ABNORMAL UTERINE

BLEEDING
• After adolescence, menstrual cycles generally conform to a cycle
length of 21 to 35 days, with the duration of menstrual flow fewer
than 7 days
• MENSTRUAL TERMINOLOGY:
TERMINOLOGY
 MENORRHAGIA
• Menorrhagia is defined as cyclic bleeding at normal intervals; the bleeding is either
excessive in amount (>80 mL) or duration (>7 days) or both.
• Causes: Menorrhagia is a symptom of some underlying pathology—organic or functional.
PELVIC CAUSES:
Due to congestion, increased surface area, or hyperplasia of the endometrium
Fibroid uterus
Adenomyosis
Pelvic endometriosis
IUCD inutero
Chronic tubo-ovarian mass
Tubercular endometritis (early cases)
 Retroverted uterus—due to congestion
 Granulosa cell tumor of the ovary
 Systemic:
 Liver dysfunction—failure to conjugate and thereby inactivates the estrogens.
 Congestive cardiac failure.
 Severe hypertension.
 Endocrinal
 Hypothyroidism
 Hyperthyroidism.
 Hematological
 Idiopathic thrombocytopenic purpura.
 Leukemia
 von Willebrand’s disease.
 Platelet deficiency.
 Emotional upset
 Functional Due to disturbed hypothalamo-pituitary-ovarianendometrial axis
POLYMENORRHEA
• Polymenorrhea is defined as cyclic bleeding where the cycle is reduced to
an arbitrary limit of less than 21 days and remains constant at that
frequency. If the frequent cycle is associated with excessive and or
prolonged bleeding, it is called epimenorrhagia.
• Causes-
 Dysfunctional: It is seen predominantly during adolescence, preceding
menopause and following delivery and abortion. Hyperstimulation of the
ovary by the pituitary hormones may be the responsible factor.
Ovarian hyperemia as in PID or ovarian endometriosis.
• Metrorrhagia is defined as irregular, acyclic bleeding from the uterus.
Amount of bleeding is variable. While metrorrhagia strictly concerns
uterine bleeding but in clinical practice, the bleeding from any part of the
genital tract is included under the heading.
• Menometrorrhagia is the term applied when the bleeding is so irregular
and excessive that the menses (periods) cannot be identified at all.
OLIGOMENORRHEA
• Menstrual bleeding occurring more than 35 days apart and which
remains constant at that frequency is called oligomenorrhea.
• CAUSES:
Age-related—during adolescence and preceeding menopause
 Weight-related—obesity
 Stress and exercise related
Endocrine disorders—PCOS (commonest), hyperprolactinemia,
hyperthyroidism
 Androgen producing tumors—ovarian, adrenal
Tubercular endometritis—late cases
Drugs: • Phenothiazines • Cimetidine • Methyldopa
HYPOMENORRHEA
• When the menstrual bleeding is unduly scanty and lasts for less than 2
days, it is called hypomenorrhea.
• Causes - The causes may be local (uterine synechiae or endometrial
tuberculosis), endocrinal (use of oral contraceptives, thyroid
dysfunction, and premenopausal period), or systemic (malnutrition).
NEWER TERMINOLOGY
DYSFUNCTIONAL UTERINE BLEEDING
(DUB)
• DUB is defined as a state of abnormal uterine bleeding without any
clinically detectable organic, systemic, and iatrogenic cause (Pelvic
pathology, e.g. tumor, inflammation or pregnancy is excluded).

• Heavy menstrual bleeding (HMB) is defined as a bleeding that

interferes with woman's physical, emotional, social and maternal
quality of life.
• Abnormal uterine bleeding is common, and etiologies include
anatomic changes, hormonal dysfunction, infection, system disease,
medications, and pregnancy complications . As a result, AUB may
affect females of all ages. Factors that influence incidence most greatly
are age and reproductive status.
• In children, the vagina, rather than the uterus, is more frequently
involved. Vulvovaginitis is often the cause, but dermatologic
conditions, neoplasms, and trauma by accident, abuse, or foreign body
are others. In addition to vaginal sources, urethra bleeding may
originate rom urethral prolapse or infection. True uterine bleeding
usually results rom increased estrogen levels, and precocious puberty,
accidental exogenous ingestion, and ovarian neoplasm are considered.
• In adolescence, AUB results rom anovulation and coagulation defects
at disproportionately higher rates compared with older reproductive-
aged women. In contrast, benign or malignant neoplastic growths are
less frequent. Pregnancy, sexually transmitted diseases, and sexual
abuse are also considered in this population.
• Following adolescence, the hypothalamic-pituitary-ovarian (HPO)
axis matures, and anovulatory uterine bleeding is encountered less o
ten. With increased sexual activity, rates o bleeding related to
pregnancy and sexually transmitted disease rise. The incidences of
bleeding from leiomyomas and endometrial polyps also increase with
age.
• During the perimenopause, as with perimenarchal girls, anovulatory
uterine bleeding rom HPO axis dysfunction is a more frequent finding.
In contrast, the incidences of bleeding related to pregnancy and
sexually transmitted disease decline. With aging, risks of benign and
malignant neoplastic growth increase.
• After menopause, bleeding typically can be traced to a benign origin
such as endometrial or vaginal atrophy or polyps. Even so, malignant
neoplasms, especially endometrial carcinoma, are found more often in
this age group. Less commonly, estrogen-producing ovarian carcinoma
may cause endometrial hyperplasia with uterine bleeding. Similarly,
ulcerative vulvar, vaginal, or cervical neoplasms can be sources. And
rarely, serosanguinous discharge from a fallopian tube cancer may
appear as uterine bleeding. Thus, bleeding in this demographic usually
prompts evaluation to exclude these cancers.
 PATHOPHYSIOLOGY
• The endometrium consists of two distinct zones, the functionalis layer and the basalis
layer . The basalis layer lies in direct contact with the myometrium, is beneath the
functionalis, and is less hormonally responsive.

• The basalis serves as a reservoir or regeneration of the functionalis layer following

menses. In contrast, the functionalis layer lines the uterine cavity, undergoes dramatic
change throughout the menstrual cycle, and ultimately sloughs during menstruation.

• Histologically, the functionalis has a surface epithelium and underlying subepithelial

capillary plexus. Beneath these are organized stroma, glands, and interspersed
• Blood reaches the uterus via the uterine and ovarian arteries. From these,
the arcuate arteries arise to supply the myometrium. These in turn branch
into the radial arteries, which extend toward the endometrium at right
angles rom the arcuate arteries .
• At the endometrium-myometrium junction, the radial arteries bifurcate to
create the basal and spiral arteries. The basal arteries serve the basalis layer
of the endometrium and are relatively insensitive to hormonal changes. The
spiral arteries stretch to supply the functionalis layer and end in a
subepithelial capillary plexus.
• At the end of each menstrual cycle, progesterone levels drop and lead to
release of lytic matrix metalloproteinases (MMP). These enzymes break down
the stroma and vascular architecture of the functionalis layer. Subsequent
bleeding and sloughing of this layer constitute menstruation . Initially, platelet
aggregation and thrombi control blood loss. In addition, the remaining
endometrial arteries, under the infuence of mediators, vasoconstrict to limit
further bleeding.
ANATOMY THAT VARIES DURING MENSTRUAL CYCLE
DIAGNOSIS
1. History and clinical examination
2. Laboratory investigations
3. Sampling methods
4. Sonography
 HISTORY AND CLINICAL EXAMINATION
• With AUB, the diagnostic goal is exclusion of pregnancy or cancer and
identification of the underlying pathology to allow optimal treatment.

• A thorough menstrual history is collected. Topics typically include age

at menarche, date of last menstrual period, birth control method, and the
timing and amount of bleeding.

• Associated symptoms such as fever, fatigue, bulk symptoms, tissue

passage, or pain can also direct evaluation.
• Importantly, medications are reviewed, as abnormal bleeding can accompany use of
nonsteroidal anti inflammatory drugs (NSAIDs), anticoagulants, and agents
associated with hyperprolactinemia . Less robust evidence implicates herbal
supplements such as ginseng, garlic, ginkgo, don quai, and St. John wort.

• Of pain symptoms, dysmenorrhea often accompanies abnormal bleeding caused by

structural abnormalities, infections, and pregnancy complications. This seems
intuitive because of the role of prostaglandins in both HMB and dysmenorrhea.

• Painful intercourse and noncyclic pain are less frequent in women with AUB and
usually suggest a structural or infectious source.
• Physical examination attempts to identify findings that may suggest an
etiology. Moreover, the site of uterine bleeding is confirmed, because
vaginal, rectal, or urethral bleeding can present similarly.

• This is more difficult if there is no active bleeding, and urinalysis or stool

evaluation may be helpful adjuncts. To complement physical findings, blood
tests, cervical cytology, sonography (with or without saline infusion),
endometrial biopsy, and hysteroscopy are used primarily.
LABORATORY EVALUATION

β-Human Chorionic Gonadotropin and Hematologic Testing

• Miscarriage, ectopic pregnancies, and hydatidiform moles may cause life-

threatening hemorrhage. Pregnancy complications are quickly excluded
with determination of urine or serum β-human chorionic gonadotropin
(hCG) levels. This is typically obtained on all reproductive-aged women
with a uterus.
• Additionally, in women with AUB, a complete blood count (CBC) will identify
anemia and the degree of blood loss. With chronic loss, erythrocyte indices will
reflect a microcytic, hypochromic anemia and show decreases in MCV, MCH,
and MCHC.
• Moreover, in women with classic iron-deficiency anemia from chronic blood
loss, an elevated platelet count may be seen. In those or whom the cause of
anemia is unclear, those with profound anemia, or in those who fail to improve
with oral iron therapy, iron studies are often indicated. Specifically, iron-
deficiency anemia produces low serum ferritin and low serum iron levels but an
elevated total iron-binding capacity.
 “Wet Prep” Examination and Cervical
Cultures
• Cervicitis often causes intermenstrual or postcoital spotting. Accordingly, microscopic
examination or a saline preparation of cervical secretions or “wet prep” can be
informative.

• With mucopurulent discharge, sheets of neutrophils (> 30 per highpower eld) and red
blood cells are typical.

• With trichomoniasis, motile trichomonads are also found. Cervicitis-related bleeding is

frequently reproduced during sampling from an inflamed cervix with a friable epithelium.
The association between mucopurulent cervicitis and cervical infection with Chlamydia
 Cervical Cytology or Biopsy
• Both cervical and endometrial cancers can bleed and evidence or these tumors
may be detected during diagnostic Pap smear evaluation. The most frequent
abnormal cytologic results involve squamous cell pathology and may reflect
cervicitis, intraepithelial neoplasia, or cancer.

• Less commonly, atypical glandular or endometrial cells are found. Thus,

depending on the cytologic results, colposcopy, endocervical curettage, and/or
endometrial biopsy may be indicated . Moreover, at times, a visibly suspicious
vaginal or cervical lesion may bleed and warrant direct biopsy with Tischler
forceps.
 Endometrial Biopsy
• Indications: In women with AUB, sampling and histologic evaluation o
the endometrium may identify infection or neoplastic lesions such as
endometrial hyperplasia or cancer. AUB is noted in 80 to 90 percent o
women with endometrial cancer. Thus, in postmenopausal women, the
need to exclude cancer intensifies, and endometrial biopsy is typically
indicated.
• Of premenopausal women with endometrial neoplasia, most are obese or
have chronic anovulation or both. Thus, women with AUB in these two
groups also warrant exclusion of endometrial cancer. Specifcally, the
• ACOG recommends endometrial assessment in any woman older than
45 years with AUB, and in those younger than 45 years with a history of
unopposed estrogen exposure such as seen in obesity or polycystic
ovarian syndrome, failed medical management and persistent AUB
Sampling Methods
• For years, dilatation and curettage (D & C) was used or endometrial
sampling. However, because of associated surgical risks, expense,
postoperative pain, and need or operative anesthesia, other suitable
substitutes were evaluated. However, disadvantages include patient
discomfort and rare procedural complications such as uterine
perforation and infection.
• To minimize these, flexible plastic samplers have been evaluated or
endometrial biopsy. Advantageously, samples from these catheters
have comparable histologic findings with tissues obtained by D & C,
hysterectomy, or stiff metal curette . Prior to performing endometrial
biopsy, pregnancy is excluded in women of reproductive age.
Pipelle cannula diagram
STEPS OF ENDOMETRIAL BIOPSY
Sonography
• Transvaginal Sonography- With improved resolution, this technology is
chosen by many instead of endometrial biopsy as a first-line tool to assess
AUB. Advantageously, it allows assessment of both the myometrium and
the endometrium. Thus, if AUB stems from myometrial pathology such as
leiomyomas, sonography offers anatomic information that is not afforded
by hysteroscopy or endometrial biopsy.
• Normal endometrial thickness in premenopausal women did not exceed 4
mm on day 4 o the menstrual cycle, nor did it measure more than 8 mm by
day 8. However, endometrial thicknesses can vary considerably among
premenopausal women, and evidence-based abnormal thresholds that have
been proposed range rom ≥ 4 mm to > 16 mm.
Saline Infusion Sonography
• This is simple, minimally invasive, and effective sonographic
procedure can be used to evaluate the myometrium, endometrium,
and endometrial cavity, also known as sonohysterography or
hysterosonography, SIS allows identification of common masses
associated with AUB such as endometrial polyps, submucous
leiomyomas, and intracavitary blood clots.
• Although not yet widely used, this technique enables directed
histologic sampling of endometrial pathology and has proved superior
to blind endometrial biopsy in providing a diagnosis or AUB in peri-
and postmenopausal women.
Limitations:
• First, it is cycle dependent and best performed in the proliferative phase to
minimize false-negative and false-positive results. For example, focal
lesions may be concealed in a thick, secretory endometrium. Also, the
amount of endometrial tissue that can develop during the normal secretory
phase can be mistaken or a small polyp or focal hyperplasia.
• Second, SIS usually has more patient discomfort than VS and
approximately 5 percent of examinations cannot be completed because of
cervical stenosis or patient discomfort.
• There ore, in postmenopausal women with AUB, and in whom the
exclusion of cancer is more relevant than evaluating focal intracavitary
lesions, SIS alone as an initial diagnostic tool may not have advantages
over VS.
Additional Sonographic Techniques
• Color and pulsed Doppler
• 3-dimensional (3-D) sonography and 3-D SIS.
• Last, although preferred to computed tomography (CT ), magnetic
resonance (MR) imaging is rarely needed or AUB evaluation but can
display endometrium in cases in which sonographic views are obstructed.
Hysteroscopy
• Endoscope, usually 3 to 5 mm in diameter, is inserted into the endometrial cavity and cavity
is then distended with saline or another medium for visualization.
• In addition to inspection, biopsy of the endometrium allows histologic diagnosis of abnormal
areas and has been shown to be a safe and accurate means of identifying pathology. Also,
focal lesions can be diagnosed and completely removed in the same session.
• Advantage: detection of intracavitary lesions such as leiomyomas and polyps that might be
missed using VS or endometrial sampling. It also permits simultaneous removal of many
lesions once identifed.
• Limitations: Cervical stenosis and heavy bleeding may hinder an adequate examination. It is
more expensive and technically challenging than VS or SIS. Costs can be lower with of ce
hysteroscopy rather than that in an operative suite. Despite the risk of peritoneal
contamination by cancer cells with hysteroscopy, patient prognosis overall does not appear to
be worsened.
CLASSIFICATION
 Endometrial polyp
• Endometrial polyps are a cause of intermenstrual bleeding, heavy menstrual
bleeding, irregular bleeding, and postmenopausal bleeding. They are
associated with the use of tamoxifen and infertility, and can cause
dysmenorrhea.
• Most endometrial polyps are asymptomatic.
• The diagnosis may be suspected on the basis of endometrial thickening on
transvaginal pelvic ultrasound and vascular patterns of feeder blood vessels
may aid in distinguishing endometrial polyps from intracavity fibroids and
from endometrial malignancy .
• Confirmation of a polyp requires visualization with hysteroscopy,
sonohysterography, or the microscopic assessment of tissue obtained by a
biopsy done in the office or with a D&C. Whether and when to recommend
removal is not well established, particularly if a polyp is asymptomatic and
is found incidentally.
Adenomyosis, AUB-A
• Traditionally adenomyosis has been diagnosed by histology at the time
of hysterectomy, making estimates of prevalence and contribution to
AUB and pelvic pain unclear.
• With improving imaging technology and evolving diagnostic criteria
for adenomyosis on ultrasound and MRI, adenomyosis can be
diagnosed prior to hysterectomy and is included as a structural cause
of abnormal bleeding.
Leiomyoma, AUB-L
• Uterine leiomyomas occur in as many as one-half of all women older
than age 35 years and are the most common tumors of the genital tract.
• Abnormal bleeding is the most common symptom for women with
leiomyomas who are symptomatic. Although the number and size of
uterine leiomyomas do not appear to influence the occurrence of
abnormal bleeding, submucosal myomas are the most likely to cause
bleeding.
Malignancy and Hyperplasia, AUB-M
• Unopposed estrogen is associated with a variety of abnormalities of
the endometrium, from cystic hyperplasia to adenomatous hyperplasia,
hyperplasia with cytologic atypia, and invasive carcinoma.
• Abnormal bleeding is the most frequent symptom of women with
invasive cervical cancer.
Coagulopathy, AUB-C
• As with adolescents, hematologic causes of abnormal bleeding should
be considered in women with heavy menstrual bleeding, particularly
in those who have had heavy bleeding since menarche.
• Of all women with menorrhagia, 5% to 20% have a previously
undiagnosed bleeding disorder, primarily the von Willebrand disease .
• Abnormal liver function, which can be seen with alcoholism or other
chronic liver diseases, results in inadequate production of clotting
factors and can lead to excessive menstrual bleeding.
Ovulatory Dysfunction, AUB-O
• Most anovulatory bleeding results from what is termed estrogen
breakthrough. In the absence of ovulation and the production of
progesterone, the endometrium responds to estrogen stimulation with
proliferation. This endometrial growth without periodic shedding results in
eventual breakdown of the fragile endometrial tissue. Healing within the
endometrium is irregular and dyssynchronous. Relatively low levels of
estrogen stimulation will result in irregular and prolonged bleeding, whereas
higher sustained levels result in episodes of amenorrhea followed by acute,
heavy bleeding.
• Many ovulatory disorders relate to endocrine disturbances. Both
hypothyroidism and hyperthyroidism can be associated with abnormal
bleeding.
When Should a Gynecologist Suspect a
Bleeding Disorder:
Conditions Associated with Anovulation and
Abnormal Bleeding:
 Endometrial, AUB-E
• In ovulatory cycles, the endometrium itself may contribute to abnormal or heavy menstrual
bleeding (AUB/HMB). There is evidence that deficiencies of vasoconstrictors or excess of
vasodilators may lead to heavy bleeding.
• Local vasoconstrictors include endothelin-1 and prostaglandin F2alpha. Local vasodilators
include prostacyclin I2 and prostaglandin E2 .
• Inflammation and infection can affect the endometrium. Menorrhagia can be the first sign of
endometritis in women infected with sexually transmissible organisms. Women with
cervicitis, particularly chlamydial cervicitis, can experience irregular bleeding and postcoital
spotting.
• A woman who seeks treatment for menorrhagia and increased menstrual pain and has a
history of light-to-moderate previous menstrual flow may have an upper genital tract
infection or pelvic inflammatory disease (PID) (endometritis, salpingitis, oophoritis).
• Occasionally, chronic endometritis will be diagnosed when an endometrial biopsy is obtained
for evaluation of abnormal bleeding in a patient without specific risk factors for PID.
 Iatrogenic, AUB-I
• Irregular bleeding that occurs while a woman is using contraceptive hormones should be
considered in a different context than bleeding that occurs in the absence of exogenous
hormone use. Breakthrough bleeding during the first 1 to 3 months of oral contraceptive
use occurs in as many as 30% to 40% of users.
• Irregular bleeding can result from inconsistent use .Counselling about the frequent side
effects of irregular bleeding is imperative before initially prescribing these methods of
contraception.
• The management of irregular bleeding with hormonal contraceptive use can range from
reassurance and initial expectant management to recommendations for a change in the
hormonal delivery system or regimen. The use of additional oral estrogen or combined
oral contraceptives for 10 to 20 days improves bleeding with both DMPA and the
subdermal levonorgestrel in some studies. The use of a 5- to 7-day course of NSAIDs
may result in decreased breakthrough bleeding .
Not Yet Classified, AUB-N
• This includes causes of AUB not yet discovered and those rarer and
less-understood causes, including myometrial hypertrophy and AV
malformations.
MANAGEMENT
TRANEXAMIC ACID
• This antifibrinolytic drug reversibly blocks lysine binding sites on
plasminogen . In addition, it requires administration only during
menstruation and has few minor reported side effects that are
predominantly gastrointestinal and dose-dependent.
• The recommended dose is two 650-mg tablets orally taken three times
daily or a maximum of 5 days during menses.
• The drug has no effect on other blood coagulation parameters such as
platelet count.
• Contraindications to XA include concurrent COC use, a history of or an
intrinsic risk or thromboembolic disease, disseminated intravascular
coagulation and color blindness.
NSAIDS
• One advantage is that they are taken only during menstruation.
• Another advantage is that frequently associated dysmenorrhea also
improves with NSAIDs. Conventional NSAIDs nonspecifically inhibit
both cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet
unction, and COX-2, which mediates inflammatory response
mechanisms. Thus, conventional NSAIDs such as ibuprofen and
naproxen may not be ideal considering their inhibitory effects on
platelet function.
Combination Oral Contraceptive pills
• These hormonal agents effectively treat AUB-E, and when used long
term, menstrual blood loss is reduced by 40 to 70 percent .
• Advantages to COC use include the additional benefits of reducing
dysmenorrhea and providing contraception. Their presumed method of
action is endometrial atrophy, although diminished prostaglandin
synthesis and decreased endometrial fibrinolysis.
Other hormonal agents
• Women with AUB-E may respond to longer treatment schedules. NE A, 5 mg, or MPA, 10 mg,
each given orally three times daily or days 5 through 26 of each menstrual cycle have proved
effective . Unfortunately, prolonged use of high-dose progestins is often associated with side
effects such as mood changes, weight gain, bloating, headaches, and atherogenic changes in the
lipid profile..
• With GnRH agonists, the profound hypoestrogenic state created induces endometrial atrophy and
amenorrhea in most women. Side effects include those typical or menopause, and thus associated
bone loss precludes their long-term use.
• Of androgens, danazol is a derivative of the synthetic steroid 17α-ethinyl testosterone, and its net
effect creates a hypoestrogenic and hyperandrogenic environment to induce endometrial atrophy.
As a result, menstrual loss is reduced by approximately half and it may even induce amenorrhea.
• Gestrinone is derived synthetically from a 19-nortestosterone steroid nucleus. Its mechanisms of
action, side effects, and indications or HMB treatment are similar to those of danazol.The
recommended treatment dose is 2.5 mg orally twice weekly.
 Uterine procedures
• For many women, conservative medical management may be unsuccessful or
associated with signifcant side effects. Surgical management of HMB may
include procedures to destroy the endometrium or hysterectomy.
• Of these, dilatation and curettage is rarely used for longterm treatment of
AUB because its effects are temporary. Occasionally, D & C is performed to
quickly remove a thickened endometrium and arrest severe HMB refractory
to high-dose estrogen administration.
• Endometrial resection or ablation attempts to permanently remove and
destroy the uterine lining. Different types use laser, radio requency, electrical,
or thermal energies. Methods are considered first- or second-generation
techniques according to when they were introduced into use and their need or
concurrent hysteroscopic guidance.
• After ablation, uterine cavity anatomy is often distorted by uterine wall
agglutination and intracavitary scar bands, termed synechiae. This may pose
several long-term problems.
First, focal hematometra or postablation tubal sterilization syndrome (PATSS)
can form from menstrual blood trapped behind synechiae. It can cause severe
distention and cyclic pain.
Second, because of distorted anatomy, endometrial sampling attempts may be
inadequate, and endometrial stripe evaluation by VS or hysteroscopic examination
may be limited .
• Uterine artery embolization (UAE) is more commonly used to treat HMB
secondary to uterine leiomyomas.Rarely, this intervention may be considered
emergently in women with excessive acute HMB who are not responding to
conservative measures.
• Hysterectomy, despite the above measures, ultimately is chosen by more
than half of women with HMB within 5 years or their referral to a
gynecologist.
• Removal of the uterus is the most effective treatment or bleeding, and
overall patient satisfaction rates are high.
• Disadvantages to hysterectomy include more frequent and severe
intraoperative and postoperative complications compared with either
conservative medical or ablative surgical procedures. Operating time,
hospitalization, recovery times, and costs are also greater.