International Journal of Gynecology and Obstetrics (2007) 97, 190194

a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

w w w. e l s e v i e r. c o m / l o c a t e / i j g o

CLINICAL ARTICLE

Efficacy, acceptability and side effects of the

levonorgestrel intrauterine system for menorrhagia
A. Kriplani , B.M. Singh, S. Lal, N. Agarwal
Department of Obstetrics and Gynecology, All-India Institute of Medical Sciences, New Delhi, India
Received 12 October 2006; received in revised form 14 January 2007; accepted 16 January 2007

KEYWORDS
Levonorgestrel
intrauterine system;
Menorrhagia

Abstract
Objective: To evaluate the efficacy, acceptability, and possible side effects of a levonorgestrelreleasing intrauterine system for menorrhagia. Methods: Sixty-three women with menorrhagia
but without uterine enlargement, endometrial hyperplasia with atypia, or endometrial carcinoma
were enrolled in this prospective, open, nonrandomized clinical trial. An intrauterine system
releasing 20 g/day of levonorgestrel (LNG-IUS; Mirena, Shering, Finland) was inserted in the
postmenstrual phase. Menstrual pattern, number of bleeding days, and subjective and objective
estimation of menstrual blood loss using a pictorial blood loss assessment chart (PBAC) were
recorded before insertion and at specific intervals for 4 years. Hemoglobin levels and endometrial
thickness were evaluated at baseline and at 12 months. Treatment continuation and hysterectomy
rates were noted as well as side effects. Results: The device was expelled spontaneously in 6
patients (9.52%) and removed prematurely in 9 patients (14.3%); 3 patients (4.8%) were lost to
follow-up; and 45 patients (71.4%) continued with the LNG-IUS. Menorrhagia was cured in 35
(77.7%) of these 45 patients at 3 months and in all patients at 36 months. There was a significant
decrease in the mean number of bleeding days (P = 0.01) and PBAC score (P = 0.00) at 1 month, and
the decrease continued with treatment duration. The subjective blood loss reduction was
considerable as well, and at 12 months the mean SD rise in hemoglobin concentration was 1.06
1.7 g/dL (P = 0.000). Endometrial thickness was decreased by 3.4 3.53 mm (P = 0.0001) at
12 months. The most common side effect was intermenstrual spotting during the first 6 months,
and 18 patients (28.57%) developed amenorrhea. Conclusion: Using the LNG-IUS is an effective
and well-accepted option overall for the medical management of menorrhagia.
2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.

Corresponding author. 3081, 3rd Floor, Teaching Block, Department of Obstetrics and Gynecology, All India Institute of Medical
Sciences, Ansari Nagar, New Delhi-110029, India. Tel.: +91 11
26594933 (O); fax: +91 11 26588641, 26588663.
E-mail address: kriplanialka@hotmail.com (A. Kriplani).

1. Introduction
Menorrhagia occurs in 20% to 30% of women of reproductive
age and is one of the most frequent reasons for gynecological
consultation [1,2]. This condition is usually defined as a

0020-7292/$ - see front matter 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.
All rights reserved.
doi:10.1016/j.ijgo.2007.01.009

Levonorgestrel intrauterine system in menorrhagia

menstrual blood loss (MBL) of at least 80 mL per cycle [2] or a
score of more than 100 on the pictorial blood loss assessment
chart (PBAC) [3]. Menorrhagia impairs the quality of life and
increases the severity of anemia, especially in developing
country where iron deficiency anemia is common. Medical
measures are often not acceptable because drugs would have
to be taken daily, with possible side effects. Hence, hysterectomy as a definitive treatment tends to be preferred by
the patients, although surgical risks are always a concern.
A levonorgestrel-releasing intrauterine system (LNG-IUS;
Mirena, Shering, Finland) was launched as a contraceptive in
1990, and its efficacy in the treatment of menorrhagia has
recently been reported in developed countries [47]. Its
insertion requires a one-time decision, and it is effective for
5 years or, possibly, for up to 7 years [2]. The T-shaped plastic
frame of the LNG-IUS comprises a 32-mm vertical stem and 2
collapsible arms 32 mm in total width. The vertical stem is
surrounded by a reservoir containing 52 mg of levonorgestrel, from which 20 g is released daily into the uterine
cavity. The strong antiproliferative action of levonorgestrel
on the endometrium causes the progressive reduction of both
menstrual blood flow and number of bleeding days [8].
There is a lack of literature from India regarding the use
of the LNG-IUS for the treatment of menorrhagia. In this study,
long-term efficacy, acceptability and possible side effects of
the LNG-IUS were assessed in Indian patients with menorrhagia.

2. Materials and methods

In this prospective, open, nonrandomized clinical trial, 63 women
with menorrhagia were enrolled from November 2001 to March
2005. Exclusion criteria were endometrial carcinoma, endometrial hyperplasia with atypia, uterine size greater than that of a 12week-pregnant uterus, uterocervical length greater than 10 cm,
or an endocrinopathy or systemic illness causing menorrhagia.
A detailed history including demographic characteristics,
menstrual and obstetric history, and medical and surgical history
was obtained from each patient. The menstrual history included
duration of symptoms, number of bleeding days, subjective and
objective assessment of menstrual blood loss (MBL), presence of
dysmenorrhea, and the passage of clots/flooding during menses.
Objective MBL was estimated using a pictorial blood loss
assessment chart (PBAC). The PBAC score was calculated by
assigning a score of 1, 5, or 20, respectively, to a lightly, moderately, or fully soiled sanitary pad, and a score of 1 or 5, respectively, for the passage of small or large clots.
All patients underwent a gynecological examination and an
ultrasonographic evaluation of the endometrial thickness; hemoglobin levels were assessed; and cervical cytologic studies as well
as an endometrial biopsy were performed. Hysteroscopy was also
performed if an intrauterine lesion was suspected. The device was
inserted in the uterine cavity in the postmenstrual phase.
Patients were followed up at 1, 3, 6, 12, 24, 36, and
48 months. At each visit menstrual pattern, number of bleeding
days, presence of intermenstrual bleeding or spotting, and
subjective and objective assessment of MBL were noted.
Bleeding was defined as a bloody vaginal discharge requiring
sanitary protection (sanitary pad or towel). Spotting was defined
as an occasional and unpredictable bloodstained vaginal
discharge that required no or minimal protection. Amenorrhea
was defined as an absence of bleeding for at least 3 months.
Oligomenorrhea was defined as the presence of bleeding at

191
intervals longer than 45 days. Polymenorrhea was defined as
menstruation occurring at intervals shorter than 21 days. Ultrasonographic evaluation of endometrial thickness and estimation
of hemoglobin concentration were repeated at 12 months. An
endometrial sample was taken again at 6 months in women who
had been diagnosed as having simple or adenomatous hyperplasia. Any treatment-related side effects were noted at each visit.
Statistical analysis was performed using the SAS statistical
package, version 8.0 (SAS Institute, Cary, NC, USA). Mean SD or
median (range) were calculated for continuous variables
whereas frequency distribution and their percentages were
calculated for categorical variables. P b 0.05 was considered
significant. Parametric and nonparametric 2-way analysis of
variance with appropriate post-hoc analysis was used to detect
significant changes in number of bleeding days and subjective
changes in MBL and PBAC score. The paired t test was used to
evaluate changes in endometrial thickness and hemoglobin
levels between baseline and 12th-month values.

3. Results
3.1. Patients' characteristics
The median age of the patients was 42 years (range, 29
52 years). Most (93.65%) were multiparas, 3 (4.8%) were
primiparas, and 1 (1.59%) was nullipara. Five patients (7.9%)
had a history of cesarean delivery (1 patient had 1, 2 patients
had 2, and 2 patients had 3). Of 22 couples (34.9%) who
underwent permanent sterilization 20 women (31.7%) had
tubectomy and 2 men (3.2%) had vasectomy; 1 woman (1.6%)
was using a Copper-T intrauterine device; 11 couples (17.5%)
were using condoms; and 29 couples (46.0%) were not using
any contraception. Thus, 41 study participants (65.1%) also
benefited from the contraceptive action of the LNG-IUS.

3.2. Gynecological evaluations and investigations

The median duration of menorrhagia was 24 months (range,
3210 months). The median number of bleeding days was 8
and the median PBAC score was 460. Forty patients (63.5%)
had dysmenorrhea and 25 (39.7%) had uterine myomas
(b 4 cm in diameter). The mean endometrial thickness was
9.51 4.21 mm. The histologic evaluation revealed a secretory endometrium in 30 patients (47.6%), a proliferative
endometrium in 12 (19%), and an interval endometrium in
9 (14.3%); simple hyperplasia without atypia in 9 (14.3%); and
adenomatous hyperplasia without atypia in 3 (4.8%).
Diagnostic hysteroscopy was performed in 22 patients
(34.9%) and the endometrium was found to be normal in 8,
hyperplasic in 4, polypoidal in 7, with polyps (2 cm 2 cm) in
2, and a submucosal myoma in 1. Polyps and myoma were
removed and the LNG-IUS was inserted when the patients
were still bleeding after their removal.

3.3. Outcome of study population

The outcome of a total of 1306 postinsertion woman-months
is shown in the Fig. 1. Three patients (4.8%) were lost to
follow-up and 45 (71.4%) were continuing the treatment at
the end of the study.

192

A. Kriplani et al.
3.3.2. Side effects
The most common side effect of the LNG-IUS was prolonged
intermenstrual bleeding/spotting (in 45 patients [71.4%])
during the first 3 months following insertion. The other side
effects were increased vaginal discharge (n = 20 [33.3%]),
weight gain (n = 18 [30.5%]), backache (n = 23 [38.3%]), leg
pain (n = 12 [2.0%]), amenorrhea (n = 17 [26.9%]), headache
(n = 8 [13.3%]), body swelling (n = 7 [11.7%]), breast tenderness (n = 6 [1.0%]), sleeping problems (n = 5 [8.3%]), mood
changes (n = 5 [8.3%]), hot flushes (n = 4 [6.7%]), cholasma
(n = 3 [5.0%]), weakness (n = 3 [5.0%]) decreased libido (n = 2
[3.3%]), depression (n = 2 [3.3%]), ovarian cysts (n = 2 [3.3%]),
hair loss (n = 1 [1.7%]), and acne (n = 1 [1.7%]).
3.3.3. Premature removal
Nine patients (14.8%) requested premature removal of the
LNG-IUS, 4 because of symptom persistence (menorrhagia in 3
and severe dysmenorrhea in 1) and 5 because of side effects
(amenorrhea in 3, cholasma in 1, and depression in 1).
3.3.4. Hysterectomy
Ten patients (15.87%) underwent hysterectomy (6 after
spontaneous expulsion of the device and 4 after premature
removal due to nonresponse).

Figure 1 Outcome of study population on follow-up of 1306

woman-months.

3.3.1. Expulsion
The device was expelled spontaneously in 6 patients (9.5%,
twice in 2 patients), all of whom eventually underwent
hysterectomy because of worsening symptoms. Two patients
(3.2%) had partial expulsion (the lower end of the device's
vertical stem protruded from the external cervical os) at 2
and 6 months, respectively. After repositioning of the device,
1 patient developed amenorrhea and there was a marked
MBL reduction in the other.

Table 1

3.4. Changes in bleeding pattern, menstrual blood

loss, and dysmenorrhea
There was a marked reduction in MBL in patients following
insertion of the LNG-IUS. After 3 months menorrhagia was
cured in 35 (77.7%) of the 45 patients who continued with the
device and at 36 months it was cured in all of these patients.
The percentages of patients having only minimal spotting
during their menstrual period or oligomenorrhea increased at
each subsequent visit. Of 18 patients (28.6%) who developed
amenorrhea using the LNG-IUS, 4 (22.2%) regained periods,
although very scant ones, at 12, 48, 24, and 24 months,
respectively; however, 14 (77.8%) remained amenorrhic
(Table 1, Fig. 1).

Menstrual patterns during the follow-up of 63 women treated with the LNG-IUS for the treatment of menorrhagia a

Bleeding pattern

No. of months of follow-up

3

12

24

36

48

(n = 59)

(n = 58)

(n = 53)

(n = 40)

(n = 18)

(n =15)

Amenorrhea

7 (11.86)

Oligomenorrhea

Only spotting during period

5 (8.48)

Menorrhagia

23
(38.98)
24
(40.68)
43
(72.88)

8
(13.79)
1
(1.72)
12
(20.68)
10
(17.24)
27
(46.55)
19
(32.75)

10
(18.87)
2
(3.78)
21
(39.62)
8
(15.09)
12
(22.64)
16
(39.62)

10
(25)
3
(7.5)
14
(35)
2
(5)
11
(27.5)
5
(12.5)

10
(55.56)
4
(22.22)
4
(22.22)
0

11
(73.33)
2
(13.33)
2
(13.33)
0

2
(11.11)

Normal period (with decreased menstrual blood loss)

Intermenstrual spotting
a

Values are given as number (percentage).

Levonorgestrel intrauterine system in menorrhagia

Table 2

193

Changes in subjective and objective assessment of menstrual blood loss in patients treated with the LNG-IUS

Menstrual blood loss

No. of bleeding days

Median
Mean SD
(Range)
PBAC
Median
Mean SD
(Range)
Subjective percentage
reduction of blood loss,
median

Preinsertion No. of months of follow-up

(n = 63)
1
3
6

12

24

36

48

(n = 18)

(n = 15)

(n = 60)

(n = 59)

(n = 58)

(n = 53)

(n = 40)

8.0
8.9 4.3
(225)

7.0
7.3 4.2
(021)

5.0
6.1 4.4
(020)

4.0
4.9 4.5
(025)

3.0
4.2 4.1
(05)

3.0
2.0
2.0
2.4 1.9 2.6 2.2 1.9 2.1
(08)
(08)
(05)

460
536.7 31.9
(2001750)

90
154.6 181.8
(0850)
70%

30
118.2 273.4
(01740)
80%

10
53.6 134.8
(0700)
90%

3.0
11.6 16.2
(063)
95%

2.5
4.9 6.8
(025)
95%

There was a significant decrease in the mean number of

bleeding days (P = 0.01) and mean PBAC score (P = 0.00) at
1 month, and it further decreased with treatment duration
(Table 2). The subjective reduction of blood loss was 70%,
80%, 90%, 95%, 95%, 95%, and 96.5% at 1, 3, 6, 12, 24, 36, and
48 months, respectively.
Dysmenorrhea was completely relieved in 31 of 40 patients
(77.5%) at 3 months. One woman had persistent and severe
dysmenorrhea warranting premature removal of the LNG-IUS
and hysterectomy 6 months after insertion. At 24 months, no
patient with the device in situ had dysmenorrhea.

3.5. Changes in hemoglobin levels, endometrial

thickness and endometrial histologic findings
Along with the MBL decrease, there was a significant mean
increase in hemoglobin level (1.06 1.7 gm/dL, P = 0.000) at
12 months. The mean hemoglobin level increased from 10.5
1.5 gm/dL at baseline to 11.5 1.4 gm/dL at 12 months.
There was also a 3.4 3.53 mm decrease in endometrial
thickness at 12 months (P = 0.0001). The mean endometrial
thickness was 9.3 3.3 mm before insertion and 5.9 2.3 mm
at 12 months. Of 12 patients with simple/adenomatous
hyperplasia with no atypia, 4 underwent hysterectomy after
a mean treatment duration of 11 months and the remaining 8
underwent a second endometrial biopsy. The histopathologic

3.0
5.1 5.2
(016)
95%

2.0
4.3 7.5
(025)
96.5%

results were an atrophic endometrium in 5 patients, a

secretory endometrium in 2, and a proliferative endometrium in 1.

3.6. Outcome in patients with uterine fibroids

Of 25 patients who had menorrhagia with uterine fibroids, 3
(12%) developed amenorrhea, 10 (40%) had intermenstrual
spotting that settled between 3 and 6 months. Expulsion of
the device occurred in 3 (12%) of these patients (twice in 1
patient), and 2 (8%) had the device prematurely removed
(because of depression in one and persistent dysmenorrhea
in the other). These 5 patients all underwent hysterectomy.
There was a marked reduction in both subjective and
objective MBL (Table 3).

3.7. Pregnancy
No patient had a intrauterine or ectopic pregnancy.

4. Discussion
This prospective trial provides longest follow-up of Indian
patients using the LNG-IUS for menorrhagia. The LNG-IUS
proved successful in reducing the number of bleeding days

Table 3 Assessment of menstrual blood loss, both subjective and objective using a pictorial blood loss assessment chart
(PBAC), in patients with uterine fibroids who were treated with the LNG-IUS
Menstrual blood loss
No. of bleeding days
Median
(Range)
PBAC score
Median
(Range)
Subjective percentage reduction
of blood loss, median

Preinsertion

No. of months of follow-up

1

12

24

36

48

7.0
(325)

6.5
(115)

5.0
(020)

5.0
(025)

4.5
(015)

4.5
(05)

3.5
(05)

5.0
(05)

514
(237910)

104
(2680)
75%

50
(2700)
77.5%

20
(0700)
80%

11
(063)
92.5%

12
(025)
87.5%

7.5
(010)
90%

5.0
(010)
92.5%

194
and MBL in patients with idiopathic menorrhagia as well as in
those with menorrhagia caused by uterine fibroids. The
bleeding reduction was significant even 1 month following
insertion of the device and the beneficial effects increased
with treatment duration. The reduction of blood loss was not
affected by the presence of small intramural and subserosal
myomas.
The effect of the LNG-IUS on menstruation is mainly due
to its antiproliferative effect on the endometrium, which
leads to endometrial suppression, decidualization, and
atrophy as well as direct vascular changes [9]. The decrease
in endometrial thickness on ultrasononography and the
histologic changes from adenomatous hyperplasia to a
proliferative or interval endometrium at 6 months was also
evidence of the device's antiproliferative action. Pakarinen
[10] reported a decrease in endometrial thickness from
11 mm to 4.5 mm during the first 3 months, followed by a
plateau. Thus, it seems that the device may also offer
treatment for patients with endometrial hyperplasia.
Excessive menstrual bleeding is a common cause of
anemia. The reduction in MBL associated with LNG-IUS
treatment in patients improves their hemoglobin levels.
Various long-term studies, including the present study, have
reported a significant rise in mean hemoglobin levels in
patients using the LNG-IUS [9,11]. This antianemic effect
may be particularly important in developing countries,
where iron-deficiency anemia resulting from poor nutrition
and parasitic infection is a frequent health problem.
The success of the LNG-IUS could be related to the
insertion technique. However, although improper insertion
was presumed to be the causative factor of expulsion in the
initial part of study, re-expulsion occurred in 2 cases,
suggesting that the nonreceptiveness of certain uteri may
also be a reason for expulsion. Fundal placement of the
device is necessary to deliver the drug over the entire
endometrial tissue, repositioning a low-lying device caused a
marked improvement of symptoms in 2 patients.
The side effects, which can lead to treatment discontinuation, are mainly due to the progesterone in the LNG-IUS.
Two patients (3.17%) underwent premature removal because
of steroidal side effects (depression in one and cholasma in
the other). Unscheduled breakthrough bleeding/spotting
during the initial 3 to 6 months was also a troublesome side
effect, as 10 patients expressed the wish to discontinue the
treatment; over time, however, their symptoms improved.
Using the device led to amenorrhea in 18 patients (28. 57%),
because of which 3 of these patients underwent removal.
Andersson [12] reported a discontinuation rate of 2.7% during
the first year of use of the LNG-IUS. Backmen [13] reviewed
various studies and observed that the gross removal rate
because of an absence of menstrual bleeding varied between
6% and 19.7% of patients. Thus, proper counseling and
advanced information is needed for women to accept this
treatment, and to reduce the rate of premature removal
over a long-term follow-up.

A. Kriplani et al.
In conclusion, the LNG-IUS is an effective device for the
treatment of menorrhagia and a viable alternative to
surgery. Its use may be extended to cure simple or
adenomatous endometrial hyperplasia even in presence of
small intramural and subserosal myomas. The device
provides added benefit to women who are anemic and/or
who need contraception.

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