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 ovulation—no 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 • s 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 ) . • s 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