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Research

Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: cost effectiveness analysis

BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d2202 (Published 26 April 2011) Cite this as: BMJ 2011;342:d2202

Commentary on: Roberts T E, Tsourapas A, Middleton L J, et al.; Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: cost effectiveness analysis. BMJ 2011; 342; d2202.

Clinical Context

Heavy menstrual bleeding (HMB) refers to excessive menstrual blood
loss that impacts a woman's physical, social, emotional, and/or material
quality of life. Estimates of global prevalence range from 4% to 52%,
although the broad range is accounted for by the different research
methods and settings (NICE 2007). The current treatment options for HMB
consist of a range of pharmaceutical therapies (e.g. NSAID, oral hormonal
agents, tranexamic acid, Mirena) and surgical interventions (e.g.
endometrial ablation, hysterectomy).

Patients' preferences and experience with HMB are complex and may not
be limited to bleeding symptoms, what should be reflected in tailored
therapeutic approach (Matteson and Clark, 2010; Fraser et al. 2008; Fraser
2011).

Commentary on Research Methodology

Roberts and colleagues developed sophisticated Markov model to
compare four alternative treatment strategies starting with hysterectomy,
Mirena, first and second generation ablation. This has been published as
an article in the BMJ by Roberts et al. 2011 and separately included in a
HTA report by Bhattacharya et al. 2011. We would like herewith to comment
on model structure and input data.

The analysis related to women with HMB unresponsive to other medical
treatment, then being treated within the NHS with up to three lines of
treatments including Mirena, first or second generation endometrial
ablation or hysterectomy. The model covered period of 10 years with
starting age of women being 42. The cost-effectiveness analysis did not
evaluate Mirena followed (if unsuccessful) by hysterectomy, a treatment
pathway that may be relevant to UK practice (Clegg et al. 2007). Other
than this, we generally concur with the authors about the feasibility of
clinical pathways for this age groups, which, however, provides a partial
view on the patient population and treatment pattern. HMB occurs along the
reproductive lifespan starting with menarche, with different bleeding,
contraceptive, fertility considerations as well as preferences towards
treatment administration. Thus, hysterectomy and ablation are unlikely to
be first and relevant treatment comparators to Mirena, when fertility is
of concern.

Clinical inputs and utility data were derived in comprehensive and
systematic way (partially published earlier by Middleton et al. 2010) and
provide a valuable evidence synthesis for HMB researchers. Authors
emphasized high uncertainty around the utility input values. Assumption of
the different utilities in response to different therapies (e.g. highest
for response to hysterectomy and lowest for the response to first
generation ablation) is obviously lacking strong empirical support and
should remain a topics for future research. In addition, long-term studies
are needed to understand the evolvement of HMB symptoms, reasons for
initiation and discontinuation of reversible HMB treatments, such as
Mirena, over the time.

Commentary on Research Findings

Deterministic base case analysis suggests that initiation of HMB
therapy with surgical intervention is in general more expensive than that
with Mirena. Initiation the therapy with hysterectomy produced more QALYs
at more costs (comparing to Mirena). Results are highly sensitive to the
utility values used as inputs. Conclusions differ in emphasis in different
parts of the BMJ article and HTA report:
- One conclusion drawn in the BMJ article is that in light of the NICE
thresholds, hysterectomy would be considered the preferred strategy
(Roberts et al. 2011).
- Another conclusion drawn in the HTA report is that owing to its invasive
nature and risk of complications, hysterectomy may be considered a final
option by gynaecological experts and patients (Bhattacharya et al. 2011).

Taking into account the above discussed uncertainty in the model
inputs as well as partial perspective on HMB population (women older than
42 years) and treatment pattern (starting with surgical intervention as
first line), we refrain from the recommendation related to hysterectomy as
preferred strategy to the general HMB population as well as to routine
clinical practice.

Conclusions and Implications for Clinical Practice and Research

As pointed out by independent researchers, this study supports the
fact, that based on the current knowledge, hysterectomy, ablation and
Mirena are highly effective for treating of HMB (Fraser 2011). Thus, since
the overall efficacy is broadly similar, individual counselling by a
specialist about the attributes of each therapy for each patient is
crucial (Fraser 2011). One important attribute, which has been ignored in
the publication is permanent loss of fertility by both of the surgical
therapeutic options. For many women, loss of fertility makes both surgical
options unacceptable treatment choices.

In general, women will usually prefer a less invasive choice, should
the option exist, also in the treatment of HMB. In this context it is
important to note that the authors could find no adverse event information
for Mirena and only considered serious complications for ablation and
surgery. Surgery may also have long-term sequalae; in a recent randomized
comparative trial of Mirena vs hysterectomy, with up to 10 years of follow
-up, showed that presence of some long-term sequalae, such as various
urinary problems and back pain, may be more common among those treated
with hysterectomy than Mirena (Helioevaara-Peippo et al. 2009, 2010). In
fact, it could be demonstrated that women who received hysterectomy used
more medication for the treatment of urinary incontinence and experienced
more often urinary tract infections, than those treated with Mirena
(Helioevaara-Peippo et al. 2010). This type of long-term sequealae have
not been taken into account in the present analysis. The issues outlined
above throw into question the QALY calculations and validity for the
treatment options concerned.

In conclusion, we believe that the authors draw too broad conclusions
about treatment choices without appropriately considering the clinical
context and that the conclusions regarding the cost-effectiveness analysis
may be valid only to a subgroup of women suffering from HMB. This subgroup
includes women who are over 42 years of age at the start of the HMB
therapy, are willing to permanently give up their future fertility, are
willing to accept the possibility of serious, albeit rare, complications
of surgery, as well as various long-term sequalae of surgery.

References

Bhattacharya S, Middleton L J, Tsourapas A, Lee AJ, Champaneria R,
Daniels J P, et al. 2011. Hysterectomy, endometrial ablation and Mirena
for heavy menstrual bleeding: a systematic review of clinical
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;15(19). Available at: http://www.hta.ac.uk/1616 . Accessed on 20th of May
2011.

Clegg J P, Guest J F, Hurskainen R. 2007. Cost-utility of
levonorgestrel intrauterine system compared with hysterectomy and second
generation endometrial ablative techniques in managing patients with
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Fraser I S, Porte R J, Kouides P A, Lukes A S. 2008. A benefit-risk
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menstrual bleeding. Drug Saf; 31:275.

Fraser I S. 2011. Hysterectomy, endometrial destruction and the
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menstrual bleeding; satisfaction rates are highest after hysterectomy.
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Helioevaara-Peippo S, Halmesmaeki K, Hurskainen R, Teperi J, Grenman
S, Kivelae A, Kujansuu E, et al. 2009.The effect of hysterectomy or
levonorgestrel-releasing intrauterine system on lower abdominal pain and
back pain among women treated for menorrhagia: a five-year randomized
controlled trial. Acta Obstet Gynecol Scand 88(12):1389-96.

Helioevaara-Peippo S, Halmesmaeki K, Hurskainen R, Teperi J, Grenman
S, Kivelae A, Tomas E, et al. 2010. The effect of hysterectomy or
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Matteson K A, and Clark M A. 2010. Questioning our questions: do
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most affected by abnormal uterine bleeding? Opinions of women with
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Middleton L J, Champaneria R, Daniels J P, Bhattacharya S, Cooper K
G, Hilken N H, et al. 2010. Hysterectomy, endometrial destruction and
Mirena for heavy menstrual bleeding: a systematic review and individual
patient data meta-analysis. BMJ; 341:c3929.

National Institute for Clinical Excellence (NICE). 2007. Heavy
menstrual bleeding. Clinical Guideline CG44. London, UK: NICE.

Roberts T E, Tsourapas A, Middleton L J, et al. 2011. Hysterectomy,
endometrial ablation, and levonorgestrel releasing intrauterine system
(Mirena) for treatment of heavy menstrual bleeding: cost effectiveness
analysis. BMJ; 342; d2202.

Competing interests: All authors are employed by Bayer plc/Bayer Healthcare Pharmaceuticals AG, which holds the UK marketing authorisation for Mirena (levonorgestrel-releasing uterine system) which was discussed in these articles.

14 June 2011
Anna Filonenko
health-economist
Pirjo Inki, MD; Dominic Muston, health-economist
Bayer Healthcare Pharmaceuticals AG