Levonorgestrel-releasing and copper-

releasing (Nova T) IUDs during five years

of use:
A randomized comparative trial

Kerstin Andersson”, Viveca Odlindf, G&an Rybo”

‘Department of Obstetrics and Gynecology, Kvinnokliniken, ijstra

sjukhuset, Giiteborg, Sweden; and tDepartment of Obstetrics and
Gynecology, Kvinnokliniken, Akademiska sjukhuset, Uppsala, Sweden

A 20 micrograms124 hours levonorgestrel-releasing intrauterine con-

traceptive device (LNG-IUD) has, in an open randomized multicenter
study, been compared to the copper-releasing device Nova T during
5 years of use; 1821 women had the LNG-IUD and 937 women had the
Nova T inserted. The 5-year cumulative gross pregnancy rate was
5.9 % for Nova T and 0.5% for the LNG-IUD. The local effect of levonor-
gestrel in the uterine cavity causes reduction of menstrual blood loss
and development of oligo-amenorrhea, and the termination rates
because of heavy and/or prolonged menstrual flow were significantly
(P < 0.001) lower among LNG-IUD users. However, thegross termination
rate because of amenorrhea was 6.0 in this group. Hb increased
during use of the LNG-IUD and decreased during Nova T use,
and the difference between the devices was statistically significant.
The incidence of pelvic inflammatory disease (PID) was low in LNG-
IUD users regardless of age, whereas in the Nova T group, the PID
rate was increased among the youngest women, which makes the differ-
ence between the devices significant (P < 0.01). The gross termination
rate for reasons considered to be hormonal was 12.1 in the LNG-
IUD group compared to 2.0 in the Nova T group (P < 0.001).
The LNG-IUD is a long-acting reversible contraceptive method for
5 years with a pregnancy rate comparable to female sterilization.

Submitted for publication January 11, 1993; accepted for publication November
24, 1993.
Address correspondence to:
Kerstin Andersson, Dept of Obstetrics & Gynecology, East Hospital, S-41685
GBteborg, Sweden.

56 Contraception 1994:49, January 0 1994 Butterworth-Heinemann

 Levonorgestrel- and copper-releasing IUDs: Andersson et al.

The incidence of PID is low even in young women. In addition, the

positive health effects such as decreased menstrual blood loss
and increased blood haemoglobin concentration make the LNG-IUD
a favorable combination of hormonal and intrauterine
contraception.

Keywords: Levonorgestrel-releasing IUD; Nova T; contraception

Introduction
Progestogen-releasing intrauterine contraceptive devices were initially
developed to reduce uterine contractility and, thus, to prevent expulsion.
However, it was found that the steroid did not influence the expulsion
rate but increased the contraceptive efficacy compared to a plain T device’
and reduced the menstrual blood 10~s.~ The progesterone-releasing IUD
(Progestasert) had to be replaced at 12-month intervals and was associated
with an increased risk of ectopic pregnancies.”
Levonorgestrel is not metabolized by the endometrium as rapidly as
progesterone and has a more uniform and profound local effect.4 An
intrauterine contraceptive device which releases 20 micrograms
levonorgestrel/24 hours (LNG-IUD) has been studied in comparative trials
with the copper-releasing IUDs, Nova T, Copper T 200, Copper T 220
and Copper T 380, and with levonorgestrel-releasing subdermal implants
(Norplant-2). The 5 years’ experience of LNG-IUD as compared to Nova
Ts and with Copper T 380” and the 3 years’ experience of LNG-IUD as
compared to Nor-plant-2’ and Copper T 200, Copper T 220 and Copper T
380x have been reported. These studies have demonstrated both high
contraceptive efficacy and decreased menstrual bleeding with LNG-IUD,
but also discontinuation because of amenorrhea. At that time, when the
5-year studies where LNG-IUD was compared to a copper IUD were
started, oligo-amenorrhea was not known to be a frequent concomitant
to intrauterine release of levonorgestrel. Therefore, the information about
the strong effect of the LNG-IUD on menstrual bleeding and the frequent
and expected development of oligo-amenorrhea was not given to the
women.
The aim of the present investigation was to more extensively, in a
randomized comparative way, study LNG-IUD and Nova T during five
years of use, and to apply an open design to ensure an efficient and high
quality counselling. The results after the first and the third year”,‘0 have
earlier been published.

Materials and Methods

Nova-T is a copper-releasing device with a silver-cored copper wire wound
around the vertical stem. The copper surface area is 200 mm2 and the

Contraception 1994:49, January 57

Levonorgestrel- and copper-releasing IUDs: Andersson et al.

effective life span is at least five years. I1 LNG-IUD has the same polyethyl-
ene skeleton as Nova T and the steroid is homogeneously dispersed in a
polydimethyl-siloxane reservoir covered by a rate-limiting membrane on
the vertical arm of the device (Figure 1). The devices used in this study
contained 46 mg of levonorgestrel. The initial in vitro release rate of
levonorgestrel is 20 micrograms/24 hours and about 15 micrograms/24
hours after five years. The life span of the LNG-IUD is at least five
years.s As the steroid reservoir is slightly thicker than the copper wire,
the insertion tube of the LNG-IUD is 4.8 mm compared to 3.7 mm for
the Nova T insertion tube. Both IUDs are manufactured by Leiras OY,
Turku, Finland.
The study was carried out in four clinics in Finland, four clinics in
Sweden, two clinics in Denmark, one clinic in Hungary and one in Nor-
way. Women, who were visiting the clinics requesting contraception, were
asked if they wanted to participate in a clinical trial and informed verbal
consent was obtained. The woman had to be healthy, 18-38 years old and
should have had at least one previous pregnancy. If she had a history
of ectopic pregnancy, was breast-feeding or had used injectable steroid

FIGURE 1. The 20 micrograms/24 hours levonorgestrel-releasing device (LNG-IUD) is shown to the left and
the copper-releasing device (Nova T) to the right.

58 Contraception 1994149, January

 Levonorgestrel- and copper-releasing IUDs: Andersson et al.

hormones for contraception during the preceding 12 months, she was not
accepted into the study. The woman had to be willing to accept an induced
abortion in case of an accidental pregnancy with the LNG-IUD, as knowl-
edge about teratogenic risks is lacking.
Into the treatment groups 2758 women were allocated, 937 had a Nova
T and 182 1 had an LNG-IUD inserted. All devices were inserted between
November 1982 and December 1984. In the Nova-T group 133 and in the
LNG-IUD group 305 women had the IUD inserted in connection with an
induced first trimester abortion, but this group is too small for separate
evaluation. The mean age was 30.3 years in both groups (SD 4.9 in the
Nova T and 5.0 in the LNG-IUD group] and the distribution of age is
shown in Table 1. The mean parity were 1.7 (SD 0.9) and 1.8 (SD 0.9) in
the Nova T and LNG-IUD groups, respectively.
At the completion of the study, life table analysis of pregnancy and
discontinuation rates was made using the terminology suggested by
Tietze & Lewit.12 Multiple-decrement life table rates (net rates) and single-
decrement (gross) rates were calculated. The differences in the cumulative
life table rates between the two groups were tested for statistical signifi-
cance with Mantel-Cox (log-rank) statistics of the BMDP software pack-
age.13 The limit of statistical significance was set at I? = 0.05.
Approval for the study was obtained from the ethics committees of all
universities involved.

Study Design
The study was an open randomized comparative multicenter trial of two
parallel groups. The IUD was inserted within 3-10 days after the onset
of menstruation. If signs of cervicitis were noted, the infection was treated
and the IUD insertion was postponed. The device could also be inserted
in connection with a first trimester abortion. A specially designed protocol

TABLE 1. Distribution of age in 2758 women receiving Nova T or a

20 micrograms/24 hours levonorgestrel-releasing device (LNG-IUD)

Nova T LNG-IUD Total

Age (years) N % N % N %

5 25 177 18.9 338 18.6 515 18.7

26-30 263 28.1 532 29.2 795 28.8
31-35 358 38.2 645 35.4 1003 36.4
236 139 14.8 306 16.8 445 16.1

TOTAL 937 100 1821 100 2758 100

Contraception 1994:49, January 59

Levonorgestrel- and copper-releasing IUDs: Andersson et al.

was used in all centers and a standardized interview was performed at

admission and at every follow-up visit, which was planned after 3 and 12
months and then yearly up to five years. Furthermore, during the first 12
months, all women were requested to note bleeding patterns continuously
on a specially designed chart.
In case of any problem, the women were immediately seen by the
investigators. Prospective uniform criteria for diagnosis and treatment of
side effects have been used, and the women were encouraged to contact
the investigator’s clinic in case of problems, and the event was reported
to the study center.
The diagnosis pelvic inflammatory disease (PID) included acute sal-
pingo-oophoritis, tubo-ovarian abscess and pelvic peritonitis. In the study
protocol, the PID diagnosis required at least two of the following symp-
toms or signs: 1) history of lower abdominal pain and body temperature
more than 38” C, 2) increased sedimentation rate over 30 mm/hour, 3)
tenderness on pelvic examination, 4) mass on pelvic examination, and 5)
laparoscopy or ultrasound examination if other clinical evidence was
controversial.

Results
Continuation Rate
In the Nova T group 133 women (14% of the acceptors) and in the LNG-
IUD group 115 women (6.3% of the acceptors) were lost to follow-up
during the study. Of the 2758 women enrolled into the study, 315 acceptors
of Nova T and 736 acceptors of LNG-IUD completed the 60 months
follow-up and the continuation rate at five years was 44.5 for Nova-T and
46.9 for the LNG-IUD (Table 2). The continuation rate was, for both IUDs,
higher in the older age groups (Table 3).

Contraceptive Efficacy
The 5-year cumulative gross pregnancy rate was 5.9 for Nova-T and 0.5
for LNG-IUD [(P < 0.001) Figure 2, Table 31.
During the 60-month observation period, 35 women in the Nova-T
and 5 in the LNG-IUD group became pregnant. Among the pregnancies,
7 were ectopic in the Nova-T group and 1 in the LNG-IUD group (Table
4). The pregnancies in the LNG-IUD group and the woman’s age at IUD
insertion are described below:

1. Occurred during the 10th month of use after an unnoticed expulsion

in a 35.year-old woman. An induced abortion was performed.
2. Occurred 23 months after insertion in a 37-year-old woman. When the

60 Contraception 1994:49, January

 Levonorgestrel- and copper-releasing IUDs: Andersson et al.

TABLE 2. Net cumulative termination rates per 100 each year in 937 women using Nova T and 1821 women
using a 20 micrograms/24 hours levonorgestrel-releasing device (LNG-IUD) during 5 years

Year
1 2 3 4 5

Event Nova T LNG-IUD Nova T LNG-IUD Nova T LNG-IUD Nova T LNG-IUD Nova T LNG-IUD

Pregnancy 0.9 0.1 2.2 0.1 3.1 0.2 4.0 0.3 4.2 0.3
Expulsion 3.4 3.4 4.1 4.2 4.8 4.8 5.3 4.9 5.5 4.9
Bleeding 5.7 5.8 9.0 8.3 12.0 9.6 14.3 10.3 16.2 10.9
problems
Amenorrhea 0.0 1.5 0.0 2.9 0.0 3.6 0.0 4.2 0.0 4.3
Pain 1.6 1.6 2.6 2.8 3.3 3.4 3.8 3.9 4.2 4.2
Hormonal 0.1 2.3 0.1 4.8 0.6 6.4 0.7 7.6 1.1 8.4
PID 0.4 0.3 1.0 0.5 1.5 0.5 1.5 0.5 1.6 0.6
Other medical 2.4 2.7 3.8 3.6 5.4 4.8 6.4 5.5 7.6 5.8
Planning 1.9 1.9 5.5 5.7 8.1 8.2 10.6 10.1 11.8 10.8
pregnancy
Other personal 0.6 0.6 1 .o 1.5 1.7 2.0 2.5 2.3 3.3 2.9
Continuation 83.0 79.9 70.7 65.6 59.4 56.7 50.8 50.6 44.5 46.9

termination of pregnancy was performed, submucous uterine fibroids

were diagnosed.
3. Ectopic pregnancy after 30 months of IUD use in a woman aged 28;
the device was found in situ. The right tube was resected.
4. Intrauterine pregnancy in a 35year-old woman 41 months after inser-
tion. The device was found in situ and spontaneous abortion occurred
in the sixth week.
5. Occurred after a complete unnoticed expulsion of the device in a 40-
year-old woman 46 months after insertion. Spontaneous abortion oc-
curred in the sixth week.

Seven ectopic pregnancies occurred in the Nova T group after 4-23

months of IUD use and the mean age of these women was 34 (range
27-38) years.

Expulsion

The 60-month cumulative gross expulsion rate was 6.7 in the Nova T
group and 5.8 in the LNG-IUD group (Table 3). Most of the expulsions
were noted during the first months after insertion.

Bleeding Problems
The gross cumulative removal rate for bleeding was 20.7 for the Nova T
and 13.7 for the LNG-IUD (P c 0.01) at five years (Table 3). Termination

Contraception 1994:49, January 61

 TABLE 3. Cumulative 60-month age-specific gross rates of use-related terminations and continu-
ation in women using Nova T (N = 937) or a 20 micrograms/24 hours levonorgestrel-releasing
device (LNG-IUD, N = 1821)

Age (years)

5 25 26-30 31-35 2 36 Total

PREGNANCY
Nova T 14.9 6.9 4.0 2.8 5.9
LNG-IUD 0.4 0.5 0.9 0.5
P ; t t NS t
Expulsion
Nova T 8.2 6.4 7.8 1.6 6.7
LNG-IUD 4.9 7.7 5.2 5.9 5.8
P NS NS NS NS NS
BLEEDING PROBLEMS
Nova T 34.7 22.2 17.2 21.4 20.9
LNG-IUD 20.9 17.8 9.7 9.0 13.7
l f l
P NS NS
AMENORRHEA
Nova T 0 0 0 0 0
LNG-IUD 9.3 8.8 4.4 2.6 6.0
*
P t t NS t
PAIN
Nova T 8.6 8.7 3.6 4.4 5.8
LNG-IUD 6.2 6.6 6.3 3.8 5.9
P NS NS NS NS NS
HORMONAL
Nova T 6.6 1.1 2.4 0 2.0
LNG-IUD 10.0 15.0 12.3 9.8 12.1
P NS t t t t
PID
Nova T 5.6 3.0 1.4 0 2.2
LNG-IUD 0.3 1.4 0.7 0.3 0.8
* *
P NS NS NS
OTHER MEDICAL
Nova T 11.3 9.4 9.2 13.0 10.6
LNG-IUD 8.2 7.1 7.7 7.3 7.7
P NS NS NS NS NS
PLANNING PREGNANCY
Nova T 40.7 25.1 7.8 2.9 16.3
LNG-IUD 42.0 19.1 6.9 2.2 15.2
P NS NS NS NS NS
OTHER PERSONAL
Nova T 12.6 7.3 4.5 4.4 5.9
LNG-IUD 5.1 3.1 5.3 3.8 4.4
P NS NS NS NS NS
CONTINUATION RATE
Nova T 18.9 37.4 54.4 58.1 53.1
LNG-IUD 29.0 39.3 54.1 63.3 55.5
P NS NS NS NS NS

NS = not significant.* = P 5 0.01. t = P < 0.001.

62 Contraception 1994:49, January

 Levonorgestrel- and copper-releasing IUDs: Andersson et al.

6- r-----
r---a

I4
, __’
_--
_I- a
_--a
4- I
r--
_I
-_a
I
__ I-
I
__
I
2- __,a-
I-
c--
-- d-

2 3 4 5
Year

FIGURE 2. Five-year cumulative gross pregnancy rate per 100 women for 937 women during use of Nova T
(- - -) and for 1821 women during use of a 20 micrograms/24 hours levonorgestrel-releasing device (-).

TABLE 4. Number of pregnancies and pregnancy rate per 100 women-years (Pearl rates) during
five years’ use of Nova T and a 20 micrograms/24 hours levonorgestrel-releasing device (LNG-
IUD)

Nova T LNG-IUD

All pregnancies (N) 35 5

Ectopic pregnancies (N) 7 1
Women-years (WY) 2776 5615
Pregnancy rate/l 00 WY 1.26 0.09
Ectopic rate/100 WY 0.25 0.02

Contraception 1994:49, January

Levonorgestrel- and copper-releasing KIDS: Andersson et al.

for heavy and prolonged menstrual flow differed significantly between the
groups in favour of the LNG-IUD, whereas the removal rate for irregular
bleeding or spotting did not differ (Table 5).
The bleeding patterns during the first year were studied in detail by
analyzing the menstrual records from 739 women in the Nova-T and 1495
in the LNG-IUD group (Figure 3). During the first three months after
insertion, there were, on average, more days with menstruation-like bleed-
ing and/or spotting in the LNG-IUD group compared to the Nova-T group
(P < 0.001). With passing time, the situation changed, and at 12-month
follow-up, the mean number of days with bleeding and/or spotting was
significantly lower in the LNG-IUD group [(P < O.OOl), [Figure 3)]. When
only days with menstruation-like bleeding were calculated, the mean
number of days were initially equal in both groups, and there was a gradual
decrease in the LNG-IUD group during the observation period, whereas
in the Nova-T group, the number of days with bleeding per month was
unchanged after the initial months.

Amenorrhea
During the first year after IUD insertion, 2.7% of the Nova-T users and
16.8% of the LNG-IUD users experienced a period of at least 90 days’
amenorrhea.
The cumulative net rate of removal because of amenorrhea was 4.3 for
LNG-IUD and 0 for Nova T ((P < O.OOl), (Table 2)]. The corresponding
gross rates in different age groups appear in Table 3. Amenorrhea led to
higher termination rate in younger women compared to older.

Pain
No difference between the groups in termination rates for pain was seen
(Table 2).

TABLE 5. Cumulative 60-month gross termination rate because of bleeding problems in women
using Nova T (N = 937) or a 20 micrograms/24 hours levonorgestrel-releasing device [(LNG-
IUD), (N = 1621)]

Nova T LNG-IUD P

Frequent irregular bleeding 3.9 5.3 NS

Heavy menstrual flow 9.7 1.3 l

Prolonged menstrual flow 6.5 2.3 *

Spotting 2.2 1.6 NS
Other bleeding problems 0.4 3.9 *

NS = not significant. * = P < 0.001.

64 Contraception 1994:49, January

 Levonorges trek- and copper-releasing I UDs: Andersson et al.

14 -

12 -

10 -

6-

4-

2-

I 1 I I 1 I I
I I I I
I
0' 8 9 10 11 12
0 1 2 3 4 5 6 7

Period

8-

6-

4-

2-

I I I I I 1
1 I I I I
I
0’ 6 7 8 9 10 17 12
0 1 2 3 4 5

Period

FIGURE 3. Mean number of days with bleeding and/or spotting or only bleeding each month during the first
year of use of Nova T (open circles) or a 20 micrograms/24 hours levonorgestrel-releasing device (solid circles).

65
Contraception 1994149, January
Levonorgestrel- and copper-releasing IUDs: Andersson et al.

Pelvic Infections
There was in neither the Nova T nor in the LNG-IUD group an increased
incidence of PID in relation to the IUD insertion (Figure 4). The 60-month
gross removal rates for PID were 2.2 in the Nova T and 0.8 in the LNG-
IUD group [(P < O.OS), (Table 3)]. In the LNG-IUD users, the incidence of
PID was low regardless of age whereas in the Nova T group, there was a
significantly (P < 0.01) increased PID rate compared to LNG-IUD among
the youngest women (Table 3).

Hormonal Side Effects

A number of side effects shown in Table 6, were considered to be related
to the levonorgestrel administration and the discontinuation rate because
of such hormonal side effects was higher in the LNG-IUD group than in
the Nova T group [(P < O.OOl), (Table 3)].

O/O

6-

4-

-_-__--
2- __-------_-------
I-’
_,-__I’
,-I--
f
-_ _--a 1 I
*_py-;;-,I, , ( 1 , , ( 1 , , , I , , I

0 1 2 3 4 5
Year

FIGURE 4. Five-year cumulative gross rate of pelvic inflammatory disease per 100 women, for 937 women
during use of Nova T (- - -) and for 1821 women during use of a 20 micrograms/24 hours levonorgestrel-
releasing IUD (- ).

66 Contraception 1994:49, January

 Levonorgestrel- and copper-releasing IUDs: Andersson et al.

TABLE 6. The cumulative 60-month gross termination rate for hormonal reasons in women
using Nova T (N = 937) or a 20 micrograms/24 hours levonorgestrel-releasing device [(LNG-
IUD) N = 18211

Nova T LNG-IUD P

Depression 0 2.9 *
Acne 0.4 2.3
Headache 0.2 1 .Q
Weight change 0 1.5 :
Breast tenderness 0 0.8
f
Nausea 0.4 0.8 NS
Hirsutism 0 0.7 NS
Other skin problems 0 0.5 NS
Other mood changes 0.7 1.5 NS

NS = not significant. * = P < 0.05. T = P < 0.01. * = P < 0.001.

Other Medical Reasons

The 60-month gross removal rate for other medical reasons than reported
above are shown in Table 3.
The termination rates per 100 women-years for enlarged follicles were
almost similar in the two groups-O.07 for Nova T and 0.09 for LNG
IUD.
Four women in the LNG-IUD group discontinued the study due to
hypertension and none in the Nova-T group discontinued for this reason.
During the observation period, there were no changes in mean systolic
or mean diastolic blood pressure in any women using LNG-IUD or copper-
releasing IUD.

Personal Reasons
Planning pregnancy and other personal reasons for termination were simi-
larly age-related in users of both IUDs and more common among young
women (Table 3).

Effect on Weight and Haemoglobin

The mean weight at admission was 61.9 (SD 10.6) kg in the Nova T group
and 62.0 (SD 10.0) in the LNG-IUD group. After five years the mean
weight had increased to 64.4 kg in both groups.
The changes in haemoglobin concentration during the observation pe-
riod are shown in Table 7. After 5 years, the mean haemoglobin concentra-
tion showed an increase of 1.6 g/l during use of LNG-IUD and a decrease
of 2.6 g/l during use of Nova T. The differences between the two device

Contraception 1994:49, January 67

Levonorgestrel- and copper-releasing IUDs: Andersson et al.

TABLE 7. Mean values (SD) of Hb during five years’ use of Nova-T or a 20 micrograms/24 hours levonorgestrel-
releasing device (LNG-IUD). Only women where values are available at admission as well as at the control
visit are included. The percentage of women completing each observation period and in whom Hb values are
available is presented (%). P values indicate the differences in change of Hb between the device groups.

Nova T LNG-IUD

Time Hb N (“A) Hb N W) P

Adm 135.8 (10.3) 618 135.7 10.7) 1227

1 year 134.9 (11.1) 618 (84) 137.6 10.4) 1227 (86) t
Adm 135.9 (10.9) 509 135.6 10.7) 1043
2 years 132.4 (10.5) 509 (84) 136.4 9.3) 1043 (91) *
Adm 134.3 (10.6) 343 133.9 10.0) 706
3 years 132.0 (11.2) 343 (72) 134.9 9.3) 706 (73) l

Adm 132.9 ( 9.8) 253 133.4 9.8) 571

4 years 132.3 ( 9.9) 253 (65) 134.5 ( 9.9) 571 (67) ’
Adm 135.4 (10.0) 254 134.6 (10.7) 622
5 years 132.8 (10.1) 254 (80) 136.2 ( 9.5) 622 (85) *

* = P< 0.05. t = P< 0.01. * = P < 0.001

groups, in change of haemoglobin concentration, are statistically signifi-

cant during the entire follow-up period.

Reported Subjective Side Effects

Main categories of side effects elicited by asking the woman the question
“How have you been feeling?” are described in Table 8. The rate of reported
side effects decreased over time but at three months there were significant
differences between the devices concerning back pain, headache, nausea,
depression, menstrual problems, acne and mastalgia which were all more
often reported in the LNG-IUD group. At five years, 25.9% of the Nova-
T users and 15.1% of the LNG-IUD users mentioned problems. Menstrual
problems were pointed out by 18.8% and 6.3%, respectively (P < O.OOl),
and other complaint categories were reported at a rate of less than 5%.

Discussion
The intrauterine release of levonorgestrel makes the endometrial glands
atrophic, the epithelial cells inactive and the stroma decidua1ized.1~ The
endometrium is converted to be insensitive to ovarian estradiol. These
changes are probably the most important for the clinical performance of
the LNG-IUD. There are only limited effects on ovulation and on the
pituitary.‘“,‘”
The contraceptive efficacy of the LNG-IUD was, in this study, compara-
ble to female sterilization,” and so far, the LNG-IUD is one of the most

68 Contraception 1994:49, January

 Levonorgestrel- and copper-releasing IUDs: Andersson et al.

TABLE 8. Subjective side effects (%) reported at 3 and 60 months in women using Nova T copper IUD or a
20 micrograms/24 hours levonorgestrel-releasing device (LNG-IUD)

3 Months 60 Months

Nova T LNG-IUD P Nova T LNG-IUD P

No problems 64.5 49.8 t 74.1 84.9 *

Back pain 1.9 3.1 l 0.3 1 .o NS
Low abdominal 1.8 10.5 NS 2.7 2.0 NS
pain
Headache 0.8 2.8 f 1 .o 1.6 NS
Nausea 0.2 2.4 * 0 0.3 NS
Depression 0.4 2.5 l 0.3 0.6 NS
Menstrual 22.2 32.1 l 18.8 6.3 l

problems
Acne 0.4 3.5 f 0.3 1.8 NS
Mastalgia 0.2 3.1 l 0.7 1 .o NS
Other 6.1 8.7 t 4.8 3.6 NS

NS = not significant. l = P < 0.001. t = P c 0.05.

effective long-term reversible contraceptive methods requiring single

application.
The rate of ectopic pregnancy in our study (0.02 per 100 women-years
in the LNG-IUD group and 0.25 per 100 women-years with Nova T) could
be compared to the ectopic pregnancy rate of 1.2-1.6 per 100 women-
years in sexually active Swedish women age 15-44 seeking pregnancy.lX
The estimated ectopic pregnancy rate in women using TCu 380 or MLCu
375 is similar to LNG-IUD; 0.02 per 100 women-years indicating that
these devices are highly effective in preventing ectopic pregnancies as
well.3 The ectopic pregnancy rate in the Nova T group (0.25 per 100
women-years) was higher in our study compared to other investigations3
This may be explained by an increased incidence in the population studied
and in Sweden the ectopic rate has been increasing the last decade.lR
Bleeding problems were the most common reason for discontinuing
the use of both IUDs, but termination for this reason was more common
in the Nova-T group. These results concerning the copper IUD are similar
to those presented by other investigators.” The termination rate for heavy
and prolonged menstrual flow was lower with LNG-IUD compared to
Nova T. However, the removal rate for irregular bleeding and spotting
was similar in both groups. Frequent irregular bleeding is more common
during the first months after LNG-IUD insertion, and during prolonged
use of the LNG-IUD, a reduction of the number of days with bleeding
and/or spotting will occur. It is crucial that the woman has been carefully

Contraception 1994149, January 69

Levonorgestrel- and copper-releasing IUDs: Andersson et al.

informed about what to expect concerning the bleeding pattern after LNG-
IUD insertion, to avoid an unnecessary removal.
The local effect on the endometrium by levonorgestrel leads to reduc-
tion of the menstrual blood loss and to oligo-amenorrhea.19,zo The nature
of this endometrial amenorrhea should be included into the information
which is given to the woman before insertion of the LNG-IUD, to prevent
uncertainties about pregnancy or later return to fertility. The 5-year gross
cumulative termination rate because of amenorrhea was 6.0, but this is
not an estimate of the incidence of amenorrhea, the menstrual diaries
have to be analyzed for calculation. In Sivin’s blind study,” the gross
removal rate because of amenorrhea was 19.7 after 5 years. When women
are well informed about the reduction of bleeding and development of
oligo-amenorrhea, they may learn to like the freedom of the non-bleeding
situation. It is important to inform the women that amenorrhea does not
reduce the ability to conceive after removal of the LNG-IUD. Return to
fertility is as rapid after removal of LNG-IUD as after Nova-T.*’
Moreover, excessive menstrual blood loss is the most common cause
of anemia in fertile women, and nonmedicated IUDs increase the blood
loss about 50-75 % .22 The LNG-IUD reduces the blood loss and increases
the hemoglobin concentration during use. This may be especially im-
portant for women in developing countries where poor nutrition and/or
diseases may contribute to an iron-deficient situation. The strong proges-
togen dominance of the endometrium has also been used as therapeutic
principle to treat excessive menstrual bleeding. It seems that the LNG-
IUD can replace hysterectomy and endometrial ablation in most women
suffering from idiopathic menorrhagia.2”
The reduced risk of PID in the LNG-IUD group compared to Nova T
use, has earlier been demonstrated. lo In other studies where LNG-IUD
has been compared to copper IUD, similar PID rates have been demon-
strated in both groups.i,6,X The incidence of PID, in the present study, is
low in both IUD groups; nevertheless, there was a decreased risk of PID
during LNG-IUD use, and the difference between the device groups is
statistically significant in women less than 25 years of age. This is the
age group where PID is most common and an increased risk of PID follow-
ing use of conventional IUDs makes intrauterine contraception unsuitable
for young women. Use of LNG-IUD may change this opinion. It is im-
portant to notice that no increase in PID was seen in relation to the
insertions. The reason for this may be that cervicitis was excluded before
and aseptic technique used at insertion.
Removal rate for reasons which were classified as “hormonal” was
higher in the LNG-IUD group compared to Nova-T. Most of the reported
side effects after three months of use were hormonal, but these side effects
decreased during the study period. However, it is obvious that the dosage of
20 micrograms levonorgestrel/24 hours exerts certain systemic hormonal

70 Contraception 1994~49, fanuary

 Levonorgestrel- and copper-releasing IUDs: Andersson et al.

effects. Therefore, it is important that counselling also includes informa-

tion that the LNG-IUD is a hormonal contraceptive method, even if the
daily dose of levonorgestrel is only a fraction of the dose which is given
in oral contraceptives.

Acknowledgments
This multicenter study was conducted by the following investigators:
Maija Haukkamaa and Tapani Luukkainen (City Maternity Hospital, Hel-
sinki, Finland), Juhani Toivonen (Planned Parenthood Association, Hel-
sinki, Finland), Pentti Holma and Tapani Pyorala (Central Hospital,
Jyvaskyla, Finland), J u h ani Terho (Health Center, Tampere, Finland),
Hannu Allonen (Leiras Oy, Turku, Finland), Elof Johansson, Viveca Od-
lind, and Sven-Eric Olsson (University Hospital, Uppsala, Sweden), Staffan
Nilsson (Falu Hospital, Falun, Sweden), Bo Sikstrom and Ann-Charlotte
Smeds (Central Hospital, Eskilstuna Sweden), Kerstin Andersson and
Goran Rybo (East Hospital, Goteborg, Sweden), Paula Atterfeldt, (Sociala
Huset, Goteborg, Sweden), Arnt Steier and Magnar Ulstein (Haukeland
Hospital, Bergen, Norway), Istvan Batar (University Medical School, De-
brecen, Hungary), Niels Christian Nielsen (Bispebjerg Hospital, Copenha-
gen, Denmark), Mogens Osler (University Hospital, Copenhagen,
Denmark).
Financial support was obtained from Leiras Oy, Turku, Finland, and
from the Hjalmar Svensson Foundation (University of Goteborg), Sweden.

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