Post on 07-May-2015
EVIDENCE BASED MEDICAL MANAGEMENT OF AUB-
DIFFERENT OPTIONS
DR NEETA DHABHAIFARIDABAD
How do you know if one treatment will work better than another, or if it will do more harm than good?“
Do I have the required skill?
What are my client/patient’s expectations?
EBM TRIAD
Medication should be tailored to …...
Achieve Individual therapeutic goals- control bleeding
Contraception
Underlying medical conditions
Tolerable side effects
“Improve Quality of life” (NICE guidelines)
Non-hormonal Non-steroidal anti-inflammatory drugs AntifibrinolyticsHormonal Combined hormonal contraceptives Levonorgestrel-releasing intrauterine system Oral progestins (long phase, days 5 to 26) Depot-medroxyprogesterone acetate Danazol GnRH-agonists Ormilexifene Desmopressin
Newer Options Modified Release Tranexamic
acid(3.9gm) Quadriphasic COC-Estradiol
valerate and Dienogest Vaginal Danazol
Lifestyle Intervention Alternative Medicine
LNG- IUS 1st line treatment of AUB NICE Guidelines 2007, Magon et al April 2013,Midlife journal
review article-
Medical therapy vs Surgery Lng as effective as Surgery in improving QOL at 1 yr
Marjori banks et al Cochrane database syst review 2006 &Meta analysis of 6 RCTs Obstet & Gynecol 2009
Progestin IUS system ,an alternative to Endo ablation
SOGC May 2013 . LNG IUS better than other Medical therapy Lng had
better outcome 64%vs 38% Gupta et al, N Eng J of Med, 2013(571 women over 2 yrs)
Other uses
Stage 1 Endometrial cancer Women on Tamoxifen for Breast cancer Fibroids Adenomyosis
Contraindications Pregnancy. Recent sexually transmitted infection (STI), unless fully
investigated and treated. Undiagnosed uterine or vaginal bleeding. Distorted or small uterine cavity. Genital malignancy. Active trophoblastic disease. Pelvic inflammatory disease. Marked immunosuppression. Current deep vein thrombosis (DVT) or pulmonary embolus
(PE). Ischaemic heart disease. Active viral hepatitis, severe decompensated cirrhosis,
benign liver tumours or malignant hepatomas. Breast cancer within the preceding 5 years.
Limiting Factors………
Expertise in Insertion technique
Counselling
Cost
TRANEXAMIC ACID -2nd line treatment for AUB NICE guidelines 2007 Blood loss decreased by 34-
54%,QOL-46-83% vs Norethisterone Naolou et al 2012, Cochrane Syst review of 10
studies (RCT,Cohort &Obsevational) No effect on duration of bleeding MR/ER formulation Less GI effects
Better option for cyclic bleeding (1st -5th day-)
Dose 1.5gm3-4 times a day
Adverse effects- are rare › Nausea, Vomiting & Diarrhea, Allergy and
occasionally an Orthostatic reaction.› Increased thrombotic tendency, like deep
vein thrombosis, during prolonged treatment as with any fibrinolysis inhibitors.
Contraindications: -› Severe renal insufficiency› Active intravascular clotting › Thrombo embolic disease › Colour vision disordersAnnals of Pharmacotherapy 2012-Sandra L
Hrometz
Use with caution
Elderly Children under 15 years of age
Ormilexifene-SERM Legally available only in India Reduces blood loss and Et by 85-97.7 %Double Blind RCT, 350 women(JSAFOG) April
2011,compared Ormilexifene with MPA Jyotsana etal JLN Med College Belgaun
Side effects –Headaches,GI upsets,Ovarian cyst ,cx erosion , Amenorrhea
Avoid in Liver, Renal,PCOS ,chr CervicitisEfficacy & Safety Neha Agarwal & Saroj
Singh(IOSR-JPBS)Mar 2013, 60 women,assesed at 3 and 6 mths of therapy, no major side effects
Cost effective, convinient dosage, quick acting,given at any age group,protective to breast and endometrium
Used for Contraception,treatment of Mastalgia and fibroadenoma breast
More RCTs required
NSAIDs More effective than Placebo in reduction of MBL
but less than Tx acid and LNG-IUS, no individual variations among NSAIDs &comparable to oral COCs and Prog
Jan 2013 Review of Cochrane database-18 RCTs –Lethaby et al.
Reduce blood loss by 20-30% Reduce Dysmenorrhea by 70%John Bonnar RCT of ethamsylate ,Mefenamic acid
& Tx acid If no relief stop treatment after 3 months Start a day before menses and cont for 3-5 days NICE Guidelines 2007,SOGC 2013
Progesterone Oral Luteal phase
progesterone does not produce significant benefit!
Extended regimen (5-26 dys) NET 5mg tds, comparable in efficacy to LNG-IUS limited only by side effects
(BJOG 1998;105:592–8) SOGC 2013
Injectable DMPA though used practically but no published trials in AUB!
Combined oral and Injectable Dmpa stopped bleeding in 2.6 days
UCLA Medical Center in Torrance UCLA- AM J of Obstet &Gynecol, 2013
CHCs Novel quadriphasic Estradiol Valerate (3-
2-1mg) + Dienogest(2-3mg) 28 day pillBetter cycle control,strict regimen,complex instrMBL decrease by 88% by 7th cycle (comp to LNG
IUS) Fraser et al 2011,-Pooled analysis of 2 RCTs Reasonable choice to reduce and control
blood loss (ACOG Practice Bulletin 2010) More likely benefit for Anovulatory bleeding COC s can cause AUB- Cochrane Systemic Review 2009
Overall reduce blood loss by 44-50%
Contraceptive patch and vaginal ring reduce blood loss in normally mensturatingwomen
Used in women desiring contraceptionSOGC May 2013 I-A
Vaginal Danazol
Does not effect HPO axis Direct effect on the Endometrial cells-DNA
synthesis High uterine and Ovarian conc Vaginal irritation ,only adverse effect Significant reduction in
MBL,Dysmenorrhea,Dyspaerunia
Danazol in cases of failed medical therapy or CI to surgery SOGC 2013
Luisi etal –Siena Italy -Fertil Steril 2009 (Am Society for reproductive medicine 2009)
“Vaginal Danazol for Menorrhagia”Prospective study in 55women aged 25-35 with
menorrhagia,200mg /day vaginal Danazol for 6 mths.Evaluation parameters- Visual Analogue scale,
Serum chemistry,TVS ,Hystersopy with biopsyResults -90% had reduction in blood flow after 3
mths,no change in Serum chemistry,no adverse effects
GnRH Used to achieve short term relief
from abnormal bleedingMedscape July 15, 2013, Millie A Behera,
Patients receiving a gonadotropin-releasing hormone agonist for longer than 6 months should be prescribed add-back hormone therapy, if not already initiated with gonadotropin-re
Desmopressin
Indicated in patients with thromboembolic disorders.
Has been used to treat abnormal uterine bleeding in patients with coagulation defects.
Transiently elevates factor VIII and von Willebrand factor-
Medscape July 15th 2013
Behaviour & Lifestyle Interventions
Prevent Obesity,Diabetes,Pcos
Help in risk correction
Improve mood,stress
Primary Care Management of AUB
ALTERNATIVE MEDICINE
Chinese Herbal Medicine for Dysfunctional Uterine Bleeding: a Meta-analysisof trials copared Chinese with Western Medicine Tu et al., 2009
Poor quality trial,but showed comparative efficacy, more RCTs needed
“There is no other organ quite like the uterus. If men had such an organ they would brag about it. So should we”
― Ina May Gaskin
THANKYOU