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Role of LNG IUS in management of AUB (Levonorgestrel intrauterine system)
1. Role of LNG IUS in management of
AUB
(Levonorgestrel intrauterine system)
Presentations based on
FOGSI AUB GUIDELINES
L.IN.MA.WH.02.2016.0746
DGF
CME
15TH SEPTEMBER
2. DISCLAIMER
• Use of these slides is permitted only for the purpose of
scientific and educational presentations.
• While every reasonable effort has been made to ensure
accuracy of content, it is the responsibility of the
practitioner, relying on experience and knowledge of
the patient, to determine dosages and the best
treatment for each individual patient. DGF shall not
be responsible or in any way liable for the continued
accuracy &/or veracity of the information or for any
errors, omissions or inaccuracies or for any injury
and/or damage to persons or property arising from
relying on the information contained in the
presentation or otherwise.
3. What is LNG IUS ?
Long acting reversible
contraception (LARC)
Releases the progestogen
levonorgestrel (initial release
rate of 20 µg/day)
Efficacy similar to or even
better than Sterilization 1
Indications:
Contraception
Treatment of heavy menstrual
bleeding (idiopathic
menorrhagia)
Protection from endometrial
hyperplasia during oestrogen
replacement therapy
1. Trussel J. Contraceptive failure in the United States. Contraception 2004;70:89–96 •March 2016 •
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4. Mechanism of action of LNG IUS
LNG IUS acts via a combination of three main
actions:
1Lewis RA, et al. Contraception 2010; 82: 491–6.
• Thickening of the cervical
mucus, making it impenetrable
to sperm1
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5. Mechanism of action of LNG IUS
LNG IUS acts via a combination of three main
actions:
1Lewis RA, et al. Contraception 2010; 82: 491–6;
2Ortiz ME & Croxatto HB. Contraception 1987; 36: 37–53.
• Thickening of the cervical mucus,
making it impenetrable to sperm1
• Inhibition of sperm motility and
function inside the uterus and
fallopian tubes2
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6. • Thickening of the cervical mucus,
making it impenetrable to sperm1
Mechanism of action of LNG IUS
LNG IUS acts via a combination of three main
actions:
• Inhibition of sperm motility and
function inside the uterus and
fallopian tubes2
• Prevention of endometrial growth3
1Lewis RA, et al. Contraception 2010; 82: 491–6;
2Ortiz ME & Croxatto HB. Contraception 1987; 36: 37–53;
3Jones RL & Critchley HO. Hum Reprod 2000; 15(Suppl. 3): 162–72.
4Barbosa I, et al. Contraception 1990; 42: 51–66.
5Nilsson CG, et al. Fertil Steril 1984; 41: 52–5.
In some women, ovulation is also inhibited4,5
•March 2016 •
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7. Endometrial effects with LNG IUS
Before LNG IUS
Endometrial changes
Ovulation
Menstruation
Reduced
menstruation
After LNG IUS
Ovulation
•March 2016 •
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9. Menstrualbloodloss(mL)
200
150
0
100
50
3 monthsBaseline 6 months 12 months
Efficacy of LNG IUS for reducing
menstrual blood loss
LNG IUS significantly reduces menstrual blood loss from as
early as 3 months after placement
Andersson JK & Rybo G. Br J Obstet Gynaecol 1990; 97: 690–4.
24
15
5
-86% -91% -97%
*
*p<0.001 vs before LNG IUS® use
* *
HMB
>80 mL
176
9L.IN.MA.WH.01.2016.0710
10. 30
0
20
10
Meanserumferritin
concentration(µg/L)
Duration of LNG IUS use (months)
Baseline 3 126
150
140
110
100
130
120
Meanserumhaemoglobin
concentration(g/L)
Duration of LNG IUS use (months)
Baseline 3 126
Efficacy of LNG IUS for increasing
haemoglobin and ferritin levels
LNG IUS use is associated with a significant increase in levels of
serum haemoglobin and ferritin
Andersson JK & Rybo G. Br J Obstet Gynaecol 1990; 97: 690–4.
Not
assessed
*
*p<0.01 vs before LNG IUS use
*
**p<0.001 vs before LNG IUS use
**
128
132
138 139
15.3
17.6
28.8
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11. Numberofdays
20
10
5
0
15
30-day reference period
7 12Baseline 1 2 3 4 5 6 8 9 10 11
Bleeding patterns with LNG IUS for the
treatment of heavy menstrual bleeding
An initial increase in bleeding/spotting frequency, which rapidly
returns to baseline levels within 2 months and decreases further
thereafter, is seen in women using LNG IUS for HMB
Jensen J, et al. Contraception 2013; 87: 107–12.
Spotting increases after LNG IUS placement, and while gradually
declining over time, remains elevated compared with baseline
Bleeding
Spotting
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12. Reduction of dysmenorrhea with LNG IUS for
the treatment of heavy menstrual bleeding
LNG IUS significantly reduces menstrual blood loss and alleviates
dysmenorrhea from as early as 3 months after placement
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
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13. 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
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
68 70
59
50
65 62
39 41 41
37 39 40
Gupta J, et al. N Engl J Med 2013; 368: 128–37.
**Tranexamic acid, mefenamic acid, combined oestrogen-progestogen, or progesterone alone •March 2016 •
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14. 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 and mefenamic
acid for heavy menstrual bleeding
LNG IUS is significantly more effective than flurbiprofen, TXA and
MFA in reducing menstrual blood loss in women with HMB1,2
-83%
-24%
-48%
-90%
-22%
*p<0.001, **p<0.01
*
**
*
*p<0.001
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.
•March 2016 •
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15. 100
80
60
0
40
20
Successwithtreatment(%)
MPALNG IUS
LNG IUS vs medroxyprogesterone
acetate for heavy menstrual bleeding
LNG IUS is significantly more effective than MPA at reducing
menstrual blood loss in women with HMB and has a higher
likelihood of treatment success
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
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16. LNG IUS vs Low dose COC pills for treatment
of heavy menstrual bleeding
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
•March 2016 •
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17. 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
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)
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18. 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 as an alternative to hysterectomy for
heavy menstrual bleeding
Both LNG IUS and hysterectomy for HMB are associated with
significant improvements in HR-QoL over 5 years of follow-up
Hurskainen R, et al. JAMA 2004; 291: 1456–63.
LNG IUS
Hysterectomy
*
*p<0.01 vs before treatment
*
**
**
*
**
*
*
**
*
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19. LNG IUS as an alternative to hysterectomy for
heavy menstrual bleeding
While women are equally satisfied with both LNG IUS and
hysterectomy for HMB over 5 years of follow-up, total healthcare
costs are approximately 40% lower with LNG IUS®
Hurskainen R, et al. JAMA 2004; 291: 1456–63.
•March 2016 •
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$)
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20. Return to fertility after use of LNG IUS
LNG IUS is reversible contraceptive; with a rapid return of fertility after as shown by
normal contraception rates.
Time % Pregnancies
3 months 57%
6 months 72%
1 year 85%
2 years 93%
Time to Conception in Fertile Couples
(without contraception) 2
1. Speroff and Fritz. Clinical Gynecologic Endocrinology and Infertility. 7th edition.
2. Andersson K et al. Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T. Contraception 1992; 46: 575-584.
87%
80%
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21. Insertion of LNG-IUS after endometrial resection is effective
treatment for menorrhagia caused by adenomyosis and has very
few adverse effects
Open, randomized, observational study:
Efficacy of LNG-IUS vs. control in women with AUB-A (N=95)
Rate of amenorrhea after 1 year: significantly higher
19% women in control group had second procedure to control
bleeding Vs. none in the LNG-IUS group
Maia et al, J Am Assoc Gynecol Laparosc. 2003;10:512-6.
•March 2016 •
LNG IUS in AUB-A (Adenomyosis)
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22. INDIA: Multicentric, retrospective, observational study
Efficacy and satisfaction of LNG IUS in women >35 years
Most common diagnosis was adenomyosis and fibrosis
At 3 months: 15% women had heavy bleeding
At 6 months: 49.3% of women were asymptomatic
At 18 months: 27.5% had amenorrhea
Overall patient satisfaction was high, in ~80% subjects
Mansukhani et al, J Midlife Health. 2013;4:31-5.
•March 2016 •
LNG IUS in AUB-A (Adenomyosis)
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
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23. LNG-IUS in women with myoma-related
menorrhagia and idiopathic menorrhagia1
-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
1. Kriplani A, Kulshrestha V, Agarwal N, et al, Int J Gynaecol Obstet. 2012;116(1):35-8
•March 2016 •
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24. LNG IUS in AUB-E (Endometrial Hyperplasia)
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)
13.7
30.3
0
5
10
15
20
25
30
35
LNG-IUS Oral
progestogen
Relapseofhyperplasia
%Patients
Relapse of complex endometrial hyperplasia
after initial regression occurs often; less often
in women treated with LNG-IUS than with oral
progestogens
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
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
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25. • LNG-IUS vs Norethisterone in women with DUB
LNG-IUS is better choice compared to Norethisterone for treatment of DUB
with better reduction in MBL and higher satisfaction levels
-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. •March 2016 •
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26. A randomized clinical trial: LNG-IUS vs. low dose COC for idiopathic
menorrhagia
Using PBAC chart,
reduction in MBL more in
LNG-IUS group than COC
87
34.9
-10
10
30
50
70
90
LNG COC
%ReductioninMBL
Alkaline haematin method
LNG
COC
LNG-IUS is a more
effective therapy
for idiopathic menorrha
gia compared to COC
Shabaan et al, Contraception 2011;83:48–54
•March 2016 •
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27. 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
33.6
49.9
8.2 7.1
1.1
8.1
51.1
29.6
9.6
1.5
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’
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28. Safety-related clinical outcomes and
biomarkers in LNG IUS users
LNG IUS use appears to have no
clinically relevant effects on:
Bone mineral density
Cardiovascular risk markers
(e.g. blood pressure, lipid metabolism)
Metabolic parameters
(e.g. glucose tolerance, liver function)
Vaginal flora and cervical cytology
Gemzell-Danielsson K, et al. Acta Obstet Gynecol Scand 2011; 90: 1177–88.
In addition, LNG IUS use appears to:
• have no association with an increased risk of breast cancer in women under
50 years of age, based on two epidemiological studies
• have a neutral effect on sexual function
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29. Adverse Effects with LNG IUS
• The most commonly reported side effects with use of LNG IUS are menstrual
problems, lower abdominal pain, and other effects.
• The occurrence of adverse effects decreases markedly over time.
• Other adverse effects – enlarged follicles, uterine or cervical perforations,
risk of pelvic infection
Andersson K, et al. Contraception 1994; 49: 56–72.
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30. Summary
• LNG-IUS is recommended as first line use in the International guidelines.5,6
• LNG-IUS shows improvement across multiple domains of quality of life compared to other
medical treatments3,4
• Compared to other medical treatments, LNG-IUS shows greater decreases in menstrual
blood loss7,8
• LNG IUS significantly reduces menstrual blood loss and alleviates dysmenorrhea from as
early as 3 months after placement2,3,
• LNG IUS is the first-line therapeutic choice of many healthcare professionals for HMB8
1. Singh S, et al. SOGC Clinical Practice Guideline. J Obstet Gynaecol Can 2013;35(5 eSuppl):S1-S28 . 2.Andersson JK & Rybo G. Br J Obstet Gynaecol 1990; 97:
690–4; 3. Yoo HJ, et al. Arch Gynecol Obstet 2012; 285: 161–6; 4. Gupta J, et al. N Engl J Med 2013; 368: 128–37; 5. Milsom I, et al. Am J Obstet
Gynecol 1991; 164: 879–83; 6. Kaunitz AM, et al. Obstet Gynecol 2010; 116: 625–32; 7. Hurskainen R, et al. JAMA 2004; 291: 1456–63;
8. Bhattacharaya S, et al. Health Technol Assess 2011; 15(19).
•March 2016 •Page 30
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31. ADDRESS
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Morh Flyover, Delhi - 51
CONTACT US
9650588339
9599044257
011-22414049
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LNG IUS consists of a white or almost-white drug core reservoir covered by an opaque membrane, which is mounted on the vertical stem of a T-shaped polyethylene frame (the T-body). The reservoir consists of a cylinder, made of a mixture of LNG and silicone (polydimethylsiloxane elastomer), containing a
total of 52 mg LNG. The initial release rate is 20 µg per 24 h. The T-body is 32 mm in both the horizontal and vertical directions, and has a loop at one end of the vertical stem and two horizontal arms at the other end. The polyethylene of the T-body is compounded with barium sulphate, making it radio-opaque. Brown monofilament polyethylene removal threads are attached to the loop at the end of the vertical stem of the T-body. The vertical stem of LNG IUS® is loaded in the insertion tube at the tip of the inserter. LNG IUS® and its inserter are essentially free of visible impurities.
LNG is a well-established progestogen, used in both contraception and hormone-replacement therapy.
IUS, intrauterine system; LNG, levonorgestrel
The contraceptive and therapeutic effects of LNG IUS are mainly based on
three local effects of levonorgestrel in the uterus:
Thickening of the cervical mucus, making it impenetrable to sperm1,2,3
Inhibition of sperm motility and function inside the uterus and the fallopian tubes, preventing fertilisation4,5
Suppression of endometrial growth by making the endometrium unresponsive to oestrogen.6,7
A weak foreign-body reaction is also present,7,8 and in some women, ovulation is inhibited.1,9
Thickening of the cervical mucus accompanied by a decrease in mucus quality, which prevents endocervical sperm transport, is thought to be the principal mechanism underlying the contraceptive action of LNG IUS.3 The contraceptive effects of LNG IUS occur before conception, therefore it cannot be regarded as an abortifacient.5
References
Barbosa I, et al. Contraception 1990; 42: 51–66.
Jonsson B, et al. Contraception 1991; 43: 447–58.
Lewis RA, et al. Contraception 2010; 82: 491–6.
Ortiz ME & Croxatto HB. Contraception 1987; 36: 37–53.
Videla-Rivero L, et al. Contraception 1987; 36: 217–26.
Jones RL & Critchley HO. Hum Reprod 2000; 15(Suppl. 3): 162–72.
Silverberg SG, et al. Int J Gynecol Pathol 1986; 5: 235–41.
Phillips V, et al. J Clin Pathol 2003; 56: 305–7.
Nilsson CG, et al. Fertil Steril 1984; 41: 52–5.
The contraceptive and therapeutic effects of LNG IUS are mainly based on
three local effects of levonorgestrel in the uterus:
Thickening of the cervical mucus, making it impenetrable to sperm1,2,3
Inhibition of sperm motility and function inside the uterus and the fallopian tubes, preventing fertilisation4,5
Suppression of endometrial growth by making the endometrium unresponsive to oestrogen.6,7
A weak foreign-body reaction is also present,7,8 and in some women, ovulation is inhibited.1,9
Thickening of the cervical mucus accompanied by a decrease in mucus quality, which prevents endocervical sperm transport, is thought to be the principal mechanism underlying the contraceptive action of LNG IUS.3 The contraceptive effects of LNG IUS occur before conception, therefore it cannot be regarded as an abortifacient.5
References
Barbosa I, et al. Contraception 1990; 42: 51–66.
Jonsson B, et al. Contraception 1991; 43: 447–58.
Lewis RA, et al. Contraception 2010; 82: 491–6.
Ortiz ME & Croxatto HB. Contraception 1987; 36: 37–53.
Videla-Rivero L, et al. Contraception 1987; 36: 217–26.
Jones RL & Critchley HO. Hum Reprod 2000; 15(Suppl. 3): 162–72.
Silverberg SG, et al. Int J Gynecol Pathol 1986; 5: 235–41.
Phillips V, et al. J Clin Pathol 2003; 56: 305–7.
Nilsson CG, et al. Fertil Steril 1984; 41: 52–5.
The contraceptive and therapeutic effects of LNG IUS are mainly based on
three local effects of levonorgestrel in the uterus:
Thickening of the cervical mucus, making it impenetrable to sperm1,2,3
Inhibition of sperm motility and function inside the uterus and the fallopian tubes, preventing fertilisation4,5
Suppression of endometrial growth by making the endometrium unresponsive to oestrogen.6,7
A weak foreign-body reaction is also present,7,8 and in some women, ovulation is inhibited.1,9
Thickening of the cervical mucus accompanied by a decrease in mucus quality, which prevents endocervical sperm transport, is thought to be the principal mechanism underlying the contraceptive action of LNG IUS.3 The contraceptive effects of LNG IUS occur before conception, therefore it cannot be regarded as an abortifacient.5
References
Barbosa I, et al. Contraception 1990; 42: 51–66.
Jonsson B, et al. Contraception 1991; 43: 447–58.
Lewis RA, et al. Contraception 2010; 82: 491–6.
Ortiz ME & Croxatto HB. Contraception 1987; 36: 37–53.
Videla-Rivero L, et al. Contraception 1987; 36: 217–26.
Jones RL & Critchley HO. Hum Reprod 2000; 15(Suppl. 3): 162–72.
Silverberg SG, et al. Int J Gynecol Pathol 1986; 5: 235–41.
Phillips V, et al. J Clin Pathol 2003; 56: 305–7.
Nilsson CG, et al. Fertil Steril 1984; 41: 52–5.
This figure shows the endometrial changes that occur with LNG IUS use, compared with the ‘normal’ cyclical changes observed without LNG IUS use.
LNG IUS induces profound morphological and biochemical changes in the endometrium, mainly as a result of the high endometrial levonorgestrel concentration. This downregulates endometrial oestrogen and progesterone receptors, making the endometrium insensitive to circulating oestradiol (thereby suppressing endometrial growth).1,2
After only a couple of months of LNG IUS use, the glands of the endometrium atrophy, the stroma becomes swollen and decidual, the mucosa thins and the epithelium becomes inactive. Vascular changes include a thickening of arterial walls, suppression of the spiral arterioles and capillary thrombosis.3 An inflammatory reaction characterised by an increase in neutrophils, lymphocytes,
plasma cells and macrophages is described3,4 and focal stromal necrosis may also occur.2,4
The endometrium becomes uniformly atrophic and suppressed within 3 menstrual cycles after LNG IUS placement,3 and persists in this thin, inactive state with no further histological development taking place over the long-term.2
The initial changes in the endometrium caused by LNG IUS may be associated with irregular bleeding or spotting, particularly in the first few months of treatment. With LNG IUS use, once the endometrial effects are established, bleeding becomes less in quantity than usual, or may cease altogether.
Following LNG IUS removal, the morphological changes in the endometrium revert to ‘normal’, and menstruation has been reported from as early as the first month afterwards.5
References
Pakarinen PI, et al. Hum Reprod 1998; 13: 1846–53.
Silverberg SG, et al. Int J Gynecol Pathol 1986; 5: 235–41.
Zhu PD, et al. Contraception 1989; 40: 425–38.
Phillips V, et al. J Clin Pathol 2003; 56: 305–7.
Nilsson CG & Lahteenmaki P. Contraception 1977; 15: 389–400.
In a study in parous women (N=20) with HMB (defined as menstrual blood loss
of ≥80 mL, determined by analysis of all used tampons/pads via the alkaline haematin method), aged ≤45 years with regular periods, no intermenstrual bleeding or spotting, and having normal or slightly enlarged uteri with no pelvic pathology, median menstrual blood loss was significantly reduced by 86%, 91% and 97% at 3, 6 and 12 months after LNG IUS placement, respectively (p<0.001), compared with the median of two consecutive baseline cycles prior to placement. Intermenstrual bleeding or spotting was common during the first 3 cycles after LNG IUS placement, but the frequency of this diminished gradually with treatment.
HMB, heavy menstrual bleeding
Reference
Andersson JK & Rybo G. Br J Obstet Gynaecol 1990; 97: 690–4.
In the Andersson and Rybo study, the reduction in menstrual blood loss with LNG IUS use in women with HMB was accompanied by significant increases in serum haemoglobin and ferritin levels (p<0.01 and 0.001, respectively, compared with levels prior to LNG IUS use).1
Overall, these data suggest that LNG IUS is effective at “normalising” serum haemoglobin and iron storage in women with HMB.
Other studies have confirmed that LNG IUS effectively reduces menstrual blood loss and improves serum haemoglobin and ferritin levels in idiopathic HMB,2 as well as HMB caused by underlying pathologies such as uterine leiomyomas and adenomyosis.3,4
HMB, heavy menstrual bleeding
References
Andersson JK & Rybo G. Br J Obstet Gynaecol 1990; 97: 690–4.
Xiao B, et al. Fertil Steril 2003; 79: 963–9.
Grigorieva V, et al. Fertil Steril 2003; 79: 1194–8.
Fedele L, et al. Fertil Steril 1997; 68: 426–9.
LNG IUS® is effective at reducing the frequency of bleeding in women with HMB.
In a post hoc pooled analysis of 4 randomised trials in women with HMB (N=163) treated with LNG IUS®, there was a transient initial increase in mean bleeding days during the first month post-placement, which declined to baseline levels at Month 2 and further decreased thereafter over the assessed 12 months of treatment.
Spotting increased with LNG IUS® use, and while the frequency gradually declined over time, it still remained elevated above baseline levels at
12 months post-placement.
The proportion of women with prolonged bleeding/spotting was 55.6% at
6 months and 25.0% at 12 months post-LNG IUS® placement. Approximately 1.7% and 8.8% of subjects had amenorrhea by 6 and 12 months, respectively.
HMB, heavy menstrual bleeding
Reference
Jensen J, et al. Contraception 2013; 87: 107–12.
In women with HMB, LNG IUS use significantly reduces menstrual blood loss and alleviates dysmenorrhea from as early as 3 months after placement.
In a retrospective study of perimenopausal women using LNG IUS for HMB and/or dysmenorrhea (N=192), analysed over a 2-year follow-up period, those women who completed the study and remained on LNG IUS® treatment (n=159) showed a success rate of 80.7%.
There was a significant reduction in menstrual blood loss (assessed via PBAC score) and dysmenorrhea (assessed via a subjective 0- to 3-point rating scale, which defines dysmenorrhea according to loss of work efficiency and need for bed rest) at all timepoints (p<0.01).
At 3, 6, 12 and 24 months after LNG IUS placement, the PBAC score reduction was 79%, 87%, 87% and 95%, respectively, compared with baseline (p<0.01).
Subjective relief from dysmenorrhea followed a similar pattern, with a decrease in assessment score of 47%, 54%, 59% and 63% at 3, 6, 12 and 24 months post-placement, respectively (p<0.01).
HMB, heavy menstrual bleeding; PBAC, pictorial blood loss assessment chart
Reference
Yoo HJ, et al. Arch Gynecol Obstet 2012; 285: 161–6.
In a multicentre, randomised trial to evaluate the effectiveness of LNG IUS® compared with other medical therapies for HMB, women aged 25–50 years with HMB (N=571) were randomly assigned
to treatment with LNG IUS or their usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen, or progesterone alone).
The primary outcome was patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS; ranging from 0 to 100, with lower scores indicating greater severity), assessed over a 2-year period.
MMAS scores for all individual domains (practical difficulties; social life; psychological health; physical health and well-being; work and daily routine; and family life and relationships) improved from baseline to 6 months in both the LNG IUS group and the usual-treatment group (mean increase, 32.7 and 21.4 points, respectively; p<0.001 for both comparisons). These improvements were maintained over a 2-year period, but were significantly greater in the LNG IUS® group than in the
usual treatment group (mean between-group difference of 13.4 points, 95% CI: 9.9 to 16.9; p<0.001).
Proportion of women free of HMB symptoms at baseline and 24 months
(LNG IUS vs usual medical treatment, respectively)
Practical difficulties: baseline 3% vs 2%, 24 months 68% vs 39% (p<0.001)
Social life during cycle: baseline 9% vs 6%, 24 months 70% vs 41% (p<0.001)
Psychological health during cycle: baseline 10% vs 9%, 24 months 59% vs 41% (p=0.0003)
Physical health and well-being during cycle: baseline 4% vs 3%, 24 months 50% vs 37% (p<0.001)
Work/daily routine during cycle: baseline 7% vs 8%, 24 months 65% vs 39% (p<0.001)
Family life/relationships during cycle: baseline 15% vs 12%, 24 months 62% vs 40% (p<0.001)
CI, confidence interval; HMB, heavy menstrual bleeding; MMAS, Menorrhagia Multi-Attribute Scale
Reference
Gupta J, et al. N Engl J Med 2013; 368: 128–37.
LNG IUS is significantly more effective than flurbiprofen, TXA and MFA in the treatment of idiopathic HMB.1,2
In the study by Milsom et al., the first 20 women to enrol were treated with LNG IUS, and 15 other women who subsequently enrolled were treated with TXA (1.5 g three times daily for 3 days and 1 g twice daily for another 4 days) or flurbiprofen (100 mg twice daily for 5 days) for two consecutive cycles before crossing over to the other treatment for the subsequent 2 cycles.1 Treatment with flurbiprofen or TXA was started on the first day of menstruation.
In women using LNG IUS, menstrual blood loss at 3 months was reduced by >80% compared with baseline. In comparison, after 2 months of treatment, flurbiprofen and TXA only reduced menstrual blood loss by an average of 24.4% and 47.5%, respectively, vs baseline. At 6 months, menstrual blood loss was reduced by 87.7% in the LNG IUS group, decreasing further to 95.6% at 12 months.
LNG IUS was the only treatment to reduce mean blood loss to below 80 ml per menstruation (i.e. below the volume of blood loss that classically defines HMB). Unlike LNG IUS®, flurbiprofen or TXA do not suppress or modulate cyclical endometrial build up.
In the open, randomised, comparative, parallel group study by Reid and Virtanen-Kari, women were assigned to treatment with either LNG IUS (n=25) or oral MFA (n=26) for 6 cycles.2
After 3 and 6 cycles, the decrease in median menstrual blood loss was significantly greater in women using LNG IUS (90.2% and 95.9%, respectively), compared with the MFA group (22.3% and 17.4%, respectively) (p<0.001).
Menstrual blood loss was objectively assessed in both studies by analysis of used tampons/pads using the alkaline-haematin method.
HMB, heavy menstrual bleeding; MFA, mefenamic acid; TXA, tranexamic acid
References
Milsom I, et al. Am J Obstet Gynecol 1991; 164: 879–83.
Reid PC & Virtanen-Kari S. BJOG 2005; 112: 1121–5.
In women with idiopathic HMB, LNG IUS reduces menstrual blood loss more effectively than MPA, and has a higher likelihood of treatment success.
In this multicentre, randomised, controlled study, women were assigned to
6 cycles of treatment with either LNG IUS (placed within 7 days of the onset
of menstruation; n=82) or oral MPA (10 mg daily for 10 days, beginning on day 16 of each cycle; n=83).
Menstrual blood loss was objectively assessed by analysis of used tampons/pads via the alkaline-haematin method.
At the end of the study, the percentage decrease in mean menstrual blood loss with LNG IUS was significantly greater than with MPA (70.8% vs 21.5%, respectively; p<0.001).
The proportion of women with successful treatment was significantly higher for LNG IUS than MPA (84.8% vs 22.2%, respectively; p<0.001).
MPA, medroxyprogesterone acetate
Reference
Kaunitz AM, et al. Obstet Gynecol 2010; 116: 625–32.
A systematic review and meta-analysis identified randomised controlled trials comparing LNG IUS with endometrial ablation for the treatment of HMB, and was restricted only to those trials in which menstrual blood loss was reported using PBAC scores.
Six randomised controlled trials that included 390 women (LNG IUS, n=196; endometrial ablation, n=194) were identified. Three studies pertained to first-generation endometrial ablation (manual hysteroscopy) and three to second-generation endometrial ablation (thermal balloon).
Both treatments were associated with similar reductions in menstrual blood loss after 6 months (weighted mean difference, PBAC score -31.96 [95% CI, -65.96 to 2.04]), 12 months (weighted mean difference, PBAC score 7.45 [95% CI, -12.37
to 27.26]) and 24 months (weighted mean difference, PBAC score -26.70 [95% CI, -78.54 to 25.15]).
The diamonds show overall PBAC score estimates and 95% CI. All of them overlap the vertical dotted line, indicating that there is no statistically significant difference in the amount of bleeding between LNG IUS® and endometrial ablation.
CI, confidence interval; HMB, heavy menstrual bleeding; PBAC, pictorial blood loss assessment chart
Reference
Kaunitz AM, et al. Obstet Gynecol 2009; 113: 1104–16.
In this study, Finnish women who were referred to 5 university hospitals
for complaints of HMB (N=236) were randomised to LNG IUS (n=119) or hysterectomy (n=117), and then followed for 5 years.
After 5 years, the two groups did not differ substantially in terms of HR-QoL
or psychosocial well-being. In both groups, HR-QoL measured by the RAND-36 improved significantly in all dimensions (p<0.01), except physical functioning.
HMB, heavy menstrual bleeding; HR-QoL, health-related quality of life;
RAND-36, 36-Item Short-Form Health Survey
Reference
Hurskainen R, et al. JAMA 2004; 291: 1456–63.
Overall satisfaction with treatment was greater than 90% in both groups, over
5 years of follow-up.
Although 42% of the women assigned to LNG IUS eventually underwent hysterectomy, the discounted direct and indirect costs were 40% lower in
the LNG IUS group than in the hysterectomy group.
These results suggest that LNG IUS is a cost-effective alternative to hysterectomy for the treatment of HMB.
HMB, heavy menstrual bleeding
Reference
Hurskainen R, et al. JAMA 2004; 291: 1456–63.
Key Points:
Naqaish et al. 2012
Patient satisfaction for LNG-IUS and Norethisterone for the treatment of Dysfunctional Uterine Bleeding (DUB) was compared in 119 female patients of reproductive age group with DUB, selected by consecutive sampling
LNGIUS vs. norethisterone:
Reduction in menstrual blood loss: 98% vs. 80%, p<0.05
Patient satisfaction with treatment: 90% vs. 20%, p<0.05
The preference of continuing the method as well as recommendation to a friend was significantly greater in Group A as compared to Group B.
The levonorgesterol-releasing intrauterine system (LNG-IUS) is a better choice as compared to Norethisterone, for treatment of DUB with 90% patients highly satisfied.
Lete et al. 2011
In a study from Spain, the cost and effectiveness of LNG-IUS versus COC and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) was compared.
Greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time)
LNG-IUS produces savings of € 174.2-309.95 and € 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years.
In addition, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1and 2 QALM compared to COC and PROG.
References:
Naqaish T, Rizvi F, Khan A, Afzal M. Patient satisfaction for levonorgestrel intrauterine system and norethisterone for treatment of dysfunctional uterine bleeding. J Ayub Med Coll Abbottabad. 2012;24(1):23-6.
Lete I, Cristóbal I, Febrer L, Crespo C, Arbat A, Hernández FJet.al Economic evaluation of the levonorgestrel-releasing intrauterine system for the treatment of dysfunctional uterine bleeding in Spain. Eur J Obstet Gynecol Reprod Biol. 2011;154(1):71-80.
Gupta B, Mittal S, Misra R, Deka D, Dadhwal V. Levonorgestrel-releasing intrauterine system vs. transcervical endometrial resection for dysfunctional uterine bleeding. Int J Gynaecol Obstet. 2006;95(3):261-6.
McCausland AM, McCausland VM. Long-term complications of minimally invasive endometrial ablation devices
A single-center, open, randomized clinical trial compared the efficacy of LNG-IUS to low dose combined oral contraceptive pills in the management of idiopathic menorrhagia.
112 women complaining of excessive menstruation who desired contraception were randomized to receive LNG-IUS or COC.
Treatment failure: need for medical or surgical treatment during the follow-up. Other outcomes included: menstrual blood loss (MBL) by alkaline hematin and by pictorial blood assessment chart (PBLAC), hemoglobin levels
Time to treatment failure was longer in LNG compared to COC group with a total of 6 (11%) patients who had treatment failure in the LNG-IUS compared to 18 (32%) in COC group with a hazard ratio of 0.30 (95% CI, 0.15-0.73, p=.007).
Using alkaline hematin, the reduction in MBL (mean ± S.D.) was significantly more in the LNG-IUS group (87.4 ± 11.3%) compared to the COC group (34.9 ± 76.9%) (p=.013).
Utilizing PBLAC scores, the reduction in the LNG-IUS (86.6 ± 17.0%) group was significantly more compared to the COC group (2.5 ± 93.2%) (p<.001). In the LNG-IUS group, increase in the hemoglobin and ferritin levels (mean ± S.D.) were noted (from 10.2 ± 1.3 to 11.4 ± 1.0 g/dL; p<.001; with reduction of the number of lost days (from 6.8 ± 2.6 to 1.6 ± 2.4 days, p=.003).
Reference
Shabaan MM, Zakherah MS, El-Nashar SA, Sayed GH. Levonorgestrel-releasing intrauterine system compared to low dose combined oral contraceptive pills for idiopathic menorrhagia: a randomized clinical trial. Contraception 2011;83:48–54.
A prospective, observational cohort study using a non-interventional model
investigated real-life treatment patterns and satisfaction in women using either LNG IUS® or conventional treatment (hormonal treatment, antifibrinolytic treatment, or a combination of both) for HMB.
The study population consisted of women aged 18–45 years (N=647) with HMB over several consecutive cycles, who were not intending to become pregnant during the next year, had no structural or histological abnormalities of the uterus, and were eligible for pharmacological treatment of fibroids (<3 cm in diameter without distortion of the uterine cavity).
Study participants were recruited from routine clinical practice in 8 countries/regions (China, Hong Kong, Indonesia, Malaysia, Pakistan, South Korea, Taiwan and Thailand).
Women who had received previous HMB treatment were asked to compare it to their current treatment, rating their experience as ‘Much better’, ‘Better’, ‘Same’ or ‘Worse’, based on retrospective recall. Previous HMB treatment of at least 2 months’ duration was recorded for 35.7% (n=156/437) of women using LNG IUS® and 44.4% (n=60/135) of women using conventional HMB treatments. Among women in the LNG IUS® group, over one-third reported their LNG IUS® as ‘Much better’ and over one-quarter as ‘Better’ than their previous therapy. Among women in the conventional treatment group, <10% of patients rated their current treatment as ‘Much better’ than previous therapy.
Reference
