Transcript Abnormal uterine bleeding

Abnormal uterine
bleeding
GENERAL OBJECTIVE
– Students will understand abnormal
uterine bleeding and causes as well as
management.
Specific objectives
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After attending lecture, the student will can:
Know what is the abnormal uterine bleeding.
List causes of abnormal uterine bleeding.
Define dysfunctional uterine bleeding , know
its types, patophysiology.
Given patient history ,examination and a set
of laboratory data, correctly diagnose the
disease. (problem-solving).
Discuses treatment.
Abnormal uterine
bleeding
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It is an descriptive term applied to any
alteration in the normal pattern of
menstrual flow and it is the uterine
bleeding that is abnormal in amount,
duration or timing. The abnormalities
of menstruation are only symptoms
and do not describe pathological
entities.
<21d
21-35d
Polymen
orrhoea
normal
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>35d
oligome
norrhoea
≥6 m
ameno
rrhoea
**Amenorrhoea: absence of menstruation
for ≥6 months.
*Oligomenorrhoea: menses at interval of
>35 days is usually caused by a prolonged
follicular phase.
*Polymenorrhoea: is a frequent
menstruation as menses occurring at < 21
days interval associated with a shortened
follicular phase or inadequate luteal phase.
Menorrhagia >80ml
blood loss
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*Menorrhagia: heavy, regular blood
loss occurring over several consecutive
cycles. More than 80 ml per period.
Because of the practical difficulties of
measuring menstrual blood loss,
subjective diagnosis based on the
history is generally accepted as the
basis of management.
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*Metrorrhagia -irregular intervals with
excessive flow and duration
*Intermenstrual bleeding –
Uterine bleeding of variable amounts occurring
between regular menstrual periods.
*Midcycle spotting :
is scanty intermenstrual discharge occurring just
before ovulation that is associated with a
decrease in estrogen at midcycle.
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*Postcoital bleeding: is non-menstrual
bleeding that occurs immediately after
sexual intercourse.
*With drawl bleeding: bleeding
occurred after stopping oestrogen and
progestrone use or progestrone use.
*Postmenopausal bleeding Recurrence of bleeding in a menopausal
woman at least 6 months to 1 year after
cessation of cycles.
Aetiology of abnormal
uterine bleeding:
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A. Organic causes:
1. Local disorders:
Uterine fibroids.
Endometrial/ Endocervical polyp.
Adenomyosis.
Pelvic endometriosis.
Intrauterine device (IUD).
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Pelvic inflammatory disease (PID).
cervicitis.
Polycystic ovary disease
Oestrogen-secreting ovarian
tumour.(granulosa or theca cell tumour).
Cervical carcinoma.
Uterine body carcinoma.
Trauma of lower genital tract
Urethral caruncle.
2. Systemic disorders:
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1. Pregnancy
Should be considered in women of
reproductive life in any patient
presenting with abnormal uterine
bleeding.
2. Systemic disorders:
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2.Endocrine disorders may interfere with
normal feedback mechanisms that regulate
secretion of gonadotrophin- releasing
hormone (GnRH), gonadotrophin, sex steroid.
A. Thyroid disorder (Hypothyroidism or
hyperthyroidism).
B. Diabetes mellitus.
C. Adrenal disease.
D. Cushing disease
E. Prolactin disorders.
2. Systemic disorders:
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3. Haemostasis disorder:
A. Von Willebrand's disease.
B. Idiopathic Thrombocytopenic
purpura (ITP).
C. Deficiencies of factors 11, V, VII,X1.
D. myeloproliferative disorders.
2. Systemic disorders:
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4. Liver disorder (may interfere with
metabolism of oestrogen, reduced
coagulation factors).
5. Renal disease (alter excretion of
oestrogen and progestrone).
6. Medications as steroid hormones,
neuroleptics, anticoagulants and cytotoxic
agents, contraceptive method.
Contraceptive method:
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*oral contraceptives method
Breakthrough bleeding may occur in
patients taking oral contraceptives that have
low doses of estrogen and progestin.
Intermenstrual bleeding may occur
secondary to missed pills, varied ingestion
times, and drug interactions.
progestin-only compounds
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An iatrogenic cause of DUB is the use of progestinonly compounds for birth control.
Medroxyprogesterone acetate (Depo-Provera), a longacting injection given every 3 months, inhibits
ovulation. An adverse effect of this drug is prolonged
uterine breakthrough bleeding; this may continue
after discontinuation of the drug because of persistent
anovulation.
-The Norplant system (surgically implanted
levonorgestrel), which acts to block some but not all
ovulatory cycles, has the same adverse effects as
Depo-Provera.
Intrauterine device (IUD): Can cause menorrhagia.
2. Systemic disorders:
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7.Psychological and emotional cause,
Excessive exercise, stress, and weight
loss. All these can cause hypothalamic
suppression leading to abnormal
uterine bleeding due to disruption
along the hypothalamus-pituitaryovarian pathway.
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B. Non –organic cause
(Dysfunctional uterine bleeding
(DUB) no specific organic cause can
be found .
Dysfunctional
uterine bleeding
Dysfunctional uterine
bleeding
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is defined as abnormal uterine bleeding in the
absence of organic disease.
It is the most common cause of abnormal
vaginal bleeding during a woman's
reproductive years.
bleeding is most common at the extreme ages
of a woman's reproductive years, either at the
beginning or near the end, but it may occur at
any time during her reproductive life.
It is a diagnosis of exclusion.
Types of dysfunctional
uterine bleeding:
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Anovulatory DUB (90%).
Ovulatory DUB regular cyclicity) 10%
of cases
Anovulatory dysfunctional
uterine bleeding
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All causes of anovulation represent a
progesterone-deficient state results from
a disturbance of the normal
hypothalamic-pituitary-ovarian axis and is
particularly seen at extreme of
reproductive life (i.e. post menarchal
(due to immature hypothalamic-pituitary
axis) and perimenopausally in patients
who are 40 years or older (where the
number and quality of ovarian follicles
decrease and altered).
Pathophysiology in
anovulatory DUB are:
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*Estrogen breakthrough bleeding.
Persistant ovarian follicle
(prolonged cycle, period of
amenorrhoea followed by excessive
bleeding)
*Estrogen breakthrough
bleeding. Persistant ovarian
follicle
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There is adequate secretions of estrogen but
ovulation does not occur and no corpus luteum so
no progesterone thus the endometrium will not
stabilized; thus, proliferative endometrium persists
and the endometrium is thick, very vascular, very
fragile and spontaneously bleeds at various sites
and bleeding is random (not universal) one site
heals the other breakdown and bleeding is
continuous, as no progesterone so there is no self
limit of bleeding . all this make Bleeding episodes
become prolonged , irregular, some times heavy
bleeding and amenorrhea are common.
Estrogen breakthrough
bleeding. Persistant ovarian
follicle
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unopposed estrogen may continuo to
secreted and result in continuing
proliferation of endometrium. if high
level maintained could cause
endometrial hyperplasia and eventually
endometrial carcinoma. for that reason
endometrial sampling is mandatory in all
cases of DUB particularly in older
premenopausal women.
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thick endometrium
seen in continuous
estrogen stimulation
The follicles might
developed but they do
not rupture. Estrogen
is produced but it is
not opposed by
progesterone and the
endometrium becomes
thick. In the latter
case there is usually
one or many estrogen
producing follicles
present. .
prolonged
bleeding in a case
of a
overstimulated
endometrium .
*Insufficient follicular
development:
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Inadequate production of estrogen
and inadequate proliferation of
endometrium without any secretary
change result in deficient or atrophic
endometrium. Large venules situated
superficially under thin endometrium
which may ruptured and may be the
commonest cause of post menopausal
bleeding (PMB) and most common in
premenopuasal women.
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thin endometrium
seen in the
absence of
estrogen.
The follicles do
not develop and
no estrogen are
produced. In this
case the
endometrium will
be thin.
ovulatory dysfunctional
uterine bleeding
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More common in women aged 35-45
years and is typified by regular heavy
and painful menstrual periods
(menorragia, dysmenorrhoea).
Pathophysiology of
ovulatory DUB:
*Corpus luteum insuffiency:
luteal phase deficiency
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(menorhgia, premenstrual spotting
and/or shortening of menstrual cycle,
prolongation of menstrual bleeding)
May cause insufficient production of
progestrone and prematurely decreased
progestrone levels and insufficient
secretory changes in endometrium and
menorrhagia. Histologically show irregular
ripinnig of endometrium in second half of
cycle.
*Persistant corpus luteum
prolonged corpus luteum
activity
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(abnormal prolongation of menstruation,
resulting in prolonged cycle or
protracted menstrual bleeding).
May result in Persistant continued
secretion of estrogen and progestrone
(in the absence of pregnancy) and
absence of the normally sharp fall in
estrogen and progestrone secretion
which precede menstruation which may
lead to irregular shedding of the
endometrium.
Evaluation and diagnosis of
abnormal uterine bleeding:
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History:
*Age, parity, marital status (single,
married, widow, divorced).
*Description of the pattern of
abnormal menstrual bleeding and it's
severity and it's duration and amount
of blood loss.
*Presence of other cyclical symptoms
as dysmenorrhoea, breast tenderness,
psychological disturbance, fatigue,
dizziness, and syncope.
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*The patient should be questioned
about the possibility of pregnancy.
*Menstrual history:
Last menstrual period (LMP), Age of
menarche, and regularity including
flow, duration, and presence of
dysmenorrhea , Postcoital bleeding or
intermenstrual bleeding.
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*Past obstetric history:
Gravida and para .
Previous abortion or recent termination of pregnancy.
*Contraceptive history:
Contraceptive method used, use of barrier protection.
*Past gynecological history:
History of sexually transmitted diseases (STDs) or
ectopic pregnancy.
cervical smear and its result history.
sexual history:
ask about dyspareunia, postcoital bleeding.
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*Ask about : Recent illness, psychological
stress, excessive exercise, or weight change
*Past medical history:
Diabetes mellitus, Thyroid disease,
Endocrine problems, pituitary tumors, Liver
disease.
*Past surgical history.
*Drug history:
Medication usage, including exogenous
hormones, anticoagulants, aspirin,
anticonvulsants, and antibiotics.
Clinical examination:
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Look for:
height and weight and body mass index (BMI).
signs of anemia or hypovolemia, vital signs.
General looking for stigmata of underlying systemic
disease is important. hirsutism, striae, thyroid
enlargement or nodularity, skin pigment changes.
Assessment for secondary sexual characteristic.
ecchymoses or petechiae (suggest coagulopathy).
Abdominal examination:
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Liver enlargement.
Pelvic masses.
Regional lymph nodes palpation.
Pelvic examination:
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Inspection of vulva for any external
evidence of bleeding or sign of local
infections.
Speculum examination: for cervix and
vagina
Bimanual palpation to assess for
uterine or adenexal enlargement or
tenderness.
Rectal examination
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if bleeding from bowel is suspected.
Laboratory
investigations:
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The patient's history and examination will
guide the selection of various tests.
a complete blood count is essential
investigation.
If there is suspicion of organic disease , it is
mandatory to undertake the fullest
investigation necessary to reach a precise
diagnosis.
Young women presenting with
intermenstrual or postcoital bleeding should
be tested for Chlamydia.
Hormonal assay:
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B-hCG if any possibility of pregnancy exists.
In patients with suspected endocrine disorders,
laboratory studies such as thyroid function tests
and prolactin levels may be helpful
A mid-luteal progestrone level in regular cycle only
(done in day 21 in 28 day cycle). level >30nmol/L
is indicative of ovulation.
Serum androgen in some cases as it is elevated in
poly cystic ovary syndrome (PCO), androgen
producing tumour, adrenal condition.
Prolactin.
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Coagulation screen and bleeding time
is important to request if bleeding
disorder is suspected.
Renal function tests and liver function
tests should be requested if systemic
condition or malignancy is suspected.
Imaging Studies
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Pelvic ultrasound.
It is useful to determine shape and size of
uterus and adnexal structures.
It may determine the etiology of the
bleeding such as a fibroid, endometrial
thickening, poly cystic ovary, adenomyosis.
Imaging Studies
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Computed tomography (CT scan) /
Magnetic resonance imaging (MRI)
is used in cases needed greater level
of detail of pelvic structures and
abnormalities and for cancer staging.
Endometrial sampling:
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Endometrial biopsy is important step in evaluation
abnormal uterine bleeding. It is indicated for the
following patients with abnormal uterine bleeding :
1.Women older than 35 years.
2.Those with abnormal endometrial thickness
(>12mm in perimenopausal women and >4mm in
postmenopausal women).
3.Obese patients.
4.Women who have prolonged periods of
unopposed estrogen stimulation
5. Women with chronic anovulation.
Endometrial biopsy can
be done by:
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1. Hysteroscopically directed biobsy:
is the gold slandered procedure as it
provides direct visualization of uterine
cavity and allows to take biopsy from
specific lesion. It is ideally done in
proliferative phase of menstrual cycle
when the endometrium is at it's thinnest.
2. Aspiration technique.
3.Curettage.
Treatment of abnormal
uterine bleeding:
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In treatment of abnormal uterine
bleeding, Consider:
1.Age group.
2.Amount and pattern of bleeding.
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Menstrual calendar day to day report
of amount of blood loss for 2-3
months is helpfull.
Oral iron should be given to patient
with menorrhagia routinely.
Treatment of secondary disease if
present.
Medical therapy:
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Non hormonal therapy:
Prostaglandin synthetase inhibitor:
antiprostaglandins (non-steroidal antiinflammatory drugs, NSAIDS): e.g.
Mefenamic acid (ponstan)
Great benefit to use in ovulatory DUB
and in menorrhagia associated with
dysmenorrhoea.
NSAIDS
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It acts by inhibiting the enzyme cyclooxygenase and reduce local prostaglandin
level. This leads to vasoconstriction and
increased platelet aggregation. These
medications may reduce blood loss by 2050%. It is used only during menstruation as
it is used with the onset of menses or just
prior to its onset and continued throughout
its duration. It is generally well tolerated.
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Note: Although aspirin is included
in this category of drugs, women
with heavy menstrual bleeding
should not use aspirin.
Antifibrinolytic agents:
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As tranexamic acid, it is potent inhbitor of
fibrinolysis so decrease menorrhagia and
also in menorrhagia related to IUD.
Given orally at time of menstruation.
Side effects: nausea, dizzeness, diarrohea,
intracrainal arterial thrombosis.
it is contraindicated in patients with history
of thromboembolism . Used alone or in
combination .
Hormone therapy
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There is some help obtained from
endometrial histology in the second
half of cycle to decide treatment. The
aim of treatment is to maintain or
restore the normal endocrine cycle.
First-line drugs:
*Cyclical Combined oral
contraceptive pills (OCPs)
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Are effective in reducing menstrual
bleeding, controlling cycle irregularities and
relieving menstrual pain giving for women
requiring contraception or for women whom
hormonal agents are acceptable. It helps to
prevent the risks associated with prolonged
unopposed estrogen stimulation of the
endometrium. It effectively manage
anovulatory bleeding in premenopausal and
perimenopausal women.
*Progestogen therapy:
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Treatment with cyclic progestins is preferred
when COCP use is contraindicated, such as
in smokers over age 35 and women at risk
for thromboembolism.
cyclical progestogens are effective for
menorrhagia when given for 21days out of
28 and first choice for control of anovulatory
dysfunctional bleeding.
withdrawal bleeding occured 3-5 days after
completion of the course.
Method of administration:
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*Arrest bleeding.
Norethisterone acetate (primolut-N )
20-30 mg daily until bleeding stops
usually in 24-48 hours and for not
more than 3days and may continued
in lower dose for up to 21 days .
Once she stopped , withdrawal
bleeding will occur in a few days later.
Cyclical:
Luteal phase treatment
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*Luteal phase treatment in second half
of cycle (from 15th to 26th day)
indicated when corpus luteum insuffiency
has been diagnosed particularly in
premenstrual spotting. Treatment continued
for 6-9 months.
Norethisterone acetate (primolut-N ) 5mg
tid (three times a day)
Or
Medroxy progestrone acetate (Provera) 10
mg tid
Whole cycle treatment:
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*Whole cycle treatment: Throughout
menstrual cycle (5th to 26th day)
Effective treatment for menorrhagia when
given at high doses between days 5 and 26 of
cycle. As luteal phase treatment is not so
effective in treating menorrhagia. Treatment
can be continued for 6-9 months.
Norethisterone acetate (primolut-N ) 5mg tid
for 21days out of 28
Or Medroxy progestrone acetate (Provera) 10
mg tid
Side effects include weight gain, headache and
bloatedness.
Long acting high dose progestogens (e.g.
Depo-Provera) may be used to induce
amenorrhoea but limited by side effects.
 Progestogen-releasing intrauterine system:
 Levonorgestrel-releasing intrauterine system
(LNG-IUS) used to relief
 Menorrhagia as it induce
progressive endometrial atrophy.
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Oestrogen therapy:
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Alone used rarely in DUB treatment.
Used in atrophic endometrium and in
cases of DUB secondary to depot
progestogen.
Second-line drugs:
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Used in:
When Simple measure have failed.
Management of severe anemia prior to
surgery.
When Surgery is contraindicated.
Danazol
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Danazol creates a hypoestrogenic and
hyperandrogenic environment,( as it is
progestogen but it is converted into testosterone
peripherally and acts as androgen which induces
endometrial atrophy resulting in reduced
menstrual loss).
200mg is effective to decrease menorrhagia
continuous for 12 weeks.
Side effects: Androgenic Side effect (breast
atrophy, hirsutism, voice changes ,weight gain,
oily skin, and acne), musculoskeletal pain and skin
rash. Because of the significant androgenic side
effects, this drug is usually reserved as a secondline treatment for short-term use prior to surgery.
Gestrinone
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Gestrinone is a 19-testosterone
derivative which has antiprogestogenic, anti-oestrogenic and
androgenic activity.it reduce menstrual
blood loss in menorrhagia. However, it
also has androgenic side effects.
Gonadotropin-releasing
hormone agonists(GnRH
analogue) such as buserelin, goserelin.
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They produce a profound hypoestrogenic state
similar to menopause (They induce medical
menopause by suppressing gonadotrophions).
Side effects include menopausal symptoms and
bone loss with long-term use so it should not
prescribed for longer than 6 months because the
risk of osteoporosis. They are also of value as
endometrial-thinning agents prior to hystroscopic
surgery. In cases of severe menorrhagia in which
simple measure have failed , long term therapy
with a GnRH agonist plus hormonal add-back can
be considered if there are contraindications to
surgery.
Golden rule
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Note: no hormone treatment
should be given unless malignant
disease has first been excluded in
women with abnormal uterine
bleeding around the menopause.
Surgical management:
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It is reserved for patients in whom
medical treatments have failed.
In acute situation (occasionally). As
dilatation and curettage in acute situation
with severe blood loss can reduce
haemorrhage .
Surgical method:
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Surgical method:
Dilatation and curettage (D&C)
Endometrial resection and
ablation.
Hysterectomy
Dilatation and curettage
(D&C):
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Dilatation and curettage (D&C):
A D&C may be done for a woman with
heavy bleeding used in acute situation
(for diagnostic and therapeutic
purpose).
Endometrial resection
and ablation:
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This procedure removes or destroys
layers of the endometrium down to
myometrium including basal layer so
no regeneration of endometrium and
layers of fibrous tissue replace it
(theraputic asherman’s syndrome). it
can be done as an office procedure in
several technique. It usually reduces
the amount of bleeding.
Endometrial resection
and ablation:
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This procedure is only appropriate for
1. women with refractory dysfunctional
bleeding who do not want to have more or any
children
2. patients with submucous fibroid.
Endometrial histology should be evaluated prior
to surgery in order to exclude carcinoma and
endometrial hyperplasia.
Amenorrhea is seen in approximately 35% of
women treated, and decreased flow is seen in
another 45%. A substantial number of patients
receiving endometrial ablation require reoperation.
Hysterectomy:
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It is the most effective treatment for
bleeding and indicted for patients who have
not respond to medical or conservative
therapy.
However, it is associated with more frequent
and severe adverse events compared with
either conservative medical or ablation
procedures. Operating time, hospitalization,
recovery times, and costs are also greater.
No need for removal of ovaries unless there
is indication as abnormal ovaries.
Emergency Department
Care:
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Treatment in cases with severe uterine bleeding and
hemodynamically unstable patients after resuscitation,
consider treatment by:
*administration of IV conjugated estrogen (Premarin)
25 mg IV every 4-6 hours until the bleeding stops.
*An oral contraceptive with 35 mcg of ethinyl estradiol
can be taken twice a day until the bleeding stops for up
to 7 days, at which time the dose is decreased to once
a day until the pack is completed.
*In women with severe, persistent uterine bleeding, an
immediate dilation and curettage (D&C) procedure may
be necessary.
Abnormal uterine bleeding
according to age :
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Abnormal uterine bleeding in
Adolcent and teenager girl:
(discussed in puberty lecture).
Abnormal uterine bleeding
in Adult 20-39years:
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It most commonly due to:
*Benign disease of genital tract
including pelvic inflammatory disease
(PID), uterine fibroid or some
complication of pregnancy.
*DUB is also common.
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Organic disease must therefore always be
excluded before a diagnosis of DUB is made
which is most commonly ovulatory, though
anovulatory bleeding seen in 20% of cases.
Most cases resolve spontaneously in
ovulatory but in anovulatory is less good
and endometrial hyperplasia may be the
cause which tend to recur.
Conservative therapy is usually indicated.
Hysterectomy may be indicated if bleeding
is severe or recurrent and patient has
completed her family.
Abnormal uterine bleeding in
Perimenopausal women (40
years and more:
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Most commonly dysfunctional, though
organic cause also common as
malignancy increase with age so it is
important to exclude these condition
so curettage is mandatory.
Conservative therapy.
Hysterectomy is often indicated.
Abnormal uterine bleeding
By bleeding pattern:
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Regular cyclical bleeding: menorrhagia
Frequently due to :
Benign organic disease of genital
tract.
DUB-ovulatory.
Rarely due to malignancy.
Considered relatively favorable.
In younger women with menorrhagia
of short duration , investigation may
be deffered as spontaneous
remission frequently occur.
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Irregular bleeding:
Frequently due to :
*It is characteristic of organic disease
of genital tract and in particular
carcinoma of cervix or endometrium.
*Anovulatoiry DUB.
So it is regarded unfavourable
particularly in perimenopausal women,
and promote investigation is
mandatory.
Intermenstrual bleeding:
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Frequently due to :
Dysfunctional due to fall in estrogen
following ovulation.
Cervical and endometrial polyp.
Submucous uterine fibroid.
Cervical carcinoma.
It is essential to regard all cases of
intermenstrual bleeding as abnormal until
proved otherwise.