the endometrium and its pathology

Review normal function Endometrial abnormalities including DUB Clinical problems with real cases Clinical management – related to patho-physiology

Compactum Spongiosum Basalis Junctional zone

Initiated by withdrawal of E and P Local mediators PG’s, PAF Spiral artery vasoconstriction  Ischaemia and tissue damage  Spiral artery relaxation  Shedding of functional endometrium Control E2 + P PGs (E + I vs F2a + Tx) Interleukins (IL – 8, 13 +16) Tissue Necrosis Factor (TNF) + Platelet Aggregating Factor (PAF) Matrix metallo-proteinases Coagulation / fibrinolysis Junctional zone For normal menstruation: Correct balance and regulation of inflammation, coagulation and fibrinolysis in the endometrium

Anything different from usual pattern Too much bleeding - Menorrhagia Bleeding too often - Polymenorrhoea IMB / PCB (intermenstrual bleeding, post-coital bleeding) Chaotic bleeding

Can be acute, intermittent or chronic Can test the frequency, regularity, duration and volume of bleeding Structural causes: Polyp (small benign growth from mucous membrane of endometrium) Adenomyosis (tissue that normally lines the uterus grows into the muscular walls of the uterus) Leiomyoma (fibroids, benign extra growth of smooth muscle) Malignancy Non structural causes: Coagulopathy Ovulatory dysnfunction Iatrogenic Endometrial Not otherwise classified

‘Pathological causes’ Fibroids – submucous Adenomyosis Endometrial pathology – benign adenomas or polyps - hyperplasia - carcinoma Cervical pathology – polyps - carcinoma Cervical Infection - Chlamydia Pregnancy!!! DUB - diagnosis of exclusion

Submucous fibroids (leiomyomas) are associated with a threefold increased risk of abnormal bleeding – invariably menorrhagia Endometrial Polyps (adenomas) are more frequent in women with menstrual disorders Causal / casual – diagnostic bias??

Exclude pregnancy Exclude cervical pathology Exclude focal benign intracavity pathology (polyps, submucous fibroids) Consider other endometrial pathology (> 40) Use the least invasive method to achieve this

Dysfunctional uterine bleeding Endometrial polyps Endometrial hyperplasia Endometrial hyperplasia with atypia (mild – severe) Endometrial adenocarcinoma Of women presenting with menorrhagia 50-60% will have NO structural or obvious pathological cause identifiable – it is a problem at the molecular level i.e. cellular dysfunction It is a diagnosis of exclusion

Where’s the dysfunction? PGs (E + I vs F2a + Tx) Interleukins (IL – 8, 13 +16) Tissue Necrosis Factor (TNF) + Platelet Aggregating Factor (PAF) Matrix metallo-proteinases Coagulation / fibrinolysis Junctional zone

Benign endometrial adenomas Focal problem Rest of endometrium is normal

Points in history LMP – was it normal? Regular or irregular periods cycle control (ovulation vs anovulation) heavy- clots, flooding? with bleeding between (IMB)? post coital bleeding (PCB)? Pain Medication, smoker, smear, operations Contraception - hormonal vs non-hormonal Points in examination BMI Abdomen Distension, scars, pain, masses Bimanual Uterine size, adnexal masses, pain Cervix polyps, suspect lesions

Pregnancy test where appropriate Hb if heavy bleeding Swabs – endocervical (Chlamydia) Cervical smear – only if due Transvaginal ultrasound \+/- Endometrial sampling \+/- Hysteroscopy - in-patient or OPD

Can assess the relationship of fibroids to the cavity Has a high detection rate for polyps Assess function – anovulatory cycles Can reliably assess structures outside the uterus (tubal and ovarian pathology) Well accepted by patients Relatively cheap with few complications Periovulatory endometrium is hard to hide pathology in – or immediately post menstrual to assess ET Cut-off values for ET are arbitrary in premenopausal women - @ 6 mm post menstrual or 12 mm anytime in cycle Hydrosonography Ultrasound is ideal for focal pathology but not good for predicting endometrial pathology – a biopsy is still needed in many cases

Obesity Nullipartity Early menarche / late menopause – length of E2 exposure – weak factor HT / DM Anovulation e.g. PCOS Genetics - FH breast / endometrial / colonic cancer – Lynch syndrome (HNPCC)

Obesity – peripheral conversion of androgen to oestrogen (aromatase) BMI most vital factor The more adipose tissue the more conversion to oestrogen Chronic anovulation e.g. PCOS Follicular ovarian oestrogen production continues Progesterone only produced after ovulation Unopposed oestrogen Over years leads to hyperplasia and sometimes cancer

Polyps Surgery TCRP Fibroids Medical Mirena IUS Surgery TCRF/Myomectomy Hysterectomy total/subtotal abdominal vaginal

Does she need or want treatment? Does she need contraception/desire pregnancy? How much is the problem affecting her quality of life? Nothing Medical Non Hormonal (what is the dysfunction????) Tranexamic acid - anti fibrinolytics 40-50% reduction in blood loss Corrects excessive fibrin breakdown in endometrium (affects plasminogen action) Mefanamic acid 30% reduction in blood loss NSAID – corrects PG imbalance to allow normal vasoconstriction and platelet aggregation Good for pain also! Hormonal Mirena IUS – 90% reduction blood loss 30% amenorrheic Local high dose progestagen - thin endometrium COCP – 20 - 30% reduction in blood loss Removes cyclical events – thin endometrium Progestagens less beneficial for volume loss Use to control cycle length in anovulatory DUB Surgery – for failed medical treatment Endometrial resection/ablation Hysterectomy - Vaginal/abdominal Remove ovaries?

Most menorrhagia is DUB and treatments reflect the dysfunction Exclude focal pathology – needs focal removal Beware erratic bleeding – pathology much more likely TVS and biopsy +/- hysterosocpy diagnosis in nearly all