Leiomyoma-related Symptoms Research Articles

Effect of Vitamin D3 supplementation on symptomatic uterine leiomyoma in women with Hypovitaminosis D

Objective:The objective of this study is to evaluate the effect of Vitamin D3 on symptoms, uterine and leiomyoma volume in women with symptomatic leiomyoma and hypovitaminosis D.Materials and Methods:In this pilot, interventional, prospective study, 30 premenopausal women with uterine leiomyoma and concomitant hypovitaminosis D (<30 ng/ml) received Vitamin D3 in doses of 60,000 IU weekly for 8 weeks followed by 60,000 IU every 2 weeks for another 8 weeks. Change in symptoms, uterine, and leiomyoma volume was evaluated at 8 weeks and 16 weeks. Serum Vitamin D3 levels were repeated at 16 weeks of therapy.Results:A significant negative correlation was observed between the baseline 25-hydroxy Vitamin D (25(OH) Vitamin D3) and leiomyoma volume (r = –0.434, P < 0.001). There was significant reduction of menstrual blood loss by 29.89% (P = 0.003) and severity of dysmenorrhea, pelvic pain, and backache by 44.12%, 35%, and 50% (P < 0.001, 0.019, and 0.002), respectively, at 16 weeks. At end of therapy, there was 6% reduction in mean uterine volume and 11% in leiomyoma volume which was not significant. Serum 25(OH) Vitamin D3 was significantly higher than baseline level (17.44 ± 5.82 vs. 39.38 ± 8.22, P < 0.001) at end of therapy.Conclusion:Vitamin D3 supplementation is effective in reducing leiomyoma-related symptoms and stabilizing uterine and leiomyoma volume.

Evaluation of goserelin effectiveness based on assessment of inflammatory cytokines and symptoms in uterine leiomyoma.

Background Uterine leiomyoma is a benign tumour of the uterine smooth muscles associated with an elevated level of inflammatory cytokines. Goserelin, a synthetic gonadotropin-releasing hormoneanalogue, suppresses the production of sex hormones and release of inflammatory cytokines in uterine leiomyoma cells. Objective The primary objective of this study was to find out the effectiveness of subcutaneous goserelin therapy on lowering serum levels of inflammatory cytokines and improving uterine leiomyoma-related symptoms in female patients diagnosed with uterine leiomyoma. The secondary objective was to assess the tolerability to goserelin therapy used in the management of this tumour. Setting Outpatient gynaecological clinic of the medical consultation department of Baghdad Teaching Hospital, Baghdad province, Iraq. Methods A single centre, prospective, longitudinal, cohort study was carried out on female patients diagnosed with uterine leiomyoma. Goserelin 3.6mg subcutaneous injection was given in a consecutive monthly dose for the total time duration of three months. Serum levels of inflammatory cytokines, tumour necrosis factor-α and monocyte chemotactic protein-1 were detected before and after goserelin therapy in a consecutive monthly assessment. The study also assessed the improvement in uterine leiomyoma-related symptoms, including pelvic pain alongside the incidence of goserelin-related side effects during therapy schedules. Main Outcome Measures Assessment of serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 alongside uterine leiomyoma-related symptoms, including pelvic pain and goserelin-related side effects. Results There was a significant decrease in serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 compared to the baseline level over the 3-month duration of goserelin therapy (0.11 ± 0.02 vs. 0.74 ± 0.19) pg/mL; (0.07 ± 0.00 vs. 0.44 ± 0.18) pg/mL respectively. Patients showed a clinical improvement regarding uterine leiomyoma-related symptoms following each of the consecutive monthly doses of goserelin therapy (n = 11, 55%, P < 0.0001; n = 15, 75%, P < 0.0001; n = 18, 90%, P < 0.0001) respectively. This also includes a significant decrease in the intensity of leiomyoma-related pelvic pain before and after goserelin therapy (7.2 ± 1.43 vs. 3.05 ± 1.14, P < 0.0001). The majority of patients reported vaginal dryness (60%) as the main goserelin-related side effect. Conclusion Goserelin therapy reduces serum levels of inflammatory cytokines, tumour necrosis factor- α and monocyte chemotactic protein-1, improving leiomyoma-related symptoms with good tolerability in patients with uterine leiomyoma.

Perioperative Interventions to Minimize Blood Loss at the Time of Hysterectomy for Uterine Leiomyomas: A Systematic Review and Meta-analysis

(Abstracted from J Minim Invasive Gynecol 2019;26:1234–1252) Almost 70% of white and more than 80% of black premenopausal women are affected by uterine leiomyomas. Medical or conservative procedures can manage many leiomyoma-related symptoms.

Effects of mifepristone on uterine leiomyoma in premenopausal women: a meta-analysis

To conduct a meta-analysis of the studies assessing the effects of mifepristone on the uterus, uterine leiomyoma, and leiomyoma-related symptoms in premenopausal women. Meta-analysis. Centers for reproductive care. Premenopausal women who suffered from leiomyoma. We identified all of the studies published before December 2012 that compared the status of patients with leiomyoma before and after treatment with mifepristone. Leiomyoma-related symptoms, uterine or leiomyoma volume, changes in endometrial thickness. A meta-analytic technique was used to study 11 randomized controlled trials involving 780 women with symptomatic uterine leiomyomas. The subjects received 2.5-25 mg/d of mifepristone for 3-6 months. Mifepristone could effectively reduce uterine and leiomyoma volume and alleviate leiomyoma symptoms, including hypermenorrhea, the mean menstrual blood loss, pelvic pain, pelvic pressure, anemia, and dysmenorrhea. There was no significant difference in the rate of atypical endometrial hyperplasia between the mifepristone treatment group and the placebo group. Mifepristone significantly reduced uterine and leiomyoma volume and alleviated leiomyoma-related symptoms. We recommend 2.5 mg of mifepristone administered daily for 3 or 6 months as the optimum clinical treatment for leiomyoma. There is insufficient evidence that mifepristone treatment led to atypical endometrial hyperplasia.

Traitements médicaux chez la femme ayant des myomes symptomatiques en période d’activité génitale

The most frequent symptom with leiomyoma is menometrorrhagia. However, it can be responsible of pelvic pain, dysmenorrhea or urinary and digestive compression when it is particularly voluminous. If no therapy is able to have them disappear, various drugs may reduce their related symptoms. Tranexamic acid, non-steroidal anti-inflammatory drugs and high dose of oestrogen may be useful in the management of acute hemorrhagic disorders. Progestin, such as lynestrenol induces small reduction in leiomyoma volume and moderate increase in hemoglobin level before surgery. Pregnane and nor-pregnane may improve menstrual bleeding in short or mild delays. The use of GnRH agonists can reduce menstrual bleeding with hemoglobin recovery. Add-back therapy using tibolone seems interesting since secondary effects encountered with GnRH agonists may be reduced. Levonorgestrel-releasing intrauterine system is proven to reduce increased menstrual bleeding and restore hemoglobin level. Aminoglutethimide and fadrozole have been underevaluated to conclude when letrozole seems as efficient as GnRH agonists to reduce leiomyoma volume and provide less hotflushes. Anastrozol is associated with reduction in leiomyomata volume, pain and menstrual bleeding. Mifepristone reduces the size of uterine leiomyomata, improves symptomatology, but could be associated with development of endometrial hyperplasia. SPRM evaluated in females have shown to improve leiomyoma related symptomatology. Ulipristal could be useful to reduce leiomyoma related symptoms in short terms.

Medical treatment of uterine leiomyoma.

Uterine leiomyomas (also called myomata or fibroids) are the most common gynecologic tumors in the United States. The prevalence of leiomyomas is at least 3 to 4 times higher among African American women than in white women. Pathologically, uterine leiomyomas are benign tumors that arise in any part of the uterus under the influence of local growth factors and sex hormones, such as estrogen and progesterone. These common tumors cause significant morbidity for women and they are considered to be the most common indication for hysterectomy in the world; they are also associated with a substantial economic impact on health care systems that amounts to approximately $2.2 billion/year in the United States alone. Uterine myomas cause several reproductive problems such as heavy or abnormal uterine bleeding, pelvic pressure, infertility, and several obstetrical complications including miscarriage and preterm labor. Surgery has traditionally been the gold standard for the treatment of uterine leiomyomas and has typically consisted of either hysterectomy or myomectomy. In recent years, a few clinical trials have evaluated the efficacy of orally administered medications for the management of leiomyoma-related symptoms. In the present review, we will discuss these promising medical treatments in further detail.

Innovative Oral Treatments of Uterine Leiomyoma

Uterine fibroids (leiomyoma), the benign tumors of the uterine wall, are very common cause of morbidity in reproductive age women usually in the form of excessive vaginal bleeding, chronic pelvic pain, miscarriage and infertility. These tumors are the leading indication for hysterectomy in the United States. Uterine fibroids are about 4 times higher in blacks compared to whites and constitute a major health disparity challenge. The estimated cost of uterine fibroids is up to $34.4 billion annually. Additionally, women who suffer from this disease and desire to maintain their future fertility have very limited treatment choices. Currently, there is no effective long-term medicinal treatment for uterine fibroids. While surgery has traditionally been the gold standard for the treatment of uterine fibroids, there is growing interest towards orally administered medications for the management of leiomyoma-related symptoms. In this paper, we will discuss these promising innovative oral medical treatments in detail.

Cell-Type Specific Actions of Progesterone Receptor Modulators in the Regulation of Uterine Leiomyoma Growth

Although the traditional concept supports a crucial role of estrogen in promoting leiomyoma growth, unequivocal evidence has emerged indicating that progesterone also plays a vital role in the regulation of leiomyoma growth. Recent clinical trials have demonstrated the efficacy of asoprisnil, a selective progesterone receptor modulator, and CDB-2914, a novel progesterone receptor modulator, for the treatment of women with symptomatic leiomyomata. These compounds significantly reduced leiomyoma and uterine volume and improved leiomyoma-related symptoms without serious complications. However, the precise mechanism whereby these compounds cause leiomyoma regression remains poorly understood. Our extensive in vitro studies have provided novel evidence for the growth inhibitory effects of asoprisnil and CDB-2914 on cultured leiomyoma cells. Both compounds exhibited antiproliferative, proapoptotic, and antifibrotic actions on cultured leiomyoma cells in the absence of comparable effects on cultured normal myometrial cells. Asoprisnil and/or CDB-2914 modulated the ratio of progesterone receptor isoforms (PR-A and PR-B) in cultured leiomyoma cells; decreased the cell viability; suppressed the expression of growth factors, angiogenic factors, and their receptors in those cells; and induced apoptosis through activating the mitochondrial and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathways and eliciting endoplasmic reticulum stress. Furthermore, these compounds suppressed types I and III collagen synthesis by modulating extracellular matrix-remodeling enzymes in cultured leiomyoma cells without affecting those syntheses in cultured normal myometrial cells. These findings indicate that both compounds exert antiproliferative, proapoptotic, and antifibrotic actions on leiomyoma cells in a cell-type specific manner. This supports the notion that asoprisnil and CDB-2914 hold promise for the nonsurgical treatment of uterine leiomyomata.

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.

The selective progesterone receptor modulator CDB4124 inhibits proliferation and induces apoptosis in uterine leiomyoma cells

To evaluate the effects of selective P receptor (PR) modulator CDB4124 on cell proliferation and apoptosis in cultured human uterine leiomyoma smooth muscle (LSM) cells and control myometrial smooth muscle (MSM) cells in matched uteri. Laboratory research. Academic medical center. Premenopausal women (n = 12) undergoing hysterectomy for leiomyoma-related symptoms. Treatment of primary LSM and MSM cells with CDB4124 (10(-8)-10(-6) M) or vehicle for 24, 48, or 72 hours. Western blot for protein expression of proliferating cell nuclear antigen, cleaved polyadenosine 5'-diphosphate-ribose polymerase, Bcl-2, and Krüppel-like transcription factor 11; 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate viable cell numbers; and real-time polymerase chain reaction (PCR) to quantify messenger RNA (mRNA) levels. Treatment with CDB4124 significantly decreased levels of the proliferation marker proliferating cell nuclear antigen, the number of viable LSM cells, and the antiapoptotic protein Bcl-2. On the other hand, treatment with CDB4124 increased levels of the apoptosis marker cleaved polyadenosine 5'-diphosphate-ribose polymerase and the tumor suppressor Krüppel-like transcription factor 11 in a dose- and time-dependent manner in LSM cells. In matched MSM cells, however, CDB4124 did not affect cell proliferation or apoptosis. CDB4124 selectively inhibits proliferation and induces apoptosis in LSM but not in MSM cells.

Understanding cellular leiomyomas: a case control study

OBJECTIVE: Rare reports suggest that cellular leiomyomas have a phenotype more consistent with malignancy that conventional leiomyomas. The purpose of this study is to examine this rare lesion to determine if cellular leiomyomas have a unique clinical presentation compared to typical leiomyomas.DESIGN: Retrospective case-control study.MATERIALS AND METHODS: This study was conducted at the Mayo Clinic, Rochester, MN. Women undergoing surgical procedures between January 1, 1989 and December 31, 2008 with a histologic diagnosis of uterine cellular leiomyomas comprised the study group (N=99). Control subjects were women undergoing the same procedure by the same surgeon within 2 years with a diagnosis of leiomyoma. Control subjects were matched in a 2:1 ratio to study subjects (N= 198). A review of hospital and ambulatory records was performed to ascertain sociodemographic and anthropometric variables as well as intraoperative and pathologic findings.RESULTS: In 99% of the uterine specimens with multiple leiomyomas, the cellular leiomyoma was the largest mass. A single uterine mass was more common among the cellular leiomyoma cases compared to women with typical leiomyomas (OR 2.1, 95% CI 1.3-3.4). Women with cellular leiomyomas were significantly younger (P=.010) and had uteri with decreased weight on pathologic exam (P<.0001) compared to typical fibroid uteri. Additionally, more women with cellular leiomyomas had surgery for leiomyoma(s) or leiomyoma related-symptoms (P=.003) than women with typical leiomyomas. In multivariable logistic regression analyses, women with cellular leiomyomas were more likely to have surgical indication for enlarging leiomyoma (OR 7.1, CI 2.4-25.1), were more likely to have more fibroid burden (OR per doubling in fibroid size 1.2, CI 1.1-1.3) and have fewer leiomyomas (OR 0.9, CI 0.9-1.0) when compared to women with typical leiomyomas.CONCLUSIONS: Cellular leiomyomas have a distinct clinical phenotype compared to typical leiomyomas and some characteristics common with leiomyosarcomas. OBJECTIVE: Rare reports suggest that cellular leiomyomas have a phenotype more consistent with malignancy that conventional leiomyomas. The purpose of this study is to examine this rare lesion to determine if cellular leiomyomas have a unique clinical presentation compared to typical leiomyomas. DESIGN: Retrospective case-control study. MATERIALS AND METHODS: This study was conducted at the Mayo Clinic, Rochester, MN. Women undergoing surgical procedures between January 1, 1989 and December 31, 2008 with a histologic diagnosis of uterine cellular leiomyomas comprised the study group (N=99). Control subjects were women undergoing the same procedure by the same surgeon within 2 years with a diagnosis of leiomyoma. Control subjects were matched in a 2:1 ratio to study subjects (N= 198). A review of hospital and ambulatory records was performed to ascertain sociodemographic and anthropometric variables as well as intraoperative and pathologic findings. RESULTS: In 99% of the uterine specimens with multiple leiomyomas, the cellular leiomyoma was the largest mass. A single uterine mass was more common among the cellular leiomyoma cases compared to women with typical leiomyomas (OR 2.1, 95% CI 1.3-3.4). Women with cellular leiomyomas were significantly younger (P=.010) and had uteri with decreased weight on pathologic exam (P<.0001) compared to typical fibroid uteri. Additionally, more women with cellular leiomyomas had surgery for leiomyoma(s) or leiomyoma related-symptoms (P=.003) than women with typical leiomyomas. In multivariable logistic regression analyses, women with cellular leiomyomas were more likely to have surgical indication for enlarging leiomyoma (OR 7.1, CI 2.4-25.1), were more likely to have more fibroid burden (OR per doubling in fibroid size 1.2, CI 1.1-1.3) and have fewer leiomyomas (OR 0.9, CI 0.9-1.0) when compared to women with typical leiomyomas. CONCLUSIONS: Cellular leiomyomas have a distinct clinical phenotype compared to typical leiomyomas and some characteristics common with leiomyosarcomas.

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.

Tibolone reverses the cognitive effects caused by leuprolide acetate administration, improving mood and quality of life in patients with symptomatic uterine leiomyomas

To investigate the effects of tibolone co-administration with GnRH agonist treatment in terms of cognition, mood, and quality of life. Randomized, controlled, single-blind, clinical trial. Department of gynecology and obstetrics at a university in Italy. One hundred ten premenopausal women with symptomatic uterine leiomyomas. Six months of treatment with leuprolide acetate depot (11.25 mg IM, every 3 mo) associated with either tibolone (2.5 mg/d orally; group A) or placebo (1 tablet per d; group B). At baseline and after 6 months of treatment, uterine and leiomyoma sizes, leiomyoma-related symptoms, climacteric-like symptoms, cognition, mood, and quality of life. At study entry, no difference was detected between groups in any parameters assessed. After treatment, the leiomyoma-related symptoms were significantly reduced in both groups, without any statistically significant differences between them. The Kupperman Index was statistically significantly higher in group B in comparison with baseline and group A. The cognition scores were statistically significantly different in comparison with baseline in group B, whereas no change was observed in group A. After treatment, mood and quality of life were statistically significantly improved in both groups, even though the improvement was significantly higher in group A than in group B. Tibolone administration reverses the deleterious effect on cognition that is caused by leuprolide acetate depot and improves mood and quality of life in patients who receive GnRH agonist for symptomatic uterine leiomyomas.

Differential expression of microRNA species in human uterine leiomyoma versus normal myometrium

To determine whether microRNAs (miRNAs) are differentially expressed in human leiomyoma versus matched myometrial tissue. Microarray with real-time polymerase chain reaction (PCR) validation. Academic medical center. Premenopausal subjects (n = 15), who were undergoing hysterectomies for leiomyoma-related symptoms. None. Statistically differential expression of miRNAs in leiomyoma versus myometrium. Forty-six miRNA species were differentially expressed in leiomyoma versus normal myometrium. Of these, 19 were overexpressed and 27 were underexpressed in leiomyomas. The changes ranged from 1.2-fold to 11.8-fold. These findings were confirmed using real-time reverse transcriptase PCR for selected miRNAs (miRNAs 21, 34a, 125b, 139, and 323). Our findings indicate that miRNAs are differentially expressed between human leiomyoma and matched myometrium. Given this differential expression, miRNAs may play a role in the pathogenesis of uterine leiomyoma and may serve as future therapeutic targets for the treatment of these tumors.

The Effect of Anastrazole on Symptomatic Uterine Leiomyomata

To evaluate the effect of anastrazole on symptomatic uterine leiomyomata. 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. 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. In premenopausal women, anastrazole reduces the size of uterine leiomyomata, improves symptomatology, and is generally well tolerated. III.

Role of magnetic resonance imaging in patient selection for uterine artery embolization

Uterine fibroids are common tumors of the female pelvis. Uterine artery embolization (UAE) is an effective treatment of symptomatic uterine leiomyoma in the appropriate candidates, reducing or eliminating leiomyoma-related symptoms of bleeding, bulk, and/or pain. Magnetic resonance imaging (MRI) can be used to assess women with symptoms potentially attributable to uterine leiomyomas, and help to determine who is an appropriate candidate for UAE. Because of soft tissue characterization, multiplanar imaging capabilities, and enhancement, MR imaging not only accurately detects and characterizes uterine leiomyomas but also may predict who will benefit from the embolization. MRI ability to detect coexistent uterine or pelvic pathology may change the diagnosis and treatment management of patients being evaluated for UAE.

Assessment of New Technology in the Treatment of Idiopathic Menorrhagia and Uterine Leiomyomata

New technologies available for the treatment of idiopathic menorrhagia include five global endometrial ablation devices that use differing ablative methods, including thermal balloon, circulated hot fluid, cryotherapy, radiofrequency electrosurgery, and microwave energy. All have been compared with rollerball endometrial ablation by way of randomized clinical trials and are associated with high patient satisfaction rates, regardless of method, but a wide range of amenorrhea rates (13.9-55.3%). They are associated with low complication rates when performed by well-trained physicians following protocols in Food and Drug Administration trials. Some serious complications have been reported subsequently. Strict adherence to patient selection criteria and manufacturer protocols is strongly recommended. New technologies for the treatment of uterine leiomyomata include uterine artery embolization, magnetic resonance-guided focused ultrasonography, laparoscopic uterine artery occlusion, and cryomyolysis. There is sound evidence for shorter hospital stay, quicker return to work, and a similar major complication rate compared with hysterectomy. Uterine artery embolization appears to be effective for up to 5 years in reducing bulk symptoms and menorrhagia associated with leiomyomata. The chance of reoperation for leiomyoma-related symptoms within 5 years is 20-29%. Women who wish to become pregnant should be cautioned about potential complications during pregnancy. There is insufficient evidence to recommend uterine artery embolization in postmenopausal women. With regard to magnetic resonance-guided focused ultrasonography, cryomyolysis, and laparoscopic uterine artery occlusion, although the initial symptom reduction outcomes have been reported as favorable, more data are needed to better understand the durability of these results.

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.

Low-Dose Mifepristone for Uterine Leiomyomata

In Brief 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. Mifepristone in daily 5- and 10-mg doses administered over 6 months shrinks uterine leiomyomata and ameliorates symptoms, with a low frequency of side effects.

New concepts in the treatment of uterine leiomyomas

Uterine leiomyomas are a common clinical occurrence for gynecologists. The current approach to treating these neoplasms is shaped by classic surgical principles and the knowledge that these tumors are responsive to the gonadal steroids estrogen and progesterone. As knowledge of leiomyomas advances through the techniques of molecular biology and molecular genetics, new concepts are developed that go beyond just myomas as steroid-responsive tumors. Understanding the molecular events involved in the transformation of a normal myometrial cell into a neoplastic cell and the subsequent growth of these leiomyoma cells will be important in determining the pathogenesis of these tumors and providing new targets for treatment. Knowing the role of peptide growth factors, including basic fibroblast growth factor and transforming growth factor-beta, in the pathogenesis of leiomyoma-related symptoms might lead to new treatments targeting these molecules or their receptors. As the effects of genes, including HMGIC and HMGI(Y), are determined; new treatments to prevent leiomyoma formation or growth may be developed. As we gain understanding of the molecular events that cause benign gynecologic conditions such as leiomyomas, safer and more effective treatments might be found as we enter the 21st century.