Dub - dr.hisham saleh

‫الرحيم‬ ‫الرحمن‬ ‫ال‬ ‫بسم‬

Abnormal Uterine BleedingAbnormal Uterine Bleeding
ByBy
Prof. Dr. Hisham SalehProf. Dr. Hisham Saleh

Abnormal Uterine BleedingAbnormal Uterine Bleeding
Abnormal uterine bleedingAbnormal uterine bleeding usually meansusually means
excessiveexcessive (menorrhagia)(menorrhagia) or prolongedor prolonged
(menostaxis)(menostaxis) loss of blood, but also includesloss of blood, but also includes
frequentfrequent (polymenorrhoea)(polymenorrhoea) or irregularor irregular
(metrorrhagia or metrostaxis(metrorrhagia or metrostaxis) losses of) losses of
blood that is neither heavy nor prolonged.blood that is neither heavy nor prolonged.

Normal Withdrawal (Menstrual) BleedingNormal Withdrawal (Menstrual) Bleeding
Most stable endometrium & most reproducibleMost stable endometrium & most reproducible
menstrual function in terms ofmenstrual function in terms of quantityquantity &&
durationduration occur with postovulatoryoccur with postovulatory estrogen-estrogen-
progesteroneprogesterone withdrawal bleeding.withdrawal bleeding.

Menstrual Period CharacteristicsMenstrual Period Characteristics
Normal Abnormal
Duration of flow 4-6 days <2; >7 days (menostaxis)
Volume of flow 30 mL >80 mL (menorrhagia)
Rhythm 24-35 days <24 (polymenorrhoea)
or >35 days

Normal Withdrawal (Menstrual) BleedingNormal Withdrawal (Menstrual) Bleeding
(cont.)(cont.)
The luteal phase averages 14 daysThe luteal phase averages 14 days
Greater variability in the proliferative phaseGreater variability in the proliferative phase
produces variations in the menstrual cycleproduces variations in the menstrual cycle
duration.duration.

Mechanism of normal menstrual bleeding:Mechanism of normal menstrual bleeding:
Vasomotor reactionVasomotor reaction
Apoptosis (programmed cell death) &Apoptosis (programmed cell death) &
endometrial breakdownendometrial breakdown
Tissue loss & menstruationTissue loss & menstruation
Menstrual flow stopsMenstrual flow stops
Withdrawal of E & P initiates important endometrialWithdrawal of E & P initiates important endometrial
events:events:

Spiral arterioles undergo rhythmicSpiral arterioles undergo rhythmic
vasoconstriction & relaxation. Each spasm isvasoconstriction & relaxation. Each spasm is
more prolonged and profound leading tomore prolonged and profound leading to
ischemia.ischemia.
Caused by prostaglandin release.Caused by prostaglandin release.
Vasomotor reaction:Vasomotor reaction:

P withdrawal releases lytic enzymes andP withdrawal releases lytic enzymes and
prostaglandins from the cells resulting inprostaglandins from the cells resulting in
tissue necrosis, extravasation of RBCs,tissue necrosis, extravasation of RBCs,
vascular thrombosis.vascular thrombosis.
endometrial breakdown:endometrial breakdown:

P withdrawal releases enzymes that digestP withdrawal releases enzymes that digest
the matrix of the endometrium (matrixthe matrix of the endometrium (matrix
metalloproteinases)metalloproteinases)

P withdrawal stimulates the secretion of aP withdrawal stimulates the secretion of a
factor (tumor necrosis factor alpha, TNF-factor (tumor necrosis factor alpha, TNF-αα))
that inhibits endometrial proliferation,that inhibits endometrial proliferation,
causes cell death, and damages vascularcauses cell death, and damages vascular
endothelium.endothelium.

Interstitial hemorrhage due to breaks inInterstitial hemorrhage due to breaks in
superficial artertioles.superficial artertioles.
With more ischemia and weakening blood isWith more ischemia and weakening blood is
extruded to the endometrial cavity.extruded to the endometrial cavity.
New thrombin-platelet clots form intra-New thrombin-platelet clots form intra-
vascularly limiting blood loss.vascularly limiting blood loss.
Tissue loss & menstruation:Tissue loss & menstruation:

A balance between fibrinolysis and clottingA balance between fibrinolysis and clotting
controls the amount of blood loss.controls the amount of blood loss.
The superficial layer of the endometriumThe superficial layer of the endometrium
(stratum spongiosum) finally desquamates(stratum spongiosum) finally desquamates
ending in a dense shallow menstrualending in a dense shallow menstrual
endometrium.endometrium.
Tissue loss & menstruation:Tissue loss & menstruation:

Prolonged vasoconstrictionProlonged vasoconstriction
Tissue collapseTissue collapse
Vascular stasis and thrombin generationVascular stasis and thrombin generation
Estrogen induced healing:Estrogen induced healing: healing starts fromhealing starts from
the remainders of the endometrial glands and fromthe remainders of the endometrial glands and from
the endometrium at the tubal ostia.the endometrium at the tubal ostia.
Menstrual flow stops as a result of:Menstrual flow stops as a result of:

33 reasons for the self-limiting character ofreasons for the self-limiting character of
estrogen-progesterone withdrawal bleeding:estrogen-progesterone withdrawal bleeding:
1.1. It is a universal endometrial event.It is a universal endometrial event.
2.2. The endometrial tissue that has responded toThe endometrial tissue that has responded to
an appropriate sequence of estrogen andan appropriate sequence of estrogen and
progesterone is structurally stable, andprogesterone is structurally stable, and
random breakdown of tissue due to fragilityrandom breakdown of tissue due to fragility
is avoided.is avoided.

33 reasons for the self-limiting character ofreasons for the self-limiting character of
estrogen-progesterone withdrawal bleeding:estrogen-progesterone withdrawal bleeding:
3.3. Inherent in the events responsible for startInherent in the events responsible for start
of menstruation following E/P are theof menstruation following E/P are the
factors involved in stopping menstrual flowfactors involved in stopping menstrual flow
(vasoconstriction, E healing)(vasoconstriction, E healing)

Definitions:Definitions:
Short cycles (less than 24 days or 5 days orShort cycles (less than 24 days or 5 days or
more shorter than the usual)more shorter than the usual)
Polymenorrhoea:Polymenorrhoea:
Excessive regular monthly periods of normalExcessive regular monthly periods of normal
durationduration
Menorrhagia (hypermenorrhoea):Menorrhagia (hypermenorrhoea):

Regular period with normal flow, but with aRegular period with normal flow, but with a
prolonged duration.prolonged duration.
Menostaxis:Menostaxis:
Irregular uterine bleeding which is notIrregular uterine bleeding which is not
related to the menstrual periods, it alsorelated to the menstrual periods, it also
includes uterine bleeding before puberty,includes uterine bleeding before puberty,
after the menopause, and that related toafter the menopause, and that related to
pregnancy.pregnancy.
Metrostaxis (Metrorrhagia):Metrostaxis (Metrorrhagia):

M e n o r r h a g i a
M e n o s t a x is
P o ly m e n o r r h o e a
C y c l i c
M e t r o s t a x is
( M e t r o r r h a g ia )
A c y c l i c
O r g a n ic
M e t r o s t a x is
A c y c lic
( A n o v u l a t o r y )
P o ly m e n o r r h o e a
M e n o r r h a g ia
M e n o s t a x is
C y c l i c
( O v u l a t o r y )
D y s f u n c t io n a l
A b n o r m a l U t e r i n e B l e e d i n g

Organic BleedingOrganic Bleeding
Fibroids of the uterus
Pelvic inflammatory disease
Endometriosis and adenomyosis
Lesions of the uterine cavity
Submucus fibroidSubmucus fibroid
IUDIUD
Intrauterine polypIntrauterine polyp
A) Causes of excessive organicA) Causes of excessive organic menstrualmenstrual
bleeding (usually cyclic)bleeding (usually cyclic)

B) Local lesions causingB) Local lesions causing nonmenstrualnonmenstrual bleedingbleeding
(usually acyclic)(usually acyclic)
SiteSite Causes
Vulva TraumaTrauma
Infection, UlcersInfection, Ulcers
VaricesVarices
Urethral caruncleUrethral caruncle
CondylomaCondyloma
DystrophyDystrophy
Benign neoplastic lesionBenign neoplastic lesion
Malignant neoplasmMalignant neoplasm

(usually acyclic) (cont.)(usually acyclic) (cont.)
SiteSite Causes
Vagina TraumaTrauma
Foreign bodyForeign body
InfectionInfection
Atrophic vaginitisAtrophic vaginitis
Prolapse with ulcerProlapse with ulcer
VaricesVarices
CondylomaCondyloma
Benign neoplasmBenign neoplasm
Malignant neoplasmMalignant neoplasm

SiteSite Causes
Cervix CervicitisCervicitis
EctropionEctropion
Prolapse and ulcerProlapse and ulcer
CondylomaCondyloma
Benign neoplasm esp polypBenign neoplasm esp polyp
Cancer of cervixCancer of cervix

SiteSite Causes
Uterus Inflammatory: endometritisInflammatory: endometritis
Benign neoplasm: polypsBenign neoplasm: polyps
Endometrial cancerEndometrial cancer
IUDIUD
Secondary to tubal diseaseSecondary to tubal disease
Pregnancy related AbortionAbortion
EctopicEctopic
Vesicular moleVesicular mole

SiteSite Causes
Urinary tract Urethral CaruncleUrethral Caruncle
Urethral diverticulumUrethral diverticulum
HematuriaHematuria
GIT HemorrhoidsHemorrhoids
FissureFissure
Intrinsic lesions of anus, rectum, colon, etcIntrinsic lesions of anus, rectum, colon, etc
Nongynecologic BleedingNongynecologic Bleeding

Dysfuctional Uterine Bleeding (DUB)Dysfuctional Uterine Bleeding (DUB)
Definition:Definition: Abnormal uterine bleeding in theAbnormal uterine bleeding in the
absence of any organic pathology that can beabsence of any organic pathology that can be
detected by clinical pelvic examination.detected by clinical pelvic examination.

Aetiology of DUB:Aetiology of DUB:
a.a. Estrogen withdrawal bleedingEstrogen withdrawal bleeding
b.b. Estrogen breakthrough bleedingEstrogen breakthrough bleeding
c.c. Progestin breakthrough bleedingProgestin breakthrough bleeding
d.d. Progestin withdrawal bleedingProgestin withdrawal bleeding
1. Anovulatory (usually acyclic) DUB:1. Anovulatory (usually acyclic) DUB: mostmost
common type of bleeding 85%. The types ofcommon type of bleeding 85%. The types of
anovulatory bleeding are:anovulatory bleeding are:

Aetiology of DUB:Aetiology of DUB:
a.a. Inadequate corpus luteum or irregularInadequate corpus luteum or irregular
ripening of the endometriumripening of the endometrium
b.b. Persistent corpus luteum or irregularPersistent corpus luteum or irregular
shedding of the endometriumshedding of the endometrium
2. Ovulatory (usually cyclic) DUB:2. Ovulatory (usually cyclic) DUB: 15%15%

Estrogen withdrawal bleedingEstrogen withdrawal bleeding
After bilateral oophorectomy, administration of EAfter bilateral oophorectomy, administration of E
to menopausal or prepubertal female and thento menopausal or prepubertal female and then
discontinue it, and midcycle spotting.discontinue it, and midcycle spotting.

Estrogen breakthrough bleedingEstrogen breakthrough bleeding
Intermediate levels of E yield intermittent spottingIntermediate levels of E yield intermittent spotting
that may be prolonged, while higher levels of Ethat may be prolonged, while higher levels of E
result in prolonged periods of amenorrhoearesult in prolonged periods of amenorrhoea
followed by acute profuse bleeding. Examples arefollowed by acute profuse bleeding. Examples are
in PCO patients, obesity, and anovulation inin PCO patients, obesity, and anovulation in
postpubertal and premenopausal females.postpubertal and premenopausal females.

Progestin breakthrough bleedingProgestin breakthrough bleeding
Occurs only when P/E ratio is very high so that inOccurs only when P/E ratio is very high so that in
absence of sufficient E continuous P therapyabsence of sufficient E continuous P therapy
results in intermittent bleeding of variableresults in intermittent bleeding of variable
duration, eg with Norplant and Depo Provera.duration, eg with Norplant and Depo Provera.

Progestin withdrawal bleedingProgestin withdrawal bleeding
Administration and discontinuation of progestinAdministration and discontinuation of progestin
even in the presence of E results in withdrawaleven in the presence of E results in withdrawal
bleeding only if the endometrium was initiallybleeding only if the endometrium was initially
proliferative by the effect of E.proliferative by the effect of E.

Why anovulatory bleeding is excessive?Why anovulatory bleeding is excessive?
Increased endometrial thickness by continuous EIncreased endometrial thickness by continuous E
exposure without structural stromal support dueexposure without structural stromal support due
to absence of growth-limiting P and periodicto absence of growth-limiting P and periodic
desquamation.desquamation.
The tissue is fragile with spontaneous superficialThe tissue is fragile with spontaneous superficial
breakage & bleeding.breakage & bleeding.

Why anovulatory bleeding is excessive?Why anovulatory bleeding is excessive?
As one site heals, another, new site of breakdownAs one site heals, another, new site of breakdown
appears.appears.
Absence of synchronous endometrial breakdownAbsence of synchronous endometrial breakdown
Absence of rhythmic vasoconstrictionAbsence of rhythmic vasoconstriction
Healing depends only on E, however, it is onlyHealing depends only on E, however, it is only
temporary as the tissues are fragile.temporary as the tissues are fragile.

Differential Diagnosis:Differential Diagnosis:
Causes of organic uterine bleeding with detectableCauses of organic uterine bleeding with detectable
pelvic pathology (see table above).pelvic pathology (see table above).
Conditions with abnormal bleeding but noConditions with abnormal bleeding but no
detectable pelvic pathologydetectable pelvic pathology
1.1. MedicationsMedications
2.2. Thyroid disease: hypothyroidism or hyperthyroidismThyroid disease: hypothyroidism or hyperthyroidism
3.3. Severe organic disease as renal or liver failureSevere organic disease as renal or liver failure
4.4. Blood dyscrasis: such as von Willebrand’s disease,Blood dyscrasis: such as von Willebrand’s disease,
factor XI deficiency, and treatment with anticoagulants.factor XI deficiency, and treatment with anticoagulants.
DUB is a diagnosis ofDUB is a diagnosis of EXCLUSIONEXCLUSION, one should, one should
exclude the followingexclude the following

Diagnostic toolsDiagnostic tools
1.1. UltrasonographyUltrasonography
2.2. Laboratory tests for hCG, PRL, thyroidLaboratory tests for hCG, PRL, thyroid
function tests, coagulation studies, CBC, renalfunction tests, coagulation studies, CBC, renal
and liver function tests, cervical cultures.and liver function tests, cervical cultures.
3.3. D & C biopsy in patients > 35 yearsD & C biopsy in patients > 35 years
4.4. Hysteroscopy, laparoscopy, & HSG.Hysteroscopy, laparoscopy, & HSG.

Treatment of Anovulatory DUBTreatment of Anovulatory DUB
The aim of treatment is to restore the naturalThe aim of treatment is to restore the natural
controlling influences in this tissue: universal,controlling influences in this tissue: universal,
synchronous endometrial events, structuralsynchronous endometrial events, structural
stability, and vasomotor rhythmicity.stability, and vasomotor rhythmicity.
In all cases correction of possible anemia, andIn all cases correction of possible anemia, and
looking for a cause for anovulation is indicated.looking for a cause for anovulation is indicated.

Treatment of Anovulatory DUBTreatment of Anovulatory DUB
1.1. Progestin TherapyProgestin Therapy
2.2. Oral Contraceptive TherapyOral Contraceptive Therapy
3.3. Estrogen TherapyEstrogen Therapy
4.4. AntiprostaglandinsAntiprostaglandins
5.5. Progestin IUDProgestin IUD
6.6. GnRH AgonistsGnRH Agonists
7.7. DesmopressinDesmopressin
8.8. Ablation of the EndometriumAblation of the Endometrium
9.9. Other ChoicesOther Choices

Progestins exert a powerful antiestrogenicProgestins exert a powerful antiestrogenic
action resulting in limitation of growth andaction resulting in limitation of growth and
marked atrophy of the endometrium.marked atrophy of the endometrium.
1. Progestin Therapy:1. Progestin Therapy:

In the treatment of DUB progestins such as medroxy-In the treatment of DUB progestins such as medroxy-
progesterone acetate (Provera tab), is given 5-10 mgprogesterone acetate (Provera tab), is given 5-10 mg
daily for 10-14 days to induce stabilizing predicidualdaily for 10-14 days to induce stabilizing predicidual
stromal changes followed by a withdrawal flow – thestromal changes followed by a withdrawal flow – the
so-called “medical curettage”. Thereafter, repeatso-called “medical curettage”. Thereafter, repeat
progestin is offered cyclically for at least 10 daysprogestin is offered cyclically for at least 10 days
each month to ensure therapeutic effect. Failure ofeach month to ensure therapeutic effect. Failure of
progestin to correct irregular bleeding requiresprogestin to correct irregular bleeding requires
diagnostic reevaluation.diagnostic reevaluation.
1. Progestin Therapy:1. Progestin Therapy:

2. Oral Contraceptive Therapy2. Oral Contraceptive Therapy
Especially used for anovulatory bleedingEspecially used for anovulatory bleeding
with prolonged endometrial buildup, andwith prolonged endometrial buildup, and
heavy bleeding.heavy bleeding.
AnyAny of the low-dose oral combinationof the low-dose oral combination
monophasic pills.monophasic pills.

1x2x5-7 days then stop the pills1x2x5-7 days then stop the pills
If bleeding does not stopIf bleeding does not stop another diagnosticanother diagnostic
possibility should be reevaluated.possibility should be reevaluated.
If bleeding stopsIf bleeding stops (usually within 12 to 24 h) the(usually within 12 to 24 h) the
endometrium becomes stable but still very thickendometrium becomes stable but still very thick
and the following withdrawal bleeding will beand the following withdrawal bleeding will be
heavy and painful, and the patient must beheavy and painful, and the patient must be
warned of that.warned of that.

Continue treatmentContinue treatment as 1x1x21 days followed by 7as 1x1x21 days followed by 7
days free (as in any CCP) for 3 cycles. The flowdays free (as in any CCP) for 3 cycles. The flow
will be reduced one cycle after the other aswill be reduced one cycle after the other as
endometrial thickness decreases one cycle afterendometrial thickness decreases one cycle after
the other until it is normalized after 3 cycles.the other until it is normalized after 3 cycles.
If contraception is not required CCP is stopped. If theIf contraception is not required CCP is stopped. If the
patient still has oligomenorrhoea, she is stillpatient still has oligomenorrhoea, she is still
anovulatory and cyclic progestin to prevent recurrenceanovulatory and cyclic progestin to prevent recurrence
is indicated.is indicated.
If contraception is desired CCP are continued.If contraception is desired CCP are continued.

3. Estrogen Therapy3. Estrogen Therapy
Patients with estrogen breakthrough bleedingPatients with estrogen breakthrough bleeding whenwhen
minimal endometrium exists & the benefits of Pminimal endometrium exists & the benefits of P
treatment are not achieved.treatment are not achieved.
An example is young anovulatory patients in whomAn example is young anovulatory patients in whom
polonged hemorrhagic desquamation leaves littlepolonged hemorrhagic desquamation leaves little
residual tissue (bleeding was heavy for many days orresidual tissue (bleeding was heavy for many days or
the endometrial curette yields minimal tissue)the endometrial curette yields minimal tissue)
High dose E is given and then P therapy follows. EHigh dose E is given and then P therapy follows. E
starts healing events and stops bleeding, P follows bystarts healing events and stops bleeding, P follows by
giving stability, then both are stopped to have agiving stability, then both are stopped to have a
withdrawal bleed.withdrawal bleed.
Indicated in:Indicated in:

3. Estrogen Therapy3. Estrogen Therapy
Patients with progestin breakthrough bleedingPatients with progestin breakthrough bleeding e.g.e.g.
use of oral contraceptives, depot forms ofuse of oral contraceptives, depot forms of
progestational agents, or Norplant. In theprogestational agents, or Norplant. In the
absence of sufficient estrogen, the endometriumabsence of sufficient estrogen, the endometrium
shrinks and is composed of stroma and bloodshrinks and is composed of stroma and blood
vessels with minimal glands. It is fragile andvessels with minimal glands. It is fragile and
liable to bleedingliable to bleeding. .. .
Treatment with short courses of E (conjugated estrogenTreatment with short courses of E (conjugated estrogen
1.25 mg daily for 7 days) rejuvenates the endometrium1.25 mg daily for 7 days) rejuvenates the endometrium
& stops bleeding.& stops bleeding.
Indicated in:Indicated in:

4. Use of Antiprostaglandins4. Use of Antiprostaglandins
Antiprostaglandins decrease menstrual blood lossAntiprostaglandins decrease menstrual blood loss
perhaps by altering the balance between theperhaps by altering the balance between the
platelet proaggregating vasoconstrictorplatelet proaggregating vasoconstrictor
thromboxane Athromboxane A22 and the antiagregatingand the antiagregating
vasodilator prostacyclin (PGIvasodilator prostacyclin (PGI22).).
They are indicated especially in ovulatory womenThey are indicated especially in ovulatory women
with dysfunction menorrhagia.with dysfunction menorrhagia.

5. Treatment with Progestin IUD5. Treatment with Progestin IUD
It is very effective in reducing the flow to lessIt is very effective in reducing the flow to less
than normal or even to amenorrhoea in womenthan normal or even to amenorrhoea in women
with ovulatory menorrhagia. It may be also usedwith ovulatory menorrhagia. It may be also used
to control bleeding in patients with intractableto control bleeding in patients with intractable
bleeding associated with chronic illness (such asbleeding associated with chronic illness (such as
renal failure).renal failure).

6. Treatment with GnRH Agonists6. Treatment with GnRH Agonists
It can be used for short-term relief from aIt can be used for short-term relief from a
bleeding problem, for example, in a patient withbleeding problem, for example, in a patient with
renal failure or a blood dysrasia. This choice is arenal failure or a blood dysrasia. This choice is a
good one for patients who bleed after organgood one for patients who bleed after organ
transplantation especially liver transplantationtransplantation especially liver transplantation
where sex steroid use is undesirable.where sex steroid use is undesirable.

7. Treatment with Desmopressin7. Treatment with Desmopressin
It is a synthetic anlogue of arginineIt is a synthetic anlogue of arginine
vasopressin. It is used as a last resort forvasopressin. It is used as a last resort for
treatment of abnormal bleeding in patientstreatment of abnormal bleeding in patients
with coagulation disorders, especially inwith coagulation disorders, especially in
patients with von Willebrand’s disease.patients with von Willebrand’s disease.

8.8. Ablation of the Endometrium &Ablation of the Endometrium &
hysterectomyhysterectomy
Used for persistent bleeding despiteUsed for persistent bleeding despite
treatment.treatment.
Ablation is successful in 90% of patients.Ablation is successful in 90% of patients.

8.8. Ablation of the Endometrium & hysterectomyAblation of the Endometrium & hysterectomy
Methods of endometrial ablation areMethods of endometrial ablation are
Hysteroscopy +Hysteroscopy +
 LaserLaser
 Resectoscope with a loopResectoscope with a loop
 Resectoscope with a rolling ballResectoscope with a rolling ball
 Radio frequency-induced thermal destructionRadio frequency-induced thermal destruction
Uterine balloonUterine balloon to expose the endometrium to an 85to expose the endometrium to an 85oo
CC
temperature for 10-15 min. using circulating hot saline.temperature for 10-15 min. using circulating hot saline.

9.9. Other Poor ChoicesOther Poor Choices
Antifibrinolytic agents (e.g., tranexamicAntifibrinolytic agents (e.g., tranexamic
acid)acid)
DanazolDanazol

Dub - dr.hisham saleh

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (16)

Similar to Dub - dr.hisham saleh

Similar to Dub - dr.hisham saleh (20)

Dub - dr.hisham saleh

Editor's Notes