Hysterectomy, endometrial ablation
and Mirena® for heavy menstrual
bleeding: a systematic review of
clinical effectiveness and cost-
S Bhattacharya,1* LJ Middleton,2 A Tsourapas,2
AJ Lee,1 R Champaneria,2 JP Daniels,2
T Roberts,2 NH Hilken,2 P Barton,2
R Gray,2 KS Khan,2 P Chien,3 P O’Donovan,4
KG Cooper5 and the International Heavy
Menstrual Bleeding Individual Patient Data
Meta-analysis Collaborative Group
1University of Aberdeen, Aberdeen, UK
2University of Birmingham, Birmingham, UK
3Ninewells Hospital, Dundee, UK
4Bradford Royal Infirmary, Bradford, UK
5Aberdeen Royal Infirmary, Aberdeen, UK
Health Technology Assessment 2011; Vol. 15: No. 19
Health Technology Assessment
NIHR HTA programme
Hysterectomy, endometrial ablation and Mirena® for
heavy menstrual bleeding
iiExecutive summary: Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding
Heavy menstrual bleeding (HMB) is a common problem that affects approximately 1.5 million
women in England and Wales and accounts for 20% of gynaecology outpatient referrals.
Although objectively defined as cyclical loss of > 80 ml of blood during each menstrual period,
HMB is diagnosed clinically in the presence of excessive menstrual blood loss that interferes with
a woman’s physical, emotional, social and material quality of life.
Medical treatments for HMB include oral drug regimens, such as tranexamic acid and mefenamic
acid, and the combined oral contraceptive pill as well as the levonorgestrel intrauterine system
(LNG IUS) (Mirena, Bayer Healthcare Pharmaceuticals, Pittsburg, PA, USA), which can reduce
menstrual loss by local release of progestogen. Surgical treatments include first- (hysteroscopic)
and second- (non-hysteroscopic) generation endometrial ablation (EA), which destroys the
lining of the cavity of the uterus (endometrium), and hysterectomy (surgical removal of the
uterus). First-generation ablation techniques include endometrial laser ablation, transcervical
resection of the endometrium and rollerball (RB) ablation. Examples of second-generation
ablative techniques are fluid-filled thermal balloon endometrial ablation, radiofrequency
(thermoregulated) balloon endometrial ablation, hydrothermal endometrial ablation, microwave
EA (MEA) and impedance-controlled bipolar radiofrequency ablation (NovaSure; Hologic Inc.,
Bedford, MA, USA).
In 1999–2000, half of the 51,858 hysterectomies performed in the public sector in England
were for HMB. In contrast, 7179 hysterectomies were performed for HMB in 2004–5 while
9701 women underwent EA – over half of these (5457) by means of second-generation (non-
hysteroscopic) techniques. The use of Mirena has increased concurrently, although its widespread
use for contraception across a number of clinical settings in primary and secondary care means
that it is difficult to gather accurate data on numbers prescribed for HMB.
The aim of this project was to determine the clinical effectiveness and cost-effectiveness of
hysterectomy, first- and second-generation EA, and Mirena for the treatment of HMB. To address
this question, the specific objectives were:
1. To determine, using individual patient data (IPD) meta-analysis of existing randomised
controlled trials (RCTs), the short- to medium-term effects of each class of treatment in
terms of patient dissatisfaction, time to resumption of normal activities and complication
rate, and to explore these outcomes in clinical subgroups.
2. To report, using population-based data from record linkage, the long-term effects of ablative
techniques and hysterectomy in terms of failure rates and complications.
3. To inform current treatment policy in this clinical area, while the value of information
component serves to highlight future research needs and agendas, and inform possible future
research funding decisions.
iii Health Technology Assessment 2011; Vol. 15: No. 19 (Executive summary)
Systematic review and individual patient data meta-analysis of available
A detailed search was carried out to identify systematic reviews and RCTs involving
hysterectomy, EA and Mirena. IPD were sought from RCTs of hysterectomy, EA techniques
and Mirena to examine their relative effectiveness. A systematic review was conducted based
on a protocol designed using widely recommended methods that complied with meta-analysis
Individual patient data on 2814 women were available from 17 of the 30 RCTs identified (14 trials
including 2448 women for first- vs second-generation EA; seven trials including 1127 women
for hysterectomy vs first-generation EA; five trials including 304 women for second-generation
EA vs Mirena; three trials including 190 women for first-generation EA vs Mirena; one trial
including 236 women for hysterectomy vs Mirena). Direct and indirect comparisons were made
where appropriate to assess the effect of interventions on the primary outcome measure of
Follow-up of women following hysterectomy and endometrial ablation by
Patient-based data for inpatient and day case activity from the whole of Scotland which are
routinely collected as Scottish Morbidity Returns (SMR) by the Scottish Information Services
Division (ISD) were used for this study. Following linkage with the Scottish Cancer Registry, an
anonymised data set containing follow-up hospital data on all women who had undergone either
hysterectomy or EA for HMB between 1989 and 2006 was made available to the researchers.
Socioeconomic status was assessed using the Carstairs index, which was divided into quintiles
for analysis. Descriptive statistics were used to summarise each of the surgical outcomes and
potential predictor variables (age, year of procedure and Carstairs quintile). Appropriate
univariate analyses across the hysterectomy and EA groups were performed. Cox proportional
hazards regression analysis was used to examine the survival experience for different surgical
outcomes in the hysterectomy and EA groups and then between different types of hysterectomy
following adjustment for age, year of primary operation and Carstairs quintile.
The authors developed a state transition (Markov) model using Microsoft excel (Microsoft
Corporation, Seattle, WA, USA). The structure was informed by the review of the clinical
literature supplemented by clinical input. The model allows a comparison of four hypothetical
cohorts of women with HMB who are treated separately by one of four alternative strategies:
(1) Mirena coil; (2) first-generation EA techniques; (3) second-generation EA techniques; and
(4) hysterectomy. Given the reliance on secondary data and the availability of data, the model-
based economic evaluation takes the form of a cost–utility analysis and was carried out from
the perspective of the UK NHS in a secondary care setting. The results are reported in terms
of incremental cost per quality-adjusted life-year (QALY) gained based on quality of life data
available from published sources. The presentation of results in QALYs allows comparison of the
results with other available and recently published studies [Garside R, Stein K, Wyatt K, Round A,
Price A. The effectiveness and cost-effectiveness of microwave and thermal balloon endometrial
ablation for heavy menstrual bleeding: a systematic review and economic modelling. Health
Technol Assess 2004;8(3)]. Resource use was estimated from the existing published evidence and
additional cost data from other sources such as the annual review of unit health and social care
costs (Personal Social Services Research Unit) and national schedule for reference costs.
ivExecutive summary: Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding
Clinical effectiveness from individual patient data meta-analysis
At around 12 months, 7.3% more women [12.6% (57/454) vs 5.3% (23/432)] were dissatisfied
with the outcome of first-generation EA than with hysterectomy [OR (odds ratio) 2.46, 95%
confidence interval (CI) 1.54 to 3.93; p = 0.0002], but hospital stay [WMD (weighted mean
difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal
activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy.
Unsatisfactory outcomes were comparable with first- and second-generation EA techniques
[12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2], although
second-generation techniques were quicker (WMD 14.5 minutes, 95% CI 13.7 to 15.3 minutes;
p < 0.00001) and women recovered sooner (WMD 0.48 days, 95% CI 0.20 to 0.75 days; p = 0.0008)
with fewer procedural complications. Indirect comparison suggested more unsatisfactory
outcomes with second-generation EA techniques than with hysterectomy [10.6% (110/1034) vs
5.3% (23/432); OR 2.32, 95% CI 1.27 to 4.24; p = 0.006].
Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs
22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Overall rates of dissatisfaction were 17.2%
(22/128) for Mirena and 18.2% (25/137) for both first- and second-generation EA. Lack of IPD
prohibited any further investigation of subgroups or repeated measures.
Indirect estimates suggest that hysterectomy is also preferable to second-generation EA (OR
2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. This is confirmed by the
repeated measures analysis over all three time points, which only include IPD (OR 3.06, 95%
CI 1.59 to 5.90; p = 0.0008). The evidence to suggest that hysterectomy is preferable to Mirena
was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07), but given the lack of precision from Mirena
comparisons this was not a surprising result.
Medium- to long-term surgical outcomes following endometrial ablation
and hysterectomy for heavy menstrual bleeding
Between 1989 and 2006, 37,120 Scottish women underwent hysterectomy and 11,299 had
EA as a primary surgical procedure for HMB. The median [interquartile range (IQR)]
duration of follow-up was 6.2 (2.7–10.8) and 11.6 (7.9–14.8) years, respectively, in the EA and
A total of 2779 women in the original EA group went on to have a hysterectomy and were
excluded from further analysis.
Of the remaining women originally treated by EA, 962 (8.5%) underwent further gynaecological
surgery. While the risk of adnexal surgery was similar in both groups, women who had
undergone hysterectomy were more likely to need further surgery for stress urinary incontinence.
Vaginal hysterectomy was associated with a significantly higher chance of further surgery
for urinary incontinence and pelvic floor repair than hysterectomy carried out through the
abdominal route. The incidence of endometrial cancer following endometrial ablation was low
The results of the cost-effectiveness model show that the strategy of hysterectomy is the most
cost-effective. Hysterectomy dominates the first-generation EA strategy and, although more
expensive, produces more QALYs than the other strategies of second-generation EA and
Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and
v Health Technology Assessment 2011; Vol. 15: No. 19 (Executive summary)
hysterectomy compared with second-generation ablation are £1440 per additional QALY and
£970 per additional QALY, respectively.
Strengths and limitations of the analysis
For the systematic review, an extensive literature search was conducted, with no language
restrictions, minimising the risk of missing information.
A limitation of the systematic review was the unavailability of IPD from at least 35% of
randomised women, which could not be accessed as a number of triallists did not agree to
collaborate or could not be contacted. Received data were sometimes incomplete and, on
occasions, failed quality checks, and so were unusable. The review’s inferences are also limited by
the inconsistent outcome measure used across trials; studies involving endometrial destruction
(ED) and Mirena focused on comparing reduction in bleeding, while hysterectomy trials focused
on patient satisfaction and quality.
The follow-up study on women who had undergone hysterectomy or EA is, to our knowledge,
the first large population-based study to use national data. Use of the International Classification
of Diseases codes allowed us to define both the cause of HMB as well as the nature of surgery,
but, as the diagnosis of dysfunctional uterine bleeding was performed by a process of exclusion,
it is possible that the hysterectomy cohort could have included a few women with other causes
of HMB. As a retrospective observational study, it is not free from problems of bias and
confounding. The analysis was compromised by the limited availability of key socioeconomic
as well as clinical variables. Although the numbers of women in the hysterectomy and ablation
cohorts were large, a major drawback was our inability to discriminate between the individual
types of first- and second-generation EA or adjust for the experience of the operator as has
been done in previous national audits. We were also unable to analyse the long-term outcomes
following laparoscopic hysterectomy as numbers were small and these were grouped with
The major strength of the economic component of this study is that it was based on a state-of-
the-art Markov model which was informed by data from an IPD meta-analysis of randomised
trials. A multidisciplinary team including economists, expert clinicians and statisticians provided
input into the model structure, primarily based on the evidence in the literature. All assumptions
used in the model were made a priori, and were based on the best available evidence.
The quality of the health economic model was affected by the paucity of good-quality data such as
those related to adverse outcomes following some types of EA and follow-up data on Mirena use.
In addition, the complexity of the model meant a long running time, which inevitably affected
the number and nature of additional sensitivity analyses undertaken.
Interpretation of available evidence and consensus regarding treatment
More women were dissatisfied following EA than hysterectomy. However, dissatisfaction rates
were low after all treatments and hysterectomy was associated with an increased hospital
stay and recovery period. The paucity of suitable trials means that definitive evidence on the
effectiveness of Mirena compared with more invasive procedures is lacking. Hysterectomy would
be considered the most cost-effective strategy in the light of the acceptable thresholds used by the
National Institute for Health and Clinical Excellence (NICE). The results concur with those of
other studies, but are sensitive to utility values used in the analysis.
viExecutive summary: Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding
A summary of the results on the clinical effectiveness and cost-effectiveness of Mirena, EA and
hysterectomy was sent electronically to 15 national experts (gynaecological surgeons) along with
a short questionnaire to encourage rapid response. After two mailings, responses were received
from 10 clinicians, 9 of whom indicated that having considered effectiveness, cost-effectiveness
and invasiveness/risks they would favour HMB LNG IUS (Mirena), second-generation EA
techniques and hysterectomy as first-, second- and third-line approaches to HMB resistant to oral
medication. This view was endorsed by three consumers who highlighted the need for a degree of
flexibility in order to accommodate the preferences of individual women.
Although hospital stay and time to resumption of normal activities were longer, more women
were satisfied after hysterectomy than after first-generation EA. In the absence of head-to-head
trials, indirect estimates suggest that hysterectomy is also preferable to second-generation
EA in terms of patient satisfaction. Dissatisfaction rates were comparable between first- and
second-generation techniques, although second-generation techniques were cheaper, quicker and
associated with faster recovery and fewer complications. There are few comparisons of Mirena
with more invasive procedures.
The few data available suggest that Mirena is potentially cheaper and more effective than
first-generation ablation techniques with rates of satisfaction that are similar to those of second-
generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that
hysterectomy is preferable to Mirena. Hysterectomy is considered the most cost-effective strategy,
but, owing to its invasive nature and higher risk of complications, is considered a final option by
gynaecological experts and consumers.
Implications for service provision
Our review provides evidence that hysterectomy reduces dissatisfaction compared with EA, and
this information could contribute to a consultation with women making a choice about treatment
options when initial drug treatment fails to control HMB. EA is satisfactory for a very high
proportion of women, but, if complete cessation of bleeding is sought, then hysterectomy may be
offered. A decision to opt for hysterectomy needs also to take into account the invasive nature of
the procedure and its potential for short- and long-term morbidity in some women.
Although conclusive evidence from randomised trials is still awaited, the evidence from
our review is consistent with a recent NICE recommendation that women should be offered
Mirena before more invasive procedures. This view reflects the minimally invasive nature of the
intervention as well as the ability to offer it in primary care. This piece of research has highlighted
the benefits and risks associated with the three broad strategies for the treatment of HMB and,
while supportive of the existing NICE guideline on this subject, our results underline the need for
a degree of flexibility in accommodating women’s preferences.
Need for further research
This project has uncovered a number of areas for future research. These include:
evaluation of the clinical effectiveness and cost-effectiveness of the best second-generation
EA technique under local anaesthetic versus Mirena
exploring the safety of second-generation EA and Mirena through a national audit
longer term follow-up of randomised cohorts of women treated for HMB
vii Health Technology Assessment 2011; Vol. 15: No. 19 (Executive summary)
evaluation of the clinical effectiveness and cost-effectiveness of hydrothermablator (HA,
the second-generation EA device which can be used under direct vision) against other
trials assessing conservative and less morbid types of hysterectomy such as laparoscopic
supracervical hysterectomy versus conventional hysterectomy and second-generation EA.
Funding for this study was provided by the Health Technology Assessment programme of the
National Institute for Health Research.
Bhattacharya S, Middleton LJ, Tsourapas A, Lee AJ, Champaneria R, Daniels JP, et al.
Hysterectomy, endometrial ablation and Mirena for heavy menstrual bleeding: a systematic
review of clinical effectiveness and cost-effectiveness analysis. Health Technol Assess 2011;15(19).
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