The document discusses the levonorgestrel intrauterine system (LNG-IUS) as a tool for managing abnormal uterine bleeding (AUB). It provides an overview of LNG-IUS, including its indications, dosage, mechanisms of action, comparative trials showing its effectiveness compared to other treatments, and side effects. The LNG-IUS is shown to significantly reduce heavy menstrual bleeding and improve quality of life more than other medical therapies. It is also more cost-effective than hysterectomy while providing similar patient satisfaction long-term. Expulsion rates are around 1 in 20 and perforation risk is 1 in 1000. The document discusses use of LNG-IUS in various types of AUB and its contraceptive benefits.

1. Dr Nupur Gupta
Department of Obstetrics & Gynecology
Levonorgestrel Intrauterine System(LNG-IUS):
An Emerging Tool In The Management of AUB

2. Abnormal Uterine Bleeding (AUB):
Spectrum of problem
Menarche to Menopause

3. Burden of AUB
Most common gynecological complaint
15% of all Gynae OPD visits &
25% of all Gynae surgeries
Affects QOL (social & personal)

4. WORLDWIDE SURVEY
 1 in 3 women experience Heavy Menstrual Bleeding (1)
 63% have IRON DEFICIENCY ANEMIA (2)
 83% say it impacts their DAILY LIFE (1)
 25% with anaemia recd multiple BLOOD TRANSFUSIONS (3)
Bitzer J et al Open Access J Contra 2013;4:21-8 (1)
Fraser I et al Prevalence of HMB & experiences of affected women 2015;128:196-200
Nelson AL et al S anemia from HMB requires heightened attention AJOG 2015;213(1):97.e1-6

5. Impact of AUB on Daily Life
Anxiety,
pscychological
Stress
Negative impact
on relationship
with partners
Pain &
Discomfort
Dec Work
Productivity
Iron Deficiency
Anemia

6. Management of AUB
Traditionally, hysterectomy (anatomical,
urological, sexual, psychological & emotional
sequaelae)
Modern Gynecology – conservative trends to
reduce costs & women’s desire to preserve their
uterus

7. Medical Management (Drug Therapy)
Oral Tablets
NSAIDS
Antifibrinolytic drugs (tranexemic acid)
Contraceptive pills
Progestins

8. Surgical Treatment
Endometrial ablation
TCRE (Transcervical Resection of Endometrium)
Hysterectomy
Conservative Surgical Treatment
 Progesterone Releasing Intrauterine Device (LNG-IUS)

9. PALM COEIN CLASSIFICATION (FIGO)
Etiopathogenesis Based
Nonstructural CausesStructural Causes

10. LNG-IUS: An Overview
Indications, dosage, MOA
Comparative Trials
Side Effects
T shaped polyethylene frame
Vertical stem has steroid reservoir & silicone
1.26 inch
height

11. Abnormal Uterine Bleeding
Contraception
During ERT (to protect against endometrial hyperplasia)
Endometriosis (not USFDA approved)
Indications

12. 52 mg progesterone
20 mcg per day (Release
rate after 5 years is 10 mcg)
Has similar efficacy as
sterilization
Dose

13. Mechanism of Action
Inhibits ovulation in 5 to 15% of cycles

14. Plasma concentration of progestin with LNG
IUS is steady & lower as compared to minipill,
OCPs & norplant
Levels reach between 100 – 200 pg/ml
LNG binds to SHBG in plasma
Pharmacokinetics

15. LNG-IUS in Menorrhagia (AUB-O)
95% Reduction in 2 years
Andersson JK & Rybo G. Br J Obstet Gynaecol 1990; 97: 690–4.

16. Effect on Ferritin & Hb Levels
Andersson JK & Rybo G. Br J Obstet Gynaecol 1990; 97: 690–4.

17. LNG IUS in Dysmenorrhea
From as early as 3 months after placement
Yoo HJ, et al. Arch Gynecol Obstet 2012; 285: 161–6.
63% reduction in 2 years

18. 0
-20
-40
-100
-60
-80
Changefrombaseline
inmenstrualbleeding(%)
LNG IUS Flurbiprofen TXA
0
-20
-40
-100
-60
-80
Changefrombaseline
inmenstrualbleeding(%) MFALNG IUS
LNG IUS vs tranexamic acid &
mefenamic acid
-83%
-24%
-48%
-90%
-22%
*p<0.001, **p<0.01
*
**
*
*p<0.001
Milsom I, et al. AJOG 1991; 164: 879–83;
Reid PC & Virtanen-Kari S. BJOG 2005; 112: 1121–5.
Menstrual Bleeding Reduction
N=25 each, 3 monthsN=35, 3 months

19. LNG IUS vs Antifibrinolytics
Tranexemic acid is more effective as compared to placebo,
NSAIDS, oral luteal progesterone, ethamsylate or herbal
remedies
LNG IUS is more effective

20. 100
80
60
0
40
20
Successwithtreatment(%)
MPALNG IUS
LNG-IUS vs MPA (6 months)
Kaunitz AM, et al. Obstet Gynecol 2010; 116: 625–32.
0
-20
-40
-100
-60
-80
Changefrombaseline
inmenstrualbleeding(%)
MPALNG IUS
-71%
-22%
*
*p<0.001
*
*p<0.001
84.8
22.2
Menstrual Bleeding Reduction Treatment Success
N=82, 6 months N=83, 6 months

21. MBL reduction & satisfaction (n=119)
-98
-80
-100
-90
-80
-70
-60
-50
-40
-30
-20
-10
0
LNG-IUS Norethisterone
%Reductioninbloodloss
90
20
0
10
20
30
40
50
60
70
80
90
100
LNG-IUS Norethisterone
%Patientswithtreatment
satisfaction
Naqaish et al, J Ayub Med
Coll Abbottabad.
2012;24(1):23-6.

22. LNG-IUS vs COCs
Shaaban MM et al., Levonorgestrel-releasing intrauterine system compared to low dose
combined oral contraceptive pills for idiopathic menorrhagia: a randomized clinical trial
Contraception. 2011;83(1):48–54
Menstrual Bleeding Reduction: More in LNG-IUS
86-87% vs 2.5 to 35%

23. LNG-IUS vs COCs
Greater reduction in HMB
Improved quality of life
More acceptable long term
Less adverse effects than oral therapy
LNG IUS is more effective

24. 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
Both are equally effective at 2 years
(6 RCTs & meta analysis)
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)
N=390
N=196 N=194

25. LNG-IUS vs Endometrial Ablation
Similar results (reduction in HMB or
satisfaction rates or QOL)
LNG IUS is more cost
effective

26. LNG-IUS vs other medical therapies
LNG IUS is more effective than tranexamic acid, mefenamic acid,
combined OCPs, or progesterone alone (At 24 months)
Gupta J, et al. N Engl J Med 2013; 368: 128–37.

27. Change in RAND-36 score over 5 years
50 10 15
General health
Emotional well-being
Physical functioning
Social functioning
Pain
Energy
Emotional role functioning
Physical role functioning
LNG-IUS Vs hysterectomy
Hurskainen R, et al. JAMA 2004; 291: 1456–63.
LNG IUS
Hysterectomy
*
*p<0.01 vs before treatment
*
**
**
*
**
*
*
**
*
After 5 years, the two groups did not differ substantially
in terms of Health Related Quality of Life
N= 236 (LNG 119, Hysterectomy 117)

28. Hurskainen R, et al. JAMA 2004; 291: 1456–63.
94 93
0
20
40
60
80
100
LNG IUS Hysterectomy
Proportionofsatisfied/
verysatisfiedpatients(%)
2817
4660
0
1000
2000
3000
4000
5000
LNG IUS Hysterectomy
Discountedtotalcosts(US$)
LNG-IUS as an alternative to hysterectomy
(satisfaction & cost)
•Satisfaction is same at 5 years of follow up,
•Total healthcare costs are approx 40% lower

29. LNG IUS vs Hysterectomy
LNG IUS is less effective than
hysterectomy in reducing HMB

30. Improves
dysmenorrhoea
LNG IUS in AUB-A (Adenomyosis)
Sheng et al Contraception 2009

31. LNG-IUS in AUB (L): myoma-related
menorrhagia & idiopathic menorrhagia
-86.8
-97.4 -97.4
-99.5 -99.5
-100
-90
-80
-70
1
month 1 year 2 years3 years4 years
%ReductionBloodloss
LNG-IUS significantly reduces
mean uterine volume in
women with menorrhagia, and
reduces MBL in women with
uterine leiomyomas
Kriplani A, Kulshrestha V, Agarwal N, et al, IJ GO 2012;116 (1):35-8

32. LNG IUS in Leiomyoma: Relative
Contraindication
Distorted uterine cavity
Submucus myoma
Upto 20% expulsion rate

33. LNG-IUS in Coagulation (Haemostatic disorders)
Improvement of menorrhagia - 68%
Chic et al Contraception 2011
Lukes AS et al Fertil Steril 2008

34. AUB-O (Ovulatory Dysfunction)
Etiology
 Polycystic ovaries
 Hypothyroidism
 Hyperprolactinemia
 Mental stress
 Obesity
 Anorexia
 Weight loss
 Extreme exercise
 Adolescence
 Menopausal transition

35. LNG IUS in AUB-E (Endometrial Hyperplasia) –
Relapse & success rate
13.7
30.3
0
5
10
15
20
25
30
35
LNG-IUS Oral
progestogen
Relapseofhyperplasia
%Patients
84
100
50
64
0
20
40
60
80
100
120
3 months 6 months
Treatmentsuccess
rate
LNG-IUS MPA
LNG-IUS is a reliable preference for younger patients with endometrial
hyperplasia without atypia and wish to preserve their uterus
Gallos et al, Hum Reprod. 2013 ;28(5):1231-6.
Dolapcioglu K et al, Clin Exp Obstet Gynecol. 2013 40 (1):
122-6

36. LNG IUS in Endometriosis Pain
Direct effect on the eutopic endometrium
Depletion of the E & P receptors
Inhibition of production of estrogen-induced growth factors
(an anti-proliferative effect, glandular atrophy &
decidualization)
Reduction of local vascular angiogenesis
Reduction in pelvic-vessel congestion
Increase in apoptosis, a reduction in peritoneal fluid
macrophage activity & cytokines

37. LNG IUS as a Contraceptive
 Long acting reversible contraceptive method
 Effective birth control without a daily pill
 Most effective low maintainence birth control option
 ESTROGEN free

38. LNG-IUS Vs CuT 380A
 Effect on menstruation & dysmenorrhoea
LNG IUS was more effective in improvement of
menstrual bleeding, dysmenorrhoea & Hb levels
Kelekci et al Contraception 2012

39. LNG IUS in Cardiovascular Disease
34 women, Japan
97% continuation rate in one year
Primary Outcome: frequency of cardiovascular &
gynecologic side effects
Secondary Outcome: changes in menstrual blood loss &
biomarkers (WBC count & the levels of CRP, Hb & brain
natriuretic peptide)
Ueda Y J Obstet Gynaecol Res. 2018 Sep 27

40. Counseling Pre insertion
 Altered bleeding for 3 to 6 months
 Amenorrhoea
 Leucorrhoea
 OPD procedure but sedation/GA if previous LSCS, anxious

41. Counseling Post insertion
Menstrual calender
FUP – one month, 4 months, yearly to check for thread
USG to R/o any ovarian cysts or incase of lost thread
Hb at 4 months

42. Side Effects of LNG-IUS
 Acne, headache
 Breast tenderness
 Nausea & bloating
 Weight gain (not enough studies)
 Ovarian cysts

43. Ovarian Cysts (12 per 1000)
A randomised trial investigated the occurrence of ovarian
cysts following LNG IUS or hysterectomy
LNG IUS group had a higher incidence at 6 months (17.5%
vs 3%) & 12 months (21.5% vs 8%)
Majortiy were asymptomatic & resolved spontaneously
If LNG IUS user complains of
abdominal pain, ovarian cyst must be
in your DD

44. Ectopic Pregnancy
Risk is very low

45. Pelvic Inflammatory Disease
<1% severe PID
No protection against STIs

46. Return to Fertility
Women can be reassured that the return to fertility is rapid
Pregnancy rate is 90 per 100 in the first year after removal
The mean time to pregnancy is 4 months after LNG-IUS
removal

47. Effect on Bone Mineral Density
No detrimental effect on bone mineral density

48. Expulsion/Perforation
Risk of expulsion is variable (one study: 1 in 20)
Risk of perforation is 1 in 1000

49. Continuation rate: 3 year study
 90.3% at 3 years
 97% alteration in menstrual pattern
 34% reduction in amount of bleeding
 17% have persistent spotting or intermenstrual bleeding
 56% temporary amenorrhoea
 29% after 2 weeks
 56% after 2 months
 69% after 6 months
 77% after 36 months
Baldaszti E et al Contraception 2003
Satisfaction rate (increases with duration of treatment)

50. Breastfeeding Mothers (New Moms)
Levels of LNG are low in breast milk (1% of daily dose in
each 600ml of milk)
So, can be recommended in women who are
breastfeeding or are >6 weeks postpartum
Risk of perforation is high

51. Difficult IUD insertion
Women who just had another IUD removed were more likely to
need cervical dilation for IUD insertion, because of spasm, pain
or shock
Narrow cervical os (stenotic cervix)
Tortuous cervical canal or extreme uterine flexion
Patient’s pain response
Previous Caesarean

52. Contraindications of LNG IUS
Pregnancy
UCL> 10cm, uterus >12 weeks
Submucus fibroid
Genital bleeding of unknown origin, Acute PID
Congenital or acquired uterine anomaly
Liver disease
Atypical endometrial hyperplasia
Endometrial or cervical malignancy or carcinoma breast

53. Contraindications contd…
Suspected cancer breast or uterus
Cancer sensitive to progesterone
Untreated pelvic infection
Serious pelvic infection in first 3 mths after a pregnancy
Can get infection easily (multiple sex partners, low
immunity, IV drug abuse)
Emergency contraception
Allergic to LNG, Silicone, BaSO4, silica

54. LNG-IUS: What’s New – SKYLA 13.5mg
 Average release rate 14 mcg per day (5mcg after 3 yrs)
 99% effective in pregnancy prevention for 3 yrs
 Approved in USA as a Contraceptive

55. LNG-IUS: What’s New- KYLEENA 19.5mg
 Average release rate 17.5 mcg per day (7.4mcg after 3 yrs)
 99% effective in pregnancy prevention for 5 yrs
 Approved in USA as a Contraceptive

56. My Experience
More than 100 insertions
One spontaneous expulsion
One lost thread (hysteroscopic removal)
Satisfaction rate is 93%
Cause for dissatisfaction : irregular spotting & bleeding
Used – multiple myeloma, multiple sclerosis, heart disease

57. Conclusion
It is an incredible nonsurgical alternative in treatment of
menorrhagia superior to medical treatment & hysterectomy
Effects are reversible
Excellent fertility-sparing device
Effective contraceptive
Efficacy in menstrual blood reduction is 80% by 4 months, 95%
by 1 year, and 100% by 2 yrs

58. Conclusion
Excellent patient satisfaction & compliance
Improves anemia
Safely used in obese patients
Alternative for women who have AUB & desire contraception
Safe in women who have undergone prior abdominal surgeries
such as Caesarean or myomectomy