ABNORMAL UTERINE BLEEDING

PROF. M.C.BANSAL.MBBS.MS.MICOG.FICOG.FOUNDER PRINCIPAL &

CONTROLLER; JHALAWAR MEDICAL COLLEGE AND

HOSPITAL JHALAWAR.EX. PRINCIPAL & CONTROLLER;

MAHATMA GANDHI MEDICAL COLLEGE AND HOSPITAL , SITAPURA,

JAIPUR

Normal Menstrual Cycle

Menstration is a cyclic physiological phenomena starting at the age of Menarche (10-12years) till

establishment of Menopause (45-55 yrs). It is regulated by hypothalmo-pituitary- ovarian

hormones secreted in pulsatile and cyclic pattern.

Also influenced by endometrial response top these (E& P ) hormones and coagulation cascade.

Cycle lenghth-21-35 days , mean menstrual blood loss -30-40 ml , duration of bleeding (period0---2-8 days.

Volume of blood flow is assessed by number of pads / tampons used whether the pads are fully/ partially soaked , presence of clots. It can be better assessed by pictorial charts-- Pad Area Soaked 1st day 2nd

Day

3rd Day

4th Day

5th day

6th Day

7th Day

X 1

// / /

X 5

/// //

X20

///

Total Points

89(<1oo)-

Normal

blood Loss

Tamponssoaked X1

// // / /

x 5

///

D X 15 Total Points

////// 111 Excessive blood loss

Pituitary

Cyclical Changes in Menstruation

ovary

Double Cell Theory of Estrogen Production

Menstruating Endometrial

Proliferative Endometrial

Early Secretary Phase ENDOMetrium

Late Secretary Phase of Endometrium

Arrest of Menstrual bleeding # mechanisms--- 1 Haemostasis by plate let plug and clot formation –

starts soon the bleeding starts and open BV are plugged .once Blood vessels are plugged , fibrin deposition occurs ---Fibrinolysis also go hand in hand to balance and keep the blood loss fluid.

2.Prostaglandin Mediation – Archadonic acid and Pg synthetase enzyme produce PGs ---pge2 –vasodilator, PGf2a--- vaso constrictor and Thromboxane – vaso constrictor. Estrogen produce PGE2 and PGF2a in ratio of 1:1 in proliferative phase ; while Progesterone produce PGE2 and PGF2a + thromboxane (a2) in a: 2 ratio in premenstrual phase so balance is shifted towards vasoconstricton which help in contrl of bleeding.

Arrest of Menstrual bleeding -- 3. Tissue Repair --- starts from the

mouths of open endometrial glands in the denuded areas , endothelium out grows and covers the raw area under the influence of Epithelial Growth Factor ( EGF) and blood vessels regrow due to Vascular endothelial Growth Factor (VEGF). Thus the raw area of remaining basal endometrium is completely epithelized under Estrogen effect.

Abnormal uterine bleedingOrganic Causes Functional Uterine bleeding(DUB)

Deseases Of Genital Tract— Pregnancy related irregularity

Abnormal Bleeding from Genital Tract without any demonstrable organic cause.

IUCD Related Irregularity Diagnosis is made by excluding organic cause .

Benign Conditions-- Altered Hypothalamus-pituitary-ovarian-

Fibroids, its polyps Function

Endometriosis (external; Adenomyosis

Altered endometrial response to Sex Hormones

Endometrial Polyp altered proprtion of estrogen and progestrone production and their effect on Endometrial

Malignant Lesions phasing may cause DUB.

Endometrial

Cervical

Vaginal

Ovarian

Systemic Causes =Coagulation disorder , thyroid and liver disease

Menstrual Patterns IN DUB

Regularity—1. regular ,2 irregular , absent.

Frequency---1. frequent < 21 days, 2. Normal 21-35 days,3. Infrequent >35 days.

Duration– Normal 2-8 days , Prolong > 8 days .shortened <2 days .

Volume – normal 20 -80ml , Heavy > 80 ml, Light < 15 ml

Terminology

Menorrhagia –Regular cycle with prolonged or heavy flow.

Polymenorrhoea – frequent cycles but normal bleeding .

Poly menorrhagia – frequent cycles with heavy bleeding .

Metrorrhagia ----Inter menstrual Bleeding . Oligomenorrhoea—Infrequent cycle with

normal bleeding . Hypomenorrhoea—Regular normal cycle

with light Bleeding.

Classification of DUB

1. Anovulatory – Metropathia Haemprrhagica. Threshold Bleeding. 2.Ovulatory --- Idiopathic ovulatory

Menorrhagia. Luteal Phase Defect.

Anovulatory DUB In some adolescent girls and perimenopausal

women, Ovarian follicles develop(FSH Stimulation) and produce estrogen in variable amount leading to proliferation of endometrium .

Dominant follicle may not develop due to insufficient LH surge – no ovulation—no development of carpus Luteum ---no progesterone --- no secretary changes in endometrium ; estrogen still secreted by follicles (grannulosa cells) .

Unopposed estrogenic Stimulation and some time hyper ( super threshold ) level of estrogen results in over growth of endometrium(hyperplasia) ----resulting in prolonged cycle and increased blood loss during period.

Anovulatory DUB When endometrium over grow s its blood

supply , lack of progesterone causes decrease PGE2 vasodilators initially and Avascular necrosis of functional endometrium occur , endometrium is shade off Lack of vasoconstrictors--- PGf2a and thromboxane results in excessive blood loss which is pain less and prolonged for 20-30days (As irregular shading of endometrium continues for such a long time ).

Persistent Follicles under go the formation of follicular cysts.

Anovlatory DUB Metropathia Hamorrhagica Accounts for 80% of DUB; at Pubertal and

perimenopausal age ,Patient has variable period of amenorrhoea followed by prolong, heavy , painless bleeding .

Prroplonged Un opposed Estrogen Proliferative Endometrium

Simple Hyperplasia

Complex Hyperplasia

Complex Hyperplasia with Atypia

Adenocarcinoma

Endometrium in Metyrpathia Haemorrhagica

Usually reveals cystic hyperplasia( simple hyperplasia with out atypia) called swiss cheese appearance .

- Hyperplastic glands and strauma.- Cystic or irregularly dilated glands.- Thick walled , tortuous , dilated spiral

arterioles and veins.- Infarction and thrombosis of blood

vessels.- Necrosis of functional endometrium .

Metropatha Hamorrhagica

Progress And Course of Metropathia Haemorrhagica

Incidence of malignancy --- simple cystic Hyperplasia---1% Complex hyperplasia with atypia---29% It is further increased in perimenopausal

women who are obese, diabetic,on E2 therapy, hypertensive and relatively infertile , H/O Ca endometrium in family and had PCOD.

Young Girls who are obese with or with out PCOD are prone to have metropathia Haemorrhagica of early changes which are reversible with progesterone / Ocs therapy.

Simple Endometrial hyperplasia

Atypia (hyperchromatic, large, variable size and shape Of Nucleus)

Endometrial Hyperplasia with Nuclear Atypia

Complex Hyperplasia

The endometrial adenocarcinoma in the polyp at the left is moderately differentiated, as a glandular structure can still be discerned. Note the hyperchromatism and pleomorphism of the cells, compared to the underlying endometrium with cystic atrophy at the right.

Threshold Bleeding

This is often seen in peri menopausal women . There is insufficient development of ovarian follicles resulting in low estrogen level not able to sustain endometrium or trigger LH surge ( no ovulation ).

Such women can have prolonged and excessive bleeding due to absence of progesterone and lack of PGF2a and thomboxane.

Bleeding PV in these women can be controlled with cyclic E2 + P Combination Therapy as both are at low level .

Ovulatory DUB

More common in women of reproductive age group (21-40 years ) .

Accounts for 20% cases of DUB.

Patient usually present Cyclic excessive bleeding / premenstrual spotting.

Periods are associated with Pain .

Idiopathic Adulatory Menorrhagia (DUB )

An alteration in ratio of PGE2 and PGF2a ( vaso dilator : vaso constrictor )occurs in some women despite of ovulation and normal progesterone production from carpus luetium .

Increase in PGE receptors in endometrium , reduction in thrombxane production and increased fibrinolytic activity has also been demonstrated in these women .

PgF2a causes Dysmenorrhea. HP report of endometrium reveals secrtory

changes

DUB: Classification, Pathophysiology And Endometrial Changes

OVULATORY

Idiopathic Ovulatory Menorrhag

ia

Corpus Luteum

insufficiency

Normal Progestero

ne

Altered PG E : PG F

Menorrhagia

Secretory Endometrium

Reduced Progesterone

Reduced PG F2

Premenstrual Spotting

(Polymenorrhoea)

Irregular ripening

ANOVULATORY

Metropathica Haemorrhagica

Prolonged Oestrogen

No Progesterone

Reduced PG F2

Amenorrhoea followed by

bleeding

Hyperplastic Endometrium

Threshold Bleeding

Low Oestrogen

No Progesterone

Reduced PG F2

Polymenorrhoea/

Polymenorrhagia

Proliferative Endometrium

Luteal Phase Defect In adequate Functioning of carpus

luteum can result in---- in sufficient and erratic production of

Progesterone. As well as alteration in the ratio of PGE : PGF

---resulting in irregular and patchy screttory changes in the endometrium

Both pathophysiological deficit leads to irregular ripening and or irregular shading

of endometrium .

History Taking In DUB Age Age at menarche. Parity. Menstrual History—regularity, frequency, duration

of bleeding , Volume of blood loss. Post coital bleeding ? Dysmenorrhoea – spasmodic / congestive . Dyspareunia. O.H.---fertility / infertility/ gravidity / parity etc. Associated Vaginal Discharge . Rescent Abortion / delivery / ectopic pregnancy . IUCD insertion , ocs, hormone therapy/ drugs. Symptoms of thyroid disease. Symptoms of any bleeding disorder.

Examination General Physical . Pallor. thyroid. BMI . Signs of PCOD . Speculum Examination. PV examination --- uterine, position, size.

Shape surface , consistency ,tenderness and mobility .

Furnaces for any anneal mass /tenderness/ indurations

Investigations Laboratory Tests HB , T/DLC, BT. CT, PT , PPT, platelets

count , ESR, Fasting Blood Sugar,,T3-T4- TSH.– to know degree of anemia, to exclude coagulation disorders and leukemia's, Diabetes and thyroid disorders.

TVS /abdominal USG –to exclude Genital tract lesions like fibroids, endometrial thickening , endometriosis, PCOD , polyps , IUCD pregnancy related conditions anneal mass etc .

Soon Historiography– intra cavity lesions like polyp fibroid .

Dilatation Curettage--- Endometrial sampling for HPR--- type of endometrial ; secretary , LPD, proliferative / hyperplasia , inflammation like tuberculosis and precancerous or cancer lesion .

Hysteroscopy---diagnostic as wells therapeutic use in IUCD sub mucous fibroid , polyps .

Endometrial curette

Differential Diagnosis—Adolescent---DUB

Differential Diagnosis

Symptoms and signs Investigations

Bleeding Disorder s previous history Present

BT, CT , Platelet count , PT APTT

Thyroid dysfunction

PCOD (hormonal disorder but ovarian enlargement can be detected )

Thyroid enlargement ,Resident of Goiter endemic area, clinical symptoms and signs present.

Obesity, Acne , hirsutism,Acanthyosis etc

T3 , T4 and TSH profile.

USG, FSH/LH ratio ,serum prolactn and SerumE2 level on day 2 of menses.

Differential diagnosis in Reproductive Age Group

Differential diagnosis

Symptoms & Signs Investigations

Evacuation of vascicular mole,Post Abortal Bleeding , ch. Ectopic ,Post delivery bleeding , retained IUCD

H/o recent abortion , missed period , delivery/ insertion of IUCD / Medical abortion Pill

urine Pregnancy test, USG

Fibroid Uterus Menorrhagia/ Poly menorrhagia , congestive dysmenorrhea , irregular enlarged uterus but not tender.

USG

Endometriosis/ Adenomyoma

Menorrhagia/ Poly menorrhea , cutting pain during menses / coital pain ,Infertility. Enlarged (Localized in adenomyoma) RV RF Fixed and tender uterus and adenexa/ mass.

USG

Chronic PID Poly menorrhagia, congestve dysmenorrhoea,leucorrhea chronic pain in lowe abdomen and sacral region. Tender uterus , fixed / restricted mobility , adnexal thickening and tenderness

USG

Differential Diagnosis In Perimenopausal Age GroupDifferential Diagnosis

Symptoms And Signs Investigations

Fibroid Uterus

Adenomyosis

Multipara, menorrhagia , congestive dysmenorrhea Uterus bossed and irregularly Enlarged firm to hard and not tender.Menorrhagia, multipara , congestive dysmenorrhoea . Uterus regularly enlarged soft and tender

USG

USG

Endometrial Carcinoma Nullipara, obese , hypertensive , delyed menopause , diabetic , family history +/_ , PCOD , Irregular /freuent cycles

Fractional Curretage and endometrial HP Examination

Treatment General Measures –> Rx of anaemia , life style

modification ---weight reduction by diet control and exercise .

Definitive Rx- Medical – 1.Non Hormonal like Antifibrinolytics, PG synthesis

inhibitors , Capillary fragility inhibitors. 2. Hormonal ---Progesterone—oral , IM, Progesterone bearing IUCD. Estrogen +progesterone combination. Estrogen only. 3. Others ---Danazoloe , GnRH analoges /

Omeloxifene., Testosterone.Surgical-- &c , Endometrial Ablation , Hysterectomy

Management Of AUB According to Endometrial TVS

Management Of AUB In Endometrial TVS

Algorithm for USG based Triage for AUB case

DUB management in Reproductive Age Group Abnormal bleeding Clinical Evaluation Normal AbnormalMedical Rx USGResponse No Response Rx AccordinglyCont. For USG3-6 months/ Polyp

NormalLNG –IUS Response

No Response

Hysterectomy

hysteroscopic polypoidecto

myEndo . Ablation

LNG -IUS= Levonorgstrel intra uterine system

Management of DUB in Adolescent Girls Abnormal Bleeding

Clinical Evaluation

? Bleeding disorder / Thyroid dysfunction/ PCOD

NO YES Investigate & Rx

Profuse bleeding Moderate Bleeding

High Dose Progesterone Cyclical combined Ocs for Followed By E+P combination 3-6 months for 3-6 Months

DUB Management in Perimenopausal age group

Abnormal Uterine Bleeding

clinical Evaluation

Risk Factors for Hyperplasia , carcinoma , irregular acyclic Bleeding

NO

Yes

Low Dose OCS

USG, Fractional Curretage, endometrial HP examination

Atypical Hyperplasia

Simple Hyperplasia

Hysterectomy

Low Dose Ocs / cyclical

Progesterone

Drugs used in RX of DUB

NonHormonal Drugs Dose

Antifibrinolytic Tranexamic Acid

500mg tid/qid for 3-5 days

PG synthetase Inhibitors Mefenamic Acid 500mg tid for 3-5days.

Capillary Fragility inhibitors Ethamsylate 500mg qid for 4-5 days

Hormone therapy in DUB

Hormone Dose

PROGESTEROGENS—Norethisterone / Medroxipogesterone/ Duphaston—to arrest bleeding----------- Cyclically----------------------

10mg 6hrly for24-48 hrs follwed by 10 mg /day for 15-25 days10mg daily from 10th -25th day for 3-6 cycles.

Estrogen + Progesterone combintion Ethinyl estradiol + norethysterone / norgestrel/

20-30 ug + o.5-0.75mg cyclically daily starting on 4th day to 25th day of cycle –for 3-6 cycles.

Estrogen only---Ethinylestradiol 50ug /day for 5 days

danzole 100-200mg /day for 3-6 months.

GnRH Analoges

Ormiloxifene

3.6mg IM once in 4 weeks

60mg twice weekly for 12 weeks

Progesterone Intra Uterine System The commonly used progesterone is

Levonorgestrel bearing IUCD (LNG-IUS). It can reduce the blood loss up to 90%. It is effective contraceptive too( 5years). It is as effective as endometrial ablation avoiding

surgical management like hysterectomy. LNG-IUS delivers 20 ug levonorgestrel daily to

endometrium . It causes glandular atrophy and stromal

decidualization. It has minimal action on Hypothalmo-pituitary –

ovarian axis. Nosystemic side effect.

LNG –IUS

Surgical Treatment of DUB Conservative -Dilatation & Curretage—routine /

Fractional -Endometrial ablation. Redical -Hysterectomy Total Pan Hysterectmy. Total with unilateral salping

overiotomy/ shalpingo oophrectomy.

Endometrial Ablation

Ablation means == elimination1. Indication failed medical therapy . Young women desires to preserve uterus. Poor surgical risk for hysterectomy (non

carcinoma lesion of endometrium) 2. Contra Indications Desire for fertility Large uterine cavity -- <12cm. Endometrial hyperplasisia with Atypia. Suspected malignancy of genital tract. Multiple or large fibroids/ nonfunctional

ovarian cysts.

Endometrial ablation Techniques First Generation Techniques

Endometrial laser . Trans cervical resection . Roller wall electro coagulation . Second generation Techniques Thermal Ballon Ablation . Microwave ablation . Radiofrequency induced ablation . Hydrotherma ablation . Electrode mash Cryo Ablation . Laser interstitial therapy.

Thermo Ablation Of Endometriun

Cryo ablation of Endometrium

Disadvantages of !st generation Ablation Technique.

Require skilled person. Require long training. Require general anasthesia. More chances of uterine perforation and fluid

over load.Long term results of Ablation--- 30% women remain amenorrhi0ec . 40-50 % women have reduced bleeding

during their menstrual periods. 10-20 % women reqquire hysterectomy due

to failure e.g. no relief from bleeding.

Hysterectomy Indications

Endometrial hyperplasia with atypia. Failed Medical therapy in women

over the age of 40-45. Failed endometrial Ablation. Other pelvic pathology that needs

surgery

Summary of DUB management

Age Group

USG Endometrial Sampling

Medical Management

syrgery

Adolescent Abdominal to rule out any organic cause

Seldom done

Usually sffice

Seldom

Reproductive

frequetly done abd / TVS

may be required as per TVS report

Always 1st line

Secod line of RX

Perimenopausal

Abd / TVS Should be done

Mostly 1st line of Rx

Some time !st Line Of Rx

Key Points AUB can be due to organic disease or functional disorder. It can occur in any age group –adolescent/ reproductive

or perimenopausal . Dub is diagnose by exclusion of organic lesions by

clinical and investigatory methods. Drug Rx (non hormonal –then hormonal should be given

first as majority of cases will get desired response. LNG –IUS has revolutionized the medical management

and has reduced the need of surgical Rx. If medical management fails – endometrial ablation can

be done. If there are contra indication for Ablation and or it fails

hysterectomy can be done in Perimenopausal women .

Rx of DUB Is to Be Individualized Approach