Immunohistochemical detection of insulin-like growth factor type I receptor and uterine volume changes in gonadotropin-releasing hormone analog-treated uterine leiomyomas

OBJECTIVE: This study was undertaken to assess the relationship between insulin-like growth factor (IGF) type I receptor (IGF-I-R) expression in uterine leiomyomas after gonadotropin-releasing hormone (GnRH) analog administration and modifications in uterine size. STUDY DESIGN: Forty-six women with menorrhagia for uterine leiomyomatosis were treated monthly with leuprolide acetate depot 3.75 mg before undergoing surgery. The uterine volume before and after therapy was assessed by transabdominal ultrasonography. Immunohistochemical detection of IGF-I-R was performed on leiomyoma tissue samples. The relationship between IGF-I-R levels and uterine volume changes was analyzed. RESULTS: Uterine volume decreased after therapy. Patients with a lower immunohistochemical expression of IGF-I-R showed a larger decrease in uterine size. CONCLUSION: The shrinkage in uterine volume induced by GnRH analogs seems to be related to the observed reduction in IGF-I-R levels. So, the IGF-I/IGF-I-R system might be involved in leiomyoma growth, and the pharmacologic action of GnRH analogs on uterine leiomyomas might also be related to the effects on IGF-I-R expression.     

Transvaginal ultrasonographic findings in the uterus and the endometrium: low prevalence of leiomyoma in a random sample of women age 25-40 years

BACKGROUND: In articles and textbooks the prevalence of uterine leiomyomas is said to be 20-25% in women over the age of 30. The aim of this study was to investigate the rate of uterine leiomyoma, the thickness and the texture of the endometrium, and the size of the uterus in a random sample of asymptomatic women 25-40 years old. METHODS: A random sample of women 25-40 years old was offered a transvaginal ultrasonographic examination and 335 (72%) accepted the invitation. RESULTS: In 18 women uterine leiomyomas were detected, i.e. 5.4% (95% CI 3.0-7.8%). The prevalence of leiomyomas increased with age, being 3.3% (95% CI 0.7-6.0%) in the 25-32 years age group and 7.8% (95% CI 3.6-12.0%) in the 33-40 age group. The size of the uterus correlated to parity, age and height. In women on combined oral contraceptives the size of the uterus was smaller than in women with natural cycles. The size of the uterus did not correlate to body mass index, cycle day or smoking habits. The endometrium increased in thickness and had in most cases a triple line appearance during the proliferative phase until day 15, whereafter it was unchanged in thickness throughout the secretory phase and hyperechogenic in appearance. CONCLUSIONS: This study confirms earlier studies on the endometrium based on selected populations. The size of the uterus increased with parity, age and height, and was smaller in combined oral contraceptive users. The prevalence figures for uterine leiomyomas in textbooks are not confirmed.     

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.     

Ultrastructural comparison of uterine leiomyoma cells from the same myoma nodule before and after gonadotropin-releasing hormone agonist treatment

OBJECTIVE: To compare ultrastructural features of leiomyoma cells from the same uterine myoma nodule before and after GnRH agonist (GnRH-a) treatment and to examine the relation between these ultrastructural changes and the extent of myoma volume reduction with GnRH-a treatment. DESIGN: Prospective clinical study. SETTING: University teaching hospital. PATIENT(S): Twenty women with uterine leiomyomas who were scheduled for surgery. INTERVENTION(S): Transcervical needle biopsy of uterine myoma, s.c. leuprolide acetate injection (3.75 mg) at least three times every 4 weeks before surgery, and hysterectomy or myomectomy. MAIN OUTCOME MEASURE(S): The changes in ultrastructural features of uterine leiomyoma cells and the percentage decrease in the volume of the largest myoma at 12 weeks of GnRH-a treatment measured by magnetic resonance imaging. RESULT(S): A decrease in myofilaments, mitochondrial swelling, and emergence of the lysosomal body were observed in relation to GnRH-a treatment. Furthermore, a positive correlation was observed between the decrease in myofilaments and myoma shrinkage. CONCLUSION(S): Cellular atrophy due to a decrease in myofilaments plays a major role in the reversible myoma shrinkage resulting from GnRH-a treatment.     

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.     

Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata

OBJECTIVE: Magnetic-resonance-guided focused ultrasound is a novel, noninvasive technique of thermoablation for uterine leiomyomata. The hypothesis of this study was that pretreatment of leiomyomata with gonadotrophin-releasing hormone (GnRH) agonists would allow effective treatment of larger uterine leiomyomata, increasing the number of women who could benefit from this technique. METHODS: We report a prospective study of women with leiomyomata in excess of 10 cm in diameter who received GnRH agonist before magnetic-resonance-guided focused ultrasound treatment. Eligible participants were recruited from the gynecology outpatient clinics. Entry criteria were a minimal leiomyoma symptom severity score and confirmation of uterine dimensions based on screening magnetic resonance imaging. These women received a 3-month course of GnRH agonists followed by magnetic-resonance-guided focused ultrasound treatment. The primary outcome measurement was reported change in symptom severity score as judged by the Uterine Fibroid Symptom and Quality of Life questionnaire. Comparison was made at enrollment, treatment, and at 3, 6, and 12 months posttreatment. A secondary outcome was the measured change in target leiomyoma volume. RESULTS: Forty-nine women were enrolled in the study. There was a 45% reduction in median symptom severity score at 6 months and 48% at 12 months posttreatment, with 83% of women achieving at least a 10-point reduction in symptom scoring at 6 months and 89% at 12 months (P < .001). There was an average reduction in target leiomyoma volume of 21% overall at 6 months (P < .001) and 37% at 12 months (P < .001). No serious infective complications or emergency operative interventions were recorded. CONCLUSION: The use of GnRH agonist therapy before magnetic-resonance-guided focused ultrasound improves the thermoablative treatment effect. LEVEL OF EVIDENCE: II-3.     

Effects of treatment with gonadotropin releasing hormone agonist on the uterine leiomyomata structure

OBJECTIVE: Our aim was to study the effects of the gonadotropin releasing hormone agonist on the uterine leiomyoma of infertile women. MATERIAL AND METHODS: Sixty-seven nulliparous women (aged 24-39 years) with uterine leiomyomas, underwent ultrasonographic study of leiomyoma volume, and were divided in two groups. Thirty-one had nodes greater than 300 cm3 and were treated with goserelin 3.6 mg every 28 days for 6 months (group I); the other 36 patients did not receive medication (group II or control group). Sixteen patients from group I had < or = 36% (median) reduction of the leiomyoma volume (subgroup Ia) and the other 15 women had reduction > 36% (subgroup Ib). All women underwent myomectomy. RESULTS: The group with the greater leiomyoma reduction after treatment with goserelin (group Ib) showed a significantly lower percentage of ER+ when compared with group Ia and the control group. Group Ib had a significantly higher percentage of PR+ in relation to the control group, but not to group Ia. The number of blood vessels, AgNOR dots, and cells, and the amount of collagen were not different between the three groups studied. Leiomyomata reduction correlated negatively with the percentage ER+ cells, but positively with the PR+ cells, amount of collagen and number of blood vessels. No correlation was found between the number of AgNOR dots and cellularity. CONCLUSION: Our data strengthen the hypothesis that the uterine leiomyoma response to steroid hormones results from the presence of specific hormone receptors, and progesterone receptors may also play a role in the development of leiomyoma.     

GnRH agonist treatment before total laparoscopic hysterectomy for large uteri

STUDY OBJECTIVE: To evaluate whether uterine shrinkage induced by gonadotropin-releasing hormone (GnRH) agonists in women with a large uterus (>14 wks) may facilitate total laparoscopic hysterectomy. DESIGN: Randomized, prospective study (Canadian Task Force classification I). SETTING: University-affiliated hospital. PATIENTS: Sixty-two women with symptomatic uterine myomas (size 16-20 wks). INTERVENTIONS: Total laparoscopic hysterectomy for benign pathology. MEASUREMENTS AND MAIN RESULTS: Before surgery, women were assigned, at a ratio of 1:1 by random selection, to receive injections of triptorelin depot 11.25 mg 3 months before surgery (group A) or no treatment (group B). Uterine volume, mean operating time, uterine weight, drop in hemoglobin, intraoperative complications, conversions to laparotomy, and hospital stay were recorded. Triptorelin decreased uterine volume, calculated by ultrasonography, by 26.5% in group A, whereas the volume remained unchanged in group B. Statistical differences were found between groups concerning uterine weight, operating time, and drop in hemoglobin level. Three patients in group B were converted to laparotomy because of uterine size. CONCLUSION: In women with a large uterus, a 3-month preoperative course of GnRH may facilitate laparoscopic hysterectomy, decreasing uterine size, operating time, and blood loss.     

GnRH analogs for the treatment of symptomatic uterine leiomyomas

Uterine leiomyomas are the most frequent benign disease of the female reproductive tract. To date, the standard treatment of uterine leiomyomas is laparotomic/laparoscopic excision in women who want to preserve their fertility, whereas the use of a more extensive surgery, such as hysterectomy, is reserved for disseminated uterine leiomyomatosis, usually in the perimenopausal period. Given the pathogenesis of uterine leiomyomas, it is clear that future treatments for leiomyomas may be medical. At present the only clinically relevant medical treatment of uterine leiomyoma is GnRH agonist administration in depot formulations. In this review, the use of GnRH agonists, with or without add-back therapy, and antagonists will be assessed.     

Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women.

OBJECTIVE: To evaluate the effects of raloxifene administration on uterine and uterine leiomyoma sizes in postmenopausal women. DESIGN: Prospective randomized, double-blind, placebo-controlled clinical trial. SETTING: Department of Gynecology, Obstetrics, and Pathophysiology of Human Reproduction, University of Naples "Federico II", Italy. PATIENT(S): Seventy spontaneous postmenopausal women affected by uterine leiomyomas. INTERVENTION(S): Twelve cycles (of 28 days each) of treatment with raloxifene (60 mg daily per os) or placebo. MAIN OUTCOME MEASURE(S): At entry and at every 3 cycles, uterine and uterine leiomyoma dimensions were measured by means of transvaginal ultrasound. The difference between uterine and leiomyoma volumes (Delta size) was calculated in all subjects. The characteristics of uterine bleeding and the side effects of the treatments were assessed using a daily diary. RESULT(S): After 6, 9, and 12 cycles of therapy, in subjects treated with raloxifene, the mean uterine and uterine leiomyoma size were significantly decreased, and the mean Delta size significantly increased in comparison with basal values and the placebo group. No significant differences in uterine bleeding were detected between the two groups. CONCLUSION(S): In postmenopausal women raloxifene appears to act selectively on uterine leiomyomas, reducing their size.     

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.     

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.     

Erythrocytosis due to an erythropoietin-producing large uterine leiomyoma

BACKGROUND: Various etiologies of myomatous erythrocytosis syndrome (erythrocytosis associated with a uterine leiomyoma), one of which is altered production of erythropoietin, have been proposed. We report a case of erythrocytosis associated with a large uterine leiomyoma in which erythropoietin activity and immunostaining for erythropoietin in the leiomyoma were found. CASE: A 64-year-old woman, gravida 2, para 1, was referred to our department for treatment of a large uterine myoma and erythrocytosis with elevated levels of erythropoietin. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed, and the results of the pathological examination confirmed the diagnosis of leiomyoma of the uterus, which weighed 920 g. The patient's postoperative course was satisfactory, and the levels of hemoglobin and erythropoietin were normalized and remained within normal ranges. The level of erythropoietin in the uterine leiomyoma measured by radioimmunoassay was elevated (372 mU/wet gram), and specific immunostaining for erythropoietin was found in the cytoplasm of leiomyoma cells. The levels of erythropoietin extracted from uterine leiomyomas of other patients who did not have erythrocytosis (control patients, n = 5) were lower (65 +/- 15.3 mU/wet gram), but specific immunostaining for erythropoietin was also found in the cytoplasm of leiomyoma cells from those patients. CONCLUSIONS: Our case was typical of myomatous erythrocytosis syndrome in which uterine leiomyoma was proved to produce erythropoietin. Our results also suggest that erythropoietin is produced in uterine leiomyomas of patients with and without erythrocytosis. Leiomyoma of the uterus may affect the production of erythropoietin and may develop into myomatous erythrocytosis syndrome when the level of erythropoietin exceeds the normal range.     

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.     

Treatment of uterine fibroids with implants of gonadotropin-releasing hormone agonist: assessment by hysterography

The effect of a potent, subcutaneously injected gonadotropin-releasing hormone (GnRH analog) (Buserelin, Hoechst, Frankfurt/Main West Germany) on the size of uterine leiomyomas and the uterine cavity area was studied in a group of 20 women. In all patients except 1, the uterine cavity area calculated by hysterosalpingography was decreased, with an average decrease of 35% (from 12.0 +/- 5.4 cm2 to 7.8 +/- 3.3 cm2) by 8 weeks of therapy. Significant decrease was observed in the group of women with initial uterine cavity area greater than 10 cm2. In patients with very large submucous fibroids, myomectomy by hysteroscopy and neodymium:YAG laser was easily performed. Rapid relief of symptoms such as menometrorrhagia permits the restoration of a normal hemoglobin concentration. In conclusion, use of GnRH analog represents an adjunct for preoperative reduction of tumor size and may permit surgical treatment by hysteroscopy.     

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

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

射频热凝固微创技术治疗子宫良性病变的初步研究

目的 :探讨射频热凝固微创治疗子宫肌瘤、腺肌瘤和功能失调性子宫出血(功血 )等子宫良性病变的临床特点和疗效。方法 :在B超监测下 ,应用凝固器 ,将射频定点介入到子宫病灶内使局部温度达 5 5℃～ 85℃ ,使病变组织热凝固坏死吸收 ,治疗各类直径小于 5 .0cm的子宫肌瘤 2 2 2例、腺肌瘤 10 4例、功血 5 1例、II度和III度子宫颈糜烂 60例和 5 3例。结果 :经 35～ 4 5W射频治疗 2～ 11min ,2～ 3月后病灶直径均不同程度的缩小 ,用本法治疗子宫肌瘤有效率为 94 .6% ,腺肌瘤为 87.5 % ,功血为 94 .1% ,宫颈糜烂为 10 0 .0 %。结论 :射频热凝固治疗子宫肌瘤 (<5 .0cm)、腺肌瘤、功血和宫颈糜烂时间短 ,见效快 ,疗效高 ,患者住院时间短 ,治疗费用低     

Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas

The incidence of leiomyosarcoma in uterine leiomyomas is estimated to be between 0.13 to 0.29%. However, the exact incidence of leiomyosarcoma in uteri removed with a preoperative diagnosis of benign uterine leiomyomas has not been previously reported. Between 1983 and 1988, a total of 1432 patients in Women's Hospital, a self-referred indigent population, had a hysterectomy planned because of abnormal uterine bleeding or abdominal pain associated with the presence of uterine leiomyomas, or because of a pelvic mass thought to be uterine leiomyoma of sufficient size or character to warrant surgical exploration. The ages of these women ranged from 36 to 62 years and the presence of leiomyosarcoma in the hysterectomy specimens increased steadily from the fourth to seventh decades of age (0.2%, 0.9%, 1.4%, and 1.7%, respectively). Preoperative histologic examination of the endometrium was performed in eight patients. Three of the eight patients had a preoperative tissue diagnosis of leiomyosarcoma that was clinically confined to the uterus. After the hysterectomy in the 1429 patients with presumed benign disease, histologic diagnosis of leiomyosarcoma was made in seven (0.49%). There was no evidence of malignancy in the endometrial sampling of any of these seven patients and the diagnosis was suspected intraoperatively in only three. Preoperative uterine size ranged from 8 to 20 weeks' gestational size and postoperative uterine weight ranged from 120 to 1100 gm. Seven of the 10 patients had symptoms of abnormal uterine bleeding. Between the ages of 40 and 60 years, 1% (8 of 817) of women with presumed uterine leiomyomas producing symptoms that necessitated hysterectomy in this series had leiomyosarcoma diagnosis postoperatively. Such treatments as gonadotropin-releasing hormone agonists, endometrial ablation, myomectomy by hysteroscopy or laparotomy instead of hysterectomy in such women could delay the diagnosis and definitive treatment of leiomyosarcoma.     

The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity

The objective of this study was to correlate, during 12 weeks of therapy with gonadotropin releasing hormone agonist (GnRH-a), the chronological effect and the hemodynamic changes on the uterine artery and the leiomyometrial supplying vessels. Twenty-three premenopausal women with clinically diagnosed uterine leiomyomas received 3.75 mg of leuprolide acetate intramuscularly every 4 weeks for 12 weeks. Pretreatment values of serum estradiol, uterine and leiomyoma volumes and blood flow characteristics of the main uterine artery and leiomyoma supplying vessels – resistance index (RI), pulsatility index (PI) and peak-systolic velocity, obtained by transvaginal color Doppler sonography – were compared with treatment values at 4, 8 and 12 weeks of leuprolide acetate therapy.

The first event in the chronological response to the GnRH-a therapy was a statistically significant increase in RI and PI values for major leiomyoma vessels, observed at the end of the 4th week (p < 0.05), which increased significantly after 8 and 12 weeks (p < 0.01 and p < 0.001, respectively). These findings were in direct correlation with a significant decrease of estradiol levels after 4, 8 and 12 weeks (p < 0.05, p < 0.001 and p < 0.001, respectively). The significant decrease of blood flow in the leiomyometrial vessels was followed by a significant decrease of the main uterine artery blood flow after 8 weeks and uterine and leiomyoma volumes by 42% and 55%, respectively, after 12 weeks of GnRH-a therapy.

We concluded that a significant increase in leiomyometrial vessels RI and PI values, which was found 4 weeks after the first dose of GnRH-a, but without major leiomyoma volume decrease, emphasizes that the first significant effect of GnRH therapy in the process of uterine and leiomyoma volume shrinkage is the reduction of leiomyometrial rather than uterine blood flow. This effect is followed by a considerable reduction of utenrine vasculariry and a significant decrease of uterine and leiomyoma volumes. If a decrease of blood loss during myomectomy is the main aim of GnRH-a therapy, we believe that 8 weeks would be an appropriate therapy duration.     

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

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