1. Vaginal Bleeding non pregnant and in pregnancy
Tim Chang MBBS(SYD), FRANZCOG Gynaecologist, Endoscopic surgeon and IVF Fertility specialist
Dr. Christiane Mayer MD, FRANZCOG Obstetrician and Gynaecologist,
139 Dumaresq street
Campbelltown
----- Meeting Notes (30/03/ :09) -----
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2. Steering committee, Accreditation and Sponsorship
This educational program has been developed with the assistance of a steering committee:
Dr. Timothy Chang MBBS (SYD), FRANZCOG,
Dr. Christiane Mayer M.D., FRANZCOG (AUS), Specialist O&G, GP (AUT)
Dr. Carina Law MBBS, FPA Certificate
4 Category 2 points have been applied for in the RACGP QI&CPD program
This program is brought to you by

3. AUSTR(AL)IA

4. Abnormal Uterine Bleeding Aetiology and Diagnosis
Dr. Christiane Mayer MD, FRANZCOG Obstetrician and Gynaecologist,
139 Dumaresq street
Campbelltown

5. Learning outcomes Identify early symptoms of Abnormal Uterine Bleeding
Recognise causes of Abnormal Uterine Bleeding
Assess women of various age groups who present with Abnormal Uterine Bleeding.
Discuss treatment options available to patients with Abnormal Uterine Bleeding
Speaker note: the following learning objectives must be reviewed at the start of the session to satisfy RACGP accreditation requirements

6. Abnormal Vaginal Bleeding
Uterus AUB
Vagina
Cervix
Vulva
Fallopian tube

7. Abnormal Uterine Bleeding (AUB)
Acute
Chronic: 10 – 35 % of women
Intermenstrual bleeding
Spontaneous
Provoked eg PCB

8. Abnormal menstrual bleeding
Abnormal quantity > 80 mls
(change pad/tampon every 1-2 hrs, interfers with daily activities/anaemia)
Abnormal duration > 5-7 days
Abnormal frequency < 21 or > 35 days

9. Heavy menstrual bleeding is common
Incidence 5% women aged 30-49
~ 12% of referrals of premenopausal women to specialist gynaecologists are for evaluation and treatment of HMB
However, because menstrual disorders are often managed conservatively by GPs, the actual prevalence could be as high as 20% of the reproductive age female population
Because a large proportion of women who might otherwise experience HMB are currently taking oral contraceptive pills (OCPs) in order to avoid pregnancy, the true incidence might may actually be even higher than 20%.1
Reference:
Knight B et al. Australian Doctor 6 March 2009:31–8.

10. FIGO classification system (PALM-COEIN) in 2011 for causes of abnormal uterine bleeding in non-gravid women of reproductive age
The PALM-COEIN classification system is applied after any STI's have been ruled out.
The basic system comprises 4 categories that are defined by visually objective structural criteria (PALM: polyp; adenomyosis; leiomyoma; and malignancy and hyperplasia), 4 that are unrelated to structural anomalies (COEI: coagulopathy; ovulatory dysfunction; endometrial; iatrogenic), and 1 reserved for entities that are not yet classified (N).1,2
The leiomyoma category (L) is subdivided into patients with at least 1 submucosal myoma (LSM) and those with myomas that do not impact the endometrial cavity (LO).1,2
Adenomyosis refers to pockets of endometrium within the uterine wall. This may sometimes be identified on ultrasound and is treated similar to endometriosis (with hormones, etc.).3
Recommend that GPs refer ultrasound to an imaging practice with experience/specialisation in women’s health, as the importance of high-quality ultrasounds cannot be underestimated.
References:
American College of Obstetricians and Gynecologists (ACOG). Committee Opinion. Management of Acute Abnormal Uterine Bleeding in Nonpregnant Reproductive-Aged Women. Number 557. April 2013.
Munro MG et al. Int J Gynaecol Obstet 2011;113:3–13.
Knight B et al. Australian Doctor 6 March 2009:31–8.

11. AUB classification - structural
Polyp
Adenomyosis
Leiomyoma
Malignancy
FIGO 2009 standardise terminology facilitate communication + research

12. Polyps
Localized proliferation of glandular + stroma with single feeder blood vessel
Exact aetiology unknown:
Abnormal proliferation basal cells
Incomplete shedding endometrium
Typical symptoms erratic IMB rarely heavy
0.5-5% polyps are malignant in AUB
recurrence after polypectomy:
blind removal 15%
visual removal 0-5%

13. Adenomyosis
Endometrial glands in the myometrium. Depth invasion varies from 2.5mm-8mm beyond endomyometrial junction
Diagnosis:
Histopathology
Ultrasound
MRI
Posterior wall > anterior wall

14. Leiomyoma
Common found in up to 70% Caucasian women at age 50 and up to 80% in African descendants
Mechanisms bleeding:
Increasing surface area
Biochemical release factors leading to bleeding eg VEGF etc.
AUB depends on:
Site commonly Submucous
Size

15. Leiomyoma SM submucosal fibroids Pedunculated intracavitary 1
Pedunculated intracavitary 1
<50% intramural 2
≥50% intramural
O other 3
Contacts endometrium 100% intramural 4
Intramural 5
Subserosal ≥ 50% intramural 6
Subserosal < 50% intramural 7
Subserosal pedunculated 8
Other eg cervical parasitic
Hybrid leiomyomas (impacts endometrium and serosal)
2 numbers separated by hyphen, endometrium first followed by serosal fibroid

16. Malignancy Endometrial Hyperplasia, Carcinoma & Sarcomas of uterus
Important to rule out in peri – and postmenopausal women
Tissue diagnosis

17. AUB classification – non structural
Coagulopathy
Ovulatory
Endometrium
Iatrogenic
Not otherwise classified
FIGO 2009 standardise terminology facilitate communication + research

18. Coagulopathy Causes: Prevalence 13% Structured history 90% sensitive
Congenital
Acquired
Iatrogenic
Prevalence 13%
Structured history 90% sensitive
PFA100 screen+ VWD
Multidisciplinary clinic
PPH, bleeding after dental / surgical procedures, epistaxis + family history etc

19. Ovulatory dysfunction
Hypothalamic pituitary dysfunction eg
weight changes, peri menarche / menopause, stress etc
PCOS
Thyroid
Hyperprolactinaemia
Episodes amenorrhoea with HMB
(Endometrial protection!)
Common in the extremes reproductive age ie adolescent + perimenopausal

20. Endometrial Regular cycles Diagnosis exclusion Mechanisms
impaired vasoconstrictor production eg endothelin and PGF2α
increased production vasodilators eg PGE2 + PGI
enhanced fibrinolysis
Common in the premenopausal AUB

21. Iatrogenic Steroid hormones IUD Increased prolactin drugs eg
OCP enhanced with
Antibiotics
Anticonvulsants
smokers
Progestins
IUD
Mirena
Copper
Increased prolactin drugs eg
Antidepressants
SSRI
Antipsychotic
OCP increased BTB antibiotics anticonvulsants + smokers

22. Not otherwise classified
Arteriovenous malformation (AVM)
Congenital
Acquired eg after post partum
Infection

23. AUB – Initial Evaluation
History
Examination
Investigations

24. Questions to ask your patients when assessing HMB
Volume
Are you bothered by the amount of bleeding?
Frequency
Do you wake up during the night to change sanitary protection or require frequent changes during the day?
Irregular 
Are you bleeding or experiencing “spotting” between your regular cycles?
Sexual activity
Do you experience bleeding after intercourse?
Pain 
Are your periods painful?
Mood
Does your period make you depressed, tired and moody?
Impact 
Are your periods affecting your social, athletic, or sexual activity or causing you to miss work?

25. 1.History taking for HMB Menstrual history Sexual history
Fertility and pregnancy
Medical history
Medications
Family history
Associated symptoms
Menstrual history:1,2
Menarche
Cycle regularity
Volume and nature of flow / clots (number and frequency of pad use)
Intermenstrual bleeding (IMB)
Post-coital bleeding (PCB)
Premenstrual spotting
Associated symptoms: pelvic pain, dysuria, urgency, dyschezia
Sexual history1,2
Age of at first intercourse
Number of sexual partners in the last 12 months
Sexually transmitted infections (STIs)
Pap tests
Contraception
Fertility and pregnancy1,2
Number of pregnancies / complications
Any fertility concerns
References:
NICE clinical guideline 44. Heavy menstrual bleeding. Issue date: January 2007.
Knight B et al. Australian Doctor 6 March 2009:31–8.

26. Associated symptoms
Anaemia: lethargy, shortness of breath, palpitations
Thyroid dysfunction: changes in weight, cold intolerance, fatigue, constipation
Androgen excess: acne, hirsutism
Pituitary adenomas/prolactinomas: galactorrhoea, headache, visual field disturbances
Bleeding disorders: easy bruising
Hypothalamic suppression: weight loss, excessive exercise, stress
Malignancy: bloating, unexplained weight loss

27. 2.Examination Vital signs
General examination - focus on etiology of AUB
(?obesity/hirsutism/thyroid/galactorrhea/anorexia…)
Abdominal examination - ?mass
Pelvic examination - ? uterine bleeding
PAP smear/STI

28. 3.Investigating AUB Type of test Laboratory
Essential: full blood count, β-HCG, Fe, TFT
Suggested: Coags, Prolactin, FSH/LH/E2/luteal P4, Androgens, SHBG,EUC/LFT, Chlamydia
Physical
Swab (for STI's)
Pap test
Imaging
Essential:Transvaginal ultrasound (TVUS)
Possible: Saline sonogram,Hysteroscopy or MRI
A full blood count test should be carried out on all women with HMB. This should be done in parallel with any AUB treatment offered.1
Testing for von Willebrand’s disease is recommended in women who have had AUB since menarche and personal or family history suggesting a coagulation disorder.1
Note: Speaker to make reference to the National Cervical Screening Program if they think it is appropriate and can use the next hidden slide to aid discussion if there is interest from the audience.
Note to speaker regarding swabs: can acknowledge sensitivity and difficulty of GPs telling certain patients that they are testing for STIs. Routine practice/investigation for gynaecologists.
Reference:
Shaw JA. Medscape, Jan 18, Available at: Accessed July 2014.

29. Management of Abnormal Uterine Bleeding
Tim Chang MBBS(SYD), FRANZCOG Gynaecologist, Endoscopic surgeon and IVF Fertility specialist
139 Dumaresq street
Campbelltown

30. Treatment of AUB Medical Mirena Surgical Estrogens OCP Progestins
Antifibrinolytics
NSAIDs
Androgens
GnRHa
Mirena
Surgical
Hysteroscopic surgery
Endometrial ablation
Hysterectomy
Others eg myomectomy
Remember iron therapy

31. Estrogens Acute bleeding high dose estrogen effect BTB
IV premarin 25mg every 6 hours
PO progynova 4mg qid
BTB
PO progynova 4mg bd for 2-3 weeks

32. OCP Acute bleeding Chronic AUB M50 2 tablets bd until bleeding stops
Reduces MBL 50%
Limited studies as effective danazol / NSAIDs in reducing MBL
Less effective than mirena with higher treatment failures
Monophasic high progestin content tailor to patient SE profile
Dienogest containing OCP for endometriosis

33. OCP and thromboembolism
OCP increase risk TE highest first 12 months
Suggested 3rd generation / cyperoterone / drosperinone has increased risk (x2)
Absolute risks remain small
Risk TE pregnancy x3-5 higher than OCP use
Conflicting studies on whether 3rd generation OCP have higher risk TE. Did the studies take in to consideration confounding factors eg obesity PCOS and preferentially prescribed cyperoterone

34. OCP and thromboembolism
Incidence thromboembolism
Non OCP use
1 in 10,000
2nd generation OCP
1 in 5000
3rd generation OCP
1 in 3000
Pregnancy
1 in 1000
Composite data personally derived

35. OCP and thromboembolism
High risk factors
Personal hx TE or family hx
Obesity
Smoker
Age
Ideally commence on 2nd generation OCP
If SE counsel use 3rd generation OCP

36. NB luteal phase progesterone NOT effective
Progestins
Acute bleeding
Useful if anovulatory and basalis not denuded
Primolut 10mg tds
Chronic AUB
Useful in AUB-O
50% reduction MBL
1/3 stop therapy at 6 months mainly SE
Either continous or cyclic 3/4 weeks eg 5-26
NB luteal phase progesterone NOT effective

37. Mirena reduction MBL 80-95% by 12 months
erratic spotting / BTB with up to 55% in the first 6 months, but only 20% BTB at 12 months
20% amenorrhoeic at 12 months and 50% at 5 years
65% patients with Mirena declined hysterectomy after insertion vs 15% on medical therapy
SE in 20% leading to discontinuation in 1st year eg bloating mastalgia, BTB, ovarian cysts
5-10% expulsion rate
perforation 1-2/1000
Mirena revolutionised treatment of AUB
Led significant reduction surgical treatments for AUB..a concern for procedural gynaecologists

38. Mirena Fibroids Adenomyosis
Can be used in fibroids, although expect lower success rate.
Soysal et al in non randomized study of mirena with SM fibroids (type II <5cm or type 0/I <3cm) had reduction MBL 90% at 12 months with 5% expulsion rate.
Adenomyosis
reduce dysmenorrhea
uterine volume
likely reduce HMB

39. Antifibrinolytics Cyklokapron 500mg 2 tab qid from onset Useful AUB -E
Reduction MBL 50% SE
Nausea, vomiting + diarrhoea
Thrombosis (theoretical) small studies show safe in women previous DVT

40. NSAIDs Useful in AUB-E with other medical therapies Dysmenorrhoea
Reduction MBL 25%
Given onset menses for the period

41. Surgical treatments 15-58% end up with surgical treatment Indications:
Failed medical therapy
SE medical therapy
No desire fertility (except myomectomy)
Patient / surgeon choice

42. Surgical treatments AUB
Hysteroscopic surgery
Endometrial ablation (non hysteroscopic)
Hysterectomy
Vaginal
Laparoscopic
Abdominal
Robotic

43. Hysteroscopic surgery
Roller ball ablation
Endometrial resection
Polypectomy
Myomectomy
Electosurgical
Mechanical

44. NREA Less skill required Quicker Less complications
Higher equipment failure
Limited normal cavities
Novasure most commonly used australia
Uses bipolar radiofrequency electrical energy delivered through mesh array (7.2mm) to ablate tissue to resistance 50 ohms with depth ablation 5mm with vacuum suction.

45. REA vs NREA NSD MBL, amenorrhoea rates, patient satisfaction rates
NREA less OT time,
perforation (OR 0.32)
fluid overload (OR 0.17)
cervical laceration ( 0.22)
haematometra (0.31)
NREA had higher equipment failure

46. Before and after ablation

47. Hysterectomy Guaranteed amenorrhoea with high satisfaction rates
Some serious complications
Vaginal hysterectomy ideal, but if not feasible, laparoscopic preferable over laparotomy.
Trend to performing prophylactic bilateral salpingectomy for ovarian cancer

48. Clinical scenarios adolescent reproductive age woman perimenopausal
postmenopausal
acute vaginal bleeding
Intermenstrual bleeding

49. Adolescent Commonly AUB-O Exclude coagulopathy / STI
Rarely intrauterine pathology
Medical therapy
OCP
Progestins
Cyklokapron
NSAIDs
Mirena
If normal US no need for D&C

50. Reproductive age Commonly AUB E US to exclude pathology
Medical therapy
Mirena

51. Perimenopausal AUB Often AUB O Exclude pathology including cancer
Hysteroscopy
Treatment
Medical
Mirena
Ablation
Hysterectomy

52. Postmenopausal Pathology Atrophic endometrium 60% Endometrial cancer
10%
Hyperplasia
15%
Polyps
Others eg sarcoma, trauma etc 5%
HRT use

53. Endometrial cancer average thickness 21mm
Ultrasound
Cut of mm in PMB
Incidence cancer
≤ 3mm
4/1000
≤ 4mm
12/1000
≤ 5mm
23/1000
Endometrial cancer average thickness 21mm

54. Hysteroscopy + sampling
Endometrial thickness >3-5mm
Persistent PMB despite thin endometrium

55. Conclusions AUB common condition encountered by the GP
Woman’s perception important
FIGO classification
Treatment based on age groups
Individualize therapy

56. Case study 1
Anna, aged 17 years

57. How would you assess and manage this patient?
Anna, aged 17 years
Presents with heavy and irregular menstrual bleeding and fatigue
Sexually active > 2 yrs, but not in stable relationship
Uses condomes
Differential diagnosis at this early stage:
Pelvic inflammatory disease
Polycystic ovarian syndrome (PCOS).
How would you assess and manage this patient?

58. Assessment History: Menarche 13yrs
Irregular heavy periods since menarche
Fatigue recently
Nil obvious bleeding disorder
Nil family Hx
Nil meds
Sexually active

59. Assessment and initial management
Physical tests:
Pap test
Swab for STIs + Chlamydia PCR
Laboratory tests:
Full blood count, Fe studies
β-HCG
Coag.profile, TSH
Ultrasound TV
Initiate acute management while awaiting results:
Tranexamic acid 1g qid
NSAIDs 2 tablets, 3-4 times a day
( both on days 1–2 of menses)
Results come back negative for chlamydia, but iron deficiency anaemia, U/S nad

60. Management (AUB – O) Most likely anovulatory HMB Immature HPO – axis
Only 56% ovulatory within 4 yrs after menarche
Treatment:
Iron supplementation
Start OCP as sexually active
Explain SE + VTE risk
Awareness STIs
Consider LNG- IUD if SE from OCP
F/U in 3-6/12

61. Case study 2
Priya, aged 32 years

62. What is in your differential diagnosis at this stage?
Priya, aged 32 years
Presents with HMB that is irregular in timing
Overweight (BMI 27 kg/m2)
Hirsutism
Acne
Three children
Family history of type 2 diabetes
Differential diagnosis:
PCOS (investigate serology for androgens)
Uterine fibroid
Endometriosis.
What is in your differential diagnosis at this stage?

63. Patient assessment Laboratory tests: Full blood count β-HCG
Androgen profile through SHBG, FAI and testosterone
Physical tests:
TVUS
Pap test
Swab for STIs
Consider Rotterdam Criteria
For diagnosis of PCOS under the Rotterdam Criteria, two of the following conditions need be met:1
oligo/anovulation
hyperandrogenism: clinical (hirsutism, or less commonly male pattern alopecia) or biochemical (raised FAI or free testosterone)
polycystic ovaries on ultrasound (“string of pearls”).
Patients may not complain to their GP about missed periods. However, anovulation is associated with an increased risk of endometrial cancer so it is Importance to detect this type of AUB (AUB-O) and treat it accordingly.2
References:
Boyle J, Teede HJ. Aust Fam Physician 2012;41:752–6.
Sweet MG et al. Am Fam Physician 2012;85:35–43.

64. Assessment findings
Androgen profile consistent with PCOS and insulin resistance (without diabetes):
TV US positive for submucous (SM) fibroid
                                       
Result
Units
Range
Testosterone
1.4
nmol/L
( )
SHBG      
23*
(30-110)
FAI
6.1* %
( )
A "rim" around the ovaries also detected. Known as a "string of pearls”, this is indicative of PCOS.
Although structurally identifiable, "string of pearls” is not included in "structural" "PALM section of "PALM-COEIN" as it is not a "structural" abnormality of the the uterine cavity.
Had patient been identified as having diabetes, referral to an endocrinologist would have been appropriate.

65. Treatment approach
Lifestyle change (5–10% weight loss + structured exercise)
Combined oral contraceptive pill
Low oestrogen doses e.g. 20 µg may have less impact on insulinresistance
Cyclic progestins
E.g. 10 mg medroxyprogesterone acetate 10–14 days every 2–3 /12
Metformin ?
Improves ovulation and menstrual cyclicity
Monitor insulin resistance
Refer to Ob/Gyn for SM fibroid
? hysteroscopic resection

66. Case study 3
Lilly, aged 45 years

67. How would you assess the patient?
Lilly, aged 45 years
Mother of two children, aged 6 and 8
Presents complaining of heavy menstrual bleeding that is interfering with many aspects of her everyday life
How would you assess the patient?

68. Patient history Changing protection every hour Cycle timing normal
Previously tried hormonal therapy and was unhappy with efficacy and side effects
Doesn’t want any more children
Had tubal ligation at time of C-section for second and final child

69. Patient assessment Laboratory tests: Full blood count β-HCG Fe
Physical tests:
TVUS
Pap test
Swab for STIs
Results:
All laboratory and physical tests are unremarkable
TVUS shows normal cavity with no structural issues
AUB-E, "endometrial" diagnosis, is arrived at by a "diagnosis of exclusion" where no other structural or histological cause may be found.1
Reference:
Munro MG et al. Int J Gynaecol Obstet 2011;113:3–13.
The patient is advised of potential endometrial disorder and treatment options, and referred to a gynaecologist

70. Endometrial biopsy in women with AUB:
Age > 40
Failure of medical treatment
Riskfactors for endometrial cancer
(Age,Obesity,Nullip.,Diabetes,PCOS,HNPCC)
Significant intermenstrual bleeding
Women with infrequent menses suggestive of anovulatory cycles

71. Effectiveness of current management approaches in reducing bleeding to normal levels or lower
Endometrial ablation*
Hormone therapy
Hysterectomy
Lilly previously tried hormonal therapy and was unhappy with efficacy and side effects.
Oral contraceptive pill reduces bleeding in less than half of patients with 77% eventually seeking surgery
Hormone-releasing IUD associated with 39% efficacy after 5 years for controlling heavy bleeding with 42% of patients undergoing a hysterectomy within 5 years
*Radiofrequency electrosurgery.

72. Lilly is considering endometrial ablation after Hysteroscopy,D&C
Destroys a thin layer of the lining of the uterus and reduces the menstrual flow in the majority of women
Menstrual flow completely stops in ~50% of women
Provides a non-hormonal option in women who have completed their family
Lilly is keen to avoid a hysterectomy due to the recovery time and a desire to avoid major surgery.
In the majority of cases in Australia, histological sampling of the endometrium occurs just prior to ablation and hysterectomy is performed if cancer is detected.

73. When to refer patients to a specialist
For further assessment to rule out possible causes, and or treat specific pathologies i.e. myomas, polyps, congenital abnormalities and malignancies
After failure of conservative management
At patient request following initial discussion of treatment options
Where the GP has concerns regarding the presentation

74. Thank YOU!