AUB menstrual cycle ppt fir diwgidvysrsvbj

Menstrual

1. ABNORMAL UTERINE BLEEDING (AUB) DR RAVINDER KAUR DHALIWAL JUNIOR RESIDENT MODERATOR –DR.PREETKANWAL SIBIA

2. PHYSIOLOGY OF MENSTRUATION Menstruation is the recurrent monthly bleeding from the uterus coming out through the vagina during reproductive life of a women . FIGO has redefined normal limits of menstrual parameters using median ,5 th and 95 th percentile. Normal frequency is >_24 days and <_38 days .Normal duration is taken as <_8 days .Normal quantity of menstrual blood is as determined by the patient .Regular cycles are taken as shortest to longest cycle variation <_7-9days . It requires intact hypothalamic –pituitary –ovarian axis and paracrine and autocrine factors and results in release of a single mature oocyte from a pool of numerous primordial follicles .

3. Divided into 3 cycles Endocrine cycle Ovarian cycle Endometrial cycle

4. Endocrine cycle HYPOTHALAMUS HORMONES – GnRH is secreted in pulsatile manner and delivered to anterior pituitary through portal vessels , PITUITARY HORMONES –FSH and LH are released from anterior pituitary under the influence of GnRH . FSH – (Glycoprotein ) – FSH has 2 Peaks on 5 th day and 12 th day.1)Promotes development of 15-20 ovarian follicles every month. 2-It stimulates estradiol secretion from granulosa cells and theca cells and also induces expression of FSH receptors by ovarian follicles .

5. LH- 1) It induces androgen secretion by theca cells of ovary which goes to granulosa cells and under the influence of FSH converted to estrogens with the help of aromatase and p450 enzymes. 2)It stimulates proliferation, differentiation and release of follicular theca cells and also increase LH receptors on the granulosa cells .

6. OVARIAN HORMONES – Ovaries secretes estrogen and progesterone ,small amounts of androgens and peptides like inhibin and activin , needed for normal menstruation.

7. OVARIAN CYCLE EARLY FOLLICULAR PHASE –It starts at the end of menstruation when estrogen and progesterone are low and it sends positive feedback to hypothalamus and leads to pulsatile release of GnRH which further stimulates pituitary to release FSH and LH. . Gradually , FSH levels rises which causes growth of ovarian follicle and which produces proliferative change in endometrium. FSH is at peak on day 5 with selection of dominant follicle by day 5-7. Estrogen levels rises along with inhibin which inhibit FSH and help in the growth and maturation of dominant follicle MID FOLLICULAR PHASE – Increase levels of estrogen and inhibin have negative feedback on FSH and positive feedback on LH . LATE FOLLICULAR PHASE- There is gradual increase in LH level .Sufficient estrogen secreted by the growing follicle induces LH surge .PEAK ESTROGEN level seen 48 hrs before ovulation and LH SURGE starts 24-36 hrs before ovulation .

8. OVULATION Ovulation is the process by which a secondary oocyte is extruded from the ovary after rupture of a mature graffian follicle .Ovulation usually occurs 14 days before the next cycle. Causes of ovulation – Endocrinal – 1)LH Surge – Sustained estradiol peak causes LH surge from anterior pituitary which persists for 24 hours .It causes increased activity of enzyme collagenase which digests the collagen fibres surrounding the follicle . 2)FSH rise – FSH rise causes increase in plasminogen activator which converts plasminogen to plasmin to help in the lysis of the wall of follicle . Thus, the combined LH/FSH midcycle surge is crucial for final stage of maturation , rupture of the follicle and extrusion of the oocyte.The enzymatic digestion of the follicular wall by proteases seems to be the main factor responsible for ovulation.

9. TIMINGS – OVULATION occurs – 24-36 hours from the onset of the LH surge. 48 hours from the estradiol peak . 12-16 hours from the peak of the LH surge .

10. LUTEAL PHASE- With the release of oocyte , the follicle converts into corpus luteum which secretes progesterone and estrogen with some inhibin for 14 days . In the absence of fertilisation , corpus luteum degerates and forms a mass of fibrous tissue called corpus albicans .The resultant fall in estrogen and progesterone levels causes menstruation. Fall in estrogen , progesterone and inhibin leads to positive feedback mechanism, stimulating hypothalamus to secrete GnRH for follicular phase of next menstrual cycle . If fertilisation occurs , corpus luteum persists for about 3-4 months and is called corpus luteum of pregnancy.

11. ENDOMETRIAL CYCLE The endometrium can be divided into 2 layers – Superficial functional layer(2/3 rd ) – which is shed during menstruation Deep basal layer (1/3 rd )- this is not shed during menstruation and is not under the control of hormones . It is with this layer that regeneration of superficial layer occurs . ENDOMETRIAL CYCLE – Divided into 3 phases- PROLIFERATIVE PHASE SECRETORY PHASE MENSTRUAL PHASE

12. PROLIFERATIVE PHASE SECRETORY PHASE (LUTEAL PHASE ) MENSTRUAL PHASE Starts from the end of menstruation until ovulation Starts with ovulation and lasts from day 14 to 28 until next menstruation. If fertilisation does not occur , corpus luteum starts regressing by day 23 of the cycle which decreases estrogen and progesterone levels .It is this withdrawal , that results in menstrual bleeding. Endometrial thickness became 4mm thick from 2 mm (thickness at the start of proliferative phase ) Endometrial thickness became about 6 mm There occurs proliferation of glands , blood vessels , stroma, and superficial endothelium The endometrial glands increase in length , breadth and became more tortuous and are filled with mucus (saw toothed appearance ).Stromal cells also proliferate and enlarge . Spiral arteries elongates to span the length of endometrium Spiral arteries became more coiled and dilated and veins become filled with blood. CERVICAL SECREATIONS – became alkaline and watery and showed FERN like pattern on slide. Cervical secretions became thick, tenacious and cellular and forms a viscous cervical mucus plug which acts as a barrier against spermatozoa and microorganisms .

13. AUB - DEFINITION Abnormal uterine bleeding is any bleeding from the genital tract which is a deviation from the normal menstrual cycle in frequency, duration, regularity and volume . Common gynaecological disease accounting for 30-40% cases of outpatient department .

14. PALM-COEIN FIGO has suggested a new etiological classification system called PALM-COEIN classification in 2010 which has been recently revised in 2018 to standardize the terminology , investigations ,diagnosis and management of AUB in non pregnant women of reproductive age. P-Polyp A-Adenomyosis L-Leiomyoma M-Malignancy and Hyperplasia C-Coagulopathy O-Ovulatory dysfunction E-Endometrial I-Iatrogenic N-Not otherwise classified.

15. The first 4 include structural etiologies and can be diagnosed by imaging methods with or without histopathology . COEIN group represents non structural causes of AUB which cannot be diagnosed by imaging or histopathology

16. NORMAL MENSTRUAL CYCLE FIGO redefined normal limits of menstrual parametes using median, 5 th and 90 th percentile. PARAMETER NORMAL ABNORMAL FREQUENCY _>24 DAYS AND <_38 DAYS ABSENT- no bleeding/amenorrhoea Abnormal <24 and >38 days DURATION <_8 days PROLONGED >_8 days REGULARITY Regular – Shortest to longest cycle variation <_7-9 days (+_4 days ) IRREGULAR- Shortest to longest cycle variation >_10 days FLOW VOLUME(Patient determined ) Normal LIGHT HEAVY

17. Any deviation from these normal parameters is AUB after ruling out pregnancy and its complications .

18. TYPES ACUTE AUB CHRONIC AUB It is defined as an episode of heavy bleeding requiring immediate intervention to prevent further blood loss It is defined as uterine bleeding which is abnormal duration, regularity, volume or frequency in absence of pregnancy and has been present for most of preceeding six months.

19. AUB- HMB Previously called menorrhagia . According to NICE , HMB is defined as excessive menstrual blood loss interfering with womens physical,social ,emotional and mental quality of life irrespective of regularity , frequency,and duration of menstrual cycle.

20. AUB-IMB(INTERMENSTRUAL BLEEDING) Previously called metrorrhagia . It is defined as bleeding occur between normally timed menstrual bleeding. It can be cyclic and predictable . It can occur in early ,middle or late cycle

21. DOCUMENTATION OF AUB Documentation of AUB as per PALM-COEIN classification while contribution of each aspect PALM-COEIN is written as 1 (present) if it is a cause of AUB and 0(absent) if it is not the cause of AUB. EXAMPLE- IF leiomyoma is a cause of AUB – Then it is P0A0L1M0-C0O0EOI0N0 Or AUB –L IF multiple etiologies present , such as a patient have adenomyosis ,hyperplasia and coagulopathy –It is written as P0A1L0M1-C1O0E0I0N0 OR AUB-A-M-C

22. POLYP (AUB-P ) Endometrial polyps are epithelial proliferation arising from, endometrial stroma and glands . Responsible for 57-60% cases. May be asymptomatic Suspected from history of intermenstrual bleeding . Diagnosis – TVS or sonohysterography can be used HYSTEROSCOPY confirms diagnosis and polyp can be removed rsurgically through hysteroscope and sent for histopathology.

23. ADENOMYOSIS (AUB-A) Adenomyosis is defined as growth of endometrial tissue in the myometrium (beneath the endometrial –myometrial junction ), Diagnosis is suspected from ultrasound but is confirmed by MRI. The revised FIGO system talks of refined sonographic MORPHOLOGICAL UTERUS SONOGRAPHIC ASSESSMENT (MUSA) based diagnostic criteria . The eight criteria suggested are – Assymetrical myometrial thickening , myometrial cysts , hyperechoic islands , fan shaped shadowing ,echogenic subendometrial lines and buds , translesional vascularity ,irregular junctional zone and interrupted junctional zone . Management depends upon age and fertility status , For pain , NSAIDS , progestogens, combined pills can be tried .LNG-IUS is first line therapy for long term management in women not desiring pregnancy . Rarely adenomyomectomy can be done in infertility cases. If family is complete then hysterectomy is the treatment of choice .

24. LEIOMYOMA (AUB-L ) Leiomyomas are also called fibroids which are benign fibromuscular tumours of myometrium .They can cause AUB , mass abdomen or pelvis , pelvic pain and infertility . Diagnosis is by ultrasound . MRI can be used in fibroid and with AUB for exact mapping of fibroid before planning the surgery (myomectomy or uterine artery embolization). In PALM –COIEN system, primary classification represents presence (L1) or absence (L0) of myoma irrespective of location , number and size . The secondary classification includes further subdivision of leiomyoma into SUBMUCOUS (SM) with atleast 1 submucous fibroid or others (O).It helps to distinguish myomas which lie adjacent to mucosa as they tend to cause AUB.

25. REVISED FIGO CLASSIFICATION OF LEIOMYOMAS -

26. Diagnosis is by ultrasound or MRI. Managemnet is indivisualised depending upon parity , sysmptoms , fertility desire ,size and location of myoma. MEDICAL MANAGEMENT is offered for small <4 cm fibroids amd to delay or avoid hysterectomy . Medical treatment is given by NSAIDS , tranexamic acid , combinmed oral pills or LNG-IUS .GnRH analogues can be given .Ulipristal 5 mg daily for 3-4 months or mifepristone 25 mg daily for 4 months can also be given . Uterine artery embolization can also be tried .HIFU(High intensity focused ultrasound can also be tried . Myomectomy is performed for large fibroids. It can be performed by laparoscopy or laparotomy and by hysteroscopy (submucous type 0-2 small myomas of size <4cm ) If family is complete and women is more than 40 years with large symptomatic fibroids, hysterectomy is the treatment of choice .

27. MALIGNANCY AND HYPERPLASIA (AUB-M) It incorporated both endometrial hyperplasia and endometrial cancer . There has been change in the classification of endometrial hyperplasia NEW WHO (2014)CLASSIFICATION OF ENDOMETRIAL HYPERPLASIA TYPES OF HYPERPLASIA ENDOMETRIAL CANCER Endometrial hyperplasia without atypia <1% Endometrial hyperplasia with atypia (atypical hyperplasia or endometroid intraepithelial neoplasia) 25-33%

28. Foe endometrial hyperplasia with atypia , hysterectomy with bilateral salpingooophorectomy is usually indicated. Hysterectomy may also be indicated for endometrial hyperplasia without atypia in high risk cases (old age, obesity,diabetes,hypertension , family history of endometrial cancer )

29. COAGULOPATHY (AUB-C) AUB caused by systemic diseases of hemostatsis comes under this category which can be responsible for 13 % cases of AUB .It includes cases of coagulation disorders like von willibrands disease, purpuras , hemophillias etc. It doesnot include cases of anticoagulation therapy as that is iatrogenic (AUB-I). TREATMENT – NSAIDS are avoided as they can cause platelet dysfunction . Tranexemic acid can be given .Combined oral pills and progestogens are effective . LNG-IUS can be tried . Option for hematologist may be taken and specific factor therapy can be tried Hysterectomy or surgical ablation can be tried after correcting coagulation profile.

30. OVULATORY DISORDERS (AUB-O) They are commom causes of AUB around menarche and menopause and in various endocrinopathies .(PCOS ,hypothyroidism ), stress ,obesity, anorexia, weight loss and excessive exercise . It also includes Aanovulatory AUB formely called dysfunctional uterine bleeding . Unopposed estrogen in anovulation causes marked proliferation and thickening of endometrium with resultant AUB. These women has long menstrual cycles >38 days Treatment is usually hormonal with progestogens or combined oral pills.

31. ENDOMETRIAL CAUSES (AUB-E) AUB due to endometrial dysfunction comes under this category. It is usually due to increased production of vasodilators locally in the endometrium and decreases local production of vasoconstrictors . There may be increased synthesis of plasminogen activator or increased lysis of endometrial clot. THEY CANNOT BE TESTED IN LABORATORY AUB due to infection or inflammation of endometrium also comes under this category. Treatment is by tranexamic acid, combined pills and progestogens .LNG –IUS can also be tried .

32. IATROGENIC (AUB-I) It includes cases of AUB due to exogenous therapy usually with steroids ( eg progestogen , combined estrogen progestogen therapy, GnRH agonists and antagonists and SERMs , SPRMs and intrauterine devices . About 5-10% women with IUCD tend to have heavy menstrual bleeding for first few months. ANOTHER IMPORTANT CAUSE – is the use of anticoagulation drugs like warfarin,heparin or low molecular weight heparin . Treatment is by withholding the culprit drug and use of alternate therapy.Dose adjustment may be needed in AUB due to anticoagulants .

33. NOT OTHERWISE CLASSIFIED (AUB-N) It include rare cases of AUB and AUB due to ill defined causes. It includes cases of – AV malformation Lower segment or upper cervical isthmocoele Cesarean scar defects Endometrial pseudoaneurysms Myometrial hypertrophy Chronic endometritis Treatment includes management of cause .For AV malformation,uterine artery embolization can be tried .

34. DIAGNOSIS OF AUB 1) HISTORY TAKING – Detailed history is very important in case of AUB to identify the underlying cause . Detailed menstrual History (age of menarche ,LMP, duration, frequency, regularity,volume ,any intermenstrual bleeding ) Any associated dysmenorrhoea (goes in favour of AUB due to structural abnormalities –PALM , infection and pregnancy complications ) History of any associated symptoms such as bowel or urinary symptoms (especially due to pressure effects in fibroid uterus ) Detailed drug intake history including herbal (ayurvedic )and homeopathic drugs as they can also cause AUB.

35. GENERAL PHYSICAL EXAMINATION –VITALS Pallor( anemia is presenr in AUB), jaundice, edema , significant lympohadenopathy ,any thyromegaly . It is performed to identify findings related to etiology ( eg - purpura can cause purpuric spots on skin and AUB ) Prescence of obesity and signs of hyperandrogenism SYSTEMIC EXAMINATION including heart , chest , breast and abdominal examination for any hepatospeenomegaly and abdominal masses

36. GYNAECOLOGICAL EXAMINATION- Local examination ,Per speculum, Bimanual examination for cervical growth or polyp, uterine size ,shape ,tenderness ,any adnexal masses and fixity.Thus fibroid ,adenomyosis and ovarian masses can be made out . One should also examine if there is vaginal bleeding and should rule out urethral and rectal bleeding as they can present as AUB. P/S, P/V can be omitted din adolescent non sexually active girls. Rectal examination is also performed for any rectal pathology

37. INVESTIGATIONS – 1) LABORATORY TESTS – UPT should be done in all cases as pregnancy complications like miscarriage ,ectopic pregnancy or H.Mole can cause serious hemorrhage resembling AUB. CBC, BT, CT , Cogulation profile ,TSH ,LFT and RFT 2)ULTRASOUND- Usually transvaginal is performed due to its better resolution. In nonsexually active females , adolescent girls , Transabdominal ultrasound with full bladder is performed.It can diagnose structural causes of AUB. 3D ULTRASOUND and colour doppler may demonstrate endometrial lesions better and can show endometrial AV malformations as well as multiple irregular branching vessels in malignancy.

38. 3 ) SALINE INFUSION SONOGRAPHY(SIS) or sonohysterography in which ultrasound is perfor,ed after the introduction of saline into the uterine cavity. It identifies structural enmdometrial and submucous lesions causing AUB . It can differentiate between intracavitary ,submucous and intramural lesions. However it has its own limitations , it is not superior to TVS

39. 4)HYSTEROSCOPY-In this procedure a 3 to 5 mm rigid hysteroscope is inserted into the uterine cavity using saline, glycine or CO2 as distension medium , It allows visual inspection and magnification of endometrial mucosa , any focal lesion and also allows directed biopsy from from the suspected area under direct vision . It allows complete removal of small focal lesions (polyp)in the same sitting. However it is invasive and expensive and technically more difficult as compared to ultrasound and endometrial sampling . 5)CT and MRI are not routinely used but may be useful in suspected cases of adenomyosis or malignancies

40. 6)CERVICAL CYTOLOGY – If not performed already, cervical cytology (PAP ) should be taken in all cases. 7)ENDOMETRIAL SAMPLING (OR BIOPSY )- It is the most important investigation in AUB especially after 40 years of age as it provides tissue specimen from endometrium for definitive pathological diagnosis. ACOG recommends it for all women of AUB older than 45 years and in young women with history of unopposed estrogen exposure ( obesity,PCOS ,uncontrolled and persistent AUB despite medicines ) It can be done in minor OT or OPD using karmans cannula no 4 , VIBRA aspirator or PIPELLE.The sample is aspirated and sent in 10%formalin solution for histopathological examination. NOTE – out of all the tests , TVS is most useful modality followed by Endometrial sampling in most cases of AUB.

41. MANAGEMENT OF AUB It depends upoin the age of patient , severity of bleeding, desire for fertility and type of AUB . MANAGEMENT OF ACUTE AUB- 1)FLUID RESUSCITATION 2)CONTROL OF HEMORRHAGE - A)Combined estrogen progesterone oral pill containing 30-50 microgram ethinyl estradiol can be given every 6-8 hrly for 7 days followed by once a day pill after the control of bleeding. B) Tab medroxyprogesterone acetate 10 mg every 4 hrly for 4 days can also be given to control acute bleeding followed by 10 mg 6 hrly for 4 days and then 10mg 8 hrly for 3 days and then 12 hrly for 2 weeks C) Inj tranexamic acid 10mg/kg iv every 8 hrly is given till bleeding becomes less followed by tab tranexamic acid 1 gm thrice a day for 5 days.

42. MANAGEMENT OF CHRONIC AUB

43. 1)Treatment of anemia is by giving hematinics (iron with folate with other multivitamins )with or without calcium and vitamin D supplementation. 2)Lifestyle modification with weight reduction ,diet and exercise in case of PCOS-related AUB. MEDICAL MANAGEMENT – It is the mainstay of treatment and should be tried first in all cases of AUB.

44. MEDICAL MANAGEMENT NON HORMONAL HORMONAL TREATMENT OTHER DRUGS 1) ANTIFIBRINOLYTIC AGENTS – Tranexemic acid (500mg-1gm thrice/four times a day during menses for 5-7 days for 6 months .DRUG OF CHOICE FOR AUB. Should be avoided in patients with history of thromboemboliv disease and should not be combine dwith combined pills. 1) PROGESTOGENS –Very effective in AUB-O and also useful in AUB-E . Norethisteron (5-10mg) thrice daily from day 5 to 25 of each cycle for 6 months . Medroxyprogesterone acetate (5-10mg)TDS from day 5-25 can also be given. DMPA 150 mg im can be used but is less popular due to irregular bleeding and amenorrhoea. 1) ANDROGENS – DANAZOL (100-200MG daily) and GESTRINONE (2.5mg BD twice weekly)–creates hypoestrogenic and hyperandrogenic environment ,causes endometrial atrophy and reduction in menstrual blood loss. 2)NSAIDS – Mefenemic acid in dose of 500mg 3 to 4 times a day during menstruation is usually given . NSAIDS with more platelet inhibiting action such as aspirin,ibuprofen and naproxen should not be used. LNG-IUS or MIRENA –contains 52mg levonorgestrel and releases 20 microgram per day locally at endometrium.FIRST LINE management for HMB and is particularly suited for reproductive age women with AUB –E who needs contraception and wish to retain fertility GnRH analogues-Leuprolide (3.75mg ) OR goserelin (3.6mg) every 28 days for 3-6 months . They are usually used for short term especially before surgery. 3 OTHERS – Ethamsylate (capillary fragility inhibitors ) and Diosmin (vascular protective agent) has also found to be effective in some studies Combined oral contraceptive pills –They are one of the most effective and popular treatment for AUB and reduce blood loss by 50%.DOSE- 30 microgram ethinyl estradiol with 75 micro.of progestogen is given from day 5 to 25 of cycle for 3-6 months . - Ormeloxifene ( centchromane )- Is is a SERM which is usually used as an oral contraceptive . Dose in AUB- 60MG twice weekly for 3-6 months and causes significant decrease in blood loss in AUB

45. SURGICAL TREATMENT It is the last resort and should be used when a six month medical treatment has failed. All types of Surgeries (both conservative and definitive )should be explained to patient. Decision of type of surgery is made taking into consideration age, parity, fertility desire and patients desire to keep uterus.

46. CONSERVATIVE SURGERY DEFINITIVE SURGERY- 1) DILATION AND CURETTAGE – Mainly used for diagnostic purpose to rule out endometrial cancer or tuberculosis . 2-It is often used in emergency in HMB for temporary and quick relief of acute bleeding resistant to hormonal treatment by removing a thickened endometrium and arrests HMB. HYSTERECTOMY –It is the last resort but commonly required for many patients of AUB when other medical method or conservative surgery fails. INDICATIONS – a)Failure of medical treatment b) Failure of conservative surgery c)In older women >40 years with complete family severe AUB. 2) ENDOMETRIAL ABLATION OR RESECTION-In these attempts are made to permanently remove or destroy the uterine lining . HYSTERECTOMY – Can be performed in following ways – VAGINAL HYSTERECTOMY LAPAROSCOPIC HYSTERECTOMY ABDMINAL HYSTERECTOMY ROBOTIC HYSTERECTOMY. 3) Uterine artery embolization –Is useful in HMB due to AUB-L but can also be used in AUB due to other disorders , severe menstrual bleeding not responding to conservative treatment, 4) Myomectomy-Myomectomy is performed in AUB-L where myoma is large in size and women desires fertility. For submucous myoma,hysteroscopic myomectomy is performed while for large intramural and subserosal fibroid ,abdominal myomectomy through laparotomy or laparoscopy is performed .

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