LNG IUSROLE IN AUB DR. JYOTI BHASKAR Dr Sharda Jain

1. LNG IUS
ROLE IN AUB
DR. JYOTI BHASKAR
Dr Sharda Jain

2. And So Is Gynaeclogy

3. AUB CHOICES
SURGICAL
MEDICAL
MY CHOICE

4. PEERS
OBSERVATION
MY
EXPERIENCE
EVIDENCE
AND
GUIDELINES

5. KNOW THE LNG IUS
• Progestin releasing
intrauterine system
• T shaped polyethylene
frame
• Contains 52 mg
levonorgestrel
• Releases 20 µg LNG daily

6. Indications
Contraception
LARC
Efficacy similar to
Sterilisation
Treatment of heavy
menstrual bleeding
Protection from
endometrial hyperplasia
during oestrogen
replacement therapy

7. LNG IUS-Pharmacokinetics
7
The semipermeable membrane surrounding the steroid
reservoir of LNG IUS releases levonorgestrel at the rate of
20 mg/day into the uterine cavity.1
There are detectable levels of LNG in plasma within 15
min, and maximum levels are achieved after a few hours
Steady and constant plasma concentration of progestin with
LNG IUS as compared to oral contraceptives2-5
Plasma levels of LNG are very low – lower than those seen
with the levonorgestrel implant Norplant, the mini pill and the
combined pill.(100-200 picograms/ml)
1. Xiao B, Zhou L, et al. Contraception 1990; 41: 353-361; 2. Diaz S et al. Contraception 1987; 35: 551-567; 3. Kuhnz W, Contraception
1992; 45: 455-469. 4. Nilsson CG, et al. Clinical Endocrinology 1982; 17(6): 529-360; 5. Lahteenmaki P. Leiras Clinical Study Report 1991,
No 1207.

8. LNG IUS
IN AUB

9. HOW DOES IT ACT?
• Changes in endometrial morphology
• In contrast to the relatively low plasma levels, the LNG-
IUS achieves high concentrations of LNG in the
endometrium and adjacent tissues.
• A small study that examined tissue concentrations found
the average level of LNG in the endometrium to be
approximately 808 ng/g in users of a prototype LNG-IUS
that released 30 μg /day compared with 3.5 ng/g in a
group of women taking oral contraceptive pills containing
250 μg LNG

10. Changes in Endometrium
• Within 2 to 3 weeks after insertion local LNG concentration
leads to decidualization of stroma, mucosal thinning and an
inactive endometrium
• A foreign body reaction is characterized by in inflammatory
cells including Neutrophils, Lymphocytes & macrophages.
These endometrial changes are finalized in first 3 month
after insertion of IUS use.

11. WHY LNG IUS?
• Patient Satisfaction
• Comparison with other techniques
• AUB Indications
• Cost Effective

12. Significant reduction in mean blood loss and increase in
serum hemoglobin levels

13. Reduction of Bleeding & Dysmenorrhoea
with LNG IUS
– LNG IUS significantly reduces menstrual blood loss and alleviates
dysmenorrhoea from as early as 3 months after placement
P
a
g
e
1
3
Yoo HJ, et al. Arch Gynecol Obstet 2012; 285: 161–6.
Pictorialbloodlossscore
200
150
0
50
Baseline 3 6 12
Duration of LNG IUS use (months)
100
24
Subjectiveassessmentscore
ofdysmenorrhea
3.0
2.5
0
0.5
Baseline 3 6 12
Duration of LNG IUS use (months)
1.5
24
-59%
* * * *
*p<0.01 vs baseline
1.0
-79%-87%-87%-95%
-47%-54% -63%
* * * *
*p<0.01 vs baseline
2.0

14. Satisfaction with HMB treatment
Very satisfied Satisfied Indifferent Dissatisfied Missing*
Women(%)
60
50
20
10
0
40
30
Satisfaction with LNG IUS for heavy menstrual
bleeding
– Over 61% of women rate LNG IUS as ‘much better’ or
‘better’ than their previous HMB treatment
P
a
g
e
1
4
LNG IUS (n=437)
Conventional medical
treatment (n=135)**
**Hormonal treatment, antifibrinolytic treatment, or a combination of both
Ling Xu et al. Satisfaction and health-related quality of life in women with heavy menstrual bleeding; results from a non-interventional trial of the
levonorgestrel-releasing intrauterine system or conventional medical therapy. International Journal of Women’s Health. 27 May 2014.
*Women with no previous treatment history were recorded as ‘Missing’

15. LNG IUS vs other medical therapies for heavy menstrual
bleeding
LNG IUS is more effective than tranexamic acid, mefenamic acid, combined
oestrogen-progestogen, or progesterone alone in reducing the effect of HMB
on women’s daily life
P
a
g
e
1
5
80
60
20
0
40
LNG IUS
(n=225)
Practical
difficulties
Social
life
Psychological
health
Physical
health
Work/daily
routine
Family life/
relationships
Other
medical
treatments**
(n=208)
*p<0.001 vs LNG IUS®
* * * * * *
Proportionofwomen
freeofHMBsymptoms
(MenorrhagiaMulti-AttributeScale)(%)
More women using LNG IUS are free of HMB symptoms at 24 months
Gupta J, et al. N Engl J Med 2013; 368: 128–37.

16. Third-line treatmentFirst-line treatment Second-line treatment
Hysterectomy
Hysterectomy or repeat EA
Depends on previous treatment
80%
10%
10%
LNG IUS®
LNG IUS® or 2nd-generation EA
LNG IUS® or 2nd-generation EA
or hysterectomy
80%
10%
10%
2nd-generation EA
2nd-generation EA
or hysterectomy
Hysterectomy
60%
30%
10%
Healthcare professionals choose LNG IUS as first-line
therapy for heavy menstrual bleeding
– In a survey of minimal-access gynaecological surgeons
in the UK (N=10), the majority chose LNG IUS as first-
line therapy for HMB
P
a
g
e
1
6 Bhattacharya S, et al. Health Technol Assess 2011; 15(19).

17. WHY LNG IUS?
• Patient Satisfaction
• Comparison with other treatments
• AUB Indications
• Cost Effective
• Practical Tips

18. 0
-20
-40
-100
-60
-80
Changefrombaseline
inmenstrualbleeding(%)
LNG IUS® Flurbiprofen TXA
LNG IUS vs Tranexamic acid and Mefenamic acid
for heavy menstrual bleeding
LNG IUS is significantly more effective than flurbiprofen, TXA in
reducing menstrual blood loss in women with HMB1,2
P
a
g
e
1
8
-83%
-24%
-48%
*p<0.001, **p<0.01
*
**
MFA, mefenamic acid; TXA, tranexamic acid
Milsom I, et al. Am J Obstet Gynecol 1991; 164: 879–83; Reid PC & Virtanen-Kari S. BJOG 2005; 112: 1121–5.

19. LNG-IUS is better choice compared to Norethisterone for
treatment of DUB with better reduction in MBL and higher
satisfaction levelsNaqaish et al, J Ayub Med Coll Abbottabad. 2012;24(1):23-6. L.IN.MA.WH.02.2016.0746

20. INDIA: LNG-IUS vs. transcervical endometrial resection
After 1 year:
Hemoglobin conc.
increased 5.5% in the LNG-
IUS group and 5.2% in the
TCRE group
Satisfaction rates and AEs
similar in both
TCRE and LNG-IUS are equally effective
LNG-IUS placement requires less operator skill, entails no
operative hazards, device provides effective contraception
1. Gupta et al, Int J Gynaecol Obstet. 2006;95(3):261-6. L.IN.MA.WH.02.2016.0746

21. 6 months
24 months
12 months
Weighted mean difference
50-30-50 10-10 0 30
Overall PBAC score estimate (95% CI)
Favours endometrial ablationFavours LNG IUS
LNG IUS vs endometrial ablation for heavy
menstrual bleeding
– LNG IUS is equally effective as endometrial ablation in reducing
menstrual blood loss up to 2 years after treatment for HMB
P
a
g
e
2
3 Kaunitz AM, et al. Obstet Gynecol 2009; 113: 1104–16.
-31.96 (-65.96 to 2.04)
7.45 (-12.37 to 27.26)
-26.70 (-78.54 to 25.15)

22. Discountedtotalcosts(US$)
5000
4000
2000
1000
0
LNG IUS®
3000
Hysterectomy
Proportionofsatisfied/
verysatisfiedpatients(%)
100
80
40
20
0
LNG IUS®
60
Hysterectomy
LNG IUS as an alternative to hysterectomy for
heavy menstrual bleeding
Both LNG IUS and hysterectomy for HMB are associated with significant
improvements in HR-QoL and patient satisfaction over 5 years of follow-up.
Total healthcare cost was 40 % less with LNG IUS
Hurskainen R, et al. JAMA 2004; 291: 1456–63.

23. WHY LNG IUS?
• Patient Satisfaction
• Comparison with other treatments
• AUB Indications
• Cost Effective

24. AUB –M - Hyperplasia without atypia
AUB - A : women desirous of fertility but not immediate
conception & Women > 40 yrs and not desirous of fertility
AUB – L : ) Type III-VI leiomyoma in peri-menopausal women
AUB- O & E In women with ovulatory dysfunction and where
COCs are contraindicated or unwilling
AUB - I due to iatrogenic causes
AUB – P to multiple polyps after hysteroscopic polypectomy if
benign lesion on HPE:
AUB-N when women are not desirous of fertility
ONE STOP APPROACH

25. Current Clinical evidences-
(AUB-P)
In population based observational study (observation period- 6 months): it
has been suggested that Oral treatment is less effective compared to LNG-
IUS regarding the occurrence of endometrial polyps after six months.
LNG-IUS has been
proved to be
therapeutic for all
patients with
endometrial polyps
after six months’
therapy
MARIT ARNES1. Levonorgestrel-impregnated Intrauterine Device Reduces Occurrence of Hyperplastic
Polyps: A Population-based Follow-up Cohort Study. ANTICANCER RESEARCH 34: 2319-2324 (2014)

26. Current Clinical Evidence (AUB-A)
INDIA: Multicentric, retrospective, observational study . Efficacy and satisfaction of LNG
IUS in women >35 years. Most common diagnosis was adenomyosis and fibroids2
LNG IUS seems to be a viable and effective
treatment option for AUB in women after 35
years. There is a high rate of patient
satisfaction
1.Maia et al, J Am Assoc Gynecol Laparosc. 2003;10:512-6 ; 2. Mansukhani et al, J Midlife Health L.IN.MA.WH.02.2016.0746

27. Endometrial
Ablation
LNG
IUS
NO
Rx
No further Rx
Better
ammenorrhea rate
19 % second
Rx
Randomized study
Maia et al. 2003
LNG IUS
And
Endometrial
ablation
No other
method
more effective in the
reduction of bleeding at 3,
6 and 12 months
Pain Reduction
same
Zheng et
al. 2013
Insertion of LNG-IUS after endometrial
resection is effective treatment for
menorrhagia caused by adenomyosis and
has very few adverse effects

28. Current clinical evidences (AUB-L)
• LNG-IUS in women with myoma-related menorrhagia and idiopathic
menorrhagia1
LNG-IUS significantly
reduces mean uterine
volume in women
with menorrhagia,
and reduces MBL in
women with uterine
leiomyomas
1. Kriplani et al, Int J Gynaecol Obstet. 2012;116(1):35-8
L.IN.MA.WH.02.2016.0746

29. Relapse of hyperplasia after initial regression with conservative treatment
(LNG-IUS and oral progestogens1 and LNG-IUS vs. MPA, for 3 and 6 months2:
followed-up for 2 yrs)
Relapse of complex endometrial hyperplasia
after initial regression occurs often; less often
in women treated with LNG-IUS than with oral
progestogens
LNG-IUS is a reliable preference for
younger patients with endometrial
hyperplasia without atypia and wish
to preserve their uterus
1. Gallos et al, Hum Reprod. 2013 May;28(5):1231-6. 2. Dolapcioglu K et al, Clin Exp Obstet Gynecol.
2013;40(1):122-6
Current Clinical evidences (AUB-M)
L.IN.MA.WH.02.2016.0746

30. Current Clinical Evidences
(AUB-C)
 Prospective cohort study1
 Women with inherited bleeding disorders, previously undergone
unsuccessful medical treatment were followed up for nine months
after LNG-IUS insertion
 All women: periods improved
 56% women: Pictorial chart scores were lower, became
amenorrhoeic
 No reported side effects
The LNG-IUS is well tolerated and effective and improves
quality of life in
women with inherited bleeding disorders
1. Kingman et al, BJOG. 2004;111:1425–8. 2.

31. Current Clinical Evidences (AUB-I)
• Postmenopausal women on Tamoxifen (for 1 yr ):
LNG-IUS (1 yr)
– Uniform decidual response (by hysteroscopic
assessment)
– No new polyps
– 13% patients had fewer fibroids compared to controls
LNG-IUS has protective action against the
uterine effects of tamoxifen
1. Gardner et al, Lancet. 2000 Nov 18;356(9243):1711-7 L.IN.MA.WH.02.2016.0746

32. AUB –M - Hyperplasia without atypia
AUB - A : women desirous of fertility but not immediate
conception & Women > 40 yrs and not desirous of fertility
AUB – L : ) Type III-VI leiomyoma in peri-menopausal women
AUB- O & E In women with ovulatory dysfunction and where
COCs are contraindicated or unwilling
AUB - I due to iatrogenic causes
AUB – P to multiple polyps after hysteroscopic polypectomy if
benign lesion on HPE:
AUB-N when women are not desirous of fertility
ONE STOP APPROACH

33. Mirena is a new horizon
to your patient and yourself
BE BOLD, WALK ALONG NEW PATHS
EXPERIENCE IT YOURSELF