ABNORMAL UTERINE

BLEEDING
Aubrey Kate Cadangen, Mark Anthony Cando, Jayceelyn Gumaru,
Odessa Lanuza, Eingelskween Luis-Miranda Jasmine Lee Masweng,
Joan Pagalilauan, Jayvin Ramani,
Nancy Margarette Roxas, Ajay Shivanagutti
Oligomenorrhea
- infrequent uterine bleeding with intervals between
bleeding episodes varying from 35 days to 6 months

Amenorrhea - no menses for at least 6 months

Mean interval between menses: 28 days +/- 7 days
* bleeding intervals of <21 days or >35 days =
ABNORMAL

Mean duration of menstrual flow: 4 days

*Few women normally bleed for 7 days
*bleeding for longer than 7 days = ABNORMAL
 PREDICTING BLOOD LOSS
ALKALINE HEMATIN METHOD
- method to predict blood loss by measuring hematin

Average menstrual blood loss = 35ml

Total volume = twice than of average, ~70ml
*menstrual blood loss increases with parity

HEAVY MENSTRUAL BLEEDING

- Menstrual blood loss of ≥ 80ml
- occurs in 9-14% of women
CAUSES OF ABNORMAL UTERINE
BLEEDING
FIGO: PALM-COEIN system
PALM – structural
or histologic
causes diagnosed
through imaging
or biopsy
COEIN – non-
structural
The acronym AUB is followed by the letters PALM-COEIN
and a subscript 0 or 1 associated with each letter to
indicate the absence or presence, respectively, of the
abnormality. “L” when present is designated as LSM or LOM

For example, a patient with abnormal bleeding that is both

irregular and heavy may have endometrial hyperplasia due
to anovulation.

AUB- P0A0L0M1-C0O1E0I0N0
 ENDOMETRIAL POLYPS
• localized overgrowths of endometrial
tissue, containing glands, stroma, and
blood vessels, covered with epithelium
• majority are benign
• most commonly found in reproductive-age women
• estrogen stimulation - play a key role in the
development
• rarely found before menarche
• Molecular mechanisms - overexpression of endometrial
aromatase and gene mutations in HMGIC and HMGI
ENDOMETRIAL POLYPS
• Oncogenic potential
• symptomatic vaginal bleeding and postmenopausal
status
• tamoxifen use and obesity
• Diabetes mellitus and hypertension
• Gynecologic examination
• Transvaginal ultrasound - detected asymptomatic
polyps in up to 12%
• < 1cm polyps - regress spontaneously
• Symptomatic polyps –treated with
hysteroscopy
 ADENOMYOSIS
• presence of endometrial glands
and stroma in the uterine
myometrium.
• ectopic endometrial tissue leads to
hypertrophy of the surrounding
myometrium.
• focal or diffuse
• peak incidence in the fifth decade of life
• Multiparity - most significant risk factor
• penetration of endometrial glands and stroma past the
basalis layer is thought to contribute
ADENOMYOSIS
• histologic diagnosis
• Ultrasound
• enlarged, asymmetric uterus
• Anechoic avascular cysts scattered
throughout the myometrium
(pathognomonic)
• MRI
• demonstrate thickening of the junctional zone,
the area between the endometrium and the
myometrium, equal to or greater than 12 mm
Leiomyoma (AUB-L ; fibroids)
• benign tumors of the uterine myometrium with a complex
and heterogeneous clinical presentation as varied as their
biologic origins
• Pathogenesis:
▪ initiated from myometrial injury leading to cellular
proliferation, decreased apoptosis and increased
production of extracellular matrix
▪ Critical in this pathway is the overexpression of
transforming growth factor beta that leads to fibrosis of
these tumors
✓Transforming growth factor beta : contributes to
implantation failure in women with fibroids who are
subfertile
 Leiomyoma (AUB-L ; fibroids)
• Prevalence
▪ 70% of women ; 50% of these will be symptomatic

• Mechanisms by which leiomyoma cause abnormal bleeding

depends on :
✓size, location, and number
• Subclassification of leiomyomas : describes their location
throughout the myometrium
✓May increase the overall surface area of the endometrial
cavity or alter uterine contractility
✓ effects in turn lead to abnormal and excessive uterine
bleeding

• In FIGO system, leiomyomas can be notated in the PALM-

COEIN system with a subscript 0 (absence) or 1 (present) ;
SM (submucosal location)

Treatments :
❑hormonal or surgical ablation of the endometrium,
❑uterine artery embolization,
❑radiofrequency ablation,
❑myomectomy
Malignancy (AUB-M)
• Malignancies associated with the female reproductive tract
include vulvar, vaginal, cervical, endometrial, uterine, and
adnexal (ovarian or fallopian tube) cancers
▪ cervical malignancy : classically presents as coital
bleeding or intermenstrual bleeding (important part of
the workup of any woman is thorough cervical
evaluation)
• coital bleeding : squamous cell carcinoma of the
cervix are present in 1.4% of patients, and 15% had
cervical intraepithelial neoplasia

▪ endometrial cancer- AUB is the most common

presenting symptom
• presents most often in the seventh decade,
• 15% of cases are diagnosed in premenopausal women,
• 3% to 5% present in women under the age of 40
Risk factors:
• Obesity with increased estrone levels
▪ due to peripheral conversion by aromatase in adipose tissue
• Impaired ovulation and the absence of progesterone withdrawal
▪ can result in sustained exposure of the endometrium to estrogen
• Hyperestrogenic state
▪ can lead to the pathologic progression from normal endometrium
to hyperplasia and ultimately to adenocarcinoma
• Lynch syndrome, or hereditary nonpolyposis colorectal cancer
(HNPCC),
▪ an autosomal dominant disease caused by a disruption in
mismatch repair (MMR) genes
▪ also carries 40% to 50% lifetime risk of endometrial cancer,
significant proportion occurring before the age of 45
• Estrogen-producing ovarian tumors
▪ may manifest by abnormal uterine bleeding
▪ Most common : Granulosa theca cell tumors
 Coagulopathy
• Adolescents with prolonged heavy menses
- Routine screening for coagulation defects
• Adults
-screening only if indicated by clinical signs
 Coagulation defects are found in:

-20% require hospitalization

-25% with hemoglobin level fall below 10g/dl
-One third require transfusion
-50% with severe menorrhagia at first
menstrual period
 Disorders and Risk factors
• Hemophilia A and B
- X linked recessive deficiencies of factor VIII and IX
• Rare inherited coagulopathies (V, VII, X,XI,XIII)
-potential symptom is menorrhagia
• Chronic anticoagulation
-result of use of heparin, LMWH, direct thrombin
inhibitors, directs
Xa inhibitors from prevention of thrombosis.
 Ovulatory dysfunction
• Alteration in neuroendocrine function
• continuous estradiol production without corpus luteum
formation and progesterone production

• Steady state estrogen stimulation results to:

1. continuously proliferating endometrium
2. outgrow blood supply/ lose nutrients
3. necrosis
4. uniform slough to basalis layer does not occur
5. excessive uterine bleeding
Anovulatory Bleeding
Extremes of reproductive life
• Adolescents Pattern
- immaturity of HPO axis • Oligomenorrhea
-and failure negative feedback • Intermenstrual
of estradiol bleeding
• Heavy menstrual
• Perimenopausal bleeding
-lack of synchronization between
HPO components
Other Causes
• PCOS
• Hypothalamic dysfunction
• Hypothyroidism
• Hyperprolactinemia
IATROGENIC (AUB-I)
⚫ Abnormal bleeding resulting from medications
I. Hormonal Preparations- most common cause
1. Selective Estrogen Receptor Modulators
2. Gonadotropic releasing hormone agonist and
antagonist

II. Contraceptives
1. Chronic progesterone therapy
2. Levonorgetrel intrauterine devices
3. Implantable progestin devices
4. Combined oral contraceptives
III. Antipsychotic medications
(Risperidone)
•- use of antipsychotic medications can
result to hyperprolactenemia. Elevated
prolactin causes disruption to the HPO
axis and can contribute to anovulation
which manifests as abnormal uterine
bleeding.
ENDOMETRIAL (AUB-E)
-presents with heavy menstrual bleeding in the absence
of other abnormalities
-previously known as “ovulatory dysfunctional uterine
bleeding”

PROLONGED AND HEAVY BLEEDING:

1. Abnormalities of the platelet plug
2. Inadequate uterine levels of PGF2a
3. Excessive uterine production of prostacyclin
4. Endometritis
5. Sub-clinical infection with Clamydia trachomatis
NOT OTHERWISE SPECIFIED (AUB-N)
-abnormal bleeding not classified in the
previous categories
-Examples: foreign bodies or trauma
-Treat the specific cause
DIAGNOSTIC APPROACH
• Von Willebrand disease
• single most common abnormality for most women
presenting with heavy menstrual bleeding due to
coagulation disorders

HISTORY:
• History of
menorrhagia
• family history of bleeding
• epistaxis
• Bruising
• gum bleeding
• postpartum hemorrhage
• Surgical bleeding
• History and physical examination
• frequency, duration, and amount of bleeding

• Serum ferritin
• provides a valid indirect assessment of iron stores in the
bone marrow
• Endometrial sampling
• recommended in patients with heavy menstrual bleeding
over the age of 45
• Measurement of the uterine length and subjective
assessment of the quantity of tissue.
• Dilation and curettage (D&C)
• when office endometrial biopsy is not possible
• the tissue sample is insufficient
• performed under anesthesia
• MRI
• Superior modality for evaluation of the extent of myoma
invasion and detecting and mapping fibroid location
• Ultrasonography
• performs similarly to MRI in the detection of uterine
fibroids with a sensitivity of 99%
• Sonohysterogram (SHG)
• to rule out an intracavitary lesion before ascribing the
diagnosis to endometrial disorders or ovulatory
dysfunction
• Office-based flexible hysteroscopy
• Therapeutic and diagnostic
• Diagnostic : Provides direct visualization of the
endometrium and has the potential
• Therapeutic: treat the abnormality --- as removal of a
polyp
Treatment of abnormal uterine bleeding
• Treatment requires an accurate diagnosis
• In the absence of an organic cause for excessive uterine
bleeding, it is preferable to use medical instead of surgical
treatment, especially if the woman desires to retain her
uterus for future childbearing or will be undergoing natural
menopause within a short time
• A definitive diagnosis is required before instituting long-
term treatment
ABNORMAL UTERINE BLEEDING:
OVULATORY DYSFUNCTION
• In adolescents:
• After ruling out coagulation disorders, the main
direction of therapy is to temporize because with
time and maturity of the HPO axis, the problem will
be corrected
• A cyclic progestogen (medroxyprogesterone acetate)
continued up to 6 months is all that is needed to
produce reliable and controlled menstrual cycle
• If the problem persists beyond 6 months, OCs
become an option in that the condition may be more
chronic
ABNORMAL UTERINE BLEEDING:
OVULATORY DYSFUNCTION
• In the perimenopausal woman
• Most of the bleeding in this setting is caused by
anovulation
• It is more efficient to use a low-dose (20-μg) OC in a
nonsmoking woman
• During reproductive life, chronic anovulatory
bleeding is primarily caused by hypothalamic
dysfunction or PCOS
• OCs work well in this setting, although an alternative
is cyclic progestogens
ABNORMAL UTERINE BLEEDING:
ENDOMETRIAL
• For women with heavy menstrual bleeding, for whom there
is no known cause and anatomic lesions have been ruled
out, the aim of therapy is to reduce the amount of
excessive bleeding
• Options for treatment to reduce blood loss include a more
prolonged regimen of progestogens (3 weeks each month)
• Doses in excess of 10 mg daily of medroxyprogesterone
acetate (MPA) have been used
• OCs will reduce the blood loss by at least 35%
• Another beneficial option is the use of the levonorgestrel
intrauterine system (IUS), whereby menorrhagia can be
substantially reduced
Local Progestogen Exposure
• The levonorgestrel-releasing intrauterine system
(LNG-IUS) has an effective duration of action of
more than 5 years
• Studies have shown that the LNG-IUS reduces MBL
by 74% to 97% and is effective in increasing
hemoglobin levels, decreasing dysmenorrhea, and
reducing blood loss caused by fibroids and
adenomyosis
• Patients with AUB due to coagulopathy, especially
secondary to anticoagulation therapy, also can be
managed successfully with the LNG-IUS
NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS
• NSAIDs are prostaglandin synthetase inhibitors that
inhibit the biosynthesis of the cyclic endoperoxides,
which convert arachidonic acid to prostaglandins.
• To decrease bleeding of the endometrium, it would be
ideal to block selectively the synthesis of prostacyclin
alone, without decreasing thromboxane formation,
because the latter increases platelet aggregation.
• NSAIDs have been shown to reduce MBL, primarily in
women who ovulate.
• Several NSAIDs have been administered during menses
to groups of women with menorrhagia and ovulatory
DUB and have been found to reduce the mean MBL by
approximately 20% to 50%
•Drugs used:
1. Mefenamic acid (500 mg, three times daily),
2. Ibuprofen (400 mg, three times daily),
3. Meclofenamate sodium (100 mg, three times
daily), and
4. Naproxen sodium (275 mg, every 6 hours after a
loading dose of 550 mg)
• These drugs are usually given for the first 3 days of
menses or throughout the bleeding episode.
• All appear to have similar levels of effectiveness.
• The greatest amount of MBL reduction occurs
in women with the greatest pretreatment
blood loss.
• NSAIDs therapy to combination with OCs or
progestogens approach, a reduction in MBL
can be achieved more effectively than with
the use of any of these agents alone
Antifibrinolytic Agents
• 1.ε-Aminocaproic acid (EACA),
• 2.tranexamic acid (AMCA), and
• 3.para-aminomethyl benzoic acid (PAMBA)
- are potent inhibitors of fibrinolysis
• There was a significant reduction in blood loss after
treatment with EACA, AMCA, and OCs, and use of
each of these agents resulted in approximately a
50% reduction in MBL
• the greatest reduction in blood loss with
antifibrinolytic therapy occurred in women who
exhibited the greatest pretreatment MBL.
Side Effects : in decreasing order of frequency,
• nausea, dizziness, diarrhea, headaches,
abdominal pain, and allergic manifestations.
• These side effects are much more common with
EACA >>than with AMCA
contraindications :
• Renal failure, pregnancy, and history of
thrombosis
• Tranexamic acid administered in doses of 3.9
g/day demonstrated a significant reduction of
MBL in women with fibroids, with greatest
reductions on days 2 and 3
• Due to the increased risks of thrombosis and
myocardial infarction, antifibrinolytic agents
should not be combined with oral
contraceptives.
• Combined treatment with tranexamic acid and
the oral contraceptive pill has been implicated
in coronary ulcerated plaque and acute
myocardial infarction
Gonadotropin-Releasing Hormone Agonists
• GnRH agonists may be used to inhibit ovarian steroid
production, as estrogen production is necessary for
endometrial proliferation.
• daily administration of a GnRH agonist for 3 months
markedly reduced MBL from 100 to 200 mL per cycle to
0 to 30 mL per cycle
• Unfortunately, after therapy was discontinued, blood
loss returned to pretreatment levels
• their use for heavy menstrual bleeding is limited to
women with severe MBL who fail to respond to other
methods of medical management and wish to retain
their childbearing capacity.
• Use of an estrogen or progestogen (add-back therapy)
together with the agonist will help prevent bone loss.
 MANAGEMENT OF ACUTE BLEEDING

CURETTAGE - quickest way to stop acute

bleeding (heavy bleeding and hemodynamically
unstable.
-preferred approach for:
1. older women
2. medical risk factors
PHARMACOLOGIC AGENTS
FOR ACUTE BLEEDING
• 1. High dose estrogen - the most effective regimen
-aimed at stopping acute bleeding
-Diagnosis-independent and temporary
measure.
-Causes rapid growth of the endometrial tissue
over the denuded and raw epithelial surfaces
-Alter platelet activity thus promote
adhesiveness
High dose estrogen
a.oral conjugated equine estrogen (CEE) 10 mg/day, in four
divided doses
• **most causes are usually controlled, but if bleeding does
not decrease within the first 24 hours, consideration must
be given to an organic cause and
Your text herecurettage should be
considered.
b. Intravenous (IV) estrogen - also effective in the acute
treatment of menorrhagia.
**several hours required to induce mitotic activity and
growth of the endometrium
** IV (rapid metab clearance) = oral as long as s/e (nausea)
can be tolerated
**uterine bleeding usually reduces within 24 hours p
initiation
High dose estrogen
• Acute heavy bleeding d/t anovulation
- Progesterone is added (MPA 10 mg OD) x 7 to
10 days

• Definitive diagnosis should be made after

endometrial histology

• Oral contraceptives – best long term

treatment in the absence of contraindications
High dose estrogen
c. Combination oral contraceptive
(COC)- a more convenient method to stop
acute bleeding

** Estrogen 30-35 ug (4 tablets every 24

hours in divided doses) up to 1 week after
the bleeding stops
(sufficient to stop acute bleeding and
simultaneously provide progestin)
2. Progestogens
-stop endometrial growth but also support and
organize the endometrium so that an organized
slough occurs after their withdrawal.
- stimulate arachidonic acid formation in the
endometrium increasing the PGF2α/PGE ratio.
* High-dose progestogens exert direct stabilizing
effects on the endometrium in a rapid sequence.

3. Androgen – used in treatment of heavy menstrual

bleeding
-side effects of weight gain (7-fold) and skin
problems(4-fold) – greater than NSAIDS
Surgical management for HMB
-Dilatation and Curettage
-Endometrial ablation
-Hysterectomy
D and C
Should not be used as therapeutic treatment
Maybe performed for acute HMB unresponsive to initial
management
Endometrial ablation
Maybe offered as initial treatment for HMB
In women with normal uterus
No structural or histological abnormality is present
Should not be used as first-line treatment for HMB
Hysterectomy
Should not be used as first-line treatment for HMBá
Summary of approaches to
treatment
Acute bleeding
• Immediate cessation
-pharmacologic estrogen
- curettage
• Curettage
-used more in older women
-not dependent on anovulatory or ovulatory state
-preferable if pathology is suspected
Determine exact cause of abnormal bleeding
• Adolescent
- 10mg MPA, for 10days each month for 3 months
-additional diagnostic studies for defects on
coagulation process

• Reproductive age
-OC and oral MPA for anovulatory bleeding for 6
months
-OC and clomiphene citrate for other indication

• Perimenopausal
-low dose OC
Chronic ovulatory menstrual bleeding
Most difficult type
• If anatomical abnormalities are absent
- long term treatment
- NSAIDS, progestin, OC, anti-fibrinolytics, and GnRH
analogues
-combination of two or more are required to obviate the
need for endometrial ablation or hysterectomy

• LNG-IUS
- first line therapy in patients with bleeding due to
anticoagulation