIDsNSAIDs

Prostaglandin synthetase inhibitorProstaglandin synthetase inhibitor Inhibits cyclic peroxidase which converts arachidonic Inhibits cyclic peroxidase which converts arachidonic

acid to prostaglandinacid to prostaglandin Block synthesis of both prostacyclin and thromboxaneBlock synthesis of both prostacyclin and thromboxane Effective in ovulatory womenEffective in ovulatory women May be used in conjunction with other treatment in May be used in conjunction with other treatment in

anovulatory DUBanovulatory DUB Mefenamic Acid, Ibuprofen, NaproxenMefenamic Acid, Ibuprofen, Naproxen

Antifibrinolytic agentAntifibrinolytic agent Inhibitors of fibrinolysisInhibitors of fibrinolysis Tranexamic Acid may be given as high as 6g/day Tranexamic Acid may be given as high as 6g/day

in divided dosesin divided doses Effective for ovulatory DUB Effective for ovulatory DUB Combined with hormonal txCombined with hormonal tx Side effects: nausea, dizziness, diarrhea, headache, Side effects: nausea, dizziness, diarrhea, headache,

abdominal pain, allergyabdominal pain, allergy

Medical ManagementMedical Management Androgenic steroid (Danazol)Androgenic steroid (Danazol)

200mg to 400mg daily for 12 weeks200mg to 400mg daily for 12 weeks Side effects: acne, weight gainSide effects: acne, weight gain

Medical ManagementMedical Management GnRH AgonistsGnRH Agonists

Inhibit ovarian steroid productionInhibit ovarian steroid production Use in women with severe MBL and wish to retain Use in women with severe MBL and wish to retain

childbearing capacitychildbearing capacity Return to pretreatment blood loss when tx is Return to pretreatment blood loss when tx is

discontinueddiscontinued

Surgical ManagementSurgical Management Dilatation and CurettageDilatation and Curettage

DUB with hypovolemiaDUB with hypovolemia Stop acute bleeding in women above 35yo when Stop acute bleeding in women above 35yo when

incidence of pathologic findings increasesincidence of pathologic findings increases Temporary treatment in anovulationTemporary treatment in anovulation Not useful in ovulatory menorrhagiaNot useful in ovulatory menorrhagia

Surgical ManagementSurgical Management Endometrial ablationEndometrial ablation

Laser photovaporizationLaser photovaporization Transcervical resection of endometrium with Transcervical resection of endometrium with

electrocautery (ball-end or loop electrode or thermal electrocautery (ball-end or loop electrode or thermal balloon)balloon)

Failed medical treatmentFailed medical treatment Severe menorrhagia with medical contraindications against Severe menorrhagia with medical contraindications against

hysterectomyhysterectomy Ovulatory DUB not amenable to medical managementOvulatory DUB not amenable to medical management Not for those who want to retain childbearing capacityNot for those who want to retain childbearing capacity

LOOPLOOP

ROLLERBALLROLLERBALL

LASERLASER

Microwave Endometrial AblationMicrowave Endometrial Ablation

Surgical ManagementSurgical Management HysterectomyHysterectomy

Reserved for women with Reserved for women with other pathologies like other pathologies like myoma or uterine prolapsemyoma or uterine prolapse

Medical treatment failureMedical treatment failure Severe MBLSevere MBL

Long term therapyLong term therapy After confirming diagnosis of DUBAfter confirming diagnosis of DUB Progestin for adolescents initially for 3 monthsProgestin for adolescents initially for 3 months For reproductive age womenFor reproductive age women

For contraception: OCPsFor contraception: OCPs For infertility: clomiphene citrateFor infertility: clomiphene citrate Just DUB: MPAJust DUB: MPA

PerimenopausePerimenopause Low dose OCPsLow dose OCPs

Chronic ovulatory DUBChronic ovulatory DUB Other medical treatment, combination Other medical treatment, combination

DysmenorrheaDysmenorrhea Painful cramping sensation in the lower Painful cramping sensation in the lower

abdomen just before or during mensesabdomen just before or during menses May be associated with sweating, tachycardia, May be associated with sweating, tachycardia,

headaches, nausea, vomiting, diarrhea and headaches, nausea, vomiting, diarrhea and tremulousnesstremulousness

Primary DysmenorrheaPrimary Dysmenorrhea No obvious No obvious

pathologypathology Effects of Effects of

endogenous endogenous prostaglandinsprostaglandins

Almost always Almost always occurs in women occurs in women younger than 20younger than 20

Usually as soon as Usually as soon as ovulatory cycles ovulatory cycles are establishedare established

Secondary Secondary dysmenorrheadysmenorrhea

Associated with Associated with pelvic conditions or pelvic conditions or pathology in pathology in conjunction with conjunction with mensesmenses

May occur in women May occur in women under 20 but most under 20 but most often seen in women often seen in women over 20over 20

Primary DysmenorrheaPrimary Dysmenorrhea Reduced Reduced

women who had vaginal deliverywomen who had vaginal delivery OCP useOCP use SmokersSmokers

IUD – no effectIUD – no effect

PathogenesisPathogenesis UnknownUnknown Close association with elevated prostaglandin Close association with elevated prostaglandin

F2F2αα in the secretory endometrium in the secretory endometrium Hypercontractility, crampingHypercontractility, cramping Prostaglandin synthetase inhibitor - NSAIDSProstaglandin synthetase inhibitor - NSAIDS

treatmentstreatments OCPs – modulating effect on hypothalamus or OCPs – modulating effect on hypothalamus or

direct reduction of endometriumdirect reduction of endometrium AnalgesicsAnalgesics TENS – transcutaneous electrical nerve TENS – transcutaneous electrical nerve

stimulation – mode of action is through the stimulation – mode of action is through the CNSCNS