DYSFUNCTIONAL UTERINE

BLEEDING/
DYSMENORRHEA/
CLIMACTERIC SYNDROME
Dysfunctional Uterine Bleeding
Abnormal bleeding brought about by
“endocrine dysfunction” with the diagnosis
made only after the exclusion of
demonstrable causes, genital or extragenital
 Mechanism of Normal
Menstruation
A. Theories
1. Estrogen &/or progesterone withdrawal
2. Inadequate lymphatic drainage
3. Enzymatic changes leading to endometrial
sloughing & depolymerization of acid
monopolysaccharide ground substance
B. Hemostasis (stop menstrual flow)
1. Platelets occlude site of injury by
adhesion & aggregation

Initiate release of potent
proaggregatory compounds

Accelerate platelet aggregation &
initiate coagulation
 2. Release substance that cause
vasoconstriction
3. Mediates clot retraction & thrombolysis

> Platelets will adhere only to damaged

vascular endothelium
(cont.)
C. Platelets convert arachidonic acid
1st pathway
- catalyzed by lypoxygenases
- leads to formation of 12 hydroxyecoisatetraenoic acid
2nd pathway
- cycloxygenase pathway
- prostaglandin endoperoxides are potent inducers
of platelet aggregation
- thromboxane A2
 Etiology of DUB
A. Anovulatory cycles
- anovulation resulting from altered
neuroendocrine &/or ovarian hormonal
events is the major cause of DUB
 ANOVULATION

CONTINOUS ESTROGEN STIMULATION UNOPPOSED

BY PROGESTERONE

PROLIFERATING ENDOMETRIUM ASYNCHRONOUS DEVELOPMENT

MAY OUTGROW ITS BLOOD OF STROMA, GLANDS, BLD VESSEL
SUPPLY OR LOSE NUTRIENTS OVERDEVELOPED LYSOSOMAL COMPLEX

RELEASE OF EXCESSIVE AMOUNTS

OF HYDROLYTIC ENZYMES

IRREGULAR ENDOMETRIAL SHEDDING

B. Ovulatory Cycles
- due to alterations in the life span of the
corpus luteum
1. Halban Syndrome - prolonged life of
corpus luteum
- uncertain etiology
2. Shortened luteal phase
- results from variable function or a premature
denouncement of corpus luteum
Categories
1. Estrogen withdrawal bleeding
- estrogen therapy is given after castration then
discontinued
2. Estrogen breakthrough bleeding
- amount of bleeding is directly proportional to
the amount of estrogen stimulation
- low dosesintermittent spotting
- high levels profuse bleeding
3. Progesterone withdrawal bleeding
- removal of corpus luteum or
discontinuation of progesterone treatment
4. Progesterone breakthrough bleeding
- occurs in the presence of favorably high
ratio of progesterone to estrogen
-OCP with very low dose estrogen
Incidence
 50 % are between 40-50 y/o
 20% adolescents
 30% reproductive age group
 Anovulatory DUB accounts for 80% of cases
usually in the postmenarcheal & premenopausal
groups
1.Premenarheal girl
-random periodic fluctuations in her FSH,LH,E2 levels
-FSH levels are higher than LH
-do not have LH surge following an acute E2 rise
-BASIC DEFECT: absence of (+) feedback mechanism
-negative feedback mechanism is intact

Following Menarche
- there is a change toward normal adult pattern & they
become ovulatory
2. In the Premenopausal woman
- failing ovarian function due to depletion of
follicles
- shortened follicular &/or luteal phase
- exhibits oligomenorrhea or amenorrhea
- Prolonged anovulation w/ cont. E2 prod.

Proliferation of endometrium

hyperplasia
In the Reproductive age group
- bleeding is more commonly organic
A. More of the ovulatory type
- Altered corpus luteum function
- Related to local endometrial causes
>overactive endometrial fibrinolysis
>alteration in the production of prostanoids
B. Anovulatory DUB
- psychogenic causes
- Nutritional
- Systemic
- Constitutional
- Functioning cyst or tumors
>PCO-frequent cause
 Symptomatology
A.Normal Menses
> interval = 28+/-days
> duration = 4+/-2days
> Total blood loss = 40+/-20ml
Abnormalities:
1.Polymenorrhea
-frequent,regular (<21 days interval)
2. Oligomenorrhea
-infrequent,irregular (40 days)
3. Hypomenorrhea
- regular,decreased in amount
-brought about by NSAID’S,OCP (low estrogen content
(cont)
4. Hypermenorrhea or Menorrhagia
- regular,excessive &/or prolonged
-due to enlarged uterus, submucous myoma
IUD, blood dyscrasia
5. Metrorrhagia
-irregular & frequent
-anovulatory
6. Menometrorrhagia
- prolonged bleeding at irregular intervals
- endometrium is hyperplastic
- CA of endometrium must be ruled out
7. Intermenstrual Bleeding
- bleeding of variable amounts occurring between
regular menstrual period.
- polyp
- OCP
8. Premenstrual Spotting
- scanty bleeding that occurs a few days to week
before menses
- associated luteal insufficient
Ovulatory Cycles
- bleeding usually regular & predictable
- presence of PMS & menstrual
molimina
Anouvulatory Cycles
- bleeding is usually irregular,
unpredictable & as a rule painless
 DIAGNOSIS
A - by exclusion of organic causes
Differential Diagnosis
1. Pregnancy complications
2. Pelvic infections
3. Pelvic tumors
4. Trauma
5. Systemic diseases
6. Iatrogenic causes
B. History > should include a good menstrual history
C. Complete PE
D. Lab.& Ancillary Procedures
1. CBC, Platelet ct., CT, BT
2. Pap Smear with cytohormonal index
3. Pregnancy test
4. Endometrial biopsy
5. Hysteroscopy/hysterography
6.Ultrasound
Treatment
Goals of Treatment
A. Control of Bleeding
B. Prevent recurrence
A. Control of Bleeding
1. If bleeding is not profuse
> Hormonal treatment with estrogen is the initial
management
a. Conjugated estrogens (Premarin)10mg daily in divided
dosage(2.5mg QID) in 2 days, if bleeding stops Premarin
is continued for 21 days + Provera 10 mg OD added to
the last 5days of Premarin
b. Premarin IV, 25 mg q 4 up to 3 doses, if bleeding is
controlled give premarin oral 2.5mg QID 21days +
Provera 10 mg OD to the last 5days.
c. Combined estrogen/progestin tx (OCP)
>1tab QID x5days-7 days,if bleeding
stops, rest for one week,then follow with
three 21 day standard OC Pills cycles
d. If hormonal treatment fails, curettage is
necessary
2. If bleeding is profuse
> dilatation & curettage is the fastest way to control the
hemorrhage
> indicated in the woman above 35 years
> if still with profuse bleeding may start high doses of estrogen
> adjunctive tx includes blood transfusion if patient is
hypovolemic & very anemic
> in younger patients (<35y/o)
- hormonal tx may be tried first
1.high dose estrogen
2. OCP
> if bleeding is not controlled, D & C becomes mandatory
B. Prevention of Recurrence
1. Anovulatory DUB
> medroxyprogesterone acetate (Provera) 10mg
OD 1st x 10 days of the month of the cycle
D16-25
2. In the anovulatory adolescent
>Provera 10mg OD x 10days
>OC pills should be avoided -delay the onset of
normal function
3. In the mature anovulatory woman
>Provera 10 mg OD x 10days
>cyclic OC pills-those who desire contraception
>clomiphine citrate-those who wants to be
pregnant
4. In the premenopausal woman
>Provera 10mg ODx10 days every 1or 2 months
Other Forms of Medical Treatment
1.Androgens
> Danazol – 200-400mg daily x 3mos
> side effects- acne and weight gain
> effective with ovulatory rather than with
anovulatory DUB
2.NSAID’S
>inhibit cyclooxygenase enzymes in the
microsomal portion of the endometrial cells
reducing the availability of endoperoxidases
>block formation of prostacyclin or PGI2
>useful in menorrhagia that is of ovulatory type
3. Antifibrionolytic +hemostatic agents
a. Tranexamic acid - 1-1.5g q 6 ° during
heavy bleeding
>SE:nausea,dizzines,rashes & abdominal pain
>contraindicated in renal failure
4.Ergot derivates
-not recommended for DUB
 Surgical Management
1.Dilatation & Curettage
- indicated for every profuse bleeding for
woman above 35 years of age
2.Hysterectomy
- pre-carcinoma lesions
- for cases when all other modalities of TX have
fails or when there is assoc pelvic pathology
3. Laser photovaporization
 Dysmenorrhea
Classification
A. Primary Dysmenorrhea
-symptoms are not attributable to any
recognizable pelvic pathology

B. Secondary Dysmenorrhea
-there is identifiable pelvic pathology
Evaluation
1. History
- age at onset
- symptoms & associated with pregnancy or menses
- duration of symptoms
- presence of symptoms suggesting organic pathology
2. Good pelvic Exam
3. Laboratory evaluation
a. USG
b. hysteroscopy
c. hysterosalpingography
d. laparoscopy
 Primary Dysmenorrhea
A. Clinical Characteristic
 Appears many months or even a few years after
menarche
 Typical symptoms: lower abdominal cramps in the
suprapubic region that may radiate the lower back or
down he upper thighs
 pain usually beginning with onset of menses & lasts
for a few hours
 Frequently associated with nausea,
vomiting,diarrhea or headache
In some women dysmenorrhea improves with
age
Intensity of pain is not progressive & may
vary from time to time
 there may be a relief after a term pregnancy due to
the destruction of the nerve endings associated with
stretching of the uterine musculature
-Progressive Dysmenorrhea Should Alert One to
the Possibility of a Secondary Nature
B.Etiology
- etiology and pathophysiology is not clearly
understood
1. Prostaglandin Theory
- under the influence of the progesterone secretory
endometrium synthesizes PG (PGF2x)
- at menstruation PG’s are released & induce
contractility of uterine muscles & vasculature
causing contractions,ischemia & pain
- Pain is thought to arrive from 3 mechanisms
a. increase uterine contractions
b. ischemia from reduction of uterine blood
flow
c. direct effect of PG endoperoxides
in lowering the pain threshold of nerve
terminals in the uterus
2. Hormonal Factors
- Estrogen  stimulates uterine contractility
- Progesterone inhibits uterine contractility
- Dysmenorrhea is associated with ovulatory
menses
- corpus luteum produces progesterone which
influences the secretory endemetrium to
synthesize PG
3. Psychogenic Factors
- pain is subjective & individuals have
different thereholds for pain
 Treatment
1. Prostaglandin synthetase inhibitors & antagonists
Phospholipids
 enzyme phospholipase
PG synth inhibitors Arachidonic Acid
enzyme cyclo-oxygenase
(prostaglandin synth)
endoperoxides
PG antagonists
PG

cell receptor site
-absorption & onset of action have been shown to
be rapid
 Side effects occur in the GI tract & CNS
nausea,vomiting,diarrhea & ulcers,
headache,dizzines,confusion and syncope
2. OC pills
- inhibit ovulation & decrease the amount of
PG’s in menstrual fluid
3. Pure progesterone (Duphaston) (Provera)
- given in the luteal phase (cycle Day 16-25)
4. Tocolytic Drugs
- inhibit uterine contractions
- increase uterine blood flow
5. Alcohol,tranquilizers,sedatives, narcotics
6. Presacral neurectomy
- limited to patient with incapacitating pain
7. Evaluation of the psychological component
 Secondary Dysmenorrhea
- dysmenorrhea which begins after the age of 25
years or after delivery
- Menstrual pain is usually progressive
A. Etiology
1.Endometriosis
pain may be explained by the premenstrual &
menstrual swelling of the ectopic endometrium
or by the leaking of an endometrial cyst in the
ovary causing peritoneal irritation
2. Adenomyosis
- pain is caused by the endometrial islands in
the myometrium
3. PID
- denuded endometrium during or immediately
after menses becomes more vulnerable to
infections.
4. Myomas,endometrial polyps & carcinomas,
IUD
5. Cervical stenosis & congenital and obstructive
abnormalities of the uterus
B. Treatment
>management is directed towards the removal
or correction of the pelvic pathology
MANAGEMENT OF DYSMENORRHEA
DYSMENORRHEA

LOOK FOR ORGANIC CAUSES

PATHOLOGY NO PATHOLOGY

SECONDARY PRIMARY
DYSMENORRHEA DYSMENORRHEA
PRIMARY DYSMENORRHEA

PROSTAGLANDIN
INHIBITORS

UNSUCCESSFUL

ORAL CONTRACEPTIVES,
PROGESTINS

UNSUCCESSFUL

WORKUP FOR SECONDARY

DYSMENORRHEA
 SECONDARY DYSMENORRHEA

SPECIFIC DIAGNOSTIC TEST

(LAPAROSCOPY, HYSTEROTOMY

ORGANIC NO ORGANIC
PATHOLOGY PATHOLOGY

SPECIFIC PAIN
TREATMENT CONSULTATION
 Climacteric Syndrome/
Menopause
Climacteric
transition from the reproductive stage of life to
the non-reproductive stage
Due to the regression of ovarian functions
despite adequate gonadotropin secretion
Menopause
Final menstruation during the climacteric
 Physiology
Granulosa and theca cells degenerate

Fail to react to endogenous gonadotropin

estrogen production

Negative feedback mech HPO axis

(-) ovulation

Less stimulation of endometrium

(-) menses
Age at Menopause
Late 40’s and early 50’s
Genetically predetermined
Earlier in cigarette smokers
Estrone
Source of circulating estrogen in climacterics
Peripheral conversion of androstenedione and
testosterone
 Climacteric Syndrome
Acute symptoms
Occur in the first few years
Menstrual irregularities
Vasomotor hot flushes
Late symptoms
Years after last menses
Atrophic vaginitis and urethritis
Dyspareunia
Osteoporosis
Menstrual Irregularities
1st clinical evidence of female climacteric
Oligomenorrhea (skipped or dodging)
Menometrorrhagia
Polymenorrhea
Hot flush
Hallmark of climacteric
sudden onset of warmth and vasodilatation
More frequent and severe at night or during at
times of stress
Atrophic vaginits and urethritis
Vaginal mucosa progressively thins out making it
susceptible to trauma and infection
Foreshortening of the vaginal canal with loss of
rugal pattern
Develop “urethral syndrome”
Osteoporosis
Major cause of morbidity and mortality
Back pain, decreased height and mobility, and
fractures
Risk factors:
White or oriental race
Underweight or thin women
Early spontaneous menopause
Early surgical menopause
Family history of osteoporosis
Diet of low calcium intake
Cigarette smoking
Sedentary lifestyle
Osteoporosis
Diagnosis
Osteoporosis is insidious
X-ray
CT scan
Bone density
Arteriosclerotic cardiovascular disease
Higher risk in women who lost their ovarian
function before age 40
Estrogen decreases levels of TC and LDL
cholesterol and increase HDL cholesterol
 Hormone Replacement Therapy
(HRT)

Estrogen replacement becomes the logical and

easily acceptable therapy in symptomatic
women
 Potential Risks
Endometrial adenocarcinoma
Breast disease
Hypertension and thrombosis
Glucose tolerance
Gallbladder stones
 Therapeutic Regimens
Women with Uterus
Estrogen + progesterone
Give progesterone challenge test
Women without uterus
Only estrogen
Women who do not like to menstruate
Continuous combined estrogen and
progesterone
 Recommended Regimen
Menstrual irregularities
Progesterone- medroxyprogesterone(MPA, Provera) or dydrogesterone
(Duphaston), 10mg tab daily from cycle day 16 to cycle day 25 or
every 1st 10 days of the month or every other month

Vasomotor symptoms
Premarin 0.3, 0.625, or 1.25 mg tab daily x 21 days

With uterus : add progestogens, 10 mg tab of MPA or dydrogesterone

or 5mg norethisterone or medrogestone to the last 10-12 days of
estrogen

17B-estradiol patches 2mg or 4mg, 2x week for 3 weeks, if with uterus

add oral progestogens to the last 10-12 days of the 3 wk regimen
 Recommended Regimen
Urogenital Symptoms
Vaginal estrogen cream (premarin 0.625 mg/gm)
Usual dose is 1-2gm/day x 2 weeks

Osteoporosis
Premarin 0.625mg tab daily x 21 days or Estraderm TTS 25 patch,
2x a wk for 3 weeks, rest for 1 wk
If with uterus, add progestogens to the last 10-12 days of estrogen
Addt’l drugs: calcitonin, biphosphonates and calcium 1-1.5gm
daily
Exercise and diet
 Recommended Regimen
Cardiovascular disease
Use natural estrogens to avoid first pass effect to the
liver
Estraderm TTS 25 or 50 patch 2x awk for 3 wks
If with uterus, the added progestogens to the last 10-12
days of estrogens should not be androgenic (Duphaston
or medrogestone are preferred)
 Side Effects
Estrogenic side effects: nausea, bloating, weight
increase, water retention, cervical d/c, breast tenderness,
leg cramps
Progesterone: tiredness, dysphoria, depressive mood,
decreased libido, dry vagina, edema, vaginal atrophy
With nortestosterone derivatives: acne, seborrhea,
hirsutism, decreased HDL cholesterol, increase appetite
 Contraindications
Severe liver disease
Existing thrombosis
Endometrial carcinoma
Breast CA w/in 3-5 years after primary
treatment
Good Day !