Transdermal hormone replacement therapy in postmenopausal women with uterine leiomyomas.

OBJECTIVE: To evaluate the effects of transdermal hormone replacement therapy (HRT) on uterine and leiomyoma size and on uterine bleeding patterns in postmenopausal women with uterine leiomyomas. METHODS: The required sample size was calculated to be 30 subjects per group to detect an effect on the size of one standard deviation (SD) with an alpha value of 0.05 (two-sided) and a power 1 - delta = 0.8. At the end of the study, the power analysis showed a value of beta = 0.826. Seventy postmenopausal women with uterine leiomyomas were enrolled and treated for 12 cycles of 28 days each with transdermal 17 beta-estradiol (E(2)) patches plus oral medroxyprogesterone acetate continuously added (group A) or with calcium carbonate (group B). At entry and every three cycles, uterine and leiomyoma dimensions were measured by transvaginal ultrasonography. To evaluate the effect of transdermal HRT on the characteristics of uterine bleeding, 35 healthy postmenopausal women without uterine leiomyomas (group C) were enrolled and treated with the same regimen as group A. A daily diary was used to record the abnormal uterine bleeding episodes, and a rank scale was used to assess the severity of bleeding. RESULTS: There were no significant changes in mean uterine or leiomyoma size between groups A and B, or in each group compared with basal values. No significant difference was detected between groups A and C in uterine bleeding patterns. CONCLUSION: Transdermal HRT did not increase the size of uterine leiomyomas or affect uterine bleeding patterns in postmenopausal women.     

Effect of different doses of progestin on uterine leiomyomas in postmenopausal women

OBJECTIVE(S): To evaluate the effects of two doses of medroxyprogesterone acetate (MPA) on uterine leiomyoma sizes and on uterine bleeding pattern in postmenopausal women treated with oral hormone replacement therapy (HRT). STUDY DESIGN: Thirty natural postmenopausal women affected by uterine leiomyomas were enrolled and treated with oral micronized estradiol (E(2)) at dose of 2 mg per day, and randomized to receive in association MPA at dose of 2.5 mg daily (group A) or of 5 mg daily (group B). At the beginning of the study and after 1 year of treatment, uterine leiomyomata dimensions were measured using transvaginal ultrasonography (TV-USG). The subjects were instructed to note on a daily dairy the number and severity of abnormal uterine bleeding (AUB) episodes. RESULTS: After 1 year of therapy, a significant changes in mean uterine leiomyomas size was observed in the group treated with higher dose of MPA. No significant differences in uterine bleeding were detected between the two groups. CONCLUSION(S): In postmenopausal women with uterine leiomyomas, it is necessary to use the minimal efficacious dose of progestin during HRT because of a higher risk to increase the tumors dimensions.     

Raloxifene prevents the growth of uterine leiomyomas in premenopausal women

OBJECTIVE: To evaluate the effects of raloxifene administration on uterine leiomyoma size in premenopausal women. DESIGN: Prospective, randomized, open-label, controlled clinical trial. SETTING: Tertiary care unit, University of Vienna, Austria. PATIENT(S): Twenty-five premenopausal women with uterine leiomyomas. INTERVENTION(S): Three months of treatment with raloxifene (180 mg/d) or no treatment. MAIN OUTCOME MEASURE(S): Baseline to end point percent change difference in leiomyoma volume between the therapy and control groups. RESULT(S): Raloxifene treatment prevented the progression of uterine leiomyomas. Compared with no medical intervention, raloxifene resulted in a decrease of myoma volume. Raloxifene was clinically well tolerated. No significant differences were detected in symptoms related to leiomyomas and hormonal status. CONCLUSION(S): In premenopausal women, high-dose raloxifene is well tolerated and inhibits the growth of leiomyomas.     

Selective estrogen receptor modulator and selective progesterone receptor modulator: therapeutic efficacy in the treatment of uterine leiomyoma

Recent advances in endocrinology open a door for clinical application of selective estrogen receptor modulator (SERM) and selective progesterone receptor modulator (SPRM) in the treatment of uterine leiomyoma. With regard to SERM, treatment with raloxifene is shown to reduce leiomyoma size in postmenopausal women. Although raloxifene causes shrinkage of leiomyomas in combination with gonadotropin-releasing hormone agonist in premenopausal women, the effects of monotherapy with raloxifene on leiomyoma growth in premenopausal women remain controversial. By contrast, tamoxifen may not be suitable for long-term treatment of leiomyomas due to an agonistic action on the endometrium. Treatment with progesterone antagonist (RU486) or SPRM (J867) has been demonstrated to inhibit leiomyoma growth and improve clinical symptoms in premenopausal women. No serious adverse effects associated with SERM or SPRM have been reported. In light of therapeutic efficacy and few adverse effects, SERM and SPRM may hold promise as novel treatment modalities for leiomyoma. Further studies are warranted to determine the optimal strategy for the treatment of leiomyoma with SERM and SPRM.     

Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature

OBJECTIVE: To review the efficacy and safety of nafarelin in the treatment of leiomyomas. STUDY DESIGN: A literature review of published clinical trials was conducted. Six studies, including a total of 602 patients with leiomyomas, were reviewed. Patients received intranasal nafarelin, 50-400 micrograms twice daily for three to six months. Vaginal bleeding patterns, leiomyoma and uterine size, surgical conditions and adverse effects were assessed. RESULTS: Nafarelin consistently suppressed estrogen production, reduced leiomyoma and uterine size, and controlled menorrhagia. The significant reduction in uterine bleeding and amenorrhea resulting from administration of nafarelin was associated with a rise in mean hemoglobin concentrations. In addition, nafarelin improved hematologic parameters in women with and without anemia. Nafarelin was well tolerated, although hot flushes were the most commonly reported adverse events. Measured bone mineral density decreased significantly during treatment, although by six to nine months post-treatment, it increased to values not significantly different from baseline. The adverse effects of nafarelin were generally reversible after treatment withdrawal. CONCLUSION: Nafarelin treatment of women with symptomatic leiomyomas effectively decreases uterine bleeding; improves hematologic parameters; manages symptoms of menometrorrhagia, dysmenorrhea and pelvic discomfort; reduces uterine and myoma size; and is well tolerated. Reduction in bone mineral density occurs, but levels return to, or near, baseline levels within six months after treatment.     

Raloxifene reduces impedance to flow within the uterine artery in early postmenopausal women: a 2-year randomized, placebo-controlled, comparative study

OBJECTIVE: We sought to investigate the long-term effect of raloxifene and continuous combined hormone replacement therapy (ccHRT) on impedance to flow within the uterine artery in postmenopausal women. STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled 2-year study was performed in 95 postmenopausal women. They received either 60 mg of raloxifene daily (raloxifene 60 group), 150 mg of raloxifene daily (raloxifene 150 group), ccHRT, or placebo. At baseline and thereafter every 6 months, color Doppler ultrasonography was used to measure the pulsatility index (PI) of the uterine artery. RESULTS: After 24 months of treatment, compared with placebo, significant decreases were found in the PI in the raloxifene 150 group (P = .021) and in the ccHRT group (P = .007). In the raloxifene 150 group compared with the placebo group, after 6 and 24 months, decreases were observed in median PI of -5% and -15%, respectively, and in the ccHRT group decreases of -2% and -19%, respectively, were found. CONCLUSION: Long-term use of 150 mg of raloxifene daily or ccHRT reduces impedance to flow within the uterine artery. This indicates that high-dose raloxifene may exert cardiovascular protection.     

Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60

OBJECTIVE: To assess the uterine effects of 3 years of therapy with raloxifene in healthy, postmenopausal women under age 60. METHODS: Integrated data from two identically designed, randomized, double-masked, placebo-controlled clinical trials were analyzed. Nine hundred sixty-nine healthy women with uteri (ages 45 through 60, 2 to 8 years postmenopausal) were assigned randomly to raloxifene 30, 60, or 150 mg per day, or an identical placebo for 3 years. Endometrial thickness was evaluated with transvaginal ultrasonography every 6 months for 2 years and again after 3 years. Further uterine evaluation, including endometrial sampling if necessary, was initiated for vaginal bleeding or findings of endometrial thickness greater than 5 mm. RESULTS: Endometrial thickness was unchanged by raloxifene and not significantly different from placebo at any time. One hundred seventy-two women had at least one episode of endometrial thickness greater than 5 mm or vaginal bleeding distributed equally among all groups. A total of 102 (10.5%) women underwent endometrial sampling at least once: 15 (1.5%) for vaginal bleeding, 78 (8.0%) for endometrial thickness greater than 5 mm, and nine (0.9%) for other reasons. There were no significant treatment differences in the proportion of women sampled, in the clinical findings, or in the histologic diagnoses. CONCLUSION: Raloxifene given to healthy postmenopausal women at doses from 30 to 150 mg per day does not stimulate uterine growth and does not cause vaginal bleeding, spotting, or discharge through 3 years of therapy. Thus, any bleeding during therapy should be deemed unexpected and prompt a clinical evaluation.     

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.     

A comparative study of the effect of raloxifene and gosereline on uterine leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically in premenopausal women

OBJECTIVE: To compare the mechanism of action of raloxifene and gosereline induced shrinkage of leiomyomas via estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically. STUDY DESIGN: Thirty-two premenopausal women affected by uterine leiomyomas were randomized into two equal groups. Group A was treated with gosereline (3.6 mg subcutaneous injection monthly) and group B was treated with raloxifene (60 mg daily per os) for 3 months before undergoing surgery. At entry and at the end of the treatment the leiomyoma volume was measured ultrasonografically and the volume change was calculated. Immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), bcl-2 and p53 were performed on leiomyoma tissue samples from group A, group B and the matched-control group. H-scores for ER, PR, bcl-2 and p53 were calculated. The mean volume changes of leiomyomas and immunohistochemical H-score differences of ER, PR, bcl-2 and p53 were compared between groups. RESULTS: The leiomyoma volume decreased significantly after treatment in gosereline group from baseline of 65 cm(3) to 35 cm(3), and in raloxifene group from 68 cm(3) to 50 cm(3), p<0.05. The difference between the before and after treatment leiomyoma volumes between the two treatments was not statistically significant. H-score of ER expression was significantly lower in gosereline group compared to control group (54.4 versus 113.2, p = 0.001), whereas H-score of PR expression was significantly lower with both gosereline and raloxifene groups compared to control group (64.8 for gosereline versus 94.6 for control, 73.6 for raloxifene versus 94.6 for control, p = 0.001). The bcl-2 expression was higher in both gosereline and raloxifene groups compared to control group (173.7 for gosereline versus 94.7 for control, 179.7 for raloxifene versus 94.7 for control, p = 0.001). The p53 expression was only lower with gosereline than the control group (169.4 versus 205.6, p = 0.001), whereas there was no significant change between the raloxifene group and the control group (201.9 versus 205.6) (p>0.05). CONCLUSION: Raloxifene was as effective as gosereline in reducing leiomyoma volumes. Decreased PR expression may be a mechanism for tumor growth reduction in raloxifene treatment. In both treatment modalities, the mechanism of shrinkage of leiomyomas could not be increased apoptosis mediated by bcl-2 and p53 expression and should be investigated by further studies.     

Raloxifene therapy in postmenopausal women is associated with a significant reduction in the concentration of serum vascular endothelial growth factor

OBJECTIVE: To determine whether raloxifene has an effect on serum vascular endothelial growth factor (VEGF) concentration in postmenopausal women. DESIGN: A randomized, placebo-controlled trial. SETTING: University-based obstetrics and gynecology unit. PATIENT(S): Fifty postmenopausal women who did not receive any hormone therapy in the 6 months preceding the study. INTERVENTION(S): The participants were randomly assigned on a one-to-one basis to receive either raloxifene (60 mg daily) or placebo for 36 weeks. MAIN OUTCOME MEASURE(S): Serum VEGF concentrations at baseline and at 12 weeks and 36 weeks after the commencement of intervention. RESULT(S): The serum VEGF concentrations in the raloxifene group were significantly reduced from 247 +/- 16 pg/mL at baseline to 195 +/- 11 pg/mL at 36 weeks after starting raloxifene. The placebo group showed no significant change in the serum VEGF concentrations throughout the intervention period. CONCLUSION(S): Raloxifene therapy in postmenopausal women is associated with a significant reduction in serum VEGF concentration.     

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.     

Long-term administration of tibolone plus gonadotropin-releasing hormone agonist for the treatment of uterine leiomyomas: effectiveness and effects on vasomotor symptoms, bone mass, and lipid profiles

OBJECTIVE: To evaluate the effects of long-term administration of GnRH agonist (GnRH-a) plus tibolone for uterine leiomyomatosis. DESIGN: Prospective open clinical trial. SETTING: Department of Gynecology, Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II", Naples, Italy. PATIENT(S): Twenty-five subjects with symptomatic uterine leiomyomas. INTERVENTION(S): Treatment for 2 years with leuprolide acetate (3.75 mg IM every 28 days) and tibolone (2.5 mg/d per os). MAIN OUTCOME MEASURE(S): Uterine and uterine leiomyoma sizes, endometrial thickness, lumbar spine bone mineral density (BMD), bone metabolism, lipid profile, myoma-related symptoms at baseline and every 6 months. Hot flashes and vaginal bleeding episodes recorded in a daily symptom diary. RESULT(S): After 6 months of treatment, a significant reduction was observed in uterine and leiomyoma volumes and myoma-related symptoms compared with baseline values. No significant change was observed in bone turnover, lumbar BMD, or serum total cholesterol, low-density lipoprotein cholesterol, or triglyceride levels. High-density lipoprotein cholesterol values were significantly lower than baseline values after 6 months of treatment but not after 18 months of therapy. A low mean number of hot flashes per day was observed. CONCLUSION(S): Long-term administration of GnRH-a plus tibolone reduces hot flashes and prevents bone loss without changing the lipid profile.     

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 raloxifene on urinary incontinence: a randomized controlled trial

OBJECTIVE: To estimate the effect of 3 years of treatment with raloxifene on urinary incontinence in postmenopausal women. METHODS: We used measures of urinary incontinence severity, frequency, and type in the Multiple Outcomes of Raloxifene trial, a multicenter randomized, controlled trial of women who were at least 2 years postmenopausal with osteoporosis. At 10 U.S. sites of this trial, 963 women randomly assigned to raloxifene or placebo completed questionnaires about incontinence at baseline and 3 years later. We analyzed the odds of worsening severity and frequency of incontinence and type of incontinence after 3 years of treatment with raloxifene. RESULTS: The mean age of our subjects was 68.3 +/- 7 years. After 3 years of treatment, there was no significant difference between raloxifene and placebo groups in urinary incontinence severity (multivariable odds ratio [OR] 1.02; 95% [CI] 0.78, 1.34). The majority of the women (60%) had no change in urinary incontinence episodes from baseline to year 3. The odds of worsening urinary incontinence severity after 3 years of raloxifene treatment were 1.05 (95% CI 0.75, 1.48). Similarly, the odds of developing new onset incontinence were 0.95 (95% CI 0.59, 1.52). Finally, raloxifene did not effect the odds of having stress (OR 1.01; 95% CI 0.71, 1.43) or urge (OR 1.20; 95% CI 0.86, 1.68) incontinence after 3 years of use. CONCLUSION: In postmenopausal women with osteoporosis, 3 years of treatment with raloxifene had no effect on urinary incontinence. LEVEL OF EVIDENCE: I     

Preclinical evidence for therapeutic efficacy of selective estrogen receptor modulators for uterine leiomyoma

OBJECTIVE: Uterine leiomyoma are the most common gynecologic neoplasm and a primary cause of hysterectomy in premenopausal women. Preclinical studies were conducted in the Eker rat model to investigate the potential efficacy of selective estrogen receptor modulators (SERMs) as therapeutic agents for this tumor. METHODS: Twelve-month-old Eker rats were randomized into five treatment arms including tamoxifen, placebo, LY 326315, vehicle, and no treatment. Additional animals received ovariectomy or sham surgery at 4 months of age to determine the effect of ovarian ablation on tumor development. The study was terminated after 2 to 4 months of treatment, and tumor incidence, size, proliferative and apoptotic indices were determined. Size and incidence data were subjected to chi-square analysis. One-way analysis of variance and Fisher's least significant difference tests were used to compare proliferative and apoptotic indices. RESULTS: Ovariectomy virtually ablated leiomyoma development, indicating that these tumors were dependent on ovarian hormones for growth and development. Treatment with tamoxifen or raloxifene analog LY 326315 reduced leiomyoma incidence by 40-60% and reduced the size of remaining tumors. The effect of SERMs on leiomyomas was mediated by a decrease in cell proliferation without a decrease in apoptotic index. CONCLUSION: SERMs have been shown to be therapeutically efficacious against breast cancer and to reduce tumor incidence in women at increased risk for this disease. The present data indicate that therapeutic efficacy may also be extended to uterine leiomyoma and demonstrate the utility of this animal model for preclinical studies to identify new therapeutic modalities.     

原发性卵巢平滑肌瘤4例临床病理分析

目的探讨原发性卵巢平滑肌瘤的临床病理特点。方法将北京协和医院妇产科自1984—2006年收治的4例原发性卵巢平滑肌瘤患者的临床病理资料进行回顾性分析。结果4例患者平均44.8岁(28～75岁),主要就诊原因分别为急性腹痛(1例),绝经后出血(1例),查体发现盆腔包块(2例)。囊肿均为单侧性,直径平均6.4cm(4.1～9.2cm)。1例患者血清CA125升高(129.1kU/L)。2例未生育患者进行了腹腔镜下肿瘤剔除术,2例已完成生育的患者进行了全子宫和附件切除术,无一例合并子宫平滑肌瘤,1例绝经后出血患者合并子宫内膜息肉。病理结合免疫组织化学染色最终明确诊断。平均随诊时间44.5个月(13～117个月),全部治愈,1例患者已完成足月妊娠分娩。结论原发性卵巢平滑肌瘤临床罕见,组织学上容易和其它梭形细胞肿瘤混淆,免疫组织化学染色可以协助诊断。手术完整切除肿瘤疗效满意,对于没有完成生育的年轻患者,可以尝试保守性手术。     

Proliferative activity of human uterine leiomyoma cells as measured by automatic image analysis.

Proliferative activity of uterine leiomyomas from premenopausal (n = 44) and postmenopausal (n = 12) women was investigated by automatic image analysis on frozen tissue sections using immunohistochemistry with anti-proliferating cell nuclear antigen antibody. The quantitative proliferation index (QPI) in premenopausal leiomyoma cells was significantly (p < 0.025) higher than that in leiomyomas in postmenopausal women. Leiomyomas proliferated most actively during the secretory phase. After the climacterium, leiomyomas showed no proliferative activity in the absence of hormone supply, while combined substitution with estrogen and progestagen considerably increased QPI.     

Potential role of preoperative serum CA125 for the differential diagnosis between uterine leiomyoma and uterine leiomyosarcoma

PURPOSE: Most comparisons between uterine leiomyoma and uterine leiomyosarcoma have been based on postoperative pathological or molecular analyses. Very few reports have investigated preoperative differentiation between uterine leiomyoma and uterine leiomyosarcoma. METHODS: Between January 1990 and December 2003, 42 consecutive patients with uterine leiomyosarcoma treated at index hospitals were analyzed. Meanwhile, 84 patients with uterine leiomyomas were used as controls. The diagnostic performance of preoperative serum CA125 for the differential diagnosis between uterine leiomyoma and uterine leiomyosarcoma using receiver operating characteristic (ROC) curves was evaluated. Data presentations were categorized into premenopausal and postmenopausal groups. Diagnostic efficiency was calculated as the sensitivity multiplied by the specificity. RESULTS: Values of preoperative serum CA125 were significantly higher in the uterine leiomyosarcoma group than those in the uterine leiomyoma group. There was significant overlapping of preoperative serum CA125 between the uterine leiomyoma group and early-stage uterine leiomyosarcoma. For both the premenopausal and postmenopausal group, there was a significant difference in the distribution of preoperative serum CA125 in early-stage and advanced-stage uterine leiomyosarcoma. The optimal cutoff values of serum CA125 for the premenopausal group and postmenopausal group was 162 U/mL and 75 U/mL, respectively. CONCLUSION: These findings demonstrated that preoperative serum CA125 had a potential role in the differential diagnosis between early-stage and advanced-stage uterine leiomyosarcoma. Further investigation with a larger sample size at adequate power is necessary to verify the current study.     

Successful treatment of a symptomatic uterine leiomyoma in a perimenopausal woman with a nonsteroidal aromatase inhibitor

OBJECTIVE: To assess the management of symptomatic leiomyomas using a nonsteroidal aromatase inhibitor in perimenopausal women. DESIGN: Case report. SETTING: Academic clinical practice. PATIENT(S): A 53-year-old woman suffering from recurrent urinary retention secondary to a uterine leiomyoma. INTERVENTION(S): Fadrozole, orally, 2 mg daily for 8 weeks and then 1 mg daily for 4 weeks. MAIN OUTCOME MEASURE(S): Measurements of leiomyoma volume, and levels of serum E(2), LH, and FSH. RESULT(S): Urinary retention resolved after 2 weeks of treatment and did not recur. Leiomyoma volume estimated by ultrasonography revealed a 71% reduction after 8 weeks of treatment. CONCLUSION(S): Fadrozole was useful for the management of a symptomatic leiomyoma without transient deterioration of symptoms. Clinical trials are warranted.     

Clinical efficacy of raloxifene in postmenopausal women.

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps) decreased significantly to the premenopausal range within 3-6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.