Leiomyoma Volume Research Articles

Phase I/II Multiinstitutional Study of Uterine Artery Embolization with Gelatin Sponge for Symptomatic Uterine Leiomyomata: Japan Interventional Radiology in Oncology Study Group Study

This multicenter prospective study was conducted to evaluate the safety and the efficacy of uterine artery embolization (UAE) with gelatin sponge for symptomatic leiomyomas. Patients with symptomatic uterine leiomyomas were enrolled and treated with UAE. In phase I, nine patients were evaluated for safety. In phase II, 24 patients were accrued, and an intent-to-treat analysis was performed on all 33 patients. The primary endpoint was safety. Secondary endpoints included technical success, hospital stay, change in symptoms, leiomyoma volume on magnetic resonance (MR) imaging, and incidence of treatment failure. UAE procedures were performed for all 33 patients. Two patients were lost to follow-up at 3 and 12 months. The median follow-up period was 33.4 months. Minor adverse events (AEs) occurred in 10 patients (33%); major AEs of permanent amenorrhea and leiomyoma expulsion occurred in two (6%). The most common AE was transient amenorrhea. Technical success was achieved in all patients. The median hospital stay was 5 days. At 12 months after UAE, menorrhagia had improved in 90% of patients, pelvic pain in 78%, and bulk-related symptoms in 97%. The mean reduction in leiomyoma volume on MR imaging at 12 months was 61%. Treatment failure occurred in one patient, who underwent hysterectomy for recurrent menorrhagia at 21 months. UAE with gelatin sponge is safe, with efficacy comparable to other embolic agents based on published data. Gelatin sponge should be an option for UAE, but a prospective comparison versus other standard UAE embolic agents may be warranted.

An enhanced leiomyoma cell response to osmotic stress is central to the mechanism of gonadotropin releasing hormone analogue treatment

OBJECTIVE: Clinical treatment of leiomyomas with gonadotropin releasing hormone (GnRH) analogue produces a rapid reduction in leiomyoma volume, but rapid regrowth occurs when treatment is withdrawn, suggesting a central role for osmotic regulation. We have previously demonstrated that transcription factor, Nuclear Factor of Activated T cells 5 (NFAT5) is augmented in human leiomyomas under osmotic stress. In these studies, we determined the role of GnRH analogue treatment in leiomyoma cell osmotic regulation.

Uterine Artery Embolization for Leiomyomas: Percentage of Infarction Predicts Clinical Outcome

To determine the effect of partial versus complete leiomyoma infarction on relief of leiomyoma-related symptoms and freedom from invasive reinterventions and to assess if patient age, location of the dominant leiomyoma, number of leiomyomas, or baseline uterine and dominant leiomyoma volume were associated with clinical failure. Study protocol was approved by the institutional review board, and informed consent was obtained. One hundred fifteen consecutive women (median age, 42 years; range, 34-61 years) with symptomatic uterine leiomyomas underwent contrast material-enhanced magnetic resonance (MR) imaging at baseline and 24-72 hours after uterine artery embolization (UAE) to determine the percentage of infarction of leiomyoma tissue (complete = 100%, almost complete = 90%-99%, and partial = 0%-89%). Clinical outcome and frequency of reinterventions were compared for up to 36 months. One hundred thirteen patients completed at least one clinical follow-up. Twenty-four months after UAE, 50% +/- 15.2 (standard error) of the patients with partial infarction and 80% +/- 13.4 (standard error) of patients with almost complete infarction had undergone no reintervention. No patient with complete infarction needed a second treatment (P < .001). The hazard ratios for reintervention between the complete infarction group and the almost complete and partial infarction groups were 15.88 (95% confidence interval [CI]: 1.22, 2225.54; P = .034) and 73.08 (95% CI: 8.33, 9636.35; P < .001), respectively. There were significant differences in hazard ratios between patients with partial and those with complete infarction for persistence or recurrence of menorrhagia (hazard ratio, 7.45; 95% CI: 2.08, 28.31; P = .002) and bulk-related symptoms (hazard ratio, 5.90; 95% CI: 1.66, 21.92; P = .007). There was no significant correlation between patient age, number of leiomyomas, location of the dominant leiomyoma, or baseline uterine and dominant leiomyoma volume and clinical failure. Women with leiomyoma infarction above 90% on contrast-enhanced MR images after UAE show significantly better symptom control and fewer reinterventions than do patients with a lower infarction rate.

Leiomyoma Volume Changes at Follow-up after Uterine Artery Embolization: Correlation with the Initial Leiomyoma Volume and Location

To study the changes in uterine leiomyoma volume after uterine artery embolization (UAE) and to correlate these changes with the initial tumor volume and location within the uterus. The study was performed retrospectively on 28 consecutive patients (age, 37-57 years; mean, 48 y +/- 4.81) with 84 uterine leiomyomas. UAE was performed between June 2006 and August 2007. All tumors in all patients were evaluated. Magnetic resonance imaging was performed before UAE and 3 months and 1 year after UAE. The volume and location of each tumor were evaluated in consensus by two radiologists. The mean pre-UAE volume of the leiomyomas was 51.6 cm(3) (range, 0.72-371.1 cm(3); SD, 79.3). Seven tumors were submucous, 28 intramural, and 49 subserous. At 3-month follow-up, 83 tumors (98.8%) showed volume reduction (mean, 52.62% +/- 21.85%; range, 12.79%-96.67%) and one (1.2%) increased in volume. At 1-year follow-up, five tumors (6%) were undetectable, 72 (85.7%) showed a further volume reduction of 20.5% +/- 11.92% (range, 2.52%-58.72%) relative to the 3-month volume, and seven (8.3%) increased in volume. A statistically significant difference (P = .026 at 3 months and P = .0046 at 1 year) in percentage of volume change was observed based on tumor location; submucous tumors showed the greatest volume reduction and subserous tumors the least reduction. The initial tumor volume showed a weak negative correlation (Spearman correlation coefficients, -0.35 at 3 months and -0.36 at 1 year) with tumor volume change. UAE results in leiomyoma volume reduction at 3-month and 1-year follow-up. The tumor location plays an important role in volume changes and the initial tumor volume plays a minor role. Further studies with larger numbers of submucous leiomyomas are needed.

Mifepristone for Treatment of Uterine Leiomyoma: A Prospective Randomized Placebo Controlled Trial

A hysterectomy is the primary therapeutic option for women with uterine leiomyomas. To avoid surgical intervention, several medical options have been explored. Because the growth of uterine leiomyomas is promoted by estrogen and progesterone, a number of studies have investigated the effect of treatment with the antiprogesterone drug mifepristone and other progesterone receptor modulators in these patients. The results of these studies have been promising. Daily oral doses of mifepristone treatment reduced bleeding in women with uterine leiomyomas in several studies. This prospective, randomized, placebo-controlled study investigated the effect of 3 months of mifepristone on leiomyoma volume, endometrium, and bleeding. This was a proof of concept study. About 30 women with leiomyoma-related problems indicating the need for surgical intervention were randomized to receive either mifepristone or a placebo for 3 months on alternate days before scheduled surgery. Until surgery, both uterine blood flow and leiomyoma volume were measured once a month. At baseline and at the end of treatment, endometrial biopsies were examined and pertinent biochemistry, symptoms, and bleeding were recorded. Reduction in uterine leiomyoma size was the primary study outcome. Compared to the control, there was a significant decrease in the percent of total leiomyoma delta volume after 3 months of treatment with mifepristone: the values for the mean within 95% confidence interval were −28 (−48% to −28%) in the mifepristone-treated-group compared to −6% (−13% to +25%) in the control group. At 3 months, a significant reduction in bleeding days was noted within the mifepristone group compared with the placebo group (P = 0.001) and there was a significant increase in blood hemoglobin values in the mifepristone group (P = 0.046). No change occurred in serum cortisol levels during the 3 months of treatment with mifepristone, and a small increase in serum androgens was found. None of the biopsies in the mifepristone-treated women revealed any evidence of hyperplasia or malignancy. The findings of this proof-of-concept study suggest that mifepristone may be an effective medical treatment option for leiomyomata, and may achieve rapid control of the associated marked uterine bleeding.

Leiomyoma Shrinkage After MRI-Guided Focused Ultrasound Treatment: Report of 80 Patients

The purpose of this study was to assess the degree of leiomyoma ablation and shrinkage after MRI-guided focused ultrasound treatment performed according to U.S. Food and Drug Administration protocols for commercial trials. A total of 147 symptomatic leiomyomas in 80 women (average age, 46 years; range, 34-55 years) were managed with MRI-guided focused ultrasound. The average volume of treated fibroids was 175+/-201 (SD) cm3. Before treatment, T2-weighted MR images in three planes were obtained to measure leiomyoma volume. Immediately after treatment, T1-weighted contrast-enhanced fat-suppressed MR images in three planes were used to measure nonperfused volume ratio. Similar images obtained 6 months after treatment were used to determine leiomyoma shrinkage. Qualitative and quantitative relations between fibroid volume, nonperfused volume ratio at treatment, and 6-month shrinkage were measured. The average nonperfused volume ratio was 55%+/-25% immediately after treatment. Six months after treatment, the average volume of treated fibroids had decreased to 112+/-141 cm3 (n=81) (p<0.0001) with an average volume reduction of 31%+/-28%. A linear regression model showed highly significant correlation between posttreatment nonperfused volume ratio and shrinkage at 6 months (p<0.0001). MRI-guided focused ultrasound therapy for leiomyoma can result in nonperfused volume ratio and shrinkage that exceed those in previous clinical trials because the treatment guidelines have been relaxed to allow a greater amount of tissue ablation. The results suggest that a larger nonperfused volume ratio can be achieved, resulting in greater shrinkage and improved relief of symptoms.

Uterine artery embolization for treatment of leiomyoma: long term results and effects on outcomes

Objective To evaluate the effects and safety of uterine artery embolization for uterine leiomyoma. Methods Total of 185 patients with uterine leiomyoma were treated by UAE. They were followed for one to 6 years to observe the changes of leiomyoma size and improvement in clinical symptoms. Ovarian function was evaluated in 44 cases. Results Bilateral embolization of uterine arteries was performed in 185 patients. Follow-up of 1 ～6 years for 292 leiomyoma indicated that one to 9 months after embolization, shrinkage of leiomyoma size was the most significant factor. One year after embolization, leiomyoma sizes decreased a little. Shrinkage of submucous leiomyoma was more significant than that of intratumoral one, and the latter was more significant than subserous one. Shrinkage of leiomyoma with large size ( volume ≥ 150cm~3) was less than that of small one. Menorrhagia, anemia and pressure symptoms were all resolved. There was no significant difference between pre- and post embolization ovarian hormone level. Conclusions The significant reduction in leiomyoma volume and resolution of clinical symptoms confirmed that the treatment validity of symptomatic leiomyomas by UAE. UAE is an effective therapeutic procedure which has no adverse effect on the ovarian function. Key words: Embolization, therapeutic; Uterine neoplasm/TH; Leiomyoma/TH

Levonorgestrel-releasing intrauterine device insertion ameliorates leiomyoma-dependent menorrhagia among women of reproductive age without a significant regression in the uterine and leiomyoma volumes

Levonorgestrel- (LNG) releasing intrauterine device (IUD) insertion revealed significant reduction in visual bleeding scores and spotting with an increase in amenorrhea and uterine pulsatility index scores. LNG-IUD can be considered as a simple and effective alternative to surgical treatment in the management of leiomyoma-dependent menorrhagia of reproductive-age women.

Radiofrequency Thermoablation of Submucosal Leiomyoma: A Preliminary Report on Health, Symptom and Quality of Life Outcomes

Study Objective: Submucosal leiomyoma commonly causes abnormal uterine bleeding, menstrual abnormalities and infertility and is usually treated by hysteroscopy. However, not all submucosal leiomyomas can be treated by hysteroscopy; patients with high- scoring submucosal leiomyoma must undergo transabdominal myomectomy to preserve their uterus. Design: Premenopausal women with symptomatic uterine submucosal leiomyoma were included in this study. The pre- and postoperative myoma volumes were measured by 3D ultrasonography. The effect of symptoms on health-related quality of life (HRQL) was assessed using the Uterine Fibroids Symptom and Quality of Life questionnaire. Setting: Observational study. Patients: Premenopausal women with symptomatic leiomyoma. Intervention: myolysis with radiofrequency. Measurements and Main Results: Submucosal leiomyoma volume reduction rate was 75.5% ± 14.1% and 80.7 ± 22.1% 3 and 6 months after surgery, respectively. No differences were seen in the volume reduction rate according to the preoperative grade of leiomyoma. Symptom scores and HRQL scores showed improvements 18 months after surgery with no differences between grades. Penetration/burn injuries of the bowel or bladder, sepsis, shock, embolism and peritonitis were not reported. Conclusion: Transvaginal RF thermal ablation is a good treatment method for symptomatic submucosal leiomyoma, especially for patients with a high leiomyoma grade and when there is no choice for treatment except hysterectomy or hysterotomy.

Osmotic stress response is altered in leiomyoma cells

OBJECTIVE: Clinical treatment of leiomyomas with GnRH analogue produces a rapid reduction in leiomyoma volume. Rapid leiomyoma regrowth when GnRH treatment is withdrawn suggests the reduction in volume is due to transport of water, yet little is known about the response of leiomyoma cells to osmotic stress. Nuclear factor of activated T cells 5 (NFAT5) is the key osmo-sensing transcription factor in human cells. Our goal was to characterize osmosensing via NFAT5 in leiomyoma cells. DESIGN: Prospective, human model experiments MATERIALS AND METHODS: Osmotic stress was induced by culturing immortalized human leiomyoma and myometrial cells in DMEM-10% FBS with additional osmolytes of NaCl at 25, 50 or 100 mM for 8 hours. Proliferation assays were performed by the sulforhodamine B method. Apoptosis was assessed by caspase 3/7 activity assay. Expression of NFAT5 in tissue and cells was determined with qRT-PCR and western blot analysis. RESULTS: Leiomyoma cell growth was inhibited 18% at 50 mM NaCl compared to 48% in myometrial cells (p<0.05), consistent with altered osmosensing in leiomyoma cells. This finding was not due to apoptosis, as evidenced by no change in caspase activity. NFAT5 transcripts were increased in leiomyoma 1.5 fold ± 0.19 compared to myometrium in 4 of 7 patient samples (p<0.05). Concentration dependent upregulation of NFAT5 mRNA was observed in osmotically stressed leiomyoma cells. At 50mM NaCl, NFAT5 transcripts were increased 2.5-fold compared to control. CONCLUSIONS: Leiomyoma cells were more resistant to changes in osmotic stress than myometrial cells, suggesting dysregulation in osmotic signaling in leiomyomas. This change was accompanied by differential expression of NFAT5 in leiomyoma tissue. Altered osmotic signaling in leiomyoma cells suggests a central role for water regulation in the rapid change of leiomyoma volume with GnRH analogue treatment.

Uterine Artery Embolization under Electroacupuncture for Uterine Leiomyomas

To evaluate whether electroacupuncture is a safe and effective alternative to pharmacologic sedation/analgesia in uterine artery embolization (UAE) for leiomyomas. A nonrandomized prospective study was undertaken in 70 consecutive patients (mean age, 39.5 years) undergoing UAE with polyvinyl alcohol (PVA) particles between August 2006 and January 2007. Thirty-three patients chose to undergo UAE under electroacupuncture anesthesia (EAA; group A) and 37 were treated under local pharmacologic anesthesia (group B). Pain scores (rated from 0 to 10) in both groups were compared during and after the procedure. The outcome of UAE was evaluated at 6 months. Mean pain scores during embolization were 0.36 in group A and 0.84 in group B; scores after embolization and before discharge were 3.00 in group A and 4.49 in group B; and scores at discharge were 0.97 in group A and 2.11 in group B. These differences were statistically significant after embolization and at hospital discharge (P= .02 and P= .0001, respectively). All patients except one in each group were discharged from the hospital 4-8 hours after UAE; the two who remained longer had severe pain. There were no significant differences in clinical outcomes, nor in uterine and leiomyoma volumes, at discharge and at 6 months (P > 0.99 and P= .72, respectively). There was a statistically significant postembolization pain reduction in patients treated under EAA versus local pharmacologic anesthesia and no differences in UAE outcomes between groups at 6 months.

Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial

Uterine leiomyomas are widely prevalent and frequently cause menorrhagia. The major therapeutic option today is hysterectomy. Medical options are of highest interest. A total of 30 women with uterine leiomyomas scheduled for surgical intervention were randomized to receive either 50 mg mifepristone or placebo every other day during 3 months prior to surgery. Uterine blood flow and leiomyoma volume were evaluated once a month until surgery. Endometrial biopsies were obtained prior to and at end of treatment. Relevant biochemistry, symptoms and bleeding were recorded. Primary outcome was reduction in uterine leiomyoma size. There was a significant percentual decrease (P = 0.021) in the total leiomyoma volume in the mifepristone-treated group, -28 (-48, -8) % (mean +/- 0, 95 confidence interval), compared with the control group values 6 (-13, 25) %. Mifepristone treatment significantly reduced the bleeding days (P = 0.001) and increased serum haemoglobin values (P = 0.046). Serum cortisol levels remained unchanged, while a mild increase in serum androgens was noted. Endometrial biopsies showed no premalignant changes or changes in mitotic indices. Mifepristone may offer an effective treatment option for women with uterine leiomyoma and the associated pronounced uterovaginal bleeding. Clinical Trials identifier: www.clinicaltrials.gov: NCT00579475.

Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN

The selective progesterone receptor modulator asoprisnil suppresses uterine bleeding and decreases leiomyoma volume while maintaining follicular phase estrogen concentrations. For safety of potential clinical applications, any proliferative effect of asoprisnil on uterine tissues, particularly endometrium, needs to be established. In a double-blind, randomized, placebo-controlled study (continuation of previously published trial No. NCT00150644 (Williams et al., 2007 and Wilkens et al., 2008)), 33 patients with symptomatic uterine leiomyomata received placebo, 10 or 25 mg asoprisnil daily for 12 weeks before hysterectomy. Proliferation markers Ki-67 and anti-phospho-histone H3 (PH3) were immunolocalized in endometrium, myometrium and leiomyoma tissue. Endometrial PTEN (phosphatase and tensin homologue, a tumour suppressor gene) expression was also assessed by immunohistochemistry. PH3-positive glandular and stromal cells were counted per measured endometrial area. Endometrial Ki-67 expression was assessed using stereological methods. Stained myometrial and leiomyoma cells were counted per 10 fields (x250). PTEN immunostaining was quantified using a histoscore. Each asoprisnil group was compared with placebo (secretory phase) with significance at 0.05 level. Endometrial epithelial proliferation and PTEN expression were not significantly different between placebo and asoprisnil groups. Decreased stromal Ki-67 expression (P < 0.05) suggested any effect of asoprisnil on endometrial proliferation to be inhibitory. Immunolocalization of PTEN expression was not different between treatment groups in any tissue compartments. Myometrial Ki-67 expression decreased following asoprisnil 25 mg (P < 0.05). Asoprisnil does not induce proliferation of uterine tissues and does not suppress endometrial PTEN expression.

Low‐dose mifepristone in treatment of uterine leiomyoma: A randomised double‐blind placebo‐controlled clinical trial

To evaluate the effect of low-dose mifepristone on leiomyoma-related symptoms, uterine and leiomyoma in women with symptomatic leiomyomata. In a double-blind placebo-controlled trial, 40 patients with symptomatic leiomyoma and normal endometrial histology were randomised to receive 10 mg mifepristone (group 1) or placebo (group 2) daily for three months. Leiomyoma-related symptoms, uterine, leiomyoma and largest leiomyoma volumes were assessed at baseline and every month for three months. Endometrial biopsy was repeated at the end of therapy. Significant change was noticed between the two groups for mean menstrual blood loss (MBL) by first month. Menstrual blood loss declined by 94.8% in group 1 at three months and 84.2% patients attained amenorrhoea in this group. In group 1 complete relief of dysmenorrhoea occurred in significant number of women (80%) but only 33% patients got rid of pelvic pain. There was no change in these symptoms in group 1 Backache, urinary complaints and dyspareunia were not relieved in either group. Uterine, leiomyoma and largest leiomyoma volume declined by 26-32% in group 1 as compared to none in group 2, and this difference was statistically significant only by the end of the third month of therapy. Mean haemoglobin increased from 9.5 to 11.2 g/dL in group 1. In group 1, at the end of therapy, 63.1% of patients had endometrial hyperplasia without atypia. Ten milligrams mifepristone for three months is effective in reducing MBL, increasing haemoglobin and reducing uterine and leiomyoma volume with side-effect of endometrial hyperplasia.

A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status

To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas. Multicenter, randomized, controlled clinical trial. University hospitals. A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B). Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks. Measurement of myoma volume and E(2), FSH, LH, and T levels. Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment. Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma.

Mifepristone for the Treatment of Uterine Leiomyomas

To estimate the efficacy of daily administration of 5 mg compared with 10 mg of mifepristone for the treatment of uterine myomas. One hundred women were randomly assigned to receive oral mifepristone 5 mg or 10 mg daily for 3 months (50 per group). Abdominal ultrasonography was performed before treatment, at 45 days, and at 3 months to evaluate leiomyoma and uterine volumes. Endometrial biopsy specimens were taken before and after treatment. Efficacy was estimated by the reduction percentages of the leiomyoma and uterine volumes. After 90 days treatment there was a 45% (95% confidence interval [CI] 37-54, P<.001) and a 57% (95% CI 48-67, P<.001) reduction in the leiomyoma volume in the 10-mg and 5-mg groups, respectively, and one of 40% (95% CI 34-46, P=.002), and 36% (95% CI 31-40, P<.001), respectively, in the uterine volume. Symptomatic improvement was noted, and the prevalence of symptoms diminished significantly. There were no significant differences in reduction of volume and symptoms in the treatment groups, P>.05 in all cases. After treatment, 44 of 49 (89.8%) women from the mifepristone 10 mg group and 45 of 50 (90.0%) from the 5-mg group, respectively, were amenorrheic (P=.487). Endometrial biopsy after treatment showed simple hyperplasia in 1 of 50 (2.0%) in the mifepristone 10 mg group. Five-milligram doses of mifepristone produce reductions in leiomyoma and uterine volumes and symptomatic improvement similar to 10-mg doses. I.

Estrogen and Progesterone Receptor Status in Leiomyoma Affects Radiofrequency Ablation Outcome

Abstract Objective: Radiofrequency ablation (RFA) is a noninvasive therapeutic technique for treating symptomatic uterine leiomyomas. This study aimed to prospectively evaluate the relationship of estrogen receptor (ER) and progesterone receptor (PR) in leiomyoma with the volume reduction rate and improvement in symptoms following RFA. Design and Methods: Forty-nine women with symptomatic single-nodule uterine leiomyoma underwent transvaginal RFA. Fine-needle aspiration biopsy was performed 1 month before RFA, and the patients were divided into two groups based on the status of ER and PR in leiomyoma: strongly to moderately positive (group I, 32 patients) and weakly positive to negative (group II, 17 patients). The leiomyoma volume was measured by three-dimensional ultrasonography before and during the operation and in postoperative months 1, 3, 6, 9, 12, and 18. The impact of the symptoms on health-related quality of life (HRQL) was assessed on first and last follow-up visits by using the Uterine Fibroid...

Uterine Leiomyomas: MR Imaging–guided Focused Ultrasound Surgery—Imaging Predictors of Success

To retrospectively assess the magnetic resonance (MR) imaging predictors of success at reducing uterine leiomyoma volume and achieving patient symptom relief 12 months after MR imaging-guided focused ultrasound surgery. This single-center retrospective analysis of 71 symptomatic fibroids in 66 women was approved by the institutional review board and was HIPAA-compliant. Patients were treated with MR imaging-guided focused ultrasound surgery. The volume of treated fibroid and nonperfused volume (NPV) were calculated with software, while symptom outcome was assessed with a symptom severity score (SSS). Fibroids were classified as hyperintense or hypointense relative to skeletal muscle on pretreatment T2-weighted MR images. Baseline volume of treated fibroids was 255.5 cm(3) +/- 201.7 (standard deviation), and baseline SSS was 61.5 +/- 14.9. Both pretreatment fibroid signal intensity (SI) and posttreatment NPV predicted 12-month volume reduction independently: Fibroids with an NPV of at least 20% or with low SI both showed significantly larger volume reduction (17.0% +/- 13.0 and 17.2% +/- 20.1, respectively) than fibroids with an NPV less than 20% or with high SI (10.7% +/- 18.2 and no significant change, respectively). Patients whose fibroids demonstrated an NPV of at least 20% also experienced a larger decrease in SSS than did patients with fibroids with an NPV less than 20% (50.1% +/- 19.8 vs 32.6% +/- 29.9). Fibroids with low SI on pretreatment T2-weighted MR images were more likely to shrink than were ones with high SI. The larger the NPV immediately after treatment, the greater the volume reduction and symptom relief were. These findings may help both in selecting appropriate patients for MR-guided focused ultrasound surgery and in predicting patient outcome.

CDB-2914 for Uterine Leiomyomata Treatment

To evaluate whether 3-month administration of CDB-2914, a selective progesterone receptor modulator, reduces leiomyoma size and symptoms. 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. 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. 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. ClinicalTrials.gov,www.clinicaltrials.gov, NCT00290251 I.

Pathological evaluation of uterine leiomyomas treated with gonadotropin‐releasing hormone agonist (GnRH‐a) therapy: Role of mast cells and a possible mechanism of GnRH‐a resistance in leiomyomas

Gonadotropin-releasing hormone agonist (GnRH-a) therapy is frequently applied to reduce the volume of uterine leiomyomas (UL). In addition, the possible relationship between mast cells (MC) within UL and the development of UL has been suggested, but the role of MC in UL remains to be determined. UL with or without GnRH-a therapy in 121 premenopausal patients were reviewed. The number of MC was evaluated between the two groups, immunohistochemistry was done for insulin-like growth factor-I (IGF-I), and the association between the IGF-I immunoreactivity in UL and the GnRH-a therapy was analyzed. The number of MC significantly increased in UL in GnRH-a therapy, while IGF-I immunoreactivity was significantly reduced in smooth muscle cells of these UL. Furthermore, IGF-I immunoreactivity in MC was inversely correlated with the size reduction rate of UL in GnRH-a therapy. Although GnRH-a therapy is considered to reduce the size of UL transiently, the regression of UL was in part hampered by the increased IGF-I secretion from the increased MC after GnRH-a therapy. Therefore, the more the IGF-I secretion from MC in UL increases, the less effective the GnRH-a therapy is on the size reduction of UL. Thus, the present study may provide an explanation of the possible mechanism of GnRH-a resistance in UL.