Pathophysiology of DUB

1. Anovulatory
Metropathia Haemorrhagica.
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 ovulationno development of corpus Luteum
--- no progesterone --- no secretory changes in
endometrium ; estrogen still secreted by follicles
(granulosa cells)

Anovulatory DUB
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 grows 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 undergo the formation of follicular
cysts.

Anovulatory DUB Metropathia Hamorrhagica

Accounts for 80% of DUB; at Pubertal and perimenopausal age ,Patient has
variable period of amenorrhoea followed by prolonged, heavy, painless bleeding
.
Prolonged Unopposed Estrogen
Proliferative Endometrium
Simple Hyperplasia
Complex Hyperplasia
Complex Hyperplasia with Atypia
Adenocarcinoma

Endometrium in Metropathia Haemorrhagica

Usually reveals cystic hyperplasia( simple
hyperplasia without atypia) called swiss cheese
appearance
- Hyperplastic glands and stroma.
- Cystic or irregularly dilated glands.
- Thick walled, tortuous, dilated spiral arterioles
and veins.
- Infarction and thrombosis of blood vessels.
- Necrosis of functional endometrium

Metropathia Haemorrhagica

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 without 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 perimenopausal 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 (2140 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
corpus luteum .
Increase in PGE receptors in endometrium , reduction in
thrombxane production and increased fibrinolytic activity
has also been demonstrated in these women .
PgF2a causes dysmenorrhea.

Luteal Phase Defect

Inadequate Functioning of corpus luteum can
result in--- insufficient and erratic production of
Progesterone. As well as alteration in the ratio of
PGE : PGF
---resulting in irregular and patchy secretory
changes in the endometrium
Both pathophysiological deficit leads to irregular
ripening and or irregular shading of endometrium
.

DUB: Classification, Pathophysiology And Endometrial Changes

OVULATORY

Idiopathic
Ovulatory
Menorrhagia
Normal
Progesterone

Luteal Phase Defect

Reduced
Progesterone

ANOVULATORY

Metropathia
Haemorrhagica
Prolonged Oestrogen
No Progesterone

Reduced PG F2
Reduced PG F2

Altered PGE : PGF

Menorrhagia

Premenstrual
Spotting
(Polymenorrhoea)

Secretory
Endometrium

Irregular ripening

Amenorrhoea followed
by bleeding
Hyperplastic
Endometrium

Threshold Bleeding
Low Oestrogen
No Progesterone
Reduced PG F2
Polymenorrhoea/
Polymenorrhagia
Proliferative
Endometrium