Dysfunctional Uterine Bleeding

1. DYSFUNCTIONAL UTERINE
BLEEDING
‘PATHO – PHYSIOLOGY’
Dr Sonali Ingole
Asst Professor
OBGY

2. DUB : Definition
• Abnormal uterine bleeding, in the absence
of any demonstrable organic disease of the
genital tract
– Neoplasm
– Infection
– Pregnancy related complication
• Abnormal uterine bleeding in the absence
of genital tract pathology or medical illness
• Abnormal uterine bleeding for which no
specific cause has been found

3. DUB : Classification
• Primary
• Secondary
– Thyroid dysfunction
– Haematologic disorders
• Thrombocytopenia
• Von Willebrands disease
• Leukemias
– Hepatic dysfunction
• Iatrogenic
– IUCD
– Progesterone only contraception
– Low dose Combined OC pills

4. DUB
• DUB occurs most often shortly after
menarche and at the end of the
reproductive years.
–20% of cases are adolescents
–50% of cases in 40-50 year olds
• Diagnosis of EXCLUSION

5. DUB
• Patients present with
“Abnormal uterine bleeding”

6. NORMAL MENSTRUATION
• Duration of flow : 2 – 7 days
– Average duration : 4 – 6 days
• Volume of flow : 20 – 70 ml
– Average flow : 30 ml
• Cycle length : 24 – 35 days*
– Average cycle length : 28 – 30 days
*Speroff L, Glass RH, Kase NG (Eds). Clinical Gynaecologic
Endocrinology & Infertility. 7th Edn. Baltimore, 2005; 549 - 554

7. MENORRHAGIA
• Volume of flow ≥ 80 ml
• Duration of flow > 7 days
• Bleeding occurs at regular intervals
• Common causes
– Fibroids
– DUB
– IUCD
– Adenomyosis
– Thyroid dysfunction
– Pregnancy related bleeding

8. HYPOMENORRHOEA
• Volume of flow < 10 ml
• Duration of flow < 2 days
• Common causes
– Endometrial tuberculosis
– Combined OC pill use
– Ashermann’s syndrome
– PCOD
– Hyperprolactinemia

9. POLYMENORRHOEA
• Frequent menses
• Bleeding intervals < 24 days*
• Common causes
– PID
– Endometriosis
– DUB
* Speroff L, Glass RH, Kase NG (Eds). Clinical Gynaecologic
Endocrinology & Infertility. 7th Edn. Baltimore, 2005; 549 - 554

10. POLYMENORRHAGIA
• Frequent & heavy / prolonged menses
• Common causes
– Fibroids uterus
– PID
– DUB
– Endometriosis
– Ovarian cysts

11. OLIGOMENORRHOEA
• Infrequent menses
• Bleeding intervals > 35 days, upto 6 months
• Common causes
– PCOD
– DUB
– Hyperprolactinemia
– Ovarian cysts
– Thyroid dysfunction
– Stress & Exercise related ( Hypothalamic)

12. METRORRHAGIA /
MENO- METRORRHAGIA
• Irregular, acyclical bleeding / Heavy or
prolonged irregular, acyclical bleeding
• Common causes
– Improper hormonal contraceptive use
– DUB
– Pregnancy related bleeding
– Submucous fibroids & Fibroid polyps
– Carcinoma cervix
– Carcinoma endometrium
– Progesterone only contraception

13. Genesis of normal menstruation

14. Alternatives for estrogen –
progesterone primed endometrium

15. Genesis of normal menstrual flow
• Estrogen – progesterone withdrawal due to
luteolysis results in enzymatic auto-digestion of
non-gestational hormonally primed endometrium
which is then discharged as menstrual flow

16. Genesis of normal menstrual flow
: Role of vascular endothelium
• Synthetic activity
– Paracrine factors
– Angiogenic factors
– Vasoactive factors
– Haemostatic factors
• Modulation of
– Vasoactivity
– Haemostasis
– Thrombolysis
– Angiogenesis

17. Autocrine / paracrine regulation of gene
transcription affecting vascular function

18. Effects of progesterone withdrawal

19. Genesis of normal menstrual flow
• Cyclic vasomotor
response of spiral
arterioles (end
arteries) in the
endometrium

20. Genesis of normal menstrual flow
• Increasing duration
and intensity of
vasospasm results
in ischaemic damage
to endometrium and
breakdown of tissue

21. Genesis of normal menstrual flow
• During periods of
relaxation of vasospasm,
blood extravasates
though damaged vessel
walls, cleaving the
endometrium between
stratum basalis and
stratum spongiosum

22. Genesis of normal menstrual flow
• Progesterone withdrawal
induces release of matrix
metalloproteinases from
the endometrial cells
resulting in breakdown of
cell membranes and
extracellular matrix

23. Genesis of normal menstrual flow
• Endometrial tissue and extravasated
blood are shed as menstrual flow

24. Haemostaisis within uterus
• Vasospasm
• Platelet plug
• Thrombin generation in
the basal endometrium
• Re-epithelialization
• Myometrial contractions do not play a part in
controlling menstrual blood loss ( in contrast
to control of post – partum hge)

25. Why is Estrogen – Progesterone
withdrawal menstrual bleeding not heavy ?
• It is a universal
event occurring
simultaneously
throughout the
entire
endometrium

26. Why is Estrogen – Progesterone
withdrawal menstrual bleeding not heavy ?
• The endometrium
primed with estrogen
and progesterone is
structurally stable
and random
breakdown due to
fragility is avoided

27. Why is Estrogen – Progesterone
withdrawal menstrual bleeding not heavy ?
• Inherent in the events
(vasospasm) that
start the menstrual
flow are the factors
involved in stopping
the menstrual flow

28. Why is Estrogen – Progesterone
withdrawal menstrual bleeding not heavy ?
• Denudation of the
functional layers of the
endometrium allows
the reparative process
of re-epithelializtion to
begin from the stratum
basalis

29. Dysfunctional Uterine Bleeding
• Hormonally imbalanced conditions can give
rise to abnormal uterine bleeding
–Hyper-estrogenic state / Unopposed
estrogen action
–Hyper-progestogenic state / Abnormal
progestogen – estrogen ratio

30. Dysfunctional Uterine Bleeding
• Anovulatory
– Estrogen withdrawal
– Estrogen breakthrough
• Threshold bleeding
• Supra-threshold bleeding
– Progesterone breakthrough
• Ovulatory
– Irregular ripening
– Irregular shedding
– Abnormal local haemostatic mechanisms

31. Estrogen withdrawal
• One of the mechanisms of anovulatory uterine
bleeding
• Occurs on withdrawal of estrogen support to the
endometrium
• Common following menarche. Midcycle spotting can
occur due to pre-ovulatory fall in E2 levels

32. Estrogen breakthrough bleeding
• Threshold bleeding
– The levels of E2 waver around the threshold below
which endometrium cannot be supported
– Results in intermittent / prolonged spotting
– May occur at extremes of reproductive age

33. Estrogen breakthrough bleeding
• Supra-threshold bleeding
–Continuous E2 production unopposed
by progesterone due to anovulation
–Delayed periods followed by prolonged
moderate to profuse bleeding
–Endometrium thick without concomitant
stromal structural support
–Random breakdown common

34. Progesterone breakthrough
bleeding
• Seen in the presence of an unfavourably high
ratio of progesterone to estrogen (use of
progesterone only contraception)
• Results in intermittent spotting of variable
duration
• Prolonged progestogenic exposure results in
atrophic changes and altered gland –stromal
ratio within the endometrium
• Bleeding occurs from unsupported
endometrial vessels

35. Progesterone withdrawal bleeding
• Medical curettage
• Poor compliance with progestogen therapy

36. Ovulatory DUB
• Luteal phase insufficiency
– Irregular ripening
– Mixed proliferative - secretory patterns
• Prolonged luteal function / Corpus luteum
cysts
– Irregular shedding / Delayed prolonged
menses
• Primary pathology of haemostatic
processes

37. Mechanisms of DUB
• Hyper-estrogenic / Hyper-progestogenic state
• Abnormal angiogenesis and vascular fragility
• Increased / Asynchronous tissue breakdown
• Impaired haemostatic mechanisms
• Impaired re-epithelialization

38. Thank You