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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


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-

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

0378-5122/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved.
160 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174

women. It is estimated that a woman has a life time defined, not as blood loss in excess of 80 ml and not
chance of 1:20 to consult her general practitioner for as a pictorial chart score.
complaints due to menorrhagia [2–4]. Menorrhagia can be caused by intracavitary abnor-
Since only 40–50% of the women who complain of malities, but it also can occur in women without such
heavy menstrual bleeding suffer from objective men- abnormalities. In the last decade, the introduction of
orrhagia, it is important to quantify the amount of transvaginal sonography, saline infusion sonography,
menstrual blood loss [5,6]. Gannon et al. found that, and hysteroscopy has improved the possibility to diag-
among women treated by endometrial ablation for nose intracavitary abnormalities [13,14]. In case when
heavy menstrual bleeding, those with quantified men- intracavitary abnormalities are not present, women
orrhagia were more likely to be satisfied with the treat- suffering from menorrhagia are said to have dysfunc-
ment result (OR 2.5, 95% CI 1.1–4.7), and less likely tional uterine bleeding. Dysfunctional uterine bleed-
to require subsequent hysterectomy (OR 1.8, 95% CI ing is defined as periodic uterine blood loss in excess
0.6–5.2), as compared to women who experienced of 80 ml per cycle occurring in the absence of struc-
their menstruation as heavy before the onset of treat- tural uterine disease. The aim of the present review is
ment without having menstrual blood loss more than to discuss the treatment options for women with dys-
80 ml [7]. Women with menstrual bleeding of more functional uterine bleeding.
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 2. Medical treatment
haemoglobin does not rule out menorrhagia (sensi-
tivity 43%, specificity 94%) [8]. Since women’s per- Medical treatment of dysfunctional uterine bleed-
ception of the heaviness of their menstrual blood loss ing includes treatment with anti-fibrinolytic tranex-
does not always correlate well with the objective as- amic acid, non-steroidal anti-inflammatory drugs
sessment, the severity of menstrual bleeding must be (NSAID’s), the combined contraception pill, pro-
quantified. Hallberg introduced the alkaline haematin gestogen, danazol, and analogues of gonadotrophin
method to measure menstrual blood loss [9]. In the al- releasing hormone (GnRH analogues). The effective-
kaline haematin method, menstrual blood is collected ness of drug therapy for dysfunctional uterine bleed-
from towels and tampons, using a 5% NaOH solution. ing was evaluated and reported in systematic reviews
Such techniques require hospital-based equipment and in the Cochrane library [15–19].
staff [10]. Furthermore, the collection of pads and tam- Antifibrinolytic tranexamic acid has proven to be
pons makes the alkaline haematin method inconve- effective in the reduction of dysfunctional uterine
nient for women. In order to get a semi-quantitative bleeding as compared to placebo. Reduction of men-
measurement of the menstrual blood loss, Higham strual bleeding after treatment with tranexamic acid is
et al. [11] developed a pictorial blood loss assessment significantly higher when compared to other medical
chart. The pictorial chart consists of a series of di- therapies (NSAID’s, oral luteal phase progestogens
agrams representing lightly, moderately and heavily and ethamsylate), without an increase in side effects
soiled pads and tampons. Multiplication of the num- [15,20,21]. Flooding, leakage, and sex life are sig-
ber of slightly, moderately and heavily soiled pads nificantly improved after anti-fibrinolytic tranexamic
and tampons with fixed absorption factors results in a acid therapy when compared with oral luteal phase
Higham score. On the Higham chart, a cut-off score progestogens.
of 100 was found to correlate with menstrual blood Non-steroidal anti-inflammatory drugs reduce dys-
loss of more than 80 ml. Janssen et al. [8] investi- functional uterine bleeding as compared to placebo,
gated the usefulness of a modified pictorial chart in but are less effective than either antifibrinolytic tranex-
a larger study, and recommended a cut-off score of amic acid or danazol [16]. In a limited number of stud-
185. Although the use of a pictorial chart might im- ies, NSAID’s show no significant differences in effec-
plicate misclassification of menorrhagia, the method tiveness as compared to other medical therapies such
is clearly more accurate than history alone [8,11,12]. as oral luteal progestogen, ethamsylate, combined
However, patient-selection in DUB trials is often not contraception pill or a levonorgestrel releasing IUD.
M.Y. Bongers et al. / Maturitas 47 (2004) 159–174 161

The combined contraception pill also decreases the 3. Levonorgestrel releasing intra uterine
amount of blood loss in women suffering from dys- device (IUD)
functional uterine bleeding [17,22]. The only small
study performed addressing this subject reports no sig- Another form of medical treatment is the lev-
nificant difference between women treated with com- onorgestrel releasing intra uterine device (IUD)
bined contraception pill, mefenamic acid, low dose (Mirena® ). The levonorgestrel releasing IUD is orig-
danazol, or naproxen [23]. It is generally known that inally developed for contraception, but it has also
women will not have a menstrual bleeding when the proven to be an effective device in the treatment of
combined contraception pill is continued without a dysfunctional uterine bleeding. Its efficacy is based
stop week, although there is lack of high quality evi- on the local release of levonorgestrel in the uterine
dence on this subject. cavity, thus suppressing endometrial growth. The
Progestogens administered from day 15 to 26 of use of levonorgestrel releasing IUD considerably de-
the cycle offer no advantage over other medical thera- creases the amount of menstrual blood loss [30–36],
pies such as danazol, anti-fibrinolytic tranexamic acid, with a reported reduction of 97% [37]. In the first
NSAID’s and the levonorgestrel releasing IUD in the few months after insertion many women suffer from
treatment of dysfunctional uterine bleeding in women intermenstrual bleeding, but at one year after inser-
with ovulatory cycle’s [18]. Progestogen therapy dur- tion most women bleed only for one day, and 15%
ing 21 days of the cycle results in a significant reduc- became amenorrhoeic [38]. The levonorgestrel re-
tion of menstrual blood loss but its strong side effects leasing IUD has proven to be more effective than
limit long-term use [18]. cyclical norethisterone (21 days) in the treatment of
Similarly, second line drug therapies, such as dysfunctional uterine bleeding [35]. Women using
danazol and GnRH analogues, are not suitable for a levonorgestrel releasing IUD are more satisfied as
long-term use due to their serious side effects [19]. compared to women with progestogen therapy, de-
Danazol appears to be an effective treatment for spite the occurrence of progestogenic side effects in
dysfunctional uterine bleeding, but is also causes hir- the IUD group such as intermenstrual bleeding and
sutism. GnRH analogues are associated with a high breast tenderness [35]. There are no data available
risk of irreversible bone loss after six months. Thus, from randomised controlled trials comparing the lev-
both danazol and GnRH analogues are meant only onorgestrel releasing IUD to either placebo or other
for short- term use, whilst decisions regarding future medical therapies for dysfunctional uterine bleeding.
treatments can be made [19–24]. Costs of the levonorgestrel IUD are high compared
Cooper et al. compared medical treatment to tran- to other medical treatment. However, this difference
scervical resection of endometrium (TCRE) in a ran- reduces over time due to the fact that the IUD is used
domised controlled trial (RCT) [25–28]. In his study, for a 5-year period.
TCRE showed a significantly higher patient satisfac- The potential advantage of the levonorgestrel re-
tion at 4 months, 2 and 5 years follow-up [25–28]. leasing IUD is its ease of use, its low costs and its low
Moreover, surgical (re)intervention rates at 5 years complication rate. However, these benefits are only of
were 77% in the medical treatment group and 27% interest if the use of the levonorgestrel releasing IUD
in the TCRE group, with hysterectomy rates being would demonstrate superior results, in terms of pa-
comparable (18% versus 19%) [25–28]. Although tient satisfaction, quality of life, and symptomatic im-
quality of life was improved in both treatment arms, provement, when compared to endometrial ablation.
the improvement was more evident in the TCRE- Transcervical resection of the endometrium (TCRE)
group. is the only ablation technique that has been compared
In conclusion, anti-fibrinolytic tranexamic acid with levonorgestrel releasing IUD in two small RCTs
is the most effective medical treatment option. Al- [34–36]. The use of a levonorgestrel releasing IUD
though good studies on the effectiveness of the con- allowed for a smaller reduction of menstrual blood
trolled contraception pill are lacking, the pill seems loss as compared to TCRE (67% versus 90%), and
a useful treatment in every day clinical practice women are not as likely to become amenorrhoeic, but
[29]. 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 scale in women suffering from dysfunctional uterine
levonorgestrel releasing IUD experienced a higher rate bleeding [40].
of progestogenic side effects as compared to women
treated with TCRE. Clinical results of the two RCTs
comparing TCRE and levonorgestrel releasing IUD 5. First generation endometrial ablation
suggested that levonorgestrel releasing IUD are not techniques
as effective as TCRE, but both studies suffer from a
lack of power, and do not allow for definite conclu- Ashermann was the first to describe the association
sions. Furthermore in both studies it was not clear if between D&C and women who became amenorrhoeic
patients were treated medically before they entered after an abortion. He found an obliterated uterine cav-
the study, which could have been favourable for the ity at hysterectomy and described this condition as
surgery group. ‘amenorrhoea atretica’ or ‘amenorrhoea traumatica’.
There is one RCT in which the levonorgestrel re- Since than, physicians have studied the possibility of
leasing IUD is compared with hysterectomy. This trial controlled injury of the basal layer of the endometrium
shows that both treatments are equal in terms of health in order to treat dysfunctional uterine bleeding [41].
related quality of life [39]. Overall costs were three Hysteroscopic resection was the first efficacious
times higher in the hysterectomy group than in the ablation therapy for intrauterine fibroids. It was in-
levonorgestrel releasing IUD group. Follow-up visits troduced in 1976 by Neuwirth et al. [42], and offered
after treatment were at 6 and 12 months. Unfortu- a surgical alternative to hysterectomy. Subsequently,
nately, the mean waiting time between randomisation laser ablation, radio-frequency monopolar resection,
and start of treatment was different in the two groups. and rollerball ablation were developed [43–45]. These
The mean waiting time for the hysterectomy group techniques, commonly addressed as first generation
was 6–7 months, with a maximum of 21 months. Thus, ablation techniques, have been studied in cohort stud-
follow-up visits in the hysterectomy group were 12 and ies and several RCTs (Fig. 1). These studies and
18 months after randomisation, whereas the follow-up their results will be discussed in the next paragraphs
visits in the levonorgestrel releasing IUD group were (Fig. 2).
at 6 and 12 months after randomisation. Consequently,
the groups were not as equal as the baseline charac- 5.1. Hysteroscopic laser ablation (HLA)
teristics suggest.
In conclusion, the effectiveness of the levonorgestrel The first neodymium-YAG laser used a dragging
releasing IUD appeared to be comparable to that of technique for ablation of the endometrium [43]. The
hysterectomy. Comparisons of the levonorgestrel re- non-touch laser technique that was developed after-
leasing IUD to endometrial ablation suffer from a lack wards resulted in a shorter treatment time, but was less
of statistical power. However, its ease of use and its effective than the touch technique. Non-randomised
low costs makes the levonorgestrel releasing IUD a prospective studies have reported that hysteroscopic
promising therapy for dysfunctional uterine bleeding. laser ablation (HLA) has high satisfaction rates with
reported amenorrhea rates between 20 and 60%
[46–55]. Surgical reintervention rates varied between
4. Surgical treatments for dysfunctional 7 and 27%. Costs of laser ablation are high due to the
uterine bleeding high costs of both the laser equipment and single use
Dilatation and curettage (D&C) causes a temporary
reduction of menstrual blood loss for the first month, 5.2. Transcervical endometrial resection (TCRE)
but at following cycles, the amount of blood loss tends
to increase as compared to the blood loss before the The use of a resectoscope allowed the performance
D&C [40]. Therefore, D&C must be considered ob- of transcervical resection of the endometrium (TCRE)
solete in the treatment of dysfunctional uterine bleed- [43]. Non-randomised prospective studies have re-
ing, but unfortunately it is still performed on a large 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
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)
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%

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 DUB
No intracav.


Ca + Ca -

Therapy Oncologic Therapy Choice of:

pathway • Medicine
• Lng IUD
• Ablation


Fig. 2. Flowchart of DUB. Intracav.: intracavitary, Ca: carcinoma.

and 92%, amenorrhea rates ranging between 26 and although patient satisfaction was higher after vaginal
40%, and reintervention rates varying between 20 and hysterectomy (94%) when compared to endometrial
27% [53,54]. The effectiveness of TCRE studied in resection (87%). From the economic perspective, en-
RCTs is comparable to the effectiveness of laser ab- dometrial destruction is less costly as compared to
lation, but operating time, fluid absorption and costs hysterectomy, but since re-treatment is often neces-
are higher with laser ablation [54–56]. sary this cost difference narrows over time [64].
The Mistletoe study reports on complications of
5.3. Rollerball endometrial ablation ablation techniques of the first generation, and shows
that endometrial ablation and endometrial resection
Rollerball ablation has been developed in Australia both performed under hysteroscopic view, are safe
[45]. The results of the rollerball ablation are compa- procedures with a low morbidity [65]. Perioperative
rable to the results of TCRE and laser ablation [57,58]. complications are perforation with the possibility of
However, rollerball ablation requires less operative bowel injury, haemorrhage, visceral burn, genital tract
skills, since there is no debris floating in the uterine burn and cardiovascular problems due to intravasation
cavity. Rollerball ablation is also less time consuming of distension fluid [66] (Table 1). Women undergoing
compared to laser ablation. laser or rollerball ablation have consistently fewer im-
mediate operative complications compared to TCRE
5.4. Studies evaluating first generation ablation [65]. Another problem of the hysteroscopic guided
techniques endometrial ablation is related to absorption of the
distension media. Glycine 1.5% and Sorbitol 5% are
Hysteroscopic endometrial ablations have been both used for uterine distension. During transcervical
compared to abdominal hysterectomy [59–61], to surgery, high intrauterine pressures are needed to dis-
vaginal hysterectomy [62], and to both techniques tend the uterine cavity resulting in risk of absorption of
[56,63]. At two years after treatment, quality of life distension fluid, characterised by hyponatraemia, wa-
was higher after abdominal hysterectomy than fol- ter intoxication, cerebral edema and cardiac overload.
lowing endometrial ablation [59–61]. Endometrial Fatal hyponatremic encephalopathy with cerebral
resection was compared to vaginal hysterectomy in edema has been reported in women undergoing TCRE
one RCT [62]. In this study, patient satisfaction, qual- [67,68]. Management of fluid overload requires accu-
ity of life, psychological status and sexual functioning rate monitoring of fluid balance, and interruption of
did not differ significantly between the two arms, the procedure before excessive fluid absorption occurs.
M.Y. Bongers et al. / Maturitas 47 (2004) 159–174 165

Table 1 in women who have endometrial hyperplasia. This

Complications of first generation ablation techniques is especially of concern in patients with diabetes,
Early complications extreme obesity or hypertension. On one hand, these
Problems with distension fluid 0.14–4% co-morbidities increase the risk of major surgery, thus
Fluid overload making less invasive procedures more attractive. On
Cardiac failure
Water intoxication, hyponatraemia
the other hand, especially these patients are at in-
Cerebral edema creased risk for endometrial cancer. However, we feel
Haemorrhage 2.4% that a pretreatment biopsy should be performed and
Perforation 1.5% the result be obtained before an ablative treatment is
Visceral burn and bowel burn 0.06% offered. Despite the fact that endometrial ablations
Genital tract burn Unknown
of the first generation exist for more than twenty
Late complications years the extent of the problem of potential delay of
Hematometra 1–2%
diagnosis of endometrial cancer is still not clear.
Tubal occlusion syndrome 6–8%
Endometrial cancer Unknown A third potential problem is the occurrence of preg-
Pregnancy related 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,
Complications that are specifically related to disten- as well as other obstetric complications. Of the 11
sion media occur in 0.14–4% of the procedures [69]. pregnancies that were ongoing after 27 weeks of ges-
The most important late post-operative compli- tation that have been reported, five (45%) were com-
cations are the occurrence of haematometra and plicated by growth retardation, and seven (63%) were
post-tubal sterilization syndrome, previously undis- complicated by preterm delivery [77]. A possible ex-
covered endometrial cancer, and pregnancy related planation for these complications is the sub-optimal
complications (Table 1). First, complications can be and/or abnormal attachment of placenta tissue to the
caused by persistence of endometrium after the ab- denuded endometrium.
lation. Haematometra occurs in 1–2% of the women Failures of first generation ablation techniques
treated with endometrial ablation. The post-ablation might be attributed to incomplete ablation of en-
tubal sterilization syndrome is caused by a focal cor- dometrial tissue or to adenomyosis [78,79]. Floating
nual hematometra with retrograde menstrual shedding debris or inadequate distension can hamper visualisa-
into an occluded fallopian tube due to recurrence or tion, thus limiting complete endometrial destruction.
survival of endometrial tissue. It occurs in 6–8% of Therefore, these techniques require intensive training
the patients [70,71], but the percentage of clinical and have a long learning curve [80,81]. The different
manifestations of this post ablation tubal sterilization methods of preparing the endometrium might also
syndrome may be higher [71]. In patients treated with be of importance for the effectiveness of treatment.
rollerball endometrial ablation, a tubal ligation is a Prethinning of the endometrium gives significantly
risk factor for the development of pelvic pain and for better results in terms of short-term postoperative out-
having a subsequent hysterectomy [71]. come and operating time [82,83]. GnRH analogues
Secondly, the potential delay of diagnosis of en- give slightly more consistent endometrial thinning
dometrial cancer is a disadvantage of all endometrial than danazol, though both agents produce satisfactory
ablation techniques. A majority of the cases of en- results.
dometrial cancer after endometrial ablation were pre- First generation ablation techniques are effective
ceded by a pretreatment biopsy containing atypical and provide an alternative to hysterectomy. A hysterec-
hyperplasia of the endometrium [72]. Thus, it is of tomy will not be necessary in 75–80% of the patients.
importance to take an accurate endometrial sampling The long-term results of the first generation ablation
before ablation treatment, and to renounce the abla- techniques might justify an increase of their use. How-
tion procedure if the biopsy contains (pre)malignant ever, both the learning curve and the complication rate
tissue [73]. Endometrial ablation should not be of- have hampered a wide implementation of these tech-
fered for the treatment of abnormal uterine bleeding niques. Moreover, these disadvantages stimulated the
166 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174

development of the second-generation ablative tech- maintained at 170 mmHg or higher. The generator,
niques. which controls temperature, pressure and time, will
switch off automatically if temperature or pressure,
especially in case of incorrect position will exceed
6. Second generation endometrial ablation the preset safe parameters.
techniques ThermaChoice® has been compared to rollerball ab-
lation in a RCT. Results have been reported at 1, 2, 3,
Second generation ablation devices have been in-
and 5 years after treatment [86–89]. At 5-year follow-
troduced in the last decade of the 20th century (Fig. 1)
up, both patient satisfaction and hysterectomy rate
[84,85]. These devices require less skill of the sur-
(30%) are comparable for both treatment modalities,
geon, and bear less risk compared to devices of the
with the amenorrhea rate being somewhat lower in the
first generation. However, these second generation ab-
ThermaChoice® group (26% versus 33%) (Fig. 1).
lation techniques do not have the advantages of di-
These results are consistent with the findings in several
rect visualization and detection of abnormal pathology
non-randomised studies in which ThermaChoice® is
with the hysteroscopic-guided ablation techniques. A
compared to TCRE [90–92], as well with the findings
preoperative endometrial biopsy should be performed
in several prospective observational studies [93,94].
prior to the ablation technique. Although the second
Pretreatment of the endometrium can be performed
generation techniques are very simple to perform, their
with GnRH analogues or with suction curettage, in or-
blind introduction can cause perforation and/or a false
der to decrease the thickness of the endometrial layer
passage. In most of these techniques the generator
prior to ablative treatment. Whether pre-operative
will switch off automatically if preset values are aug-
thinning of the endometrium with GnRH analogues
mented. These preset values should not be overruled,
will improve success rate of balloon ablation, is still
while they mostly implicate that the position of the
a matter of debate. Although, statistically higher rates
device is not correct.
of post procedure amenorrhea in women who received
In the next paragraphs we will discuss second gen-
depot GnRH agonist before balloon treatment has
eration devices with Table 2 giving a general overview
been reported, it did not improve treatment outcome
of these endometrial ablation systems. Devices that
in terms of the need for surgical re-intervention [93].
are not available will only be mentioned shortly.
Serious complications of ThermaChoice® ablation
6.1. Thermal balloon endometrial ablation have not been reported.
The Cavaterm® hot water balloon device consists of
The thermal balloon endometrial ablation tech- a disposable silicone balloon catheter with a heating
niques consist of a balloon for insertion in the uterine element connected to a battery-operated controller. A
cavity and a generator. After insertion, the balloon pump with oscillating pressure vigorously circulates
is filled with liquid, and the liquid is then heated glycine 1.5% inside the balloon. There is one very
to destroy the endometrium. There are several ther- small RCT comparing rollerball and Cavaterm® with
mal balloon devices that are currently commercially a short follow-up (9–15 months), showing similar re-
available, such as ThermaChoice® , Cavaterm® , and sults for both ablation techniques [95]. Amenorrhea
Menotreat® . rates in non-randomised studies have been reported to
ThermaChoice® was the first second-generation be 30–60% (Fig. 1) [96,97].
ablation technique, and has been evaluated thor- The Menotreat® thermal balloon ablation system
oughly [85–93]. Thermal balloon endometrial ab- is similar to the Cavaterm® system. It uses a dispos-
lation was first reported on in 1994. This device able closed system without any electrical component.
(ThermaChoice® , Gynecare Johnson & Johnson, NJ, The circulating fluid is heated inside the controller.
USA) consists of a generator and a latex balloon One observational study has reported an amenorrhoea
catheter (Table 2). A thermistor in the balloon is rate at 1 year of follow-up of 10% (Fig. 1) [98]. The
used to monitor the temperature of the fluid within Vestablade balloon device with electrodes on the out-
the balloon and a heating element is employed to side developed by Vancaillie is no longer commer-
raise the temperature of the fluid, with pressure being 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
MEA® Microsulis Microwave ablation Magnetic energy 9.2 GHz 3/unknown minute 8 mm Tactile tissue Yes Yes
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

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

6.2. Endometrial ablation by hysteroscopic 6.4. Cryo endometrial ablation

instillation of hot saline solution
Cryo ablation was the first non-chemical technique
This device has been developed by Goldrath (Hy- of endometrial ablation, and was reported on for the
drotherm ablator (HTA® ) BEI Medical Systems, first time in 1967 [107]. Since then, several articles
Boston Scientific, Teterboro, NJ, USA). It is the only on cryo ablation with CO2 probes were published
second-generation device that is applied under direct reporting amenorrhea rates of up to 50% [108]. The
hysteroscopic view. Externally heated 0.9% normal Her Option® Uterine cryo ablation therapy (CryoGen,
saline of 90 ◦ C is infused directly into the uterine cav- Inc., American Medical Systems, San Diego, CA,
ity through the in-flow channel of a continuous flow USA) was the first technique of cryo ablation that
outer plastic sheath that houses a diagnostic hystero- was suitable for use in clinical practice. Her Option®
scope. The infusion takes place at a pressure of less cryo ablation uses a new mixed gas coolant to gen-
than 45 mmHg resulting in an intrauterine net pres- erate temperatures of −90 ◦ C to −100 ◦ C. The cryo
sure of 50–55 mmHg, thus preventing flow through probe is inserted in the uterine cavity and saline is
the fallopian tube. The system automatically shuts injected to bathe the probe. Freezing thawing of the
down after 10 ml saline is lost. Hydrotherm ablation intrauterine ice ball is monitored with transabdominal
is compared to rollerball ablation in a RCT that re- ultrasound [108–110] and assures correct position.
ports amenorrhea rates at 12 months of 40% in the The Her Option® cryo ablation has been compared
hydrotherm ablation group and 51% in the rollerball with rollerball ablation in a RCT. Preliminary results
group [101]. Among potential complications of the at 6 months after treatment show an overall success
HTA® , burning of the cervix caused by leakage of (defined as pictorial chart score below 75) of 86% for
the heated saline has been encountered [102]. cryo ablation and 89% for rollerball ablation (Fig. 1)
[110]. Safety and effectiveness of this technique have
6.3. Microwave endometrial ablation to be established.

Sharp et al. [103] were the first to describe the 6.5. Endometrial laser thermal ablation
use of microwave energy (MEA® , Microsulis Plc.,
Waterlooville, UK). Microwave energy (9.2 GHz) is This technique uses a diffuse laser light that reaches
generated by a magnetron. Application of energy is the entire uterine cavity, including areas such as
controlled by a footswitch that is operated by the the cornua. It does not require direct contact with
surgeon. The temperature achieved inside the uterus the endometrium to induce photocoagulation. The
is monitored constantly by thermocouples. Once the 830 nm-wavelength of the diode laser light pene-
probe is activated and the tip temperature reaches trates the uterine wall to a precise depth, where it
95 ◦ C the probe is moved laterally to place the tip in is absorbed by haemoglobin. The absorbed light is
the uterine cornua. After the temperature has reached than transformed to heat, thus coagulating the en-
95 ◦ C, the tip is moved again to the other cornual dometrium. Therapy may not be effective in the
area. Thereafter, the probe is gradually withdrawn, presence of intrauterine bleeding. Endometrial Laser
while maintaining the probe temperature between Intrauterine Thermal Therapy (ELITT® ) (GyneLase,
85 and 90 ◦ C to ensure complete endometrial de- ESC Sharplan, Needham, MA, USA) has been devel-
struction. Pretreatment of the endometrium has been oped by Donnez et al. [111,112]. The three optical
prescribed in all trials. The microwave endometrial laser lights fill the uterine cavity ensuring complete
ablation system is compared to TCRE in a RCT. therapy of the endometrium. The treatment has been
Amenorrhea-rates (40%) and satisfaction-rates (75%) evaluated in a prospective observational study. At 12
were similar at one and two years of follow-up (Fig. 1) months after treatment 91% of the women were satis-
[104–106]. Hysterectomy was performed in 12 and fied, and the amenorrhea rate was 71% (Fig. 1) [112].
13% of the patients, respectively. Bowel injury after There were no complications during the treatment,
the use of the microwave endometrial ablation system but two patients suffered from severe dysmenorrhoea
has been reported in one patient [104]. and had a hematometra after ablation. Results from
M.Y. Bongers et al. / Maturitas 47 (2004) 159–174 169

RCTs using this treatment modality are not currently rate of 91% after 1 year of follow-up [114]. No com-
available. plications during treatment have been reported.

6.6. Bipolar impedance controlled 6.7. Hysterectomy

endometrial ablation
Hysterectomy is the only treatment for dysfunc-
This bipolar device consists of a single-use, three tional uterine bleeding that guarantees a definite
dimensional bipolar ablation device and radio fre- solution. Hysterectomy is a major operation associ-
quency controller (NovaSure® , Novacept, Palo Alto, ated with morbidity and even mortality that neces-
CA, USA). Endometrial pretreatment is not required sitates hospitalisation and several weeks of recovery
and active bleeding at the time of the operative visit [115–122]. Despite this fact, hysterectomy provides a
is not a limiting factor (Table 2). The NovaSure® Ra- high quality of life and a high satisfaction rate after
dio Frequency generator is a constant power output treatment. Large population based studies showed the
generator with a maximum power delivery of 180 W. mortality rate of hysterectomy for benign conditions
The generator functions at 500 kHz and has a power to be 1 in 2000 in women under age of 50 [116]. The
cut off limit set at 50  tissue impedance. The vac- CREST study reported a complication rate for minor
uum pump is contained within the radio frequency and major operations of 25% for vaginal hysterec-
generator and provides suction through the handle, tomy and of 43% for abdominal hysterectomy. The
and the electrical array, via a central tube within the rates of major complication are reported to be 5%
NovaSure® endometrial ablation device. The applica- for vaginal hysterectomy [60] and 7% for abdomi-
tion of the suction draws the endometrial lining into nal hysterectomy [117]. These complication rates are
contact with the electrode array and removes moisture significantly higher than the complication rates of en-
generated during the ablation process. The NovaSure® dometrial ablations of the first generation. Although
device consists of a single use, conformable bipolar hysterectomies have been performed for many years,
electrode mesh, mounted on an expandable frame their effectiveness has only recently been assessed in
that can create a confluent lesion within the cavity of comparison with the endometrial ablations and lev-
the uterus that involves the entire inner surface area. onorgestrel releasing IUD [39,59–63]. As mentioned
Continuous monitoring of tissue impedance controls before, quality of life is higher after hysterectomy
the depth of the ablation. Once the myometrial layer than after endometrial ablation when first generation
is reached, tissue impedance increases rapidly to 50  devices were used.
and the generator will switch off automatically. This Randomised clinical trials comparing hysterectomy
is a key aspect of this system, which is not based on to second generation ablation techniques are not cur-
time and temperature, but on tissue-specific physical rently available.
characteristics. A cavity integrity assessment system
is implemented to automatically detect uterine wall
perforation. To do so, CO2 is inflated into the cavity. 7. Discussion
Inability to pressurise and/or maintain pressure in the
uterine cavity will be detected by the controller and Dysfunctional uterine bleeding can be treated with
alarm the physician of a possible perforation. The medical therapy, a levonorgestrel releasing IUD, en-
corner to corner distance is measured by the device dometrial ablation using first and second generation
and assures correct intracavitary position. techniques, and hysterectomy. In The Netherlands,
A RCT comparing NovaSure® with rollerball ab- where most patients with dysfunctional uterine bleed-
lation at 12 months follow-up reported 41% amenor- ing are initially treated by the general practitioner,
rhea and 93% satisfaction in the NovaSure® arm and medical therapy is the treatment of first choice for
35% amenorrhea and 94% satisfaction in the rollerball most patients. However, the single RCT in which
arm (Fig. 1) [113]. These results have been confirmed medical treatment has been compared to endometrial
in prospective studies, in which NovaSure® demon- ablation indicates a significantly higher patient satis-
strated an amenorrhea rate of 56% and a satisfaction 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 There is evidence from various specialties in health
treated medically avoided surgical intervention. In care that patient’s satisfaction improves if patients can
the health system in The Netherlands, direct surgi- participate in the decision-making process [122,123].
cal treatment requires that patients with menorrhagia In the partial RCT of Cooper et al., women who
should be referred directly to a gynaecologist. How- were randomised to medical therapy were compared
ever, the applicability and role of the levonorgestrel to women who refused randomisation, but preferred
releasing IUD remains to be established. The lev- medical therapy. The women who choose medical
onorgestrel releasing IUD is effective when compared therapy for their heavy menstrual bleeding were
to hysterectomy, but its effectiveness as compared to significantly more satisfied than those who were
endometrial ablation has to be established [34–36,39]. randomised to medical treatment [26].
If the effectiveness of the levonorgestrel releasing IUD Why should women prefer endometrial ablation
would appear to be comparable to the effectiveness of over hysterectomy? When women who had been
endometrial ablation, a levonorgestrel releasing IUD treated with endometrial ablation were asked about
could be the treatment of first choice in the Dutch sit- their attitude towards endometrial ablation, more than
uation. The advantages of the levonorgestrel releasing half indicated that they would find endometrial abla-
IUD over the ablation techniques are the lower cost, tion still acceptable if there was no chance of amen-
the avoidance of hospitalisation, and preservation of orrhea, and if the odds of the menstruation becoming
fertility prospects, thus making it an ideal treatment lighter was at least 4:10 [124]. Furthermore, women
to be offered by the general practitioner, before the perceived avoidance of major surgery as one of the
patient is referred for specialist care. most important advantages of ablation over hysterec-
Since this review shows that none of the treatments tomy. Thus, women are inclined to take a chance of
for dysfunctional bleeding is superior to one of the failure to avoid a hysterectomy.
others, and since all treatments have their advantages In conclusion, none of the treatments for dysfunc-
and disadvantages, counselling of patients with dys- tional bleeding is radically superior to one another,
functional bleeding by a specialist should incorporate and since all treatments have their advantages and dis-
all treatment modalities described. It is imperative advantages, counselling of patients with dysfunctional
for the gynaecologists to be well acquainted with all bleeding should incorporate medical approach, lev-
treatment options, and have the possibility to offer onorgestrel releasing IUD, endometrial ablation and
these modalities to their patients. Second generation hysterectomy.
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 References
invasive treatment choice. Ablation therapy using first
generation ablation devices can be offered by gynae- [1] Royal College of Obstetricians and Gynaecologists. The
cologists who are trained and skilled in hysteroscopic management of menorrhagia in secondary care; 1999.
[2] Vessey MP, Villard-Mackintosh L, McPherson K, Coulter
ablation. Less experienced gynaecologists should pro- A, Yeates D. The epidemiology of hysterectomy: findings in
cure a second-generation device to avoid the effects a large cohort study. Br J Obstet Gynaecol 1992;99:402–7.
of a learning curve of the first generation techniques. [3] Luoto R, Rutanen EM, Kaprio J. Five gynecologic diagnoses
Another issue with respect to the learning curve associated with hysterectomy—trends in incidence of
of endometrial ablations of the first generation is hospitalizations in Finland, 1971–1986. Maturitas 1994;19:
the decreasing number of ablations, in case if lev- [4] Luoto R, Keskimaki I, Reunanen A. Socioeconomic
onorgestrel releasing IUD will become the treatment variations in hysterectomy: evidence from a linkage study
of first choice. In that situation, this will be an ad- of the Finnish hospital discharge register and population
ditional argument for the use of simple and easy to census. J Epidemiol Commun Health 1997;51:67–73.
use second generation ablation techniques instead of [5] Fraser IS, MacCarron G, Markham R. A preliminary study
of factors influencing perception of menstrual blood loss
the skill dependent first generation techniques. The volume. Am J Obstet Gynecol 1984;149:788–93.
device of choice will depend on success, amenorrhea [6] Chimbira TH, Anderson AB, Turnbull AC. Relation between
rates, safety and costs. measured menstrual blood loss and patient’s subjective
M.Y. Bongers et al. / Maturitas 47 (2004) 159–174 171

assessment of loss, duration of bleeding, number of sanitary [23] Fraser IS, McCarron G. Randomized trial of 2 hormonal and
towels used, uterine weight and endometrial surface area. 2 prostaglandin-inhibiting agents in women with a complaint
Br J Obstet Gynaecol 1977;84:763–8. of menorrhagia. Aust NZ J Obstet Gynaecol 1991;31:66–
[7] Gannon MJ, Day P, Hammadieh N, Johnson N. A new 70.
method for measuring menstrual blood loss and its use in [24] Higham JM, Shaw RW. A comparative study of danazol, a
screening women before eudiometrical ablation. Br J Obstet regimen of decreasing doses of danazol, and norethindrone
Gynaecol 1996;103:1029–33. in the treatment of objectively proven unexplained
[8] Janssen CA, Scholten PC, Heintz AP. A simple visual menorrhagia. Am J Obstet Gynecol 1993;169:1134–9.
assessment technique to discriminate between menorrhagia [25] Cooper KG, Parkin DE, Garratt AM, Grant AM. A
and normal menstrual blood loss. Obstet Gynecol 1995;85: randomised comparison of medical and hysteroscopic
977–82. management in women consulting a gynaecologist for
[9] Hallberg L, Hogdahl AM, Nilsson L, Rybo G. Menstrual treatment of heavy menstrual loss. Br J Obstet Gynaecol
blood loss—a population study. Acta Obstet Gynecol Scand 1997;104:1360–6.
1966;45:320–51. [26] Cooper KG, Grant AM, Garratt AM. The impact of using
[10] Vasilenko P, Kraicer PF, Kaplan R, deMasi A, Freed N. A a partially randomised patient preference design when
new end simple method of measuring menstrual blood loss. evaluating alternative managements for heavy menstrual
J Reprod Med 1988;33:293–7. bleeding. Br J Obstet Gynaecol 1997;104:1367–73.
[11] Higham JM, O’Brien PMS, Shaw RW. Assessment of [27] Cooper KG, Parkin DE, Garratt AM, Grant AM. Two-year
menstrual blood loss using a pictorial chart. Br J Obstet follow up of women randomised to medical management
Gynaecol 1990;97:734–9. or transcervical resection of the endometrium for heavy
[12] Deeny M, Davis JA. Assessment of menstrual blood loss menstrual loss: clinical and quality of life outcomes. Br J
in women referred for endometrial ablation. Eur J Obstet Obstet Gynaecol 1999;106:258–65.
Gynecol Reprod Biol 1994;57:179–80. [28] Cooper KG, Parkin DE, Garratt AM, Grant AM. Five-year
[13] Vercellini P, Cortesi I, Oldani S, Moschetta M, De Giorgi follow up of women randomised to medical management
O, Crosignani PG. The role of transvaginal ultrasonography or transcervical resection of the endometrium for heavy
and outpatient diagnostic hysteroscopy in the evaluation menstrual loss: clinical and quality of life outcomes. Br J
of patients with menorrhagia. Hum Reprod 1997;12:1768– Obstet Gynaecol 2001;108:1222–8.
71. [29] Coulter A, Kelland J, Peto V, Rees MC. Treating
[14] Dijkhuizen FPHLJ, De Vries LID, Mol BWJ. Comparison of menorrhagia in primary care. An overview of drug trials and
transvaginal ultrasonography and saline infusion sonography a survey of prescribing practice. Intern J Technol Assess
for the detection of intracavitary abnormalities. Ultrasound Health Care 1995;11:456–71.
Obstet Gynecol 2000;15:372–6. [30] French RS, Cowan FM, Mansour D, Higgins JPT, Robinson
[15] Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for A, Procter T, et al. Levonorgestrel-releasing (20 ug/ day)
heavy menstrual bleeding (Cochrane Review). The Cochrane intrauterine systems (Mirena) compared with other methods
Library, vol. 4. Oxford: Update Software; 2002. of reversible contraceptives. Br J Obstet Gynaecol 2000;
[16] Lethaby A, Augood C, Duckitt K. Nonsteroidal anti- 107:1218–25.
inflammatory drugs for heavy menstrual bleeding (Cochrane [31] Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkila
Review). The Cochrane Library, vol. 4. Oxford: Update A, Walker JJ, Cameron IY. Randomised comparative study
Software; 2002. of the levonorgestrel intrauterine system and morethisterone
[17] Iyer V, Farquhar C, Jepson R. Oral contraceptive pills for for the treatment of idiopathic menorrhagia. Br J Obstet
heavy menstrual bleeding (Cochrane Review). The Cochrane Gynecol 1998;105:592–8.
Library, vol. 4. Oxford: Update Software; 2002. [32] Lahteenmaki P, Haukkamaa M, Puolakka J, Sainio S,
[18] Lethaby A, Irvine G, Cameron I. Cyclical progestogens for Suvisaari J. Open randomised study of use of levonorgestrel
heavy menstrual bleeding (Cochrane Review). The Cochrane releasing intrauterine system as alternative to hysterectomy.
Library, vol. 4. Oxford: Update Software; 2002. BMJ 1998;316:1122–6.
[19] Beaumont H, Augood C, Duckitt K, Lethaby A. Danazol for [33] Tang GW, Lo SS. Levonorgestrel intrauterine device in the
heavy menstrual bleeding (Cochrane Review). The Cochrane treatment of menorrhagia in Chinese women: efficacy versus
Library, vol. 4. Oxford: Update Software; 2002. acceptability. Contraception 1995;51:231–5.
[20] Preston JT, Cameron IT, Adams EJ, Smith SK. Comparative [34] Crosignani PG, Vercellini P, Mosconi P, Oldani S,
study of tranexamic acid and norethisterone in the Cortesi I, De Giorgi O. Levonorgestrel-releasing intrauterine
treatment of ovulatory menorrhagia. Br J Obstet Gynaecol device versus hysteroscopic endometrial resection in
1995;102:401–6. treatment of dysfunctional uterine bleeding. Obstet Gynecol
[21] Bonnar J, Sheppard BL. Treatment of menorrhagia during 1997;90:257–63.
menstruation: randomised controlled trial of ethamsylate. [35] Lethaby AE, Cooke I, Rees M. Progesterone/progestogen
BMJ 1996;313:579–82. releasing intrauterine systems for heavy menstrual bleeding
[22] Prentice A. Medical management of menorrhagia. BMJ (Cochrane Review). The Cochrane Library, vol. 4. Oxford:
1999;319:1343–5. Update Software; 2002.
172 M.Y. Bongers et al. / Maturitas 47 (2004) 159–174

[36] Istre O, Trolle B. Treatment of menorrhagia with the [55] Scottish Hysteroscopy Audit Group. A Scottish audit of
levonorgestrel intrauterine system versus endometrial rese- hysteroscopic surgery for menorrhagia: complications and
ction. Fertil Steril 2001;76:304–9. follow-up. Br J Obstet Gynaecol 1995;102:249–54.
[37] Andersson JK, Rybo G. Levonorgestrel-releasing intrauterine [56] Aberdeen Endometrial Ablation Trials Group. A randomised
device in the treatment of menorrhagia. Br J Obstet Gynaecol trial of endometrial ablation versus hysterectomy for the
1990;97:690–4. treatment of dysfunctional uterine bleeding: outcome at four
[38] Luukkainen T, Toivonen J. Levonorgestrel-releasing IUD years. Br J Obstet Gynaecol 1999;106:360–6.
as a method of contraception with therapeutic properties. [57] Teirney R, Arachchi GJ, Fraser IS. Menstrual blood loss
Contraception 1995;52:269–76. measured 5–6 years after endometrial ablation. Obstet
[39] Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman Gynecol 2000;95:251–4.
S, Kivela A, et al. Quality of life and cost-effectiveness [58] Martyn P, Allan B. Long-term follow-up of endometrial
of levonorgestrel-releasing intrauterine system versus hyste- ablation. J Am Assoc Gynecol Laparosc 1998;5:115–8.
rectomy for treatment of menorrhagia: a randomised trial. [59] Dwyer N, Hutton J, Stirrat GM. Randomised controlled
Lancet 2001;357:273–7. trial comparing endometrial resection with abdominal
[40] Haynes PJ, Hodgson H, Anderson AB, Turnbull AC. hysterectomy for the surgical treatment of menorraghia. Br
Measurement of menstrual blood loss in patients J Obstet Gynaecol 1993;100:237–43.
complaining of menorrhagia. Br J Obstet Gynaecol 1977;84: [60] Pinion SB, Parkin DE, Abramovich DR, et al. Randomised
763–8. trial of hysterectomy, endometrial laser ablation and trans-
[41] Ashermann JG. Amenorrhea traumatica (atretica). Obstet cervical resection for dysfunctional uterine bleeding. BMJ
Gynecol 1948;55:23. 1994;309:979–83.
[42] Neuwirth RS, Amin HK. Excision of submucus fibroids with [61] Gannon MJ, Holt EM, Fairbank J, Fitzgerald M, Milne MA,
hysteroscopic control. Am J Obstet Gynecol 1976;126:95–9. Crystal AM, et al. A randomised trial comparing endometrial
[43] Goldrath MH, Fuller TA, Segal S. Laser photovaporization resection and abdominal hysterectomy for the treatment of
of the endometrium in the treatment of menorrhagia. Am J menorrhagia. BMJ 1991;303:1362–4.
Obstet Gynecol 1981;140:14–9. [62] Crosignani PG, Vercellini P, Apolone G, De Giorgi
[44] DeCherney A, Polan ML. Hysteroscopic management of O, Cortesi I, Meschia M. Endometrial resection versus
intrauterine lesions and intractable uterine bleeding. Obstet vaginal hysterectomy for menorrhagia: long-term clinical
Gynecol 1983;61:392–7. and quality-of-life outcomes. Am J Obstet Gynecol 1997;
[45] Vancaillie TG. Electrocoagulation of the endometrium with 177:95–101.
the ball-end resectoscope. Obstet Gynecol 1989;74:425–7. [63] O’Connor H, Broadbent JA, Magos AL, McPherson
[46] Lethaby A, Sheppard S, Cooke I, Farquhar C. Endometrial K. Medical research council randomised trial of endo-
resection and ablation versus hysterectomy for menstrual metrial resection versus hysterectomy in management of
bleeding. The Cochrane Library, vol. 4. Oxford: Update menorrhagia. Lancet 1997;349:897–901.
Software; 2002. [64] Lethaby A, Shepperd S, Cooke I, Farquhar C. Endometrial
[47] Garry R, Shelley-Jones D, Mooney P, Phillips G. Six hundred resection and ablation versus hysterectomy for heavy mens-
endometrial laser ablations. Obstet Gynecol 1995;85:24–9. trual bleeding (Cochrane Review). The Cochrane Library,
[48] Bhattacharya S, Cameron IM, Parkin DE, Abramovich DR, vol. 4 Oxford: Update Software; 2002.
Mollison J, Pinion SB, et al. A pragmatic randomised [65] Overton C, Hargreaves J, Maresh M. A national survey of
comparison of transcervical resection of the endometrium the complications of endometrial destruction for menstrual
with endometrial laser ablation for the treatment of disorders the MISTLETOE study. Br J Obstet Gynaecol
menorrhagia. Br J Obstet Gynaecol 1997;104:601–7. 1997;104:1351–9.
[49] Phillips G, Chien PF, Garry R. Risk of hysterectomy after [66] Vilos GA, Brown S, Graham G, McCulloch S, Borg
1000 consecutive endometrial laser ablations. Br J Obstet P. Genital tract electrical burns during hysteroscopic
Gynaecol 1998;105:897–903. endometrial ablation: report of 13 cases in the United States
[50] Baggish MS, Sze EHM. Endometrial ablation: a series of and Canada. J Am Assoc Gynecol Laparosc 2000;7:141–7.
568 patients treated over an 11-year period. Am J Obstet [67] Rosenberg MK. Hyponatremic encephalopathy after roller-
Gynecol 1996;174:908–13. ball endometrial ablation. Anesth Analg 1995;80:1046–8.
[51] Erian J. Endometrial ablation in the treatment of [68] Baggish MS, Brill AI, Rosenweig B, et al. Fatal acute
menorrhagia. Br J Obstet Gynaecol 1994;101:19–22. glycine and sorbitol toxicity during operative hysteroscopy.
[52] Kammerer-Doak DN, Rogers RG. Endometrial ablation: J Gynecol Surg 1993;9:137–42.
electrocautery and laser techniques. Clin Obstet Gynaecol [69] Jansen FW, Vredevoogd CB, van Ulzen K, Hermans J,
2000;43:561–74. Trimbos JB, Trimbos-Kemper TC. Complications of hystero-
[53] Tsaltas J, Taylor N, Healy M. A 6-year review of the scopy: a prospective, multicenter study. Obstet Gynecol
outcome of endometrial ablation. Aust NZ J Obstet Gynaecol 2000;96:266–70.
1998;38:69–72. [70] Cooper JM, Brady RM. Late complications of operative
[54] O’Connor H, Magos A. Endometrial resection for the treat- hysteroscopy. Obstet Gynecol Clin North Am 2000;27:367–
ment of menorrhagia. N Engl J Med 1996;335:151–6. 74.
M.Y. Bongers et al. / Maturitas 47 (2004) 159–174 173

[71] Mall A, Shirk G, Van Voorhis BJ. Previous tubal ligation [88] Loffer FD. Three-year comparison of thermal balloon and
is a risk factor for hysterectomy after rollerball endometrial rollerball ablation in treatment of menorrhagia. J Am Assoc
ablation. Obstet Gynecol 2002;100:659–64. Gynecol Laparosc 2001;8:48–54.
[72] Valle RF, Baggish MS. Endometrial carcinoma after [89] Loffer FD, Grainger D. Five-year follow-up of patients
endometrial ablation: high-risk factors predicting its participating in a randomized trial of uterine balloon therapy
occurrence. Am J Obstet Gynecol 1998;179:569–72. versus rollerball ablation for treatment of menorrhagia. J
[73] Dijkhuizen FP, Mol BWJ, Brolmann HAM, Heintz AP. Am Assoc Gynecol Laparosc 2002;9:429–35.
The accuracy of endometrial sampling in the diagnosis [90] Bongers MY, Mol BWJ, Brölmann HAM. Comparison of 8
of patients with endometrial carcinoma and hyperplasia: a versus 16 minutes heating in the treatment of menorrhagia
meta-analysis. Cancer 2000;89:1765–72. with hot fluid balloon ablation. J Gynecol Surg 1999;15:
[74] Pugh CP, Crane JM, Hogan TG. Successful intrauterine 143–7.
pregnancy after endometrial ablation. J Am Assoc Gynecol [91] Bongers MY, Mol BWJ, Dijkhuizen FPHLJ, Brölmann
Laparosc 2000;7:391–4. HAM. Is balloon-ablation as effective as endometrial
[75] Ismail MS, Torsten U, Serour GI, Weitzel H, Berlien HP. Is electro-resection in the treatment of menorrhagia? J Lap
endometrial ablation a safe contraceptive method? Pregnancy Adv Surg Techn 2000;10:85–92.
following endometrial ablation. The Eur J Contract Reprod [92] Gervaise A, Fernandez H, Capella-Allouc S, Taylor S, La
Health Care 1998;3:99–102. Vieille S, Hamou J, et al. Thermal balloon ablation versus
[76] Pinette M, Katz W, Drouin M, Blackstone J, Cartin endometrial resection for the treatment of abnormal uterine
A. Successful planned pregnancy following endometrial bleeding. Hum Reprod 1999;14:2743–7.
ablation with the YAG laser. Am J Obstet Gynecol 2001;185: [93] Amso NN, Stabinsky SA, McFaul P, Blanc B, Pendley
242–3. L, Neuwirth R. Uterine thermal balloon therapy for the
[77] Rogerson I, Gannon, O’Donnovan P. Outcome of pregnancy treatment of menorrhagia: the first 300 patients from a
following endometrial ablation. J Gynecol Surg 1994; multi-center study. Br J Obstet Gynaecol 1998;105:517–23.
170:1370–1. [94] Vilos GA, Fortin CA, Sanders B, Pendley L, Stabinsky SA.
[78] Hart R, Magos A. Endometrial ablation. Cur Opin Obstet Clinical trial of the uterine thermal balloon for treatment of
Gynecol 1997;9:226–32. menorrhagia. J Am Assoc Gynecol Laparosc 1997;4:559–
[79] McCausland AM, McCausland VM. Depth of endometrial 65.
penetration in adenomyosis helps determine outcome of [95] Romer T. The treatment of recurrent menorrhagias-Cavaterm
rollerball ablation. Am J Obstet Gynecol 1996;174:1786– balloon-coagulation versus rollerball-endometrial ablation—
94. a prospective randomized comparative study. Zentrallbl
[80] Abbott JA, Garry R. The surgical management of menorr- Gynakol 1998;120:511–4.
hagia. Hum Reprod Update 2002;8:68–78. [96] Hawe JA, Phillips AG, Chien PFW, Erian J, Garry R.
[81] Overton C, Maresh MJA. Audit of currently available Cavaterm thermal balloon ablation for the treatment of
endometrial ablative techniques. Baillieres Clin Obstet menorrhagia. Br J Obstet Gynaecol 1999;106:1143–8.
Gynaecol 1995;9:357–72. [97] Friberg B, Joergensen C, Ahlgren M. Endometrial thermal
[82] Donnez J, Vilos G, Gannon MJ, Maheux R, Emanuel coagulation—degree of uterine fibrosis predicts treatment
MH, Istre O. Goserelin acetate (Zoladex) plus endometrial outcome. Gynecol Obstet Invest 1998;45:54–7.
ablation for dysfunctional uterine bleeding: a 3-year follow- [98] Ulmsten U, Carstensen H, Falconer C, Holm L, Lanner L,
up evaluation. Fertil Steril 2001;75:620–2. Nilsson S, et al. The safety and efficacy of MenoTreat, a
[83] Sowter MC, Lethaby A, Singla AA. Pre-operative new balloon device for thermal endometrial ablation. Acta
endometrial thinning agents before endometrial destruction Obstet Gynecol Scand 2001;80:52–7.
for heavy menstrual bleeding (Cochrane Review). The [99] Corson SL, Brill AI, Brooks PG, Cooper JM, Indman PD,
Cochrane Library, vol. 4. Oxford: Update Software; 2002. Liu JH, et al. Interim results of the American Vesta trial
[84] Lethaby A, Hickey M. Endometrial destruction techniques of endometrial ablation. J Am Assoc Gynecol Laparosc
for heavy menstrual bleeding (Cochrane Review). The 1999;6:45–9.
Cochrane Library, vol. 4. Oxford: Update Software; 2002. [100] Corson SL, Brill AI, Brooks PG, Cooper JM, Indman
[85] Neuwirth RS, Duran A, Singer A, MacDonald R, Bolduc L. PD, Liu JH, et al. One-year results of the vesta system
The endometrial ablator: a new instrument. Obstet Gynecol for endometrial ablation. J Am Assoc Gynecol Laparosc
1994;83:792–6. 2000;7:489–97.
[86] Meyer WR, Walsh BW, Grainger DA, Peacock LM, Loffer [101] Corson SL. A multicenter evaluation of endometrial ablation
FD, Steege JF. Thermal balloon and rollerball ablation by Hydro ThermAblator and rollerball for treatment of
to treat menorrhagia: a multi-center comparison. Obstet menorrhagia. J Am Assoc Gynecol Laparosc 2001;8:359–
Gynecol 1998;92:98–103. 67.
[87] Grainger D, Tjaden B. Thermal balloon and rollerball [102] Bustos-Lopez HH, Baggish M, Valle RF, Vadillo-Otrega F,
ablation to treat menorrhagia: two-year results from a Ibarra V, Nava G. Assessment of the safety of intrauterine
multicenter prospective, randomized clinical trial. J Am instillation of heated saline for endometrial ablation. Fertil
Assoc Gynecol Laparosc 2000;7:175–9. 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, and efficacy of the NovaSure System in the treatment of
Ellis S. Microwaves for menorrhagia: a new fast technique menorrhagia. J Am Assoc Gynecol Laparosc 2002;9:418–28.
for endometrial ablation. Lancet 1995;346:1003–4. [114] Gallinat A, Nugent W. NovaSure impedance-controlled
[104] Cooper KG, Bain C, Parkin DE. Comparison of microwave system for endometrial ablation. J Am Assoc Gynecol
endometrial ablation and transcervical resection of the Laparosc 2002;9:283–9.
endometrium for treatment of heavy menstrual loss: a [115] Carlson KJ. Outcomes of hysterectomy. Clin Obstet Gynecol
randomised trial. Lancet 1999;354:1859–63. 1997;40:939–46.
[105] Downes E, O’Donovan P. Microwave endometrial ablation [116] Carlson KJ, Miller BA, Fowler FJ. The main women’s
in the management of menorrhagia: current status. Cur Op health study: I. Outcomes of hysterectomy. Obstet Gynecol
Obstet Gynecol 2000;12:293–6. 1994;83:556–65.
[106] Bain C, Cooper KG, Parkin DE. Microwave endometrial [117] Lumsden MA, Twaddle S, Hawthorn R, Traynor I,
ablation versus endometrial resection: a randomized Gilmoe D, Davis J, et al. A randomised comparison and
controlled trial. Obstet Gynecol 2002;99:983–7. economic evaluation of laparoscopic-assisted hysterectomy
[107] Dobak JD, Ryba E, Kovalcheck S. A new closed-loop and abdominal hysterectomy. Br J Obstet Gynaecol 2000;
cryosurgical device for endometrial ablation. J Am Assoc 107:1386–91.
Gynecol Laparosc 2000;7:245–9. [118] Harris WJ, Daniell JF. Early complications of laparoscopic
[108] Dobak JD, Willems J, Howard R, Shea C, Townsend DE. hysterectomy. Obstet Gynecol Sur 1996;38:559–67.
Endometrial cryoablation with ultrasound visualization in [119] Harris WJ. Complications of hysterectomy. Clin Obstet
women undergoing hysterectomy. J Am Assoc Gynecol Gynecol 1997;40:928–38.
Laparosc 2000;7:89–93. [120] Munro MG, Deprest J. Laparoscopic hysterectomy: does it
[109] Rutherford TJ. Cryosurgery is a simple modality for work? A bicontinental review of the literature and clinical
endometrial ablation. J Am Assoc Gynecol Laparosc 1996; commentary. Clin Obstet Gynecol 1995;38:401–25.
3:S44–45. [121] Mittendorf R, Aronson MP, Berry RE, et al. Avoiding
[110] Korn AP. Endometrial cryoablation and thermal ablation. serious infections associated with abdominal hysterectomy:
Clin Obstet Gynecol 2000;43:575–83. a meta-analysis of antibiotic prophylaxis. Am J Obstet
[111] Donnez J, Polet R, Mathieu PE, Konwitz E, Nisolle M, Gynecol 1993;169:1119–24.
Casanas-Roux F. Endometrial laser interstitial hyperthermy: [122] Coulter A. Partnerships with patients: the pros and cons of
a potential modality for endometrial ablation. Obstet shared clinical discision making. J Health Serv Res Policy
Gynecol 1996;87:459–64. 1997;2:112–21.
[112] Donnez J, Polet R, Rabinovitz R, Ak M, Squifflet J, Nisolle [123] Gambone JC, Reiter RC. Hysterectomy: improving the
M. Endometrial laser intrauterine thermotherapy: the first patient’s decision-making process. Clin Obstet Gynecol
series of 100 patients observed for 1 year. Fertil Steril 1997;40:868–77.
2000;74:791–6. [124] Nagele F, Rubinger T, Magos A. Why do women choose
[113] Cooper J, Gimpelson R, Laberge P, Galen D, Garza-Leal endometrial ablation rather than hysterectomy? Fertil Steril
JG, Scott J, et al. A randomized, multicenter trial of safety 1998;69:1063–6.