Bleeding and Associated Anomalies Evidence and Treatment Tamara N FullerEddins MD Assistant Clinical Professor Obstetrics and Gynecology University of South Dakota Sanford School of Medicine ID: 587186
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Abnormal Uterine Bleeding and Associated Anomalies:Evidence and Treatment
Tamara N. Fuller-Eddins, MD
Assistant Clinical Professor Obstetrics and Gynecology
University of South Dakota
Sanford School of MedicineSlide2
Disclosures
I have no financial relationship with a commercial entity producing health-related products and or servicesSlide3
ObjectivesAfter this lecture, the healthcare provider should be able to
Use the “new” classification system developed by the FIGO Menstrual Disorders Working Group to describe the symptoms and etiologies related to abnormal uterine bleeding (AUB)
Identify management options for abnormal uterine bleeding
Critically evaluate medical and surgical therapies for Abnormal Uterine Bleeding
and their associate anomalies as well as those not
caused by structural abnormalities or systemic etiologiesSlide4
Prevalence
Abnormal Uterine Bleeding
Alterations in the volume, amount or pattern of menstrual bleeding or blood flow
Estimated that AUB can affect 10%-35% of women
Most common group of gynecological disorders for which women seek care
Approximately 5%-10^ of women of reproductive age seek medical care for heavy bleeding
Oceans Womb by Ciska
Maie et al 1990 Prentice et al 1999, Lui et al 2007
Slide5
Why do we care about AUB?
Women with AUB are less likely to quantify their health as excellent or good
Women with significant AUB work an average of 3.6 weeks less per year than women without AUB
Average work loss from heavy bleeding is estimated to be $1692 per woman
Estimated total direct cost AUB $1-1.55 billion annually
Menorrhagia Healing by Barbara Bruch
Costs et al 2002, Cote et al 2003, Liu et al 2007Slide6
Confusing definitionsThe Menstrual Disorders Working Group FIGO developed a nomenclature and classification system to describe the symptoms and etiologies of AUB
Approved by the FIGO executive board and supported by ACOG
Simple symptom descriptions
Classification system for etiologies
Fraser and Sungurtekin 2000;
Fraser et al 2007, Munro et al 2011Slide7
Confusing definitionsTime for clarification…
Heavy Menstrual Bleeding
Irregular and Heavy Menstrual Bleeding
DUB should no longer be used as a symptoms, sign or diagnosis ( new ICD-10) will reflect this change
Replaced with more precise categories of etiology: AUB-E and AUB-O ( more to follow)Slide8
Simplified clarification system
Frequency
Frequent
Norma
Infrequent
Absent
< every 24 days
Q 24-38 days
Every 38 days
Regularity
Regular
Irregular
Variation +/- 2-20 days
Variation > 20 days
Duration
Prolonged
Normal
Shortened
8 days
4.5 to 8 days
< 4.5 days
Volume
Heavy
Normal
Light
80 mls per cycle
5-80 mls per cycle
< 5 mls per cycleSlide9
Volume??Traditionally, bleeding measured by volume of menstrual blood lost (> 80 mls)
Actual volume of MBL per cycle is not the main reason women seek medical attention
Heavy menstrual bleeding (HMB) is defined as excessive blood loss which interfere with a woman’s physical social, emotional and/or material quality of life. It can occur alone or in combination with other symptoms.
UK NICE GUIDELINES 2007Slide10
Abnormal Uterine Bleeding (AUB)
PALM Structural
Causes
Polyp
AUB-P
Adenomyosis
AUB-A
Leiomyoma's
AUB-L (Fibroids)
Malignancy
& hyperplasia
AUB-M
COEIN: Nonstructural
Causes
Coagulopathy
AUB-C
Ovulatory and Endometrial
AUB-O; AUB-E
Iatrogenic and Not classified
AUB-I; AUB-NSlide11
AUB-O DysfunctionHEAVY and IRREGULAR
Absent ovulation-no corpus lutuem-ovary does not produce progesterone
(Fragile vascular endometrium with insufficient stromal support)
Continued estrogen stimulation without progesterone stimulated withdrawal bleed
(As one are heals another begins bleeding)
(Erratic unpredictable non-cyclic bleeding with inconsistent volume)Slide12
AUB-E: Endometrial DysfunctionHEAVY AND IRREGULAR
Caused by local disturbances in endometrial function-deficiencies or excess of proteins that have an impact on coagulation
REDUCED LEVELS
Vasoconstrictors and Clotting Mechanisms
PG F@ alpha Endothelin-1
Tissue Factor pathwaySlide13
AUB treatment modalities
PALM
Treat structural problems you think are causing the bleeding
-Wide variety depends
on problem
AUB-O and AUB-E
LNG IUS
Oral Progestin
COC’s
NSAIDS
Trenexaminic
Acid
Endometrial Ablation
AUB-C
Refer to treatment
of the coagulopathy
AUB-I and AUB-N
Address the iatrogenic or other factor , may consider AUB-O and E treatment optionsSlide14
Treatment of AUB-O and AUB-EA small piece of the puzzle:
Other consideration: desire for future fertility, regional availability, contraindications or risk factors for adverse event costs, other treatments attemptedSlide15
Treatment of AUB-E and AUB-OEffectiveness varies from patient to patient based on acuity, women with ovulatory dysfunction, and women with anovulatory dysfunction
Studies can be difficult to compare and interpret, population not always clear
Most studies excluded women with irregular menses
Most studies included only women with > 80 mls MBLSlide16
Acute AUBThis is an episode of bleeding characterized by significant blood loss in a large quantity to warrant immediate intervention to prevent further blood lossSlide17
Case ScenarioA 40 yo GO non pregnant woman presents to ER with heavy vaginal bleeding for the past reported 12 days.
On examination her vitals are stable and you observer a moderate amount of bleeding. Her Hgb is 9 g/dl. She is a non-smoker and has an otherwise negative history.Slide18
Which of the following would not be the best first line treatment for this patient?
A. Dilation and Curettage
B. Conjugated equine estrogen 25mg IV q6 hours
C. Oral contraceptives TID x 1 week
D. Medroxyprogesterone acetate 20mg TID x 1 weeksSlide19
EstrogenUse of IV Premarin in the treatment of DUB –Double blind RCT of 34 women
Compared proportion of patients in whom bleeding stopped in response to either 25 mg IV conjugated equine estrogen or IV placebo
In 5 hours, Bleeding stopped in 72% of patients who received IV estrogen therapy and in 38% who received placebo
Devors et al 1982Slide20
COC Tapers/CascadesInitially based on expert opinion until RCT by Munro et al October 2006
Compared COC taper and oral progestin
16 women in COC group
95% avoided surgery in the next 28 days
Average 3 days to bleeding cessation
COC with 35 microgram E2/1mg norethindrone TID x 1 week then qd x 3 weeks
Munro et al 2006Slide21
Oral Progestin
Oral progestin arm of the Munro et al study
All 17 women in MPA group avoided unplanned surgical intervention
65% stopped bleeding at 1 month follow-up with a mean time of 3 days
Medroxyprogesterone acetate 20 mg po tid x 1 week daily x 3 weeks
Munro et al 2006Slide22
Tranexamic acidGiven its mechanism of action ( decreasing fibrinolysis) effective option for Acute AUB
Supported as a rx by experts both (PO and IV)
No studies for acute AUB
Shown to reduce intra-operative bleeding for orthopedic procedures
1.3 grams po tid x 5 days or 10 mg/hg IV q 8h for up to 5 days
James et al 2011; Alshyrda et al 2011
Lethaby et al 2000;Lukes et al 2010Slide23
Case scenarioA 28 yo G0 non-pregnant woman seeks treatment for her heavy irregular bleeding which has been unpredictable for the last few weeks. This patient has a normal baseline transvaginal ultrasound and normal pelvic exam. She has no medical problems.Slide24
Which of the following are not options for this patient’s bleeding?A. COC’s
B. Luteal phase progestin ( 10-14) d/cycles
C. LARC-IUDS
D. Trenexamic Acid
E. NSAID’SSlide25
Combination Oral Contraceptives
For AUB-O: May work by inhibiting the growth and development of the endometrium exogenously cycling hormones
Physiologically makes sense though evidence is limited
One RCT compared the efficacy of a triphasic combination COC’s in the treatment of women with irregular bleeding (some heavy, some not)
73.2% of COC group reported bleeding was improved (vs. 39.6% of placebo group)
Davis et al 2000
Cochrane Review by Hickey et al , updated 2009
Slide26
Levonorgestrel IUS-(MIRENA)Suppression of endometrial proliferation, inactive histology, thin endometrium and decidualization of stroma
Most studies only AUB-E
Excluded women with irregular menses suggestive of AUB-O
Probably a good chance for AUB-O as well given its mechanism of action
Magnon et al, 2013Slide27
Levonorgestrel IUS (MIRENA)
LNG-IUS reduces MBL by 715-95%
Most effective best tolerated non-surgical option for heavy and regular menstrual bleeding
Reduction in MBL same for LNG-IUS and extended cycle oral progestin
Patient satisfaction much less for oral progestin
More effective than COC’s, luteal phase oral progestin, DEPO MPA, NSAIDS
Matteson et al 2013, Lethabey et al updated 2009
Lee et al 2012, Endrikat et al 2009Slide28
NSAIDSLimited studies have shown NSAIDS effective in treating heavy and regular bleeding
No difference between NSAIDS in effectiveness (Naproxen, Mefenamic acid)
Less effective than tranexamic acid
Data limited comparing to luteal phase progestin, LNG IUS, COC’s
Cochrane Review by Lethaby et al updated 2009Slide29
Endometrial Ablation1
st
generation Resectoscopic
Rollerball
Transcervical endometrial resection
2
nd
generation; Non-
R
esectoscopic
Heated fluid (Hydrothermal Ablation)
Thermal Balloon ablation
Microwave
Cryotherapy
Radiofrequency bipolarSlide30
Global endometrial ablation
Most studies: only heavy and regular bleeding
Satisfaction: 50%-90%
Amenorrhea: 13%-64%
Failure rate: 8%-42%
No difference between resectoscopic and global methods in bleeding reduction and QOL
Matteson et al; 2012 Dickerson et al 2007, ACOG PB 2007
Penninx et al 2011; Cochrane review by Lethaby et al 2009Slide31
Success and Failure of AblationsPredictors of amenorrhea
> 45yo
Uterine length > 9 cm
Endometrial stripe < 4mm
Predictors of failure
< 45yo
Parity greater than or equal to 5
History of dysmenorrhea
El-Nashar et al 2009Slide32
Hysterectomy versus Ablation
Hysterectomy better
Bleeding reduction at 1 year
Satisfaction at 2 yrs post-op
Some evidence of improved health status
Ablation better
Surgery duration, hospital stay and recovery time
Most adverse events ( both major and minor)
Overall “costs” but not cost-effectiveness
Dickerson et al 2007; Cochrane review by Lethaby et al 2009Slide33
Summary PointsMust consider the etiology behind the patient’s heavy bleeding Some treatments:
Effective for irregular bleeding, not regular bleeding
Only studied for regular bleeding-but does that mean the WON’T work for irregular bleeding
Man studies only include patient with confirmed MBL > 80 mls
Research in this area by small sample size variety of comparison groups, limited number of studiesSlide34
Summary Points
Active AUB
IV estrogen, multiple pill regimens of progestin and COC;’s appear to be effective, TCS also effective
AUB-E-Heavy and regular
LNG IUS and ablation-most effective TX
Shown effective-COC’s, TXA, 21 day Progestin, NSAID’s
AUB-O Heavy and irregular
Cyclic COC’s, luteal phase progestin
Limited date on other treatments (most studies excluded irregular bleedersSlide35
Key referencesReferences listed on slides by author and year of publication
Key references to review:
Systematic Reviews
Clinical Guidelines on Heavy Menstrual Bleeding. National Institute of Clinical Excellence National Collaborating Centre for Women’s and Children’s Health 2007
Matteson KA, Rahn DD. Wheeler TL 2
nd
Siddiqui N. Casiano E. Harvey H. Marntik M, Sung VW. Balk EM. Society of Gynecologic Surgeons Systematic Review Group. A systematic review comparing hysterectomy with less-invasive treatments for abnormal uterine bleeding. J Minim Invasive Gynecol 2012 JAN 19 (1) 13-28Slide36
Key referencesSystematic reviews continued
Marjoribanks J. Lethaby A. Farquhar C. Surgery versus therapy for heavy menstrual bleeding. Cochrane Database if Systematic Reviews 2006 Issue 2. Art. No : CD003855 DQI 10. 1001/14651858. CD003855 pub2.
Lethaby A. Shepperd S. Farquhar C, Cooke I. Endometrial resection and ablation verus hysterectomy for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 1999 Issue 2 Art No CD000329 Doi: 10. 1002/14651858 CD000329.
Hickey M, Higham HM, Fraser I. Progestogens versus oestrogens and progestogens for irregular bleeding associated with anovulation. Cochrane Database of Systematic Reviews 2007, Issue 4 Art No: CD001895. DOI: 10. 1002/14651858. CD001895.pub2.
Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 1998 Ussye 4. Art NO: CD001016.DOI: 10. 1002/14651858 CD001016. (2)Slide37
Original Research
Lukes AS, Moore KA, Muse KN, Gersten JK, Hecht, BR, Edlunc M, et al Tranexamic acid treatment for heavy menstrual bleeding. ARCT Obstet Gynecol 2010, 116 (4) 865-75
Jensen JT, Parks S, Mellinger U, Machlitt A, Fraser IS. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogist. A RCT Obstet Gynecol 2011; 117(4) 777-87.
Munro, MG, Critchley HOD, Broder, MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in non gravid women of reproductive age. Int J Gynecol Obstet 113 (20110, 3-13.
Penninx
JP, Herman MC, Mol BW Bongers MY. Five-year follow-up after comparing bipolar endometrial ablation with hydrothermal ablation for menorrhagia. Obstet Gynecol 2011 DEC; 118(6) 1287-92