Laparoscopic occlusion compared with embolization of uterine vessels: a randomized controlled trial

OBJECTIVE: To compare clinical outcome 6 months after treatment with bilateral laparoscopic occlusion of the uterine artery versus uterine leiomyoma embolization. METHODS: Sixty-six premenopausal women with symptomatic uterine leiomyomata were randomized to treatment with either laparoscopic occlusion of uterine arteries or uterine leiomyoma embolization. The primary outcome was reduction of blood loss from pretreatment to 6 months postoperatively, measured by a Pictorial Bleeding Assessment Chart. Secondary outcomes included patients' own assessment of symptom reduction, postoperative pain assessed using visual analog scales, ketobemidone used postoperatively, complications, secondary interventions, and failures. RESULTS: Fifty-eight women were included; 6-month follow-up data were available for 28 participants in each group. The percentage reduction in Pictorial Bleeding Assessment Chart scores did not differ between the treatment groups (52% after uterine leiomyoma embolization and 53% after laparoscopy, P=.96). The study had 52% power to detect a 20% difference on the Pictorial Bleeding Assessment Chart. Fewer participants in the group treated with uterine leiomyoma embolization complained of heavy bleeding after 6 months (4% compared with 21%, P=.044). The postoperative use of ketobemidone was higher after uterine leiomyoma embolization (46 mg compared with 12 mg, P<.001). CONCLUSION: Both laparoscopic occlusion of uterine vessels and embolizaton of uterine leiomyoma improved clinical symptoms in the majority of patients. Participants with the laparoscopic procedure had less postoperative pain but heavier menstrual bleeding 6 months after treatment. A larger study and longer follow-up is necessary before a definite conclusion can be made regarding the most effective treatment. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov), NCT00277680 LEVEL OF EVIDENCE: I.     

The effect of anastrazole on symptomatic uterine leiomyomata

OBJECTIVE: To evaluate the effect of anastrazole on symptomatic uterine leiomyomata. METHODS: This was a prospective intervention study carried out in a university department of obstetrics and gynecology. Forty-one premenopausal women eligible for hysterectomy with 45 uterine leiomyomata were enrolled and treated with anastrazole 1 mg daily for three cycles of 28 days each. The effect of treatment was evaluated on leiomyoma and uterine volumes, endometrial thickness, gonadotrophins, estradiol and hematocrit levels, menstrual pattern, severity of leiomyoma-related symptoms, and adverse effects. The effects of leiomyoma location, size, and age of participants on tumor volume changes were evaluated. RESULTS: Thirty-five women with 39 leiomyomata finished the study. Anastrazole resulted in a mean 55.7% reduction of leiomyoma volumes (163 mL to 72 mL, P<.001), a 29.9% reduction in total uterine volumes (278 mL to 195 mL, P<.001), and an 11.3% increase of the hematocrit levels (33.4% to 37.2%, P<.001) at the end of the treatment. Leiomyoma location had no significant effect on volume decrease. Leiomyoma volume decreased in women aged older than 40 years (P=.002), whereas no difference was found in women younger than 40. The size of large (greater than 50 mm) leiomyomata decreased significantly (P=.004). Less difference was observed in small (50 mm or less) leiomyomata (P=.031). No differences were detected in hormonal status. Anastrazole improved leiomyoma-related symptomatology and caused no serious adverse effects. CONCLUSION: In premenopausal women, anastrazole reduces the size of uterine leiomyomata, improves symptomatology, and is generally well tolerated. LEVEL OF EVIDENCE: III.     

Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial

OBJECTIVE: To assess the effect of low-dose mifepristone on quality of life, pain, bleeding, and uterine size among women with symptomatic leiomyomata. METHODS: Forty-two women with symptomatic uterine leiomyomata and uterine volume of 160 mL or more were randomized to mifepristone, 5 mg daily, or placebo for 26 weeks. Quality of life (Uterine Fibroid Symptoms Quality of Life Questionnaire and Medical Outcomes Study 36-Item Short Form survey) and uterine and leiomyoma size (ultrasonography) were assessed at baseline, and at 1 month, 3 months, and 6 months of treatment. Bleeding (daily logs and pictorial charts) and pain (McGill Pain Questionnaire) were assessed monthly. Endometrial pathology was assessed at baseline and 6 months. RESULTS: Forty-two women were randomized; 37 women completed all 6 months. Women randomized to mifepristone showed an improvement in leiomyoma-specific quality of life. Forty-one percent became amenorrheic, rates of anemia improved, and adjusted uterine size was reduced by 47%. Compared with the placebo group, improvements in these outcomes in the treatment group were significantly greater (P<.05 to .001). There were no significant differences in adverse effects between the groups. No endometrial hyperplasia was noted in any participant. CONCLUSION: Low-dose mifepristone improves leiomyoma-specific quality of life and reduces leiomyoma size among women with symptomatic leiomyomata. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov www.clinicaltrials.gov NCT00133705 LEVEL OF EVIDENCE: I.     

Systematic review of mifepristone for the treatment of uterine leiomyomata

OBJECTIVE: To systematically review the effect of mifepristone on uterine leiomyoma size and symptoms and to summarize its adverse effects. DATA SOURCES: A computerized search in MEDLINE, EMBASE, LILACS, and Cochrane databases from 1985 to 2002 and hand searches of conference proceedings from 1995 to 2002 were performed with the search terms "mifepristone" and "leiomyomata" and publication type "clinical trial." METHODS OF STUDY SELECTION: Titles and abstracts were reviewed by 2 authors; there were no areas of disagreement. Inclusion criteria were clinical trials of daily mifepristone for uterine leiomyomata that measured uterine or leiomyoma volume before and after treatment. TABULATION, INTEGRATION, AND RESULTS: Data from each article were abstracted by 2 reviewers. The search identified 6 before-and-after clinical trials involving a total of 166 women with symptomatic uterine leiomyomata. The subjects received 5 to 50 mg/d of mifepristone for 3 to 6 months. No study was placebo-controlled or blinded. Meta-analytic techniques were not performed due to variation in outcome and mifepristone dose. Daily treatment with all doses of mifepristone resulted in reductions in uterine and leiomyoma volumes ranging from 27% to 49% and 26% to 74%, respectively. Mifepristone treatment reduced the prevalence and severity of dysmenorrhea, menorrhagia, and pelvic pressure. Rates of amenorrhea ranged from 63% to 100%. Transient elevations in transaminases occurred in 4%. Endometrial hyperplasia was detected in 10 (28%) of 36 women screened by endometrial biopsy. CONCLUSION: Published trials of mifepristone showed reduction in leiomyoma size and improvement in symptoms. A notable adverse effect of mifepristone was development of endometrial hyperplasia.     

Effect of nafarelin on uterine fibroids measured by ultrasound and magnetic resonance imaging

Administration of the LHRH agonist, Nafarelin (D-(Nal2)6 GnRH), at a dosage of 200 micrograms twice daily intranasally in 13 patients with uterine leiomyomata resulted in a reduction in uterine volume to a mean of 55.1% at 3 months and 44.5% at 6 months as measured using ultrasound. Re-enlargement occurred on discontinuing therapy and the uterus was back to the original volume at three months. Magnetic resonance imaging (MRI) performed in five patients showed advantages over ultrasound in identification of fibroid number in two patients. Mean reduction in uterine area measured using MRI was 61.3%, and mean reduction of fibroid area 57%. Oestradiol was suppressed with treatment to a mean of 69 pmol/l.     

Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas

OBJECTIVE: This study was designed to evaluate the potential usefulness of the levonorgestrel-releasing intrauterine system (LNG IUS) in treating women with uterine leiomyomas. DESIGN: Prospective before-and-after study. SETTING: Family planning unit in an academic research institute. PATIENT(S): Sixty-seven women with uterine leiomyomas who chose the LNG IUS as their method of contraception. INTERVENTION(S): Clinical and ultrasound examinations were performed prior to and 3, 6, and 12 months after the LNG IUS insertion. MAIN OUTCOME MEASURE(S): Menstrual blood loss assessed with pictorial blood loss assessment charts, ferritin and hemoglobin concentrations, and uterine and leiomyoma volume. RESULT(S): Use of the LNG IUS was associated with a marked reduction in menstrual blood loss. After 12 months of use, the mean pictorial blood loss assessment chart score declined from 97 to 16 (P<.001). Hemoglobin and ferritin levels increased significantly over 1 year of use. Eighteen of 19 women (95%) who were anemic at the beginning of the study were no longer anemic at 12 months, as judged by hemoglobin levels. No pregnancies occurred during the study. CONCLUSION(S): The LNG IUS was associated with a profound reduction in menstrual blood loss. For women with leiomyomas of this size, the LNG IUS provides effective medical treatment of bleeding.     

Prospective clinical and sonographic assessment of uterine artery embolization as the treatment of symptomatic uterine leiomyomata

OBJECTIVE: To evaluate the effectiveness of the uterine artery embolization as the treatment of symptomatic uterine leiomyomata. PATIENTS AND METHODS: Eighty-five women with symptoms caused by uterine leiomyomata underwent uterine artery embolization as an alternative to surgery from january 1997 to june 2000. The effectiveness of this method was evaluated by clinical and sonographic examination. RESULTS: The recession average was of 18.9 months. There were ten failures. We had immediate failures (n = 5) with a case of technical failure, one endometrium cancer, one adenomyosis, one larger subserosal leiomyomata and one parametrial leiomyomata. We had recurrences (n = 5) with the occurrence of new leiomyomatas (1 intramural and 3 submucosal) and an evolution of previous leiomyomata. The average volume reduction was 51% for the uterus and 65% for the main fibroid at one year follow-up. Minor complications occurred in 5%. Permanent amenorrhoea was observed for 3.75% of the women. Using cox model, no predictive factors of embolisation effectiveness were found. DISCUSSION AND CONCLUSION: In the treatment of symptomatic uterine leiomyoma, uterine artery embolization is an effective alternative to surgery. After one year and half, we had 12.5% of failures.     

超声消融治疗子宫黏膜下肌瘤的安全性和疗效评价

目的 探讨超声消融治疗突入宫腔体积＜50%的子宫黏膜下肌瘤的安全性及疗效.方法 前瞻性选择2006年10月至2009年9月在解放军总医院妇产科就诊有明显临床症状的、经MRI确诊的突出官腔体积＜50%的子宫黏膜下肌瘤患者66例(68个肌瘤),行超声引导下的聚焦超声消融治疗,记录消融治疗过程中及消融治疗后出现的不良反应;消融治疗后即刻采用超声造影评价消融治疗的疗效,消融治疗后第3、6、12和24个月,超声评价肌瘤体积变化;采用子宫肌瘤相关症状评分表(SSS)和月经期症状评分表评估症状变化.结果 共66例患者的68个黏膜下肌瘤消融治疗前肌瘤平均体积为(151±134)cm3,消融治疗后即刻超声造影中无灌注区平均体积为(114±104)cm3,肌瘤体积消融率为(77±16)%.所有患者均顺利完成治疗,随访时间为6～44个月,中位随访时间24个月,至今未出现显著并发症.消融治疗后有52%(34/66)的患者出现阴道排液症状,均于消融治疗3～4个月经周期后自行恢复正常.消融治疗后第3、6、12和24个月时,SSS评分与消融治疗前比较,分别降低20.9%、38.0%、45.1%、47.1%;月经期症状评分与消融治疗前比较,分别降低42.0%、63.8%、64.2%、68.8%,分别与治疗前比较,差异均有统计学意义(P＜0.05),坏死肌瘤逐渐吸收缩小,肌瘤体积较消融治疗前平均缩小44.7%、66.0%、77.7%和89.8%.结论 超声消融治疗突入宫腔体积＜50%的子宫黏膜下肌瘤安全、有效,黏膜下肌瘤相关症状改善显著.

Abstract：

Objective To evaluate the efficacy and safety of focused ultrasound ablation in the treatment of submucosal fibroids which broke into uterine cavity less than 50%. Methods From Oct. 2006 to Sept. 2009, 66 patients with 69 submucosal fibroids broke into uterine cavity less than 50% diagnosed by MRI in Chinese People's Liberation Army General Hospital were enrolled in this study. They were treated by ultrasound-guided focused ultrasound ablation in the outpatient department, which using the contrast enhanced ultrasonography to assess the efficacy after ablation immediately, to measure reduction of fibroids volume and record adverse effect before and after ultrasound ablation. At 3, 6, 12 and 24 months after treatment, ablation outcome and fibroids volumes were evaluated by contrast ultrasound. The changes of clinical symptom were evaluated by the symptom severity score ( SSS) of the uterine fibroid quality-of-life instrument( UFS-QOL). Results The average volume of fibroids in 66 patients with 68 submucosal fibroids were (151 ±134) cm3 before treatment and (114 ± 104) cm3 no enhanced regional after treatment. The ablation rate of target fibroids was (77 ±16)%. All patients completed this treatment successfully, they were followed up for 6 - 44 months, the median follow-up time was 24 months. No serious complication was observed. However, there were 52% (34/66) patients presented vaginal discharge after ablation, it disappeared gradually after 3 to 4 menstrual cycles. The SSS and the menstrual period symptom scores were significantly lower than that before ablation at the follow-up of 3,6, 12 and 24 months, the rates were 20. 9% , 38. 0% , 45. 1% , 47. 1% and 42. 0% , 63. 8% , 64. 2% , 68. 8% , which all reached statistical difference (P ＜ 0. 05 ). The necrotic fibroids were absorbed gradually, the reduction rates of fibroid volume were 44. 7% ,66. 0% ,77. 7% and 89. 8% . Conclusion It was safe and efficacy that focused ultrasound ablation was used in treatment of submucosal fibroids which broke into the uterine less than 50%.     

Selective uterine artery embolization as primary treatment for symptomatic leiomyomata uteri.

STUDY OBJECTIVE: To analyze initial experience with uterine artery embolization for treatment of symptomatic leiomyomata. DESIGN: Prospective, longitudinal study (Canadian Task Force classification II-2). SETTING: Private practice, university-affiliated hospital. PATIENTS: Three hundred five women (age 26-52 yrs). INTERVENTIONS: Uterine artery embolization, performed over 2 years by a single radiologist working in collaboration with a single gynecology practice. MEASUREMENTS AND MAIN RESULTS: Embolization was technically successful in 96% of patients. No major complications occurred. Average reduction in uterine volume was 48%. Control of menorrhagia was reported by 86% of patients at 3 months, 85% at 6 months, and 92% at 12 months after the procedure. Bulk symptoms were satisfactorily controlled in 64% of patients at 3 months, 77% at 6 months, and 92% at 12 months. Six women subsequently underwent hysterectomy and five had myomectomy. CONCLUSION: Uterine artery embolization appears to be a highly effective treatment for symptomatic uterine leiomyomata. Its impact on fertility and pregnancy remain to be investigated fully. (J Am Assoc Gynecol Laparosc 6(3):279-284, 1999)     

Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group

The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms.     

Low-dose mifepristone for uterine leiomyomata

OBJECTIVE: To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms, and to measure side effects. METHODS: Forty premenopausal women with large, symptomatic leiomyomata were randomized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study. Uterine volume was measured at bimonthly intervals by sonography. Serum concentrations of hemoglobin levels, follicle-stimulating hormone, and liver enzymes were obtained, and endometrial samples, symptoms, and menstrual bleeding were also assessed. RESULTS: Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study. Mean uterine volume shrank by 48% (P <.001) in the 5-mg group and 49% (P <.001) in the 10-mg group, a nonsignificant difference. Leiomyoma-related symptoms were comparably reduced in both groups. Amenorrhea occurred in 60-65% of both groups. Hemoglobin levels increased by 2.5 g/dL in anemic subjects. The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group. Simple endometrial hyperplasia occurred in 28% of all subjects, with no difference between groups. No atypical hyperplasia was noted. CONCLUSION: Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression, improvement in symptoms, and few side effects. Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone.     

Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist ganirelix

OBJECTIVE: To assess maximal volume reduction of leiomyomas and uterus and the duration of treatment required to reach these reductions with daily GnRH antagonist treatment. DESIGN: Prospective, open-label study. SETTING: Large teaching hospital in The Netherlands. POPULATION: Premenopausal women with symptomatic fibroids, who were scheduled for surgery. METHODS: Twenty women were treated with daily 2 mg of subcutaneous ganirelix. Prior to the first injection and weekly during treatment, the volume of leiomyomas and the uterus were assessed by ultrasound (USS) and serum hormones were measured. Prior to treatment and when maximal size reduction was observed by USS, the volume of the leiomyomas and the uterus were also assessed by magnetic resonance imaging (MRI). MAIN OUTCOME MEASURES: Leiomyoma and uterine size reduction, time to maximal reduction. RESULTS: One woman was excluded from the study due to incorrect administration dose of ganirelix. Data on the remaining 19 women (average age 39 years) with subserosal (n= 9), submucosal (n= 7), intramural (n= 10) and transmural (n= 1) leiomyomas were evaluated. Baseline leiomyoma volumes ranged from small (3-4 mL) to large (>1000 mL). The median duration of treatment up to maximal leiomyoma size reduction was 19 days (range 1-65 days). The maximal size reduction in leiomyomas measured by USS was -42.7% (-77.0% to 14.1%) and -29.2% (-62.2% to 35.6%) by MRI. Comparable uterine size reductions of -46.6% (-78.6% to -6.1%) and -25.2% (-63.6% to 28.9%) were observed by USS and MRI. During the first three weeks of treatment, 8 out of 19 women reported adverse events related to the induced hypoestrogenic state. Most of these events resolved within one week after treatment was discontinued. CONCLUSION: Daily treatment with 2 mg of ganirelix results in rapid reduction of leiomyoma and uterine volume in premenopausal women with minor side effects. If longer-acting GnRH antagonists become available, pretreatment with GnRH antagonist should be preferred over GnRH agonists prior to surgery.     

Effect of gonadotropin-releasing hormone agonist treatment upon angiogenesis in uterine leiomyoma

OBJECTIVE: To assess the effect of gonadotropin-releasing hormone (GnRH) agonist treatment upon angiogenesis in uterine leiomyomata. METHODS: Uterine leiomyomata specimens of 49 consecutive patients who underwent myomectomy or hysterectomy following presurgical treatment with (n = 23) and without (n = 26) GnRH agonist were stained immunohistochemically with antibody to factor VIII-related antigen. For each subject, age, parity, number of Lupron treatments, leiomyoma size (cm), and mean microvessel counts calculated from three fields (x400) were recorded. Differences in patient age, parity, microvessel counts and leiomyoma size between GnRH agonist treated and untreated patients were tested by unpaired Student's t test. Differences among the various number of doses were tested by one-way ANOVA, with Bonferonni and Neuman-Keuls post hoc tests between specific dose-number groups. The relationship between microvessel counts and leiomyoma size was tested by Pearson correlation test. Multivariate stepwise regression tested the relationship between the number of Lupron doses and microvessel counts, correcting for age, parity, and leiomyoma size. p < 0.05 was considered significant. RESULTS: Patient age and parity were similar in GnRH treated and untreated patients (mean 43.3 +/- 6.6 versus 43.9 +/- 7.5 years and median 2 (range 0-7) versus 1 (range 0-5), p = 0.78 and p = 0.45, respectively). Microvessel counts of leiomyomata specimens treated presurgically with GnRH agonist therapy (median 22.7, range 6.7-65.7) were not significantly different from microvessel counts of specimens without presurgical GnRH agonist treatment (median 19.8, range 6-53; p = 0.77). No correlation between leiomyoma size and microvessel counts was noted (r = 0.06, P = 0.7). CONCLUSION: Angiogenesis as assessed by microvessel counts in surgically removed leiomyomata is not affected by presurgical medical management with GnRH agonist therapy.     

Self-reported heavy bleeding associated with uterine leiomyomata

OBJECTIVE: To characterize the relationship between self-reported bleeding symptoms and uterine leiomyoma size and location. METHODS: The leiomyoma status of a randomly selected sample of women aged 35-49 in the Washington, DC, area was determined using abdominal and transvaginal ultrasound to measure size and location of leiomyomata found at screening. Women were asked about symptoms of heavy bleeding (gushing-type bleeding, long menses, pad/tampon use) in a telephone interview. Using multivariable regression, we examined the relationships between leiomyoma characteristics and heavy bleeding symptoms among 910 premenopausal women. RESULTS: Women with leiomyomata (n = 596) were more likely to report gushing-type bleeding than women without leiomyomata; risk increased with leiomyoma size. Adjusted relative risks with 95% confidence intervals (CI) for women in each leiomyoma size category compared with the reference category (women without leiomyomata) were as follows: adjusted relative risk of 1.4 (95% CI 1.1, 1.9) for diffuse only, adjusted relative risk of 1.4 (95% CI 1.1, 1.8) for small leiomyomata (less than 2 cm), adjusted relative risk of 1.6 (95% CI 1.3, 2.0) for medium leiomyomata (2-5 cm), and adjusted relative risk of 1.9 (95% CI 1.5, 2.5) for large leiomyomata (greater than 5 cm). Reported use of eight or more pads/tampons on the heaviest days of menstrual bleeding increased with leiomyoma size, with a nearly 2.5-fold risk for women with large leiomyomata compared with women without leiomyomata (adjusted relative risk of 2.4; 95% CI 1.8, 3.1). Nonsubmucosal leiomyomata were associated with essentially the same increase in heavy bleeding as submuscosal leiomyomata of similar size. CONCLUSION: Small leiomyomata were associated with increased risk of heavy bleeding, and risk increased with size. Contrary to published articles, nonsubmucosal leiomyomata were associated with heavy bleeding to the same extent as submucosal leiomyomata.     

Treatment of estrogen-dependent gynecological disorders with the gonadotropin releasing hormone agonist buserelin.

The authors examined the effect and tolerability of buserelin in 40 women with endometriosis and ten women with uterine leiomyoma. Buserelin was given intranasally, 200 micrograms three times a day for 6 months. Laparoscopy was performed before and after, and ultrasonography during the treatment. Hormone and lipid profiles and other biochemical tests were run during the treatment. The bone mineral density was tested by dual photon absorptiometry before and after therapy in a group of patients. Although most of the patients complained of hot flushes, no women dropped out. AFS mean pelvic score decreased from 24.10 to 6.95 and the size of the fibroids decreased by 69% at the end of 6 months of treatment. In conclusion, our data suggest that the use of GnRH agonist has a place in the treatment of endometriosis and uterine leiomyoma but further studies are needed to conclude that buserelin given intranasally at a dose of 600 micrograms/day for 6 months is an alternative to other conventional medical treatment modalities in terms of pregnancy and recurrence rates.     

Reduction by 98% in Uterine Myoma Volume Associated with Significant Symptom Relief After Peripheral Treatment with Magnetic Resonance Imaging–Guided Focused Ultrasound Surgery

Magnetic resonance imaging–guided focused ultrasound surgery is a noninvasive treatment for symptomatic uterine myomas. Previous studies have demonstrated a correlation between the treated volume of the myoma, improvement in symptoms, and lesion shrinkage. We report a case in which MRgFUS treatment only at the periphery of the myoma resulted in a 98% reduction in tumor volume at 8 months posttreatment, and at 12-month follow-up, only a small lesion was visible at magnetic resonance imaging. The patient's symptoms, as assessed using the Uterine Fibroids Symptom and Quality of life (UFS-QOL) questionnaire, were substantially improved at both 6 and 12 months posttreatment. We also provide a hypothesis to explain this dramatic reduction in myoma volume after only partial MRgFUS treatment of the lesion.     

CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial

OBJECTIVE: To evaluate whether 3-month administration of CDB-2914, a selective progesterone receptor modulator, reduces leiomyoma size and symptoms. METHODS: Premenopausal women with symptomatic uterine leiomyomata were randomly assigned to CDB-2914 at 10 mg (T1) or 20 mg (T2) daily or to placebo (PLC) for 3 cycles or 90-102 days if no menses occurred. The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy. Secondary outcomes included the proportion of amenorrhea, change in hemoglobin and hematocrit, ovulation inhibition, and quality-of-life assessment. RESULTS: Twenty-two patients were allocated, and 18 completed the trial. Age and body mass index were similar among groups. Leiomyoma volume was significantly reduced with CDB-2914 administration (PLC 6%; CDB-2914 -29%; P=.01), decreasing 36% and 21% in the T1 and T2 groups, respectively. During treatment, hemoglobin was unchanged, and the median estradiol was greater than 50 pg/mL in all groups. CDB-2914 eliminated menstrual bleeding and inhibited ovulation (% ovulatory cycles: CDB-2914, 20%; PLC, 83%; P=.001). CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality-of-life subscale (P=.04). One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia. No serious adverse events were reported. CONCLUSION: Compared with PLC, CDB-2914 significantly reduced leiomyoma volume after three cycles, or 90-102 days. CDB-2914 treatment resulted in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment. In this small study, CDB-2914 was well-tolerated without serious adverse events. Thus, there may be a role for CDB-2914 in the treatment of leiomyomata. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,www.clinicaltrials.gov, NCT00290251 LEVEL OF EVIDENCE: I.     

Natural history of uterine polyps and leiomyomata

OBJECTIVE: To estimate the incidence and regression rates of uterine leiomyomata and polyps in a cohort of asymptomatic, premenopausal women. METHODS: Saline infusion sonography was performed twice, 2.5 years apart, in a cohort of 64 initially asymptomatic women. Subjects completed a questionnaire that assessed the development of abnormal uterine bleeding. RESULTS: The mean age of women (at second ultrasound) was 44 years. In four of seven women with polyps at the original ultrasound, their polyps regressed. Polyps that regressed tended to be smaller than polyps that persisted. Ten women had endometrial polyps at the second ultrasound for a point prevalence of 16% and a cumulative incidence rate of 12% per 2.5 years. A higher percentage of women with uterine polyps had complaints of abnormal uterine bleeding than women with no uterine abnormalities (70% versus 33%, P =.04). Six leiomyomata in four women were no longer detected in the second ultrasound. Leiomyomata that regressed were in older premenopausal women and were smaller than leiomyomata that persisted. The point prevalence and incidence rates of leiomyomata were 27% and 13% per 2.5 years, respectively. Leiomyomata grew an average of 1.2 cm per 2.5 years, but great variation in growth rates were noted. CONCLUSION: Small uterine polyps frequently regressed spontaneously, whereas larger polyps were more likely to persist and were associated with the development of abnormal bleeding. Smaller leiomyomata in older premenopausal women also regressed whereas larger leiomyomata tended to grow while often remaining asymptomatic.     

Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa.

Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg sc every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group.

In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.