«PacifiCare’s medical management guidelines represent the recommendation of the PacifiCare Medical Management Guideline (MMG) committee. They are ...»
However, endometrial ablation may not be the definitive treatment." The guidelines do not delineate the means of endometrial ablation. (ACOG, 2000) Thermal balloon endometrial ablation (TBEA) and hydrothermal endometrial ablation (HTEA) Five randomized controlled trials of TBEA met the criteria for detailed review and although none of these studies compared TBEA with hysterectomy for treatment of menorrhagia, all of them compared TBEA with another minimally invasive treatment. Two of the reviewed studies compared TBEA with rollerball endometrial ablation (RBEA), a trial by Meyer et al. that enrolled 255 patients (Meyer, 1998) and a trial by Soysal et al. that enrolled 93 patients ( Soysal, 2001).
The latter study involved only 1 year of follow-up but two subsequent reports have extended follow-up of the Meyer et al.
study to 3 years. Both trials comparing TBEA with RBEA indicated that these treatments have essentially equal efficacy with TBEA completely eliminating menstrual blood loss for 11% to 15% of women. The larger of these two trials also found that 3 years after TBEA, 50% of patients had below normal menstrual blood loss and another 29% had normal loss.
Meyer et al. did not find any statistically significant differences between TBEA and RBEA in patient outcomes; however, Soysal et al. reported that there was a 10% rate of intraoperative complications during RBEA versus no intraoperative complications during TBEA.
Although none of the studies that met the criteria for review compared HTEA with hysterectomy for menorrhagia treatment, the sole reviewed study of HTEA did compare this treatment with RBEA, a minimally invasive technique that uses a heated electrode to ablate the endometrium. In a multicenter, randomized controlled trial in which 276 women underwent HTEA or RBEA and 1 year of follow-up, no significant differences were found in menstrual blood loss outcomes. After HTEA, 40% of women had no menstrual blood loss, 42% had normal or below normal blood loss, and 1% underwent a subsequent hysterectomy. (Corson, 2001) RBEA did have a small, statistically significant advantage over HTEA in postoperative nausea and/or vomiting which occurred in 22% of women after HTEA versus 7% of women after RBEA.
Barrington et al. reported no significant differences between TBEA and the levonorgestrel-intrauterine system (LNGIUS), an intrauterine device that continuously releases a hormone. In this study, 50 women were randomized to menorrhagia treatment with TBEA or the LNG-IUS and at 6 months follow-up, the two treatments had essentially equal efficacy. After TBEA, menstrual blood loss ended for 9% of patients and menstrual blood loss decreased for another 70%.(Barrington, 2003) A randomized controlled trial by Hawe et al. enrolled 71 patients and compared TBEA with endometrial ablation using a surgical laser. Again, the two minimally invasive techniques for endometrial ablation had essentially equal efficacy and 1 year after TBEA, 29% of women had no menstrual blood loss, 44% had loss that was less than normal menstrual blood loss, and 12% had normal levels of blood loss. (Hawe, 2003) Three case series studies of women with menorrhagia (total n = 205) treated by thermal balloon ablation with a follow-up ranging from 6 months to 3 years had overall improvement rates ranging from 65 to 85% with only minor complications.
(Clark, 2004; Gallinat, 2004; Shaamash, 20004) Dysfunctional Uterine Bleeding and Uterine Fibroids- Commercial Medical Management Guideline Cooley et al. determined the medium-term (1-3 years) and long-term (3-5 years) outcome for 44 women who underwent ablation by uterine balloon technique and 40 women who had ablation by VESTA (radiofrequency) technique. Outcome measures were the amenorrhea rate and patient satisfaction and were determined by chart review and questionnaire.
Combined medium-term follow-up had a success rate of 90%; long-term follow-up had a success rate of 80% and a patient satisfaction rate of 73%. (Cooley, 2005) Two cohort studies evaluated HTEA for the management of menorrhagia in women with myomata. One year after treatment, Glasser and Zimmerman evaluated twenty-two women with myomata up to 4 cm. in diameter who were treated for menorrhagia with HTEA. Twelve patients reported complete amenorrhea (7 of these women were premenopausal and 5 were postmenopausal), five women reported oligomenorrhea and 3 reported eumenorrhea. There were 2 failures which resulted in one woman having a repeat HTEA for menorrhagia and another electing to have a vaginal hysterectomy.
(Glasser, 2003) Rosenbaum et al. evaluated HTEA in 47 premenopausal women with abnormal uterine bleeding; 20 of these women had normal endometrial cavities and 27 had had intracavitary pathology, most often leiomyomas. Follow-up ranged from 5 to 25 months with a mean of 12.7 months. Baseline and follow-up scores were similar for both groups. (Rosenbaum, 2005) Levonorgestrel-releasing intrauterine device (LNG-IUD) There is evidence from several randomized controlled trials and a few nonrandomized controlled trials and prospective case series that the LNG-IUD is a relatively safe and efficacious minimally invasive therapy for DUB in premenopausal women with confirmed menorrhagia that is refractory to oral medications or for whom surgery has been recommended, who have no benign or malignant pelvic pathology that requires another type of therapy, who do not want or are ineligible for surgery, who cannot tolerate the drug side effects, and/or who wish to retain their childbearing capacity. Overall, treatment with the LNG-IUD for 3 to 12 months resulted in significant reductions in menstrual blood loss (MBL) (ranging from 67% to 96%), improvement in menstrual bleeding patterns in the majority of patients, increases in blood hemoglobin and iron levels, high levels of satisfaction, and improved quality of life (QOL). Surgery was cancelled or postponed in approximately 70% of patients on surgical waiting lists whose menstrual bleeding improved during LNG-IUD therapy.
The rates of treatment discontinuation or failure varied from 3% to 52%. The percentage of patients who had surgery when IUD therapy failed ranged from 4% to 43% for hysterectomy and 6% to 20% for endometrial ablation. Treatment with the LNG-IUD may obviate the need for or delay surgical therapies in a number of patients although additional, welldesigned studies with longer follow-up are needed to evaluate the durability of the treatment effects, treatment discontinuation rates, and safety issues as well as to compare the device with other medical and surgical therapies.
Although most side effects reported for LNG-IUD use were minor and transient, e.g. weight gain, acne, greasy hair, spotting and pain and did not generally lead to device removal, the occurrence of side effects (range, 1% to 53%), persistent menorrhagia, or intermenstrual bleeding led to treatment discontinuation for 9% to 53% of patients.
(Hurskainen, 2001; Lahteenmaki, 1998; Istre, 2001; Crosignani, 1997; Barrington, 1997; Fedele, 1997; and Romer, 2000) The evidence from the randomized controlled trials comparing the LNG-IUD with drug therapy (the progestin norethisterone, an NSAID, and an antifibrinolytic) showed that the IUD reduced MBL by over 90% and induced amenorrhea in 32% to 44% of patients. While patients were more satisfied with the LNG-IUD than with oral norethisterone, and no serious side effects were reported, IUD use was associated with a higher incidence of spotting and intermenstrual bleeding at 3 months. While spotting and intermenstrual bleeding are initially common following insertion of the LNG-IUD, these symptoms tend to lessen or disappear. LNG-IUD was significantly more efficacious than the NSAID flurbiprofen and the antifibrinolytic tranexamic acid for reducing MBL and improving blood Hb and ferritin levels; however, the IUD was removed in 15% of patients due to side effects or persistent menorrhagia, and 5% of patients had a hysterectomy after device expulsion. No major side effects were associated with the LNG-IUD. (Hurskainen, 2001;
Lahteenmaki, 1998; Istre, 2001; Crosignani, 1997; Barrington, 1997; Fedele, 1997; and Romer, 2000) Lethaby et al. conducted a metaanalysis of randomized controlled trials of women of reproductive age treated for heavy menstrual bleeding with progesterone or progestogen-releasing intrauterine devices. (Lethaby, 2005) One trial compared LNG-IUD with medical therapy, two trials compared it with transcervical resection of the endometrium (TCRE), three Dysfunctional Uterine Bleeding and Uterine Fibroids- Commercial Medical Management Guideline trials compared it with balloon ablation. There was a significantly greater mean reduction in menstrual bleeding in one trial in women who had balloon ablation, a lower score on the pictorial blood loss chart and higher rates of successful treatment in 3 trials including both balloon and TCRE. The LNG-IUD was compared to hysterectomy in one trial and the LNG-IUD treatment had lower costs than the hysterectomy at one- and at five-year follow-up.
Busfield et al. compared LNG-IUD (n=40) to thermal balloon ablation (n=39) in a prospective, randomized trial.
(Busfield, 2006) Both treatments resulted in significant reductions in pictorial bleeding assessment chart (PBAC) scores.
However at 12 and 24 months, median PBAC scores in women treated by LNG-IUD were significantly lower than those of women treated by thermal balloon (11.5 versus 60.0 and 12.0 versus 56.5, respectively) supporting LNG-IUD as more efficacious. Treatment failed in 11 (28%) women using the LNG-IUD and in 10 (26%) women treated with thermal balloon ablation.
Ongoing Research: Researchers at the National Women's Hospital in Auckland, New Zealand reported that the Thermoablation versus the Levonoregestrel Intrauterine System trial (TALIS), a single-center, randomized, controlled trial, has been underway since April 1999. The primary objective of the study is to determine whether the LNG-IUD is equivalent to endometrial ablation performed with the ThermaChoice(TM) Uterine Balloon Therapy endometrial ablation system. The goal is to evaluate a minimum of 80 women with heavy menstrual bleeding for 12 months after therapy. The researchers noted that of 101 women seen at their clinic over an 18-month period, 81 were offered entry to the trial, and of these, 62 were randomized and treated, 3 were awaiting randomization, and 16 refused entry. No further details are available at this time. (Johnson, 2001) American College of Obstetricians and Gynecologists (ACOG) In an updated practice bulletin, ACOG states that the levonorgestrel intrauterine system leads to minimal systemic effects, and the localized endometrial effect is beneficial for treatment of menorrhagia. Small studies suggest that the levonorgestrel intrauterine system may be effective for treatment of heavy uterine bleeding in women with leiomyomas.
However, these women may have a higher rate of expulsion and vaginal spotting. (ACOG, 2008) Radiofrequency endometrial ablation (RFA) was directly compared to resection/rollerball ablation and thermal balloon ablation in 4 studies. (Corson, 2000; Cooper, 2002; Abbott, 2003; Laberge, 2003) In two multicenter, 2-arm, randomized clinical trials, RFA, using the Vesta DUB or NovaSure endometrial ablation devices, was compared with resection/rollerball ablation. RFA reduced mean PBAC scores from 535 (Corson, 2000) and 652 (Cooper, 2002) at baseline to 18 and 27 at 1-year follow-up, respectively. This improvement was similar to that achieved with resection/rollerball ablation. PBAC scores were reduced from 445 (Corson, 2000) and 562 (Cooper, 2002) to 28 and 36, respectively. The treatment was successful in 87% (Corson, 2000) and 91% of RFA patients compared with 83% (Corson,
2000) and 88% (Cooper, 2002) of resection/rollerball ablation patients. Amenorrhea was achieved in 31% of RFA patients and 35% of resection/rollerball ablation patients. The complication rate was similar for both procedures (2.2% and 13% for RFA; 3.5% and 25.3% for resection/rollerball ablation) but differed considerably between studies. Differences in the devices, training and experience of the investigators, and the definition of what constitutes a complication may account for some of these differences. Nevertheless, additional studies may be needed to address the issue of procedure safety. At least one of these studies (Corson, 2000) had the statistical power to detect a 20% difference in efficacy based on the PBAC scores. The results therefore suggest that the efficacy of RFA compares to that of resection/rollerball ablation.
Thermal balloon ablation was compared with RFA in 1 randomized, 2-arm clinical trial and in 1 nonrandomized, multicenter, 2-arm trial. (Abbott, 2003; Laberge, 2003) In these studies, treatment time was significantly shorter for RFA (3 to 4 minutes) compared with thermal balloon ablation (12 to 23 minutes). At 12 months follow-up, RFA was effective in 96% of patients; 43% of patients developed amenorrhea, 27% hypomenorrhea, and 16% eumenorrhea. (Abbott, 2003) Thermal balloon ablation was effective in 100% of patients; 12% of patients developed amenorrhea, 59% hypomenorrhea, and 29% eumenorrhea. RFA caused less intra- and postoperative pain compared with thermal balloon ablation. (Laberge 2003) The Abbott et al. study had the statistical power to detect a 20% difference in efficacy based on the PBAC scores. The results therefore suggest that the efficacy of RFA compares to that of thermal balloon ablation.