DUB

Anovulatory DUB
Ovulatory DUB

Pathophysiology of ovulatory DUB

Defect in the processes regulating blood loss
during menstrual breakdown, primarily the
processes of vasoconstriction and haemostasis

Pathophysiology of ovulatory DUB

- Related to local hemostatic factors or
impaired density of spiral arterioles
- Total endometrial PGs
- Synthesis and receptors of PGE2 PGI2
prolonged vasodilation
poor platelet aggregation & plug formation

Pathophysiology of ovulatory DUB

- endothelins
- parathyroid hormone- related protein
- lysosomal enz. activity
- fibrinolysis
plasminogen activator
- endometrial heparin-like activity

Pathophysiology of anovulatory DUB

Abnormal endometrial growth
epithelial & stromal cell,
microvasculature
- suppressed spiral arterioles
- increased no.of venous capillaries
dilated & irregular vascular channels
disorganized microvilli& multiple blebs

Pathophysiology of ovulatory DUB

vascular density with structural abnormalities

Rupture/ degradation of the microvascular system

release of lysosomal proteolytic enz.
from epithelial/stromal cell, leukocytes, macrophages

Focal stromal breakdown

- located near or at the surface of the endometrium
- surrounded by intact endometrial mucosa

Pathophysiology of anovulatory DUB

Leukocytes:
PGE2

Endometrial granulocytes &

Activated NK cells: Perforins

inhibit capillary plug formation &

degrade the capillary venous network

Excessive & prolonged breakthrough bleeding

Persistent proliferative endometrium. A focus of stromal

breakdown with RBCs,the adjacent endometrium is intact.

A focus of tissue
necrosis, fibrin
thrombi near surface
endometrium

Dilated, ectatic capillaries in area of tissue necrosis

Abnormal architecture of capillary plexus including luminal ectasia

in superficial endometrial mucosa

Ruptured capillary near surface endometrium

Pathophysiology of anovulatory DUB

Focal & superficial stromal breakdown
no denudation of the basalis

poor vasoconstriction of basal endometrial

& superficial myometrial vv.
The best therapeutic result
aspiration biopsy or curettage

Bleeding patterns
Ovulatory DUB (AUB-E)
Regular episodes of heavy menstrual blood loss

Anovulatory DUB (AUB-O)

Irregular, prolonged and usually excessive bleeding

Treatment of DUB
Ovulatory DUB?
(AUB- E )
or
Anovulatory DUB?
(AUB-O)

Treatment of anovulatory DUB

Goals
1. Establish and/or maintenance of hemodynamic
stability
2. Correction of acute or chronic anemia
3. Return to a pattern of normal menstrual cycles
4. Prevention of recurrence
5. Prevention of long term consequence of anovulation

Treatment of anovulatory DUB

Consider
1. Active or chronic bleeding ?
2. If active bleeding
affect cardiovascular status?
3. Severity: Mild
Hb> 12 gm/dl
Moderate
Hb 10-12 gm/dl
Severe
Hb< 10 gm/dl
4. Age, parity, desire of fertility, contraceptive needs,
coexistent pathology, risk factors

1. Active bleeding & severe DUB

Hospitalization
- Initial Hb < 7 g/dl
- Hemodynamic instability
- Heavy active bleeding & Hb< 10 g/dl
Hb 8-10 g/dl, stable hemodynamics, reliable pt.
possible outpatient management

1. Active bleeding & severe DUB

1.1) High dose estrogen
conjugated equine estrogen ( CEE )
25 mg IV q 4-6 hr for 24 hr
- unstable
- unable to tolerate oral medication
- continue to bleed despite maximal oral therapy
contraindications
- breast CA
- active or past venous thrombosis/arterial
thromboembolism
- liver dysfunction/disease

Treatment of anovulatory DUB

1. Active bleeding & severe DUB
CEE 2.5 mg qid x 21 d
add MPA 10 mg OD
NET 5-15 mg OD
Micronized P 200-300 mg OD

1.2) OCPs (EE 30-35 ug)

1 tab bid-qid x 7 d

10-12 days

regular / continuous use

MPA: Medroxyprogesterone acetate ( Provera )

NET: Norethindrone acetate ( Primolut-N )

1. Active bleeding & severe DUB

1 tab q 4 hrs (usually 24hrs)
1 tab qid x 4 days
1 tab tid x 3 days
1 tab bid x 2 weeks

1. Active bleeding & severe DUB

- IV fluid, blood transfusion if necessary
( Hb < 10 g/dl & continue bleeding )
- Iron supplement 60-120 mg/day
severe anemia: add folic acid+ multivitamin
- Antiemetic drug eg. Promethazine ( Phenergan)
Ondansetron
- If not improved within 48 hrs
uterine curettage
reevaluation (USG, EUA)

2. Active bleeding & moderate DUB

CEE 1.25 mg q 4 hr x 24 hr ( E2 2 mg )
CEE 1.25 mg daily x 21d

MPA 10 mg / NET 5-10 mg OD 10-12 d

- antiemetic drug
- F/U every 2-3 d until bleeding stop
- iron supplement

2. Active bleeding & moderate DUB

low- dose OCs: 1 tab tid x 7 days
1tab OD x 3 wks

withdrawal bleed

withdrawal bleed

Medroxyprogesterone acetate
20 mg tid x 7 days

20 mg OD x 3 weeks

Munro et al. Obstet Gynecol 2006; 108: 924-9.

2. Active bleeding & moderate DUB

low- dose OCs: 1 tab tid
until bleeding stop ( usually 48 hr)

1 tab bid x 5 days

1 tab OD until complete 21 days of Rx

3. Chronic bleeding
Mild bleeding & Hb > 12 g/dl
advice & reassure, iron supplement (60 mg/day)
record menstrual cycle, reevaluate in 3-6 mo
Hb 10-12 g/dl, not currently bleeding
OCPs
MPA 10 mg OD/ NET 5-15 mg OD
micronized P 200-300 mg OD
for 10- 12 days

Long- term management

Maintenance therapy: 3-6 mo.
depends on - the presence of anemia
- desire for contraception
Hb> 10 g/dl cyclic OCs, cyclic progestins
Hb< 10 g/dl continuous OCs for > 3 mo.

Long- term management

F/U
mild DUB F/U in 3-6 mo.
moderate/severe DUB closer F/U in 1-2 mo.

If contraception is not desirable after

complete long term Rx

stop Rx & observe menstrual patterns
If no period > 3 mo.
- progestins hormonal workup
- induce periods every 1-3 mo./ OCs

Ovulatory DUB
1. OCPs (monthly or extended cycle)
desire of contraception
primary dysmenorrhea
amount nearly 50 %

2. NSAIDs (for mild severity)

: Mefenamic acid , Naproxen
250-500 mg, bid- qid
Ibuprofen
600-1,200 mg/d
: Duration: 3-5 days or
: throughout menstrual cycle

Ovulatory DUB
- Antifibrinolytic agents:
tranexamic acid, aminocaproic acid
not approved by the FDA in patients < 18 yr
effective for both chronic and acute bleeding
should be considered in case of persistent, heavy
bleeding despite maximal hormonal Rx
contraindication
- acquired impaired color vision
- current thrombosis/ thromboembolism
- DIC
- macroscopic hematuria
side effects: nausea, dizziness

Doses of tranexamic acid

Tranexamic acid (IV dose)

10 mg/kg (max. 600 mg/dose) every 8 hours
James et al. Eur J Obstet Gynecol Reprod Biol 2011; 158: 124-34.

Ovulatory DUB
- Progestins
1. Extended cycle progestin
norethindrone 5 mg tid, day 5-26
2. DMPA
80 % amenorrhea in 1 yr
3. Levonorgestrel releasing

intrauterine system (LNG-IUS)

Ovulatory DUB
*** Stop bleeding promptly
1. Norethindrone acetate 15 mg/d or MPA 30 mg/d
for 3-4 weeks
2. Norethindrone acetate or
MPA
5-10 mg every 4 hr
10 mg every 4 hr
(up to 80 mg/day)

Until bleeding stops qid x 4 days tid x 3 days

bid x 2 days to 2 weeks, then OD thereafter

Efficacy of medical treatment in reduction of

menstrual bleeding
Medications

Decreased menstrual blood

(%)

Combined OCPs
NSAIDs
Tranexamic acid

35-69
10-52
26-54

Extended cycle oral progestins

LNG-IUS

87
71-95

Matteson et al. Obstet Gyncol 2013;121:632-43.

Matteson et al. Obstet Gyncol 2013;121:632-43.

Ovulatory DUB
Surgical treatment: endometrial ablation
Indications - failure of medical Rx
- contraindication for medical Rx
- poor tolerance to medical Rx
Contraindications
- postmenopausal women
- endometrial CA/ hyperplasia
- preserve fertility
Exclude significant uterine pathology/ medical
conditions

Ovulatory DUB
1st generation endometrial ablation
1). Hysteroscopic laser ablation (HLA)
- amenorrhea rate 20-60%
- surgical reintervention rates 7-27%

2). Transcervical endometrial resection ( TCRE)

- amenorrhea rates 26-40%
- reintervention rates 20-27%
- operating time, fluid resorption,costs >TCRE

Ovulatory DUB
1st generation endometrial ablation
3). Rollerball endometrial ablation
- comparable to HLA & TCRE
- require less operative skill
- less time consuming ( compare to HLA )

Ovulatory DUB
2nd generation endometrial ablation
No differences in the improvement in menstrual
blood loss or patient satisfaction
Advantages
- require less skill
- shorter operative time
- local anesthesia
- less risk: fluid overload, uterine perforation,
cervical laceration, hematometra
Lethaby A. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001501. Review

Ovulatory DUB
2nd generation endometrial ablation
Disadvantages
- cannot directly visualize & detect
abnormal pathology
- preoperative endometrial biopsy
- more likely to have N/V, uterine cramping

Lethaby A. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001501. Review

Ovulatory DUB
2nd generation endometrial ablation
1). Thermal balloon endometrial ablation

Ovulatory DUB
2nd generation endometrial ablation
2) Hysteroscopic instillation of hot saline solution
0.9% NSS of 90 C ( externally heated )

3) Microwave endometrial ablation

- 9.2 GHz ( by a magnetron )
- Temperature 85- 95 C

Ovulatory DUB
4) Cryo endometrial ablation
a mixed gas coolant - 90 C to -100 C

5) Bipolar impedance controlled endometrial ablation

Ovulatory DUB
6) Endometrial laser thermal ablation

absorbed by hemoglobin

Heat

coagulate the endometrium