Penninx, Josien P. M. MD; Herman, Malou C. MD; Mol, Ben W. PhD, MD; Bongers, Marlies Y. PhD, MD
Heavy menstrual bleeding is a common gynecologic problem in women of reproductive age and is one of the most important reasons for consulting a gynecologist.1,2 Hysterectomy is a definitive solution for the treatment of menorrhagia. Based on cost-effectiveness, hysterectomy should be considered as the preferred strategy for the treatment of heavy menstrual bleeding.3 Nevertheless, it is a major surgical procedure with physical complications and social and economic costs.4 Many women opt a less invasive treatment, even when they are informed of the fact that success is not always assured.5 So, further research should focus on different treatment options and will need to conform to patient preference.
Many endometrial ablation techniques have been evaluated as a treatment for menorrhagia and currently have been established as a common practice. The first-generation techniques (laser, transcervical resection of the endometrium, and rollerball) require a hysteroscopy with the use of distension medium and the risk of intravasation with fluid overload. These procedures require skilled surgeons to minimize adverse events. Second-generation techniques have been developed. These techniques are more simple and easy to perform, without the need of a hysteroscopy. Second-generation techniques are at least as effective as first-generation techniques, but often are easier to perform.6 However, 5-year follow-up is frequently limited in most of the second-generation studies. The aim of ablative therapies is to offer patients a desirable and long-term solution. Therefore, adequate follow-up of these therapeutic interventions is needed for good evidence-based clinical decision-making.
From March 2005 until August 2007, we performed a randomized controlled trial in which we compared bipolar radiofrequency impedance–controlled endometrial ablation with hydrothermablation. The primary outcome measure was amenorrhea; secondary outcome measures were reintervention and patient satisfaction. We concluded that bipolar endometrial ablation is superior to hydrothermablation in the treatment of menorrhagia within a follow-up of 12 months.7 This study evaluates the primary and secondary outcomes at 5-year follow-up.
MATERIALS AND METHODS
A randomized controlled trial comparing the bipolar radiofrequency impedance-controlled endometrial ablation device (NovaSure, Hologic) and hydrothermablation (Hydro ThermAblator System, Boston Scientific) was performed in the Maxima Medical Centre, a teaching hospital with 500 beds in the south of the Netherlands. The trial previously has been described in detail by Penninx et al.7 The randomization techniques were performed by the CONSORT guidelines. The individuals gave informed consent at the start of the study so that we could contact them in future for a follow-up study. The ethics committee of Maxima Medical Centre in Veldhoven, the Netherlands, approved the study.7 Women with menorrhagia as indicated on the pictorial chart described by Higham et al8 with a minimum score of 150 points were eligible for the trial. They were referred by their general practitioner and hormonal treatment was already tried but unsuccessful, or patients were not motivated to use hormonal treatment. During their menstrual period, the patient recorded the use of tampons and towels and the loss of clots on a scoring system. A lightly stained towel or tampon scored 1 point, a moderately stained towel or tampon 5 points, a towel or tampon that was saturated with blood scored 20 points. A small clot scored 1 point, a moderate clot scored 5 points, and flooding also scored 5 points. One menstrual period was counted and a minimum score of 150 points was described as menorrhagia.
Further inclusion criteria were an uterine depth between 6 and 11 cm and premenopausal state. Patients with minimal intracavitary pathology, such as leiomyomata, of which less than 50% of the myoma was present in the uterine cavity and small polyps (less than 2 cm), were also included. Women with presence of coagulopathies, a desire to preserve fertility, and uterine malignancy were excluded.
All participants had to complete a written informed consent form before enrollment. Computer-generated randomization was performed by one of the authors (J.P.) just before the beginning of treatment, at which time 82 women were allocated to the bipolar group and 78 women were allocated to the hydrotherm group. Patients and doctors who performed the follow-up visits and telephone calls were masked for the randomization allocation and remained so during the study. The doctor performing the endometrial ablation did, of course, know at that moment which device was used. The patient did not know. The physician who saw the patient at the follow-up visits was masked and did not know which device was used.
To obtain insight into the 5-year follow-up, postal questionnaires were sent from November 2010 until January 2011 (4–5 years of follow-up). The mean follow-up time was 4.5 years after the original procedure (range 3 to 5–6 years). All patients were asked to complete the questionnaires. Outcomes were amenorrhea, reinterventions, and patient satisfaction with the result of the treatment, which was similar to what we previously reported at 12-month follow-up. The preablation bleeding was already asked at trial entry.
Patients who did not return the questionnaires received a single reminder after 1 week. If questionnaires were not returned after this reminder in 4 weeks, then we tried to contact the patients by telephone. A simplified questionnaire was used for the telephonic interviews. Women were asked about their menstruation (days, clots, and dysmenorrhea), treatment satisfaction, and reintervention. We contacted patients' general practitioners if we had missing addresses or telephone numbers. In case of lacking information, we searched patients' medical records for information about reinterventions.
The analysis was performed according to the intention-to-treat principle, ie, patients were analyzed in the group to which they had been allocated. We considered women who have undergone a hysterectomy as not having amenorrhea and as being dissatisfied with their ablation treatment. Both hysterectomy and reablation were scored as a surgical reintervention. Time to surgical reintervention was compared with Kaplan Meier analysis. Dichotomous outcomes, such as presence of amenorrhea, absence of clots, absence of dysmenorrheal, and reinterventions were compared by calculating a relative risk (RR) and its 95% confidence interval (CI). Repeated-measures analysis of variance was used to evaluate changes over time (time effect) between both groups (treatment effect) and interaction between changes in effect over time and treatment group (time by treatment effect).
Between March 2005 and August 2007, 160 women were included in the trial, of whom 82 women were allocated to the bipolar group and 78 women were allocated to the hydrotherm group. In November 2010, we sent questionnaires to all patients, after which 125 women returned the questionnaire. Of the nonresponding 35 women, 19 women were contacted by telephone, after which eight women returned the questionnaires, eight women were interviewed by telephone, and three women did not want to participate. Seven women had unknown addresses or telephone numbers (or both), four women died, and five did not answer their telephone multiple times. Nonresponse was mostly attributable to the fact that patients had moved houses or changed telephone numbers. Overall, 21 women (eight in the bipolar group and 13 in the hydrotherm group) were lost to follow-up. The 5-year follow-up rate was 90.2% (n=74) in the bipolar group and 83.3% (n=65) in the hydrotherm group (Fig. 1). The baseline characteristics of both groups were comparable (Table 1) and resembled those reported in our previous study.5
After 5-year follow-up, the number of patients with amenorrhea in the bipolar endometrial ablation group was 41 of 74 (55.4%) compared with 23 of 65 (35.4%) in the hydrotherm group (RR 1.5, 95% CI 1.05–2.3). Table 2 shows the percentage of women with amenorrhea, absence of dysmenorrhea, and absence of clots after bipolar endometrial ablation and hydrotherm ablation. A sensitivity analysis showed that when we did consider women who have undergone a hysterectomy as being amenorrheic, as we did in our previous study, the RR would have been 1.2 (95% CI 0.9–1.5). When we consider all women who were lost to follow-up after the endometrial ablation as nonamenorrheic, the RR at 5-year follow-up would have been 1.6 (95% CI 1.1–2.4).
We recorded 43 reinterventions all because of persisting menorrhagia; there were 14 in the bipolar group compared with 29 in the hydrotherm group (RR 0.43, 95% CI 0.25–0.74). Two patients in the bipolar group had undergone bipolar endometrial ablation again, whereas nine women had a hysterectomy, two women received a levonorgestrel intrauterine device, and one patient underwent a hysteroscopy. In the hydrotherm group, 10 patients underwent bipolar endometrial ablation, 13 patients underwent a hysterectomy, four patients started oral hormonal therapy, and two patients had a levonorgestrel intrauterine device placed. When reintervention was limited to surgical procedures, 11 women in the bipolar group had a surgical reintervention compared with 23 women in the hydrotherm group (RR 0.43, 95% CI 0.23–0.80). When we consider the women who were lost to follow-up as having had a reintervention, the RR at 5-year follow-up would have been 0.52 (95% CI 0.34–0.80). The life table analysis is shown in Figure 2. Pathologic examination of the hysterectomy specimens in the bipolar group showed adenomyosis (n=2), leiomyomata (n=4), and no abnormalities (n=3). In the hydrotherm group, pathologic examination showed adenomyosis (n=2), leiomyomata (n=5), a combination of adenomyosis and leiomyomata (n=3), and no abnormalities (n=3).
Figure 3 shows satisfaction rates after randomization at 12-month and 5-year follow-up. Patients were more often satisfied in the bipolar group compared with those in the hydrotherm group (80.6% compared with 48.4%, RR 1.7, 95% CI 1.3–2.2). When we consider the nonresponders as not satisfied, the RR would have been the same 1.7 (95% CI 1.3–2.2). Repeated-measures analysis showed a significant treatment effect (P<.001). Nevertheless, in both groups satisfaction rates were decreased as compared with rates at 12 months (time effect P<.001); time-by-treatment effect showed no significant interaction (P=.107).
In this follow-up study, we compared the treatment of two second-generation endometrial ablation techniques in women with menorrhagia 5 years after treatment. Amenorrhea rates were higher in the bipolar group than the hydrotherm group, respectively (55.4% and 35.3%, RR 1.5, 95% CI 1.05–2.3), and the number of surgical reinterventions was lower (11 compared with 23, RR 0.43, 95% CI 0.23–0.80). Overall, more women were satisfied in the bipolar group compared with the hydrotherm group.
We analyzed the study according to the intention-to-treat principle. Unlike our previous study, we evaluated women who had a hysterectomy as being nonamenorrheic because of the fact that those women chose this treatment because of their persisting menorrhagia. We considered patients who had an additional hysterectomy as failures of treatment. Scoring hysterectomy as being amenorrheic, as in our previous study, would not give direct results of the ablation effect, especially not with this higher number of surgical reinterventions compared with 12-month follow-up.
Compared with the 1-year follow-up, the 5-year follow-up showed an increase in amenorrhea rates in both groups. Because the patient characteristics were comparable at the beginning of the randomized controlled trial, we would estimate that by randomization the amount of women who would be postmenopausal would be approximately the same in both groups. The amenorrhea rate of the bipolar group is comparable with that seen in previously reported long-term follow-up studies (48–65%).9,10 Long-term studies of hydrothermablation are limited, and amenorrhea rates differ from 38% to 53%.11,12 We found lower amenorrhea rates in the hydrotherm group compared with those found in the literature, but this is in line with our previously reported 12-month result.7 In most studies, hydrotherm ablation is performed after gonadotropin-releasing hormone pretreatment. This might give better treatment results because it thins the endometrial layer.13 In the Netherlands, we do not administer gonadotropin-releasing hormone pretreatment before endometrial ablation; therefore, we scheduled the procedure just after menstruation. Differences in numbers comparing absence of clots and absence of dysmenorrhea between 12 months and 5 years were explained by the fact that we considered women with a hysterectomy as being amenorrheic at the 12-month follow-up.
At 5-year follow-up, we saw a comparable increase in reinterventions in both groups. We chose to report the surgical reinterventions rather than hysterectomies alone, whereas both hysterectomy and reablation are invasive ways of treatment. At 12-month follow-up, the hydrotherm ablation already showed significantly more reinterventions, and so does this follow-up study for reintervention in total as surgical reintervention.
We observed a high surgical reintervention rate in both groups compared with other studies.9–14 Kopeika et al11 reported a hysterectomy rate of 11% for the hydrotherm ablation at a follow-up of 8 years, but this was a retrospective study. As mentioned, it is possible that gonadotropin-releasing hormone pretreatment is necessary for an optimal result in this group.13 The thickness of the endometrial layer could be a predictor for failure of hydrotherm ablation treatment. As shown in our previous article, there was no difference in baseline endometrial thickness.7 In the group with reinterventions, the average endometrial thickness was 7.7 in the hydrotherm group and 7.9 in the bipolar group. Comparing pathology of hysterectomy specimens, differences in both ablation groups were not found. Literature reporting on long-term follow-up after bipolar ablation describes hysterectomy rates from 3% to 9.8%.9,10,14 However, only Kleijn et al reported a patient-blinded and observer-blinded randomized controlled trial, comparable to our study.10 Because of lack of blinding in previous studies, the hysterectomy rate might have been overstated in earlier studies.
This trial described a high satisfaction level for the bipolar ablation 5 years after the procedure, whereas satisfaction rates for the hydrotherm group were low. Although we saw an increase in amenorrhea rate in both groups, we also saw a significant reduction in satisfaction level in both groups over time. In the literature, a few trials use satisfaction as an outcome measure and, because of this, it is difficult to compare these results with other trials. However, Middleton et al15 describes that more women are dissatisfied after endometrial destruction than after hysterectomy, but the rates of dissatisfaction are still relatively low. They also noticed that absence of leiomyomata or polyps shows a trend toward reduced dissatisfaction (P=.07).15 In our study, we did not exclude women with leiomyomata, because we wanted to evaluate the results of ablation in patients with menorrhagia with or without little uterine leiomyomata and in women with menorrhagia without hormonal pretreatment. This could have influenced our results. Data of success, satisfaction, and health-related quality of life are essential to offer patients a desirable and long-term solution for menorrhagia. Therefore, adequate follow-up of these therapeutic interventions is still needed for clinical decision-making and counseling of patients.
The results from this follow-up study showed that bipolar ablation has many advantages over hydrotherm ablation. Higher amenorrhea rate, less reinterventions, and higher levels of satisfaction were shown. So, the bipolar radiofrequency endometrial ablation system is more effective than hydrotherm ablation in the treatment of menorrhagia.
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© 2011 by The American College of Obstetricians and Gynecologists.