Maturitas 47 (2004) 159–174

Current treatment of dysfunctional uterine bleeding

Marlies Y. Bongers a,∗ , Ben W.J. Mol b , Hans A.M. Brölmann c
a Department of Obstetrics and Gynaecology, Máxima Medical Centre, P.O. Box 7777, 5500 MB Veldhoven, The Netherlands
b Department of Obstetrics and Gynaecology, Twee Steden Hospital, Tilburg, The Netherlands
c Department of Obstetrics and Gynaecology, Free University Medical Centre, Amsterdam, The Netherlands

Received 25 February 2003; received in revised form 10 July 2003; accepted 7 August 2003

Abstract

Objectives: We performed a review of the treatment modalities for dysfunctional uterine bleeding. Methods: Dysfunctional uter-
ine bleeding can be treated medically or surgically. Medical treatment consists of anti-fibrinolytic tranexamic acid, non-steroidal
anti-inflammatory drugs, the combined contraception pill, progestogen, danazol, or analogues of gonadotrophin releasing hor-
mone. The levonorgestrel releasing intra uterine device is developed for contraception, but is also effective in the treatment of
dysfunctional uterine bleeding. Surgical treatment includes endometrial ablation of the first and second-generation, and hysterec-
tomy. This review contains current available evidence on the effectiveness of these therapies. Results: Antifibrinolytic tranexamic
acid is the most effective medical therapy to treat dysfunctional uterine bleeding. In general medical therapy is not as effective as
endometrial resection in terms of patient satisfaction and health related quality of life. The levonorgestrel releasing intra uterine
device is an effective treatment for dysfunctional uterine bleeding. No difference in quality of life was observed in patients treated
with a levonorgestrel releasing intra uterine device as compared to hysterectomy. Ablation techniques of the first generation are
effective and safe when used by trained surgeons, but have a learning curve. Ablation techniques of the second generation are
effective, but long-term follow-up data are not available. Similarly, there are no large randomised controlled trials comparing
the levonorgestrel releasing intra uterine device to first and second-generation ablation techniques. Hysterectomy, the traditional
standard of care, has a relatively high complication rate, but it generates a high satisfaction rate and good health related quality
of life scores. Conclusion: Since none of the treatments for dysfunctional bleeding is superior to one of the others, and since
all treatments have their advantages and disadvantages, counselling of patients with dysfunctional bleeding should incorporate
medical approach, levonorgestrel releasing IUD, endometrial ablation and hysterectomy.
© 2003 Elsevier Ireland Ltd. All rights reserved.

Keywords: Dysfunctional uterine; Bleeding; Levonorgestrel

1. Introduction prolonged and/or heavy menstrual bleeding (menor-

Abnormal premenopausal uterine bleeding can
be irregular, non-cyclic bleeding (metrorrhagia) or
∗ Corresponding author. Tel.: +31-40-8888385;
fax: +31-40-8888387.
E-mail address: my.bongers@iae.nl (M.Y. Bongers).
rhagia). Menorrhagia is defined as heavy menstrual
bleeding (menstrual blood loss more than 80 ml) with
a cyclical character over several consecutive cycles,
thereby implying that irregular vaginal bleeding, as
well as other abnormal bleeding patterns should be
excluded from the definition of menorrhagia [1].
Menorrhagia is a frequent problem in premenopausal

0378-5122/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.maturitas.2003.08.002
160 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
women. It is estimated that a woman has a life time
chance of 1:20 to consult her general practitioner for
complaints due to menorrhagia [2–4].
Since only 40–50% of the women who complain of
heavy menstrual bleeding suffer from objective men-
orrhagia, it is important to quantify the amount of
menstrual blood loss [5,6]. Gannon et al. found that,
among women treated by endometrial ablation for
heavy menstrual bleeding, those with quantified men-
orrhagia were more likely to be satisfied with the treat-
ment result (OR 2.5, 95% CI 1.1–4.7), and less likely
to require subsequent hysterectomy (OR 1.8, 95% CI
0.6–5.2), as compared to women who experienced
their menstruation as heavy before the onset of treat-
ment without having menstrual blood loss more than
80 ml [7]. Women with menstrual bleeding of more
than 80 ml have a higher incidence of anaemia. Al-
though a low serum haemoglobin (<12 g/dl) increases
the chance of objective menorrhagia, a normal serum
haemoglobin does not rule out menorrhagia (sensi-
tivity 43%, specificity 94%) [8]. Since women’s per-
ception of the heaviness of their menstrual blood loss
does not always correlate well with the objective as-
sessment, the severity of menstrual bleeding must be
quantified. Hallberg introduced the alkaline haematin
method to measure menstrual blood loss [9]. In the al-
kaline haematin method, menstrual blood is collected
from towels and tampons, using a 5% NaOH solution.
Such techniques require hospital-based equipment and
staff [10]. Furthermore, the collection of pads and tam-
pons makes the alkaline haematin method inconve-
nient for women. In order to get a semi-quantitative
measurement of the menstrual blood loss, Higham
et al. [11] developed a pictorial blood loss assessment
chart. The pictorial chart consists of a series of di-
agrams representing lightly, moderately and heavily
soiled pads and tampons. Multiplication of the num-
ber of slightly, moderately and heavily soiled pads
and tampons with fixed absorption factors results in a
Higham score. On the Higham chart, a cut-off score
of 100 was found to correlate with menstrual blood
loss of more than 80 ml. Janssen et al. [8] investi-
gated the usefulness of a modified pictorial chart in
a larger study, and recommended a cut-off score of
185. Although the use of a pictorial chart might im-
plicate misclassification of menorrhagia, the method
is clearly more accurate than history alone [8,11,12].
However, patient-selection in DUB trials is often not
defined, not as blood loss in excess of 80 ml and not
as a pictorial chart score.
Menorrhagia can be caused by intracavitary abnor-
malities, but it also can occur in women without such
abnormalities. In the last decade, the introduction of
transvaginal sonography, saline infusion sonography,
and hysteroscopy has improved the possibility to diag-
nose intracavitary abnormalities [13,14]. In case when
intracavitary abnormalities are not present, women
suffering from menorrhagia are said to have dysfunc-
tional uterine bleeding. Dysfunctional uterine bleed-
ing is defined as periodic uterine blood loss in excess
of 80 ml per cycle occurring in the absence of struc-
tural uterine disease. The aim of the present review is
to discuss the treatment options for women with dys-
functional uterine bleeding.
2. Medical treatment
Medical treatment of dysfunctional uterine bleed-
ing includes treatment with anti-fibrinolytic tranex-
amic acid, non-steroidal anti-inflammatory drugs
(NSAID’s), the combined contraception pill, pro-
gestogen, danazol, and analogues of gonadotrophin
releasing hormone (GnRH analogues). The effective-
ness of drug therapy for dysfunctional uterine bleed-
ing was evaluated and reported in systematic reviews
in the Cochrane library [15–19].
Antifibrinolytic tranexamic acid has proven to be
effective in the reduction of dysfunctional uterine
bleeding as compared to placebo. Reduction of men-
strual bleeding after treatment with tranexamic acid is
significantly higher when compared to other medical
therapies (NSAID’s, oral luteal phase progestogens
and ethamsylate), without an increase in side effects
[15,20,21]. Flooding, leakage, and sex life are sig-
nificantly improved after anti-fibrinolytic tranexamic
acid therapy when compared with oral luteal phase
progestogens.
Non-steroidal anti-inflammatory drugs reduce dys-
functional uterine bleeding as compared to placebo,
but are less effective than either antifibrinolytic tranex-
amic acid or danazol [16]. In a limited number of stud-
ies, NSAID’s show no significant differences in effec-
tiveness as compared to other medical therapies such
as oral luteal progestogen, ethamsylate, combined
contraception pill or a levonorgestrel releasing IUD.
 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
The combined contraception pill also decreases the
amount of blood loss in women suffering from dys-
functional uterine bleeding [17,22]. The only small
study performed addressing this subject reports no sig-
nificant difference between women treated with com-
bined contraception pill, mefenamic acid, low dose
danazol, or naproxen [23]. It is generally known that
women will not have a menstrual bleeding when the
combined contraception pill is continued without a
stop week, although there is lack of high quality evi-
dence on this subject.
Progestogens administered from day 15 to 26 of
the cycle offer no advantage over other medical thera-
pies such as danazol, anti-fibrinolytic tranexamic acid,
NSAID’s and the levonorgestrel releasing IUD in the
treatment of dysfunctional uterine bleeding in women
with ovulatory cycle’s [18]. Progestogen therapy dur-
ing 21 days of the cycle results in a significant reduc-
tion of menstrual blood loss but its strong side effects
limit long-term use [18].
Similarly, second line drug therapies, such as
danazol and GnRH analogues, are not suitable for
long-term use due to their serious side effects [19].
Danazol appears to be an effective treatment for
dysfunctional uterine bleeding, but is also causes hir-
sutism. GnRH analogues are associated with a high
risk of irreversible bone loss after six months. Thus,
both danazol and GnRH analogues are meant only
for short- term use, whilst decisions regarding future
treatments can be made [19–24].
Cooper et al. compared medical treatment to tran-
scervical resection of endometrium (TCRE) in a ran-
domised controlled trial (RCT) [25–28]. In his study,
TCRE showed a significantly higher patient satisfac-
tion at 4 months, 2 and 5 years follow-up [25–28].
Moreover, surgical (re)intervention rates at 5 years
were 77% in the medical treatment group and 27%
in the TCRE group, with hysterectomy rates being
comparable (18% versus 19%) [25–28]. Although
quality of life was improved in both treatment arms,
the improvement was more evident in the TCRE-
group.
In conclusion, anti-fibrinolytic tranexamic acid
is the most effective medical treatment option. Al-
though good studies on the effectiveness of the con-
trolled contraception pill are lacking, the pill seems
a useful treatment in every day clinical practice
[29].
161
3. Levonorgestrel releasing intra uterine
device (IUD)
Another form of medical treatment is the lev-
onorgestrel releasing intra uterine device (IUD)
(Mirena® ). The levonorgestrel releasing IUD is orig-
inally developed for contraception, but it has also
proven to be an effective device in the treatment of
dysfunctional uterine bleeding. Its efficacy is based
on the local release of levonorgestrel in the uterine
cavity, thus suppressing endometrial growth. The
use of levonorgestrel releasing IUD considerably de-
creases the amount of menstrual blood loss [30–36],
with a reported reduction of 97% [37]. In the first
few months after insertion many women suffer from
intermenstrual bleeding, but at one year after inser-
tion most women bleed only for one day, and 15%
became amenorrhoeic [38]. The levonorgestrel re-
leasing IUD has proven to be more effective than
cyclical norethisterone (21 days) in the treatment of
dysfunctional uterine bleeding [35]. Women using
a levonorgestrel releasing IUD are more satisfied as
compared to women with progestogen therapy, de-
spite the occurrence of progestogenic side effects in
the IUD group such as intermenstrual bleeding and
breast tenderness [35]. There are no data available
from randomised controlled trials comparing the lev-
onorgestrel releasing IUD to either placebo or other
medical therapies for dysfunctional uterine bleeding.
Costs of the levonorgestrel IUD are high compared
to other medical treatment. However, this difference
reduces over time due to the fact that the IUD is used
for a 5-year period.
The potential advantage of the levonorgestrel re-
leasing IUD is its ease of use, its low costs and its low
complication rate. However, these benefits are only of
interest if the use of the levonorgestrel releasing IUD
would demonstrate superior results, in terms of pa-
tient satisfaction, quality of life, and symptomatic im-
provement, when compared to endometrial ablation.
Transcervical resection of the endometrium (TCRE)
is the only ablation technique that has been compared
with levonorgestrel releasing IUD in two small RCTs
[34–36]. The use of a levonorgestrel releasing IUD
allowed for a smaller reduction of menstrual blood
loss as compared to TCRE (67% versus 90%), and
women are not as likely to become amenorrhoeic, but
no difference was observed in the rate of satisfaction
162 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
between the two treatment modalities. Women with a
levonorgestrel releasing IUD experienced a higher rate
of progestogenic side effects as compared to women
treated with TCRE. Clinical results of the two RCTs
comparing TCRE and levonorgestrel releasing IUD
suggested that levonorgestrel releasing IUD are not
as effective as TCRE, but both studies suffer from a
lack of power, and do not allow for definite conclu-
sions. Furthermore in both studies it was not clear if
patients were treated medically before they entered
the study, which could have been favourable for the
surgery group.
There is one RCT in which the levonorgestrel re-
leasing IUD is compared with hysterectomy. This trial
shows that both treatments are equal in terms of health
related quality of life [39]. Overall costs were three
times higher in the hysterectomy group than in the
levonorgestrel releasing IUD group. Follow-up visits
after treatment were at 6 and 12 months. Unfortu-
nately, the mean waiting time between randomisation
and start of treatment was different in the two groups.
The mean waiting time for the hysterectomy group
was 6–7 months, with a maximum of 21 months. Thus,
follow-up visits in the hysterectomy group were 12 and
18 months after randomisation, whereas the follow-up
visits in the levonorgestrel releasing IUD group were
at 6 and 12 months after randomisation. Consequently,
the groups were not as equal as the baseline charac-
teristics suggest.
In conclusion, the effectiveness of the levonorgestrel
releasing IUD appeared to be comparable to that of
hysterectomy. Comparisons of the levonorgestrel re-
leasing IUD to endometrial ablation suffer from a lack
of statistical power. However, its ease of use and its
low costs makes the levonorgestrel releasing IUD a
promising therapy for dysfunctional uterine bleeding.
4. Surgical treatments for dysfunctional
uterine bleeding
Dilatation and curettage (D&C) causes a temporary
reduction of menstrual blood loss for the first month,
but at following cycles, the amount of blood loss tends
to increase as compared to the blood loss before the
D&C [40]. Therefore, D&C must be considered ob-
solete in the treatment of dysfunctional uterine bleed-
ing, but unfortunately it is still performed on a large
scale in women suffering from dysfunctional uterine
bleeding [40].
5. First generation endometrial ablation
techniques
Ashermann was the first to describe the association
between D&C and women who became amenorrhoeic
after an abortion. He found an obliterated uterine cav-
ity at hysterectomy and described this condition as
‘amenorrhoea atretica’ or ‘amenorrhoea traumatica’.
Since than, physicians have studied the possibility of
controlled injury of the basal layer of the endometrium
in order to treat dysfunctional uterine bleeding [41].
Hysteroscopic resection was the first efficacious
ablation therapy for intrauterine fibroids. It was in-
troduced in 1976 by Neuwirth et al. [42], and offered
a surgical alternative to hysterectomy. Subsequently,
laser ablation, radio-frequency monopolar resection,
and rollerball ablation were developed [43–45]. These
techniques, commonly addressed as first generation
ablation techniques, have been studied in cohort stud-
ies and several RCTs (Fig. 1). These studies and
their results will be discussed in the next paragraphs
(Fig. 2).
5.1. Hysteroscopic laser ablation (HLA)
The first neodymium-YAG laser used a dragging
technique for ablation of the endometrium [43]. The
non-touch laser technique that was developed after-
wards resulted in a shorter treatment time, but was less
effective than the touch technique. Non-randomised
prospective studies have reported that hysteroscopic
laser ablation (HLA) has high satisfaction rates with
reported amenorrhea rates between 20 and 60%
[46–55]. Surgical reintervention rates varied between
7 and 27%. Costs of laser ablation are high due to the
high costs of both the laser equipment and single use
fibers.
5.2. Transcervical endometrial resection (TCRE)
The use of a resectoscope allowed the performance
of transcervical resection of the endometrium (TCRE)
[43]. Non-randomised prospective studies have re-
ported patient satisfaction rates varying between 79
 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174 163

HLA 48-51(>5yr FU, n=1000)

1981 Satisf 80-93% Amen 22-62% Reinterv 7-27%
RCT: HLA/Hysterectomy(2yr FU, n=200)
Satisf 78% Amen 22% Reinterv 6% CI1.8-4,9
to 11-19,7
Lng-IUD
1983 4,36
TCRE57,58 (>5yr FU, 50->500) RCT: IUD/TCRE3 (1yr FU)
Satisf 79-92% Amen 26-40% Reinterv 20-27% Satisf 85/94% Amen 65/71% Reinterv -/-
59-63 RCT:IUD/Hysterectomy39(1yr FU)
RCT: TCRE/Hysterectomy, (2yr FU,n=200)
Satisf 68/100% Amen - Reinterv 20%/-
Satisf 85-87%/90-94% (CI 1.1-17.5%)
Reinterv 10-28%/--(CI1.8-4,9 to 11-19,7)

Rollerball®53(>5yr FU, n=600)

Satisf:80-92% Amen 27-46% Reinterv 27%
1989 RCT: RB/2e generatie(5yr FU, n=>260)
Success 82-89% Amen 27-46%
Reinterv 30%-7%

® 85-94
ThermaChoice (3yr FU)
Satisf 85-90% Amen 15-20%
1994 RCT:ThermaChoice/RB (5yr FU n=275)
Success 86/82% Amen 15/26% Reinter 6/14%

1995 HTA® 101,102

RCT:HTA/RB(1yr FU, n=276)
Success 77/82% Amen 40/51%
Reinterv 2%/0
1996 ® 95-97
Cavaterm (1yr FU, n=50)
Satisf 91-96% Amen 33-60%
Reinterv 5-7% (CI 0.84-1.0)

® 104-106
MEA (2yr FU, n=263)
1999 RCT: MEA/TCRE
Satisf 77/75%(CI -12 to 17) Amen 40/40%
Reinterv 12/12%

® 111,112
ELITT (1yr FU, n=100)
2000 Satisf 91% Amen 70-71% ® 107-110
Her Option (½yr FU, n=279)
Preliminary RCT: HO/RB
Success 86/89% Amen - Reinterv -
® 98
Menotreat (1yr FU; n=51,)
2001 Success 85% (CI=74-94%) Amen 10%
Reinterv-

NovaSure® 113,114(1yr FU, n=107)

2002 Satisf 90% Amen 58% Reinterv 3%
RCT: NovaSure/RB(1yr FU; n=265)
Satisf 93% Amen 41% Reinterv 3%

Fig. 1. Time-table of development of the endometrial ablation techniques. Results in terms of satisfaction (Satisf.), amenorrhea (Amen.), and
re-intervention (Reinterv.) of the different techniques are added. A differentiation between observational studies and randomised controlled
trials (RCT) is made. Length of follow-up and power of the studies are added. Abbreviations: FU: follow-up, HLA: hysteroscopic laser
ablation, TCRE: transcervical resection of the endometrium, Lng-IUD: levonorgestrel releasing intra uterine device, RB: rollerball, HTA:
hydrotherm ablation, MEA: microwave endometrial ablation, ELITT: endometrial laser intrauterine thermal therapy, FO: first option.
164 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
Diagnosis
No intracav.
pathology
Ca +
Therapy Oncologic
pathway
Fig. 2. Flowchart of DUB. Intracav.: intracavitary, Ca: carcinoma.
and 92%, amenorrhea rates ranging between 26 and
40%, and reintervention rates varying between 20 and
27% [53,54]. The effectiveness of TCRE studied in
RCTs is comparable to the effectiveness of laser ab-
lation, but operating time, fluid absorption and costs
are higher with laser ablation [54–56].
5.3. Rollerball endometrial ablation
Rollerball ablation has been developed in Australia
[45]. The results of the rollerball ablation are compa-
rable to the results of TCRE and laser ablation [57,58].
However, rollerball ablation requires less operative
skills, since there is no debris floating in the uterine
cavity. Rollerball ablation is also less time consuming
compared to laser ablation.
5.4. Studies evaluating first generation ablation
techniques
Hysteroscopic endometrial ablations have been
compared to abdominal hysterectomy [59–61], to
vaginal hysterectomy [62], and to both techniques
[56,63]. At two years after treatment, quality of life
was higher after abdominal hysterectomy than fol-
lowing endometrial ablation [59–61]. Endometrial
resection was compared to vaginal hysterectomy in
one RCT [62]. In this study, patient satisfaction, qual-
ity of life, psychological status and sexual functioning
did not differ significantly between the two arms,
DUB
Biopsy
Ca -
Therapy Choice of:
• Medicine
• Lng IUD
• Ablation
Hysterectomy
although patient satisfaction was higher after vaginal
hysterectomy (94%) when compared to endometrial
resection (87%). From the economic perspective, en-
dometrial destruction is less costly as compared to
hysterectomy, but since re-treatment is often neces-
sary this cost difference narrows over time [64].
The Mistletoe study reports on complications of
ablation techniques of the first generation, and shows
that endometrial ablation and endometrial resection
both performed under hysteroscopic view, are safe
procedures with a low morbidity [65]. Perioperative
complications are perforation with the possibility of
bowel injury, haemorrhage, visceral burn, genital tract
burn and cardiovascular problems due to intravasation
of distension fluid [66] (Table 1). Women undergoing
laser or rollerball ablation have consistently fewer im-
mediate operative complications compared to TCRE
[65]. Another problem of the hysteroscopic guided
endometrial ablation is related to absorption of the
distension media. Glycine 1.5% and Sorbitol 5% are
both used for uterine distension. During transcervical
surgery, high intrauterine pressures are needed to dis-
tend the uterine cavity resulting in risk of absorption of
distension fluid, characterised by hyponatraemia, wa-
ter intoxication, cerebral edema and cardiac overload.
Fatal hyponatremic encephalopathy with cerebral
edema has been reported in women undergoing TCRE
[67,68]. Management of fluid overload requires accu-
rate monitoring of fluid balance, and interruption of
the procedure before excessive fluid absorption occurs.
 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
Table 1
Complications of first generation ablation techniques
Early complications
Problems with distension fluid
Fluid overload
Cardiac failure
Water intoxication, hyponatraemia
Cerebral edema
Haemorrhage
Perforation
Visceral burn and bowel burn
Genital tract burn
Late complications
Hematometra
Tubal occlusion syndrome
Endometrial cancer
Pregnancy related
Complications that are specifically related to disten-
sion media occur in 0.14–4% of the procedures [69].
The most important late post-operative compli-
cations are the occurrence of haematometra and
post-tubal sterilization syndrome, previously undis-
covered endometrial cancer, and pregnancy related
complications (Table 1). First, complications can be
caused by persistence of endometrium after the ab-
lation. Haematometra occurs in 1–2% of the women
treated with endometrial ablation. The post-ablation
tubal sterilization syndrome is caused by a focal cor-
nual hematometra with retrograde menstrual shedding
into an occluded fallopian tube due to recurrence or
survival of endometrial tissue. It occurs in 6–8% of
the patients [70,71], but the percentage of clinical
manifestations of this post ablation tubal sterilization
syndrome may be higher [71]. In patients treated with
rollerball endometrial ablation, a tubal ligation is a
risk factor for the development of pelvic pain and for
having a subsequent hysterectomy [71].
Secondly, the potential delay of diagnosis of en-
dometrial cancer is a disadvantage of all endometrial
ablation techniques. A majority of the cases of en-
dometrial cancer after endometrial ablation were pre-
ceded by a pretreatment biopsy containing atypical
hyperplasia of the endometrium [72]. Thus, it is of
importance to take an accurate endometrial sampling
before ablation treatment, and to renounce the abla-
tion procedure if the biopsy contains (pre)malignant
tissue [73]. Endometrial ablation should not be of-
fered for the treatment of abnormal uterine bleeding
165
in women who have endometrial hyperplasia. This
is especially of concern in patients with diabetes,
extreme obesity or hypertension. On one hand, these
0.14–4% co-morbidities increase the risk of major surgery, thus
making less invasive procedures more attractive. On
the other hand, especially these patients are at in-
creased risk for endometrial cancer. However, we feel
2.4% that a pretreatment biopsy should be performed and
1.5% the result be obtained before an ablative treatment is
0.06% offered. Despite the fact that endometrial ablations
Unknown
of the first generation exist for more than twenty
years the extent of the problem of potential delay of
1–2%
diagnosis of endometrial cancer is still not clear.
6–8%
Unknown A third potential problem is the occurrence of preg-
0.2–1.6% nancy after an ablation procedure. Pregnancy is esti-
mated to occur in 0.2–1.6% of the cases [74–76]. Such
pregnancies have an increased risk of pregnancy loss,
as well as other obstetric complications. Of the 11
pregnancies that were ongoing after 27 weeks of ges-
tation that have been reported, five (45%) were com-
plicated by growth retardation, and seven (63%) were
complicated by preterm delivery [77]. A possible ex-
planation for these complications is the sub-optimal
and/or abnormal attachment of placenta tissue to the
denuded endometrium.
Failures of first generation ablation techniques
might be attributed to incomplete ablation of en-
dometrial tissue or to adenomyosis [78,79]. Floating
debris or inadequate distension can hamper visualisa-
tion, thus limiting complete endometrial destruction.
Therefore, these techniques require intensive training
and have a long learning curve [80,81]. The different
methods of preparing the endometrium might also
be of importance for the effectiveness of treatment.
Prethinning of the endometrium gives significantly
better results in terms of short-term postoperative out-
come and operating time [82,83]. GnRH analogues
give slightly more consistent endometrial thinning
than danazol, though both agents produce satisfactory
results.
First generation ablation techniques are effective
and provide an alternative to hysterectomy. A hysterec-
tomy will not be necessary in 75–80% of the patients.
The long-term results of the first generation ablation
techniques might justify an increase of their use. How-
ever, both the learning curve and the complication rate
have hampered a wide implementation of these tech-
niques. Moreover, these disadvantages stimulated the
166 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
development of the second-generation ablative tech-
niques.
6. Second generation endometrial ablation
techniques
Second generation ablation devices have been in-
troduced in the last decade of the 20th century (Fig. 1)
[84,85]. These devices require less skill of the sur-
geon, and bear less risk compared to devices of the
first generation. However, these second generation ab-
lation techniques do not have the advantages of di-
rect visualization and detection of abnormal pathology
with the hysteroscopic-guided ablation techniques. A
preoperative endometrial biopsy should be performed
prior to the ablation technique. Although the second
generation techniques are very simple to perform, their
blind introduction can cause perforation and/or a false
passage. In most of these techniques the generator
will switch off automatically if preset values are aug-
mented. These preset values should not be overruled,
while they mostly implicate that the position of the
device is not correct.
In the next paragraphs we will discuss second gen-
eration devices with Table 2 giving a general overview
of these endometrial ablation systems. Devices that
are not available will only be mentioned shortly.
6.1. Thermal balloon endometrial ablation
The thermal balloon endometrial ablation tech-
niques consist of a balloon for insertion in the uterine
cavity and a generator. After insertion, the balloon
is filled with liquid, and the liquid is then heated
to destroy the endometrium. There are several ther-
mal balloon devices that are currently commercially
available, such as ThermaChoice® , Cavaterm® , and
Menotreat® .
ThermaChoice® was the first second-generation
ablation technique, and has been evaluated thor-
oughly [85–93]. Thermal balloon endometrial ab-
lation was first reported on in 1994. This device
(ThermaChoice® , Gynecare Johnson & Johnson, NJ,
USA) consists of a generator and a latex balloon
catheter (Table 2). A thermistor in the balloon is
used to monitor the temperature of the fluid within
the balloon and a heating element is employed to
raise the temperature of the fluid, with pressure being
maintained at 170 mmHg or higher. The generator,
which controls temperature, pressure and time, will
switch off automatically if temperature or pressure,
especially in case of incorrect position will exceed
the preset safe parameters.
ThermaChoice® has been compared to rollerball ab-
lation in a RCT. Results have been reported at 1, 2, 3,
and 5 years after treatment [86–89]. At 5-year follow-
up, both patient satisfaction and hysterectomy rate
(30%) are comparable for both treatment modalities,
with the amenorrhea rate being somewhat lower in the
ThermaChoice® group (26% versus 33%) (Fig. 1).
These results are consistent with the findings in several
non-randomised studies in which ThermaChoice® is
compared to TCRE [90–92], as well with the findings
in several prospective observational studies [93,94].
Pretreatment of the endometrium can be performed
with GnRH analogues or with suction curettage, in or-
der to decrease the thickness of the endometrial layer
prior to ablative treatment. Whether pre-operative
thinning of the endometrium with GnRH analogues
will improve success rate of balloon ablation, is still
a matter of debate. Although, statistically higher rates
of post procedure amenorrhea in women who received
depot GnRH agonist before balloon treatment has
been reported, it did not improve treatment outcome
in terms of the need for surgical re-intervention [93].
Serious complications of ThermaChoice® ablation
have not been reported.
The Cavaterm® hot water balloon device consists of
a disposable silicone balloon catheter with a heating
element connected to a battery-operated controller. A
pump with oscillating pressure vigorously circulates
glycine 1.5% inside the balloon. There is one very
small RCT comparing rollerball and Cavaterm® with
a short follow-up (9–15 months), showing similar re-
sults for both ablation techniques [95]. Amenorrhea
rates in non-randomised studies have been reported to
be 30–60% (Fig. 1) [96,97].
The Menotreat® thermal balloon ablation system
is similar to the Cavaterm® system. It uses a dispos-
able closed system without any electrical component.
The circulating fluid is heated inside the controller.
One observational study has reported an amenorrhoea
rate at 1 year of follow-up of 10% (Fig. 1) [98]. The
Vestablade balloon device with electrodes on the out-
side developed by Vancaillie is no longer commer-
cially available [99,100].
Table 2
Endometrial ablation devices of the second generation

M.Y. Bongers et al. / Maturitas 47 (2004) 159–174

Device/company Technique Method of destroying Treatment/procedure Diameter Assurance of RCT Pretreatment
time of probe placement
Therma Choice® Balloon ablation Temperature 87 ◦ C 8/14 min 4 mm Tactile, pressure Yes Yes
Gynecare J&J
Cavaterm® Wallsten Med. Balloon ablation Circulating fluid 85 ◦ C 15/unknown minute 8 mm Tactile, pressure Yes Yes
First Option® CryoGen Cryo ablation Freezing −100 ◦ C 10/20 min 5.5 mm Ultrasound Yes Yes
HTA® BEI Hysteroscope Saline of 90 ◦ C 10/20 min 8.5 mm Visual Yes Yes
Circulating heated
saline
MEA® Microsulis Microwave ablation Magnetic energy 9.2 GHz 3/unknown minute 8 mm Tactile tissue Yes Yes
temperature
ELITT® Storz Diode laser Thermal energy 7/unknown minute 7 mm Tactile No Yes
Menotreat® Atos Balloon ablation Heated circulating saline 11/unknown minute 8 mm Tactile, pressure No Yes
85 ◦ C
NovaSure® Novacept Three-dimensional Bipolar RF current up to 1.5/5 min 7 mm Measurement cornu Yes No
bipolar electrode 180 W to cornu

167
168 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
6.2. Endometrial ablation by hysteroscopic
instillation of hot saline solution
This device has been developed by Goldrath (Hy-
drotherm ablator (HTA® ) BEI Medical Systems,
Boston Scientific, Teterboro, NJ, USA). It is the only
second-generation device that is applied under direct
hysteroscopic view. Externally heated 0.9% normal
saline of 90 ◦ C is infused directly into the uterine cav-
ity through the in-flow channel of a continuous flow
outer plastic sheath that houses a diagnostic hystero-
scope. The infusion takes place at a pressure of less
than 45 mmHg resulting in an intrauterine net pres-
sure of 50–55 mmHg, thus preventing flow through
the fallopian tube. The system automatically shuts
down after 10 ml saline is lost. Hydrotherm ablation
is compared to rollerball ablation in a RCT that re-
ports amenorrhea rates at 12 months of 40% in the
hydrotherm ablation group and 51% in the rollerball
group [101]. Among potential complications of the
HTA® , burning of the cervix caused by leakage of
the heated saline has been encountered [102].
6.3. Microwave endometrial ablation
Sharp et al. [103] were the first to describe the
use of microwave energy (MEA® , Microsulis Plc.,
Waterlooville, UK). Microwave energy (9.2 GHz) is
generated by a magnetron. Application of energy is
controlled by a footswitch that is operated by the
surgeon. The temperature achieved inside the uterus
is monitored constantly by thermocouples. Once the
probe is activated and the tip temperature reaches
95 ◦ C the probe is moved laterally to place the tip in
the uterine cornua. After the temperature has reached
95 ◦ C, the tip is moved again to the other cornual
area. Thereafter, the probe is gradually withdrawn,
while maintaining the probe temperature between
85 and 90 ◦ C to ensure complete endometrial de-
struction. Pretreatment of the endometrium has been
prescribed in all trials. The microwave endometrial
ablation system is compared to TCRE in a RCT.
Amenorrhea-rates (40%) and satisfaction-rates (75%)
were similar at one and two years of follow-up (Fig. 1)
[104–106]. Hysterectomy was performed in 12 and
13% of the patients, respectively. Bowel injury after
the use of the microwave endometrial ablation system
has been reported in one patient [104].
6.4. Cryo endometrial ablation
Cryo ablation was the first non-chemical technique
of endometrial ablation, and was reported on for the
first time in 1967 [107]. Since then, several articles
on cryo ablation with CO2 probes were published
reporting amenorrhea rates of up to 50% [108]. The
Her Option® Uterine cryo ablation therapy (CryoGen,
Inc., American Medical Systems, San Diego, CA,
USA) was the first technique of cryo ablation that
was suitable for use in clinical practice. Her Option®
cryo ablation uses a new mixed gas coolant to gen-
erate temperatures of −90 ◦ C to −100 ◦ C. The cryo
probe is inserted in the uterine cavity and saline is
injected to bathe the probe. Freezing thawing of the
intrauterine ice ball is monitored with transabdominal
ultrasound [108–110] and assures correct position.
The Her Option® cryo ablation has been compared
with rollerball ablation in a RCT. Preliminary results
at 6 months after treatment show an overall success
(defined as pictorial chart score below 75) of 86% for
cryo ablation and 89% for rollerball ablation (Fig. 1)
[110]. Safety and effectiveness of this technique have
to be established.
6.5. Endometrial laser thermal ablation
This technique uses a diffuse laser light that reaches
the entire uterine cavity, including areas such as
the cornua. It does not require direct contact with
the endometrium to induce photocoagulation. The
830 nm-wavelength of the diode laser light pene-
trates the uterine wall to a precise depth, where it
is absorbed by haemoglobin. The absorbed light is
than transformed to heat, thus coagulating the en-
dometrium. Therapy may not be effective in the
presence of intrauterine bleeding. Endometrial Laser
Intrauterine Thermal Therapy (ELITT® ) (GyneLase,
ESC Sharplan, Needham, MA, USA) has been devel-
oped by Donnez et al. [111,112]. The three optical
laser lights fill the uterine cavity ensuring complete
therapy of the endometrium. The treatment has been
evaluated in a prospective observational study. At 12
months after treatment 91% of the women were satis-
fied, and the amenorrhea rate was 71% (Fig. 1) [112].
There were no complications during the treatment,
but two patients suffered from severe dysmenorrhoea
and had a hematometra after ablation. Results from
 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
RCTs using this treatment modality are not currently
available.
6.6. Bipolar impedance controlled
endometrial ablation
This bipolar device consists of a single-use, three
dimensional bipolar ablation device and radio fre-
quency controller (NovaSure® , Novacept, Palo Alto,
CA, USA). Endometrial pretreatment is not required
and active bleeding at the time of the operative visit
is not a limiting factor (Table 2). The NovaSure® Ra-
dio Frequency generator is a constant power output
generator with a maximum power delivery of 180 W.
The generator functions at 500 kHz and has a power
cut off limit set at 50  tissue impedance. The vac-
uum pump is contained within the radio frequency
generator and provides suction through the handle,
and the electrical array, via a central tube within the
NovaSure® endometrial ablation device. The applica-
tion of the suction draws the endometrial lining into
contact with the electrode array and removes moisture
generated during the ablation process. The NovaSure®
device consists of a single use, conformable bipolar
electrode mesh, mounted on an expandable frame
that can create a confluent lesion within the cavity of
the uterus that involves the entire inner surface area.
Continuous monitoring of tissue impedance controls
the depth of the ablation. Once the myometrial layer
is reached, tissue impedance increases rapidly to 50 
and the generator will switch off automatically. This
is a key aspect of this system, which is not based on
time and temperature, but on tissue-specific physical
characteristics. A cavity integrity assessment system
is implemented to automatically detect uterine wall
perforation. To do so, CO2 is inflated into the cavity.
Inability to pressurise and/or maintain pressure in the
uterine cavity will be detected by the controller and
alarm the physician of a possible perforation. The
corner to corner distance is measured by the device
and assures correct intracavitary position.
A RCT comparing NovaSure® with rollerball ab-
lation at 12 months follow-up reported 41% amenor-
rhea and 93% satisfaction in the NovaSure® arm and
35% amenorrhea and 94% satisfaction in the rollerball
arm (Fig. 1) [113]. These results have been confirmed
in prospective studies, in which NovaSure® demon-
strated an amenorrhea rate of 56% and a satisfaction
169
rate of 91% after 1 year of follow-up [114]. No com-
plications during treatment have been reported.
6.7. Hysterectomy
Hysterectomy is the only treatment for dysfunc-
tional uterine bleeding that guarantees a definite
solution. Hysterectomy is a major operation associ-
ated with morbidity and even mortality that neces-
sitates hospitalisation and several weeks of recovery
[115–122]. Despite this fact, hysterectomy provides a
high quality of life and a high satisfaction rate after
treatment. Large population based studies showed the
mortality rate of hysterectomy for benign conditions
to be 1 in 2000 in women under age of 50 [116]. The
CREST study reported a complication rate for minor
and major operations of 25% for vaginal hysterec-
tomy and of 43% for abdominal hysterectomy. The
rates of major complication are reported to be 5%
for vaginal hysterectomy [60] and 7% for abdomi-
nal hysterectomy [117]. These complication rates are
significantly higher than the complication rates of en-
dometrial ablations of the first generation. Although
hysterectomies have been performed for many years,
their effectiveness has only recently been assessed in
comparison with the endometrial ablations and lev-
onorgestrel releasing IUD [39,59–63]. As mentioned
before, quality of life is higher after hysterectomy
than after endometrial ablation when first generation
devices were used.
Randomised clinical trials comparing hysterectomy
to second generation ablation techniques are not cur-
rently available.
7. Discussion
Dysfunctional uterine bleeding can be treated with
medical therapy, a levonorgestrel releasing IUD, en-
dometrial ablation using first and second generation
techniques, and hysterectomy. In The Netherlands,
where most patients with dysfunctional uterine bleed-
ing are initially treated by the general practitioner,
medical therapy is the treatment of first choice for
most patients. However, the single RCT in which
medical treatment has been compared to endometrial
ablation indicates a significantly higher patient satis-
faction and quality of life after endometrial ablation
170 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
[25–28]. Only 23% of the women who were initially
treated medically avoided surgical intervention. In
the health system in The Netherlands, direct surgi-
cal treatment requires that patients with menorrhagia
should be referred directly to a gynaecologist. How-
ever, the applicability and role of the levonorgestrel
releasing IUD remains to be established. The lev-
onorgestrel releasing IUD is effective when compared
to hysterectomy, but its effectiveness as compared to
endometrial ablation has to be established [34–36,39].
If the effectiveness of the levonorgestrel releasing IUD
would appear to be comparable to the effectiveness of
endometrial ablation, a levonorgestrel releasing IUD
could be the treatment of first choice in the Dutch sit-
uation. The advantages of the levonorgestrel releasing
IUD over the ablation techniques are the lower cost,
the avoidance of hospitalisation, and preservation of
fertility prospects, thus making it an ideal treatment
to be offered by the general practitioner, before the
patient is referred for specialist care.
Since this review shows that none of the treatments
for dysfunctional bleeding is superior to one of the
others, and since all treatments have their advantages
and disadvantages, counselling of patients with dys-
functional bleeding by a specialist should incorporate
all treatment modalities described. It is imperative
for the gynaecologists to be well acquainted with all
treatment options, and have the possibility to offer
these modalities to their patients. Second generation
ablation techniques allow all hospitals with a gynae-
cological service to satisfy the needs of the patients
with dysfunctional uterine bleeding and offer a less
invasive treatment choice. Ablation therapy using first
generation ablation devices can be offered by gynae-
cologists who are trained and skilled in hysteroscopic
ablation. Less experienced gynaecologists should pro-
cure a second-generation device to avoid the effects
of a learning curve of the first generation techniques.
Another issue with respect to the learning curve
of endometrial ablations of the first generation is
the decreasing number of ablations, in case if lev-
onorgestrel releasing IUD will become the treatment
of first choice. In that situation, this will be an ad-
ditional argument for the use of simple and easy to
use second generation ablation techniques instead of
the skill dependent first generation techniques. The
device of choice will depend on success, amenorrhea
rates, safety and costs.
There is evidence from various specialties in health
care that patient’s satisfaction improves if patients can
participate in the decision-making process [122,123].
In the partial RCT of Cooper et al., women who
were randomised to medical therapy were compared
to women who refused randomisation, but preferred
medical therapy. The women who choose medical
therapy for their heavy menstrual bleeding were
significantly more satisfied than those who were
randomised to medical treatment [26].
Why should women prefer endometrial ablation
over hysterectomy? When women who had been
treated with endometrial ablation were asked about
their attitude towards endometrial ablation, more than
half indicated that they would find endometrial abla-
tion still acceptable if there was no chance of amen-
orrhea, and if the odds of the menstruation becoming
lighter was at least 4:10 [124]. Furthermore, women
perceived avoidance of major surgery as one of the
most important advantages of ablation over hysterec-
tomy. Thus, women are inclined to take a chance of
failure to avoid a hysterectomy.
In conclusion, none of the treatments for dysfunc-
tional bleeding is radically superior to one another,
and since all treatments have their advantages and dis-
advantages, counselling of patients with dysfunctional
bleeding should incorporate medical approach, lev-
onorgestrel releasing IUD, endometrial ablation and
hysterectomy.
References
[1] Royal College of Obstetricians and Gynaecologists. The
management of menorrhagia in secondary care; 1999.
[2] Vessey MP, Villard-Mackintosh L, McPherson K, Coulter
A, Yeates D. The epidemiology of hysterectomy: findings in
a large cohort study. Br J Obstet Gynaecol 1992;99:402–7.
[3] Luoto R, Rutanen EM, Kaprio J. Five gynecologic diagnoses
associated with hysterectomy—trends in incidence of
hospitalizations in Finland, 1971–1986. Maturitas 1994;19:
141–52.
[4] Luoto R, Keskimaki I, Reunanen A. Socioeconomic
variations in hysterectomy: evidence from a linkage study
of the Finnish hospital discharge register and population
census. J Epidemiol Commun Health 1997;51:67–73.
[5] Fraser IS, MacCarron G, Markham R. A preliminary study
of factors influencing perception of menstrual blood loss
volume. Am J Obstet Gynecol 1984;149:788–93.
[6] Chimbira TH, Anderson AB, Turnbull AC. Relation between
measured menstrual blood loss and patient’s subjective
 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
assessment of loss, duration of bleeding, number of sanitary
towels used, uterine weight and endometrial surface area.
Br J Obstet Gynaecol 1977;84:763–8.
[7] Gannon MJ, Day P, Hammadieh N, Johnson N. A new
method for measuring menstrual blood loss and its use in
screening women before eudiometrical ablation. Br J Obstet
Gynaecol 1996;103:1029–33.
[8] Janssen CA, Scholten PC, Heintz AP. A simple visual
assessment technique to discriminate between menorrhagia
and normal menstrual blood loss. Obstet Gynecol 1995;85:
977–82.
[9] Hallberg L, Hogdahl AM, Nilsson L, Rybo G. Menstrual
blood loss—a population study. Acta Obstet Gynecol Scand
1966;45:320–51.
[10] Vasilenko P, Kraicer PF, Kaplan R, deMasi A, Freed N. A
new end simple method of measuring menstrual blood loss.
J Reprod Med 1988;33:293–7.
[11] Higham JM, O’Brien PMS, Shaw RW. Assessment of
menstrual blood loss using a pictorial chart. Br J Obstet
Gynaecol 1990;97:734–9.
[12] Deeny M, Davis JA. Assessment of menstrual blood loss
in women referred for endometrial ablation. Eur J Obstet
Gynecol Reprod Biol 1994;57:179–80.
[13] Vercellini P, Cortesi I, Oldani S, Moschetta M, De Giorgi
O, Crosignani PG. The role of transvaginal ultrasonography
and outpatient diagnostic hysteroscopy in the evaluation
of patients with menorrhagia. Hum Reprod 1997;12:1768–
71.
[14] Dijkhuizen FPHLJ, De Vries LID, Mol BWJ. Comparison of
transvaginal ultrasonography and saline infusion sonography
for the detection of intracavitary abnormalities. Ultrasound
Obstet Gynecol 2000;15:372–6.
[15] Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for
heavy menstrual bleeding (Cochrane Review). The Cochrane
Library, vol. 4. Oxford: Update Software; 2002.
[16] Lethaby A, Augood C, Duckitt K. Nonsteroidal anti-
inflammatory drugs for heavy menstrual bleeding (Cochrane
Review). The Cochrane Library, vol. 4. Oxford: Update
Software; 2002.
[17] Iyer V, Farquhar C, Jepson R. Oral contraceptive pills for
heavy menstrual bleeding (Cochrane Review). The Cochrane
Library, vol. 4. Oxford: Update Software; 2002.
[18] Lethaby A, Irvine G, Cameron I. Cyclical progestogens for
heavy menstrual bleeding (Cochrane Review). The Cochrane
Library, vol. 4. Oxford: Update Software; 2002.
[19] Beaumont H, Augood C, Duckitt K, Lethaby A. Danazol for
heavy menstrual bleeding (Cochrane Review). The Cochrane
Library, vol. 4. Oxford: Update Software; 2002.
[20] Preston JT, Cameron IT, Adams EJ, Smith SK. Comparative
study of tranexamic acid and norethisterone in the
treatment of ovulatory menorrhagia. Br J Obstet Gynaecol
1995;102:401–6.
[21] Bonnar J, Sheppard BL. Treatment of menorrhagia during
menstruation: randomised controlled trial of ethamsylate.
BMJ 1996;313:579–82.
[22] Prentice A. Medical management of menorrhagia. BMJ
1999;319:1343–5.
171
[23] Fraser IS, McCarron G. Randomized trial of 2 hormonal and
2 prostaglandin-inhibiting agents in women with a complaint
of menorrhagia. Aust NZ J Obstet Gynaecol 1991;31:66–
70.
[24] Higham JM, Shaw RW. A comparative study of danazol, a
regimen of decreasing doses of danazol, and norethindrone
in the treatment of objectively proven unexplained
menorrhagia. Am J Obstet Gynecol 1993;169:1134–9.
[25] Cooper KG, Parkin DE, Garratt AM, Grant AM. A
randomised comparison of medical and hysteroscopic
management in women consulting a gynaecologist for
treatment of heavy menstrual loss. Br J Obstet Gynaecol
1997;104:1360–6.
[26] Cooper KG, Grant AM, Garratt AM. The impact of using
a partially randomised patient preference design when
evaluating alternative managements for heavy menstrual
bleeding. Br J Obstet Gynaecol 1997;104:1367–73.
[27] Cooper KG, Parkin DE, Garratt AM, Grant AM. Two-year
follow up of women randomised to medical management
or transcervical resection of the endometrium for heavy
menstrual loss: clinical and quality of life outcomes. Br J
Obstet Gynaecol 1999;106:258–65.
[28] Cooper KG, Parkin DE, Garratt AM, Grant AM. Five-year
follow up of women randomised to medical management
or transcervical resection of the endometrium for heavy
menstrual loss: clinical and quality of life outcomes. Br J
Obstet Gynaecol 2001;108:1222–8.
[29] Coulter A, Kelland J, Peto V, Rees MC. Treating
menorrhagia in primary care. An overview of drug trials and
a survey of prescribing practice. Intern J Technol Assess
Health Care 1995;11:456–71.
[30] French RS, Cowan FM, Mansour D, Higgins JPT, Robinson
A, Procter T, et al. Levonorgestrel-releasing (20 ug/ day)
intrauterine systems (Mirena) compared with other methods
of reversible contraceptives. Br J Obstet Gynaecol 2000;
107:1218–25.
[31] Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkila
A, Walker JJ, Cameron IY. Randomised comparative study
of the levonorgestrel intrauterine system and morethisterone
for the treatment of idiopathic menorrhagia. Br J Obstet
Gynecol 1998;105:592–8.
[32] Lahteenmaki P, Haukkamaa M, Puolakka J, Sainio S,
Suvisaari J. Open randomised study of use of levonorgestrel
releasing intrauterine system as alternative to hysterectomy.
BMJ 1998;316:1122–6.
[33] Tang GW, Lo SS. Levonorgestrel intrauterine device in the
treatment of menorrhagia in Chinese women: efficacy versus
acceptability. Contraception 1995;51:231–5.
[34] Crosignani PG, Vercellini P, Mosconi P, Oldani S,
Cortesi I, De Giorgi O. Levonorgestrel-releasing intrauterine
device versus hysteroscopic endometrial resection in
treatment of dysfunctional uterine bleeding. Obstet Gynecol
1997;90:257–63.
[35] Lethaby AE, Cooke I, Rees M. Progesterone/progestogen
releasing intrauterine systems for heavy menstrual bleeding
(Cochrane Review). The Cochrane Library, vol. 4. Oxford:
Update Software; 2002.
172 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
[36] Istre O, Trolle B. Treatment of menorrhagia with the
levonorgestrel intrauterine system versus endometrial rese-
ction. Fertil Steril 2001;76:304–9.
[37] Andersson JK, Rybo G. Levonorgestrel-releasing intrauterine
device in the treatment of menorrhagia. Br J Obstet Gynaecol
1990;97:690–4.
[38] Luukkainen T, Toivonen J. Levonorgestrel-releasing IUD
as a method of contraception with therapeutic properties.
Contraception 1995;52:269–76.
[39] Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman
S, Kivela A, et al. Quality of life and cost-effectiveness
of levonorgestrel-releasing intrauterine system versus hyste-
rectomy for treatment of menorrhagia: a randomised trial.
Lancet 2001;357:273–7.
[40] Haynes PJ, Hodgson H, Anderson AB, Turnbull AC.
Measurement of menstrual blood loss in patients
complaining of menorrhagia. Br J Obstet Gynaecol 1977;84:
763–8.
[41] Ashermann JG. Amenorrhea traumatica (atretica). Obstet
Gynecol 1948;55:23.
[42] Neuwirth RS, Amin HK. Excision of submucus fibroids with
hysteroscopic control. Am J Obstet Gynecol 1976;126:95–9.
[43] Goldrath MH, Fuller TA, Segal S. Laser photovaporization
of the endometrium in the treatment of menorrhagia. Am J
Obstet Gynecol 1981;140:14–9.
[44] DeCherney A, Polan ML. Hysteroscopic management of
intrauterine lesions and intractable uterine bleeding. Obstet
Gynecol 1983;61:392–7.
[45] Vancaillie TG. Electrocoagulation of the endometrium with
the ball-end resectoscope. Obstet Gynecol 1989;74:425–7.
[46] Lethaby A, Sheppard S, Cooke I, Farquhar C. Endometrial
resection and ablation versus hysterectomy for menstrual
bleeding. The Cochrane Library, vol. 4. Oxford: Update
Software; 2002.
[47] Garry R, Shelley-Jones D, Mooney P, Phillips G. Six hundred
endometrial laser ablations. Obstet Gynecol 1995;85:24–9.
[48] Bhattacharya S, Cameron IM, Parkin DE, Abramovich DR,
Mollison J, Pinion SB, et al. A pragmatic randomised
comparison of transcervical resection of the endometrium
with endometrial laser ablation for the treatment of
menorrhagia. Br J Obstet Gynaecol 1997;104:601–7.
[49] Phillips G, Chien PF, Garry R. Risk of hysterectomy after
1000 consecutive endometrial laser ablations. Br J Obstet
Gynaecol 1998;105:897–903.
[50] Baggish MS, Sze EHM. Endometrial ablation: a series of
568 patients treated over an 11-year period. Am J Obstet
Gynecol 1996;174:908–13.
[51] Erian J. Endometrial ablation in the treatment of
menorrhagia. Br J Obstet Gynaecol 1994;101:19–22.
[52] Kammerer-Doak DN, Rogers RG. Endometrial ablation:
electrocautery and laser techniques. Clin Obstet Gynaecol
2000;43:561–74.
[53] Tsaltas J, Taylor N, Healy M. A 6-year review of the
outcome of endometrial ablation. Aust NZ J Obstet Gynaecol
1998;38:69–72.
[54] O’Connor H, Magos A. Endometrial resection for the treat-
ment of menorrhagia. N Engl J Med 1996;335:151–6.
[55] Scottish Hysteroscopy Audit Group. A Scottish audit of
hysteroscopic surgery for menorrhagia: complications and
follow-up. Br J Obstet Gynaecol 1995;102:249–54.
[56] Aberdeen Endometrial Ablation Trials Group. A randomised
trial of endometrial ablation versus hysterectomy for the
treatment of dysfunctional uterine bleeding: outcome at four
years. Br J Obstet Gynaecol 1999;106:360–6.
[57] Teirney R, Arachchi GJ, Fraser IS. Menstrual blood loss
measured 5–6 years after endometrial ablation. Obstet
Gynecol 2000;95:251–4.
[58] Martyn P, Allan B. Long-term follow-up of endometrial
ablation. J Am Assoc Gynecol Laparosc 1998;5:115–8.
[59] Dwyer N, Hutton J, Stirrat GM. Randomised controlled
trial comparing endometrial resection with abdominal
hysterectomy for the surgical treatment of menorraghia. Br
J Obstet Gynaecol 1993;100:237–43.
[60] Pinion SB, Parkin DE, Abramovich DR, et al. Randomised
trial of hysterectomy, endometrial laser ablation and trans-
cervical resection for dysfunctional uterine bleeding. BMJ
1994;309:979–83.
[61] Gannon MJ, Holt EM, Fairbank J, Fitzgerald M, Milne MA,
Crystal AM, et al. A randomised trial comparing endometrial
resection and abdominal hysterectomy for the treatment of
menorrhagia. BMJ 1991;303:1362–4.
[62] Crosignani PG, Vercellini P, Apolone G, De Giorgi
O, Cortesi I, Meschia M. Endometrial resection versus
vaginal hysterectomy for menorrhagia: long-term clinical
and quality-of-life outcomes. Am J Obstet Gynecol 1997;
177:95–101.
[63] O’Connor H, Broadbent JA, Magos AL, McPherson
K. Medical research council randomised trial of endo-
metrial resection versus hysterectomy in management of
menorrhagia. Lancet 1997;349:897–901.
[64] Lethaby A, Shepperd S, Cooke I, Farquhar C. Endometrial
resection and ablation versus hysterectomy for heavy mens-
trual bleeding (Cochrane Review). The Cochrane Library,
vol. 4 Oxford: Update Software; 2002.
[65] Overton C, Hargreaves J, Maresh M. A national survey of
the complications of endometrial destruction for menstrual
disorders the MISTLETOE study. Br J Obstet Gynaecol
1997;104:1351–9.
[66] Vilos GA, Brown S, Graham G, McCulloch S, Borg
P. Genital tract electrical burns during hysteroscopic
endometrial ablation: report of 13 cases in the United States
and Canada. J Am Assoc Gynecol Laparosc 2000;7:141–7.
[67] Rosenberg MK. Hyponatremic encephalopathy after roller-
ball endometrial ablation. Anesth Analg 1995;80:1046–8.
[68] Baggish MS, Brill AI, Rosenweig B, et al. Fatal acute
glycine and sorbitol toxicity during operative hysteroscopy.
J Gynecol Surg 1993;9:137–42.
[69] Jansen FW, Vredevoogd CB, van Ulzen K, Hermans J,
Trimbos JB, Trimbos-Kemper TC. Complications of hystero-
scopy: a prospective, multicenter study. Obstet Gynecol
2000;96:266–70.
[70] Cooper JM, Brady RM. Late complications of operative
hysteroscopy. Obstet Gynecol Clin North Am 2000;27:367–
74.
 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
[71] Mall A, Shirk G, Van Voorhis BJ. Previous tubal ligation
is a risk factor for hysterectomy after rollerball endometrial
ablation. Obstet Gynecol 2002;100:659–64.
[72] Valle RF, Baggish MS. Endometrial carcinoma after
endometrial ablation: high-risk factors predicting its
occurrence. Am J Obstet Gynecol 1998;179:569–72.
[73] Dijkhuizen FP, Mol BWJ, Brolmann HAM, Heintz AP.
The accuracy of endometrial sampling in the diagnosis
of patients with endometrial carcinoma and hyperplasia: a
meta-analysis. Cancer 2000;89:1765–72.
[74] Pugh CP, Crane JM, Hogan TG. Successful intrauterine
pregnancy after endometrial ablation. J Am Assoc Gynecol
Laparosc 2000;7:391–4.
[75] Ismail MS, Torsten U, Serour GI, Weitzel H, Berlien HP. Is
endometrial ablation a safe contraceptive method? Pregnancy
following endometrial ablation. The Eur J Contract Reprod
Health Care 1998;3:99–102.
[76] Pinette M, Katz W, Drouin M, Blackstone J, Cartin
A. Successful planned pregnancy following endometrial
ablation with the YAG laser. Am J Obstet Gynecol 2001;185:
242–3.
[77] Rogerson I, Gannon, O’Donnovan P. Outcome of pregnancy
following endometrial ablation. J Gynecol Surg 1994;
170:1370–1.
[78] Hart R, Magos A. Endometrial ablation. Cur Opin Obstet
Gynecol 1997;9:226–32.
[79] McCausland AM, McCausland VM. Depth of endometrial
penetration in adenomyosis helps determine outcome of
rollerball ablation. Am J Obstet Gynecol 1996;174:1786–
94.
[80] Abbott JA, Garry R. The surgical management of menorr-
hagia. Hum Reprod Update 2002;8:68–78.
[81] Overton C, Maresh MJA. Audit of currently available
endometrial ablative techniques. Baillieres Clin Obstet
Gynaecol 1995;9:357–72.
[82] Donnez J, Vilos G, Gannon MJ, Maheux R, Emanuel
MH, Istre O. Goserelin acetate (Zoladex) plus endometrial
ablation for dysfunctional uterine bleeding: a 3-year follow-
up evaluation. Fertil Steril 2001;75:620–2.
[83] Sowter MC, Lethaby A, Singla AA. Pre-operative
endometrial thinning agents before endometrial destruction
for heavy menstrual bleeding (Cochrane Review). The
Cochrane Library, vol. 4. Oxford: Update Software; 2002.
[84] Lethaby A, Hickey M. Endometrial destruction techniques
for heavy menstrual bleeding (Cochrane Review). The
Cochrane Library, vol. 4. Oxford: Update Software; 2002.
[85] Neuwirth RS, Duran A, Singer A, MacDonald R, Bolduc L.
The endometrial ablator: a new instrument. Obstet Gynecol
1994;83:792–6.
[86] Meyer WR, Walsh BW, Grainger DA, Peacock LM, Loffer
FD, Steege JF. Thermal balloon and rollerball ablation
to treat menorrhagia: a multi-center comparison. Obstet
Gynecol 1998;92:98–103.
[87] Grainger D, Tjaden B. Thermal balloon and rollerball
ablation to treat menorrhagia: two-year results from a
multicenter prospective, randomized clinical trial. J Am
Assoc Gynecol Laparosc 2000;7:175–9.
173
[88] Loffer FD. Three-year comparison of thermal balloon and
rollerball ablation in treatment of menorrhagia. J Am Assoc
Gynecol Laparosc 2001;8:48–54.
[89] Loffer FD, Grainger D. Five-year follow-up of patients
participating in a randomized trial of uterine balloon therapy
versus rollerball ablation for treatment of menorrhagia. J
Am Assoc Gynecol Laparosc 2002;9:429–35.
[90] Bongers MY, Mol BWJ, Brölmann HAM. Comparison of 8
versus 16 minutes heating in the treatment of menorrhagia
with hot fluid balloon ablation. J Gynecol Surg 1999;15:
143–7.
[91] Bongers MY, Mol BWJ, Dijkhuizen FPHLJ, Brölmann
HAM. Is balloon-ablation as effective as endometrial
electro-resection in the treatment of menorrhagia? J Lap
Adv Surg Techn 2000;10:85–92.
[92] Gervaise A, Fernandez H, Capella-Allouc S, Taylor S, La
Vieille S, Hamou J, et al. Thermal balloon ablation versus
endometrial resection for the treatment of abnormal uterine
bleeding. Hum Reprod 1999;14:2743–7.
[93] Amso NN, Stabinsky SA, McFaul P, Blanc B, Pendley
L, Neuwirth R. Uterine thermal balloon therapy for the
treatment of menorrhagia: the first 300 patients from a
multi-center study. Br J Obstet Gynaecol 1998;105:517–23.
[94] Vilos GA, Fortin CA, Sanders B, Pendley L, Stabinsky SA.
Clinical trial of the uterine thermal balloon for treatment of
menorrhagia. J Am Assoc Gynecol Laparosc 1997;4:559–
65.
[95] Romer T. The treatment of recurrent menorrhagias-Cavaterm
balloon-coagulation versus rollerball-endometrial ablation—
a prospective randomized comparative study. Zentrallbl
Gynakol 1998;120:511–4.
[96] Hawe JA, Phillips AG, Chien PFW, Erian J, Garry R.
Cavaterm thermal balloon ablation for the treatment of
menorrhagia. Br J Obstet Gynaecol 1999;106:1143–8.
[97] Friberg B, Joergensen C, Ahlgren M. Endometrial thermal
coagulation—degree of uterine fibrosis predicts treatment
outcome. Gynecol Obstet Invest 1998;45:54–7.
[98] Ulmsten U, Carstensen H, Falconer C, Holm L, Lanner L,
Nilsson S, et al. The safety and efficacy of MenoTreat, a
new balloon device for thermal endometrial ablation. Acta
Obstet Gynecol Scand 2001;80:52–7.
[99] Corson SL, Brill AI, Brooks PG, Cooper JM, Indman PD,
Liu JH, et al. Interim results of the American Vesta trial
of endometrial ablation. J Am Assoc Gynecol Laparosc
1999;6:45–9.
[100] Corson SL, Brill AI, Brooks PG, Cooper JM, Indman
PD, Liu JH, et al. One-year results of the vesta system
for endometrial ablation. J Am Assoc Gynecol Laparosc
2000;7:489–97.
[101] Corson SL. A multicenter evaluation of endometrial ablation
by Hydro ThermAblator and rollerball for treatment of
menorrhagia. J Am Assoc Gynecol Laparosc 2001;8:359–
67.
[102] Bustos-Lopez HH, Baggish M, Valle RF, Vadillo-Otrega F,
Ibarra V, Nava G. Assessment of the safety of intrauterine
instillation of heated saline for endometrial ablation. Fertil
Steril 1998;69:155–60.
174 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174
[103] Sharp NC, Cronin N, Feldberg I, Evans M, Hodgson D,
Ellis S. Microwaves for menorrhagia: a new fast technique
for endometrial ablation. Lancet 1995;346:1003–4.
[104] Cooper KG, Bain C, Parkin DE. Comparison of microwave
endometrial ablation and transcervical resection of the
endometrium for treatment of heavy menstrual loss: a
randomised trial. Lancet 1999;354:1859–63.
[105] Downes E, O’Donovan P. Microwave endometrial ablation
in the management of menorrhagia: current status. Cur Op
Obstet Gynecol 2000;12:293–6.
[106] Bain C, Cooper KG, Parkin DE. Microwave endometrial
ablation versus endometrial resection: a randomized
controlled trial. Obstet Gynecol 2002;99:983–7.
[107] Dobak JD, Ryba E, Kovalcheck S. A new closed-loop
cryosurgical device for endometrial ablation. J Am Assoc
Gynecol Laparosc 2000;7:245–9.
[108] Dobak JD, Willems J, Howard R, Shea C, Townsend DE.
Endometrial cryoablation with ultrasound visualization in
women undergoing hysterectomy. J Am Assoc Gynecol
Laparosc 2000;7:89–93.
[109] Rutherford TJ. Cryosurgery is a simple modality for
endometrial ablation. J Am Assoc Gynecol Laparosc 1996;
3:S44–45.
[110] Korn AP. Endometrial cryoablation and thermal ablation.
Clin Obstet Gynecol 2000;43:575–83.
[111] Donnez J, Polet R, Mathieu PE, Konwitz E, Nisolle M,
Casanas-Roux F. Endometrial laser interstitial hyperthermy:
a potential modality for endometrial ablation. Obstet
Gynecol 1996;87:459–64.
[112] Donnez J, Polet R, Rabinovitz R, Ak M, Squifflet J, Nisolle
M. Endometrial laser intrauterine thermotherapy: the first
series of 100 patients observed for 1 year. Fertil Steril
2000;74:791–6.
[113] Cooper J, Gimpelson R, Laberge P, Galen D, Garza-Leal
JG, Scott J, et al. A randomized, multicenter trial of safety
and efficacy of the NovaSure System in the treatment of
menorrhagia. J Am Assoc Gynecol Laparosc 2002;9:418–28.
[114] Gallinat A, Nugent W. NovaSure impedance-controlled
system for endometrial ablation. J Am Assoc Gynecol
Laparosc 2002;9:283–9.
[115] Carlson KJ. Outcomes of hysterectomy. Clin Obstet Gynecol
1997;40:939–46.
[116] Carlson KJ, Miller BA, Fowler FJ. The main women’s
health study: I. Outcomes of hysterectomy. Obstet Gynecol
1994;83:556–65.
[117] Lumsden MA, Twaddle S, Hawthorn R, Traynor I,
Gilmoe D, Davis J, et al. A randomised comparison and
economic evaluation of laparoscopic-assisted hysterectomy
and abdominal hysterectomy. Br J Obstet Gynaecol 2000;
107:1386–91.
[118] Harris WJ, Daniell JF. Early complications of laparoscopic
hysterectomy. Obstet Gynecol Sur 1996;38:559–67.
[119] Harris WJ. Complications of hysterectomy. Clin Obstet
Gynecol 1997;40:928–38.
[120] Munro MG, Deprest J. Laparoscopic hysterectomy: does it
work? A bicontinental review of the literature and clinical
commentary. Clin Obstet Gynecol 1995;38:401–25.
[121] Mittendorf R, Aronson MP, Berry RE, et al. Avoiding
serious infections associated with abdominal hysterectomy:
a meta-analysis of antibiotic prophylaxis. Am J Obstet
Gynecol 1993;169:1119–24.
[122] Coulter A. Partnerships with patients: the pros and cons of
shared clinical discision making. J Health Serv Res Policy
1997;2:112–21.
[123] Gambone JC, Reiter RC. Hysterectomy: improving the
patient’s decision-making process. Clin Obstet Gynecol
1997;40:868–77.
[124] Nagele F, Rubinger T, Magos A. Why do women choose
endometrial ablation rather than hysterectomy? Fertil Steril
1998;69:1063–6.