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