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.     

The effect of anastrazole on symptomatic uterine leiomyomata

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

Self-reported heavy bleeding associated with uterine leiomyomata

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

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

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

The use of GnRH agonists in severe uterine hemorrhages in adolescence caused by congenital aplastic and hypoplastic anemias

GnRH agonists, applied for a long period of time or as depot forms, lead to blocking of gonadotropin and ovarian steroid synthesis. We used their property to induce amenorrhea for treating menorrhagic and menometrorrhagic bleeding in adolescence caused by inborn aplastic and hypoplastic anaemia. In patients with uterine bleeding during the first regular menstrual period or recurring during menstrual periods Zoladex (depot GnRH agonist) has been applied, resulting in stop of bleeding in 2 to 4 days. The drug-induced amenorrhea provides the possibility for physiologic restoring of hemoglobin levels, improvement of therapeutic results from adjuvant antianaemic therapy. Thus a more favourable basis for treating of the main disorder is being created. When surgery is indicated, GnRH agonists provide the opportunity for planning of operating management or for laser ablation of endometrium.     

Therapeutic potential for the selective progesterone receptor modulator asoprisnil in the treatment of leiomyomata

Asoprisnil is a novel selective progesterone receptor modulator that exhibits partial agonist and antagonist activities in animals and humans. It demonstrates a high degree of progesterone receptor specificity and tissue selectivity. Although asoprisnil at high doses exhibited some antiglucocorticoid activity in animal models, no antiglucocorticoid effects were observed at therapeutic doses in humans. In male rats, asoprisnil showed mixed androgenic and antiandrogenic properties. Unlike antiprogestins, asoprisnil at high doses exhibited only marginal labor-inducing activity in guinea pigs during midpregnancy and was completely ineffective in inducing preterm parturition. In nonhuman primates, asoprisnil completely eliminated menstrual cyclicity and induced endometrial atrophy. Early clinical studies of asoprisnil in healthy volunteers demonstrated a dose-dependent suppression of menstruation, irrespective of the effects on ovulation, with no change in basal estrogen concentrations and no breakthrough bleeding. Phase 2 studies in subjects with uterine fibroids demonstrated that asoprisnil induced amenorrhea and reduced the volume of the dominant leiomyoma in a dose-dependent manner without altered basal estrogen and with virtually no clinical symptoms of estrogen deprivation. Asoprisnil seems to exhibit a direct inhibitory effect on both the endometrium and leiomyoma. In all studies to date, asoprisnil has maintained a favorable safety and tolerability profile. Thus, asoprisnil has the potential to target the major clinical symptoms of leiomyomata related to both menorrhagia and the size of the tumors and may, therefore, reduce or eliminate the need for surgery.     

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

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

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

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

Efficacy and Safety of Oral GnRh Antagonists in Patients With Uterine Fibroids: A Systematic Review

ObjectiveThis review aimed to assess the efficacy and safety of GnRH antagonists in patients with symptomatic uterine fibroids.Data SourcesA literature search was performed on PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov using the MeSH and Emtree terms “leiomyoma” and “gonadotropin-releasing hormone.”Study SelectionAll clinical trials that provided efficacy and safety data in clinical terms (i.e., reduction in menstrual bleeding and discomfort, changes in the size of leiomyoma and uterine volume, etc.) were included. We excluded all preclinical studies, case reports, meta-analyses, review articles, and clinical studies irrelevant to the study question.Data Extraction and SynthesisTwo authors extracted data from 9 clinical studies. The extracted data included the study's characteristics, participants' baseline characteristics, treatment drugs, efficacy measures, and toxicity.ConclusionAmong oral GnRH antagonists, relugolix, elagolix, and linzagolix were safe in patients with uterine fibroids. These drugs, alone and in combination with E2/NETA (estradiol/norethindrone acetate), showed significantly better efficacy than placebo in improving bleeding, discomfort, uterine/leiomyoma sizes, and quality of life in premenopausal patients with symptomatic uterine fibroids. However, more randomized, double-blind, multicentre clinical trials are needed to confirm these results and to see long-term benefits.     

Aromatase and leiomyoma of the uterus

In leiomyoma of the uterus, both aromatase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type I are overexpressed compared with myometrium. This suggests that leiomyoma cells convert circulating androstenedione into estrone (via aromatase), then into the active form of estrogen, estradiol (via 17beta-HSD type I). In vitro experiments and several clinical findings support the notion that in situ estrogen plays a role in leiomyoma growth under hypoestrogenemic conditions, such as natural menopause and therapy with gonadotropin-releasing hormone (GnRH) agonists. GnRH agonists abolish estrogen production both in situ in leiomyoma and in the ovary, leading to quick and profound regression of the leiomyoma. Aromatase inhibitors also inhibit estrogen synthesis in both leiomyoma and the ovary and may be used therapeutically. Certain doses of competitive aromatase inhibitors would completely inhibit estrogen production in leiomyoma, whereas ovarian production of estrogen would continue at reduced levels. This may lead to advantageous therapeutic conditions in which leiomyoma regresses without adverse symptoms related to estrogen depletion because levels of ovarian estrogen would be insufficient to support leiomyoma growth but sufficient to prevent symptoms associated with deficiency. This article discusses the potential uses of aromatase inhibitors.     

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.     

Predictors of leiomyoma recurrence after myomectomy

OBJECTIVE: The purpose of this study was to evaluate the factors associated with the recurrence of leiomyomata after myomectomy. METHODS: One hundred forty-five consecutive cases of myomectomy by laparotomy were studied retrospectively. Leiomyoma recurrence, diagnosed by transvaginal ultrasonography, was evaluated by life-table analysis and log-rank tests according to clinical characteristics of patients. RESULTS: The 5-year cumulative rates for leiomyoma recurrence and subsequent major surgery were 62% and 9%, respectively. At 5 years, the cumulative probability of recurrence was significantly lower in patients with a single leiomyoma removed (11%), compared with patients with multiple leiomyomata (74%) (P = .011); it was also lower in patients with intraoperative uterine size 10 menstrual weeks or less (46%), compared with more than 10 menstrual weeks (82%) (P = .032). However, there was a strong association of uterine size with the number of leiomyomata removed (P = .009). Childbirth after myomectomy was associated with a lower recurrence rate; the 5-year cumulative probability of recurrence was 26% in patients with subsequent parity, compared with 76% in those without subsequent parity (P = .010). CONCLUSION: Solitary myomectomy and smaller intraoperative uterine size are associated with lower rates of leiomyoma recurrence after myomectomy; the significance of uterine size may be affected by its correlation with the number of leiomyomata removed. Subsequent parity is associated with a lower probability of recurrence, but the cause and effect relationship between these two variables is unclear. LEVEL OF EVIDENCE: II-3.     

子宫平滑肌瘤长入右心腔一例报道

子宫平滑肌瘤是女性生殖器官中最常见的良性肿瘤,进入静脉或淋巴管内称为脉管内平滑肌瘤病,局限于子宫可出现月经量增多、经期延长,肿瘤过大压迫可导致下肢肿胀、下腹部不适,累及髂静脉可引起腹痛,肿瘤向上生长累及下腔静脉、右心房、右心室、肺动脉等可出现呼吸困难、心悸、胸痛、胸闷、晕厥等,甚至可出现突发性大出血及休克。报道1例49岁女性患者因子宫平滑肌瘤长入右心腔导致下肢水肿3年,胸闷、胸痛2个月的病例,入院完善检查后予经腹全子宫+双侧附件+盆腔包块切除术,开胸行下腔静脉、右心房、右心室、肺动脉肿物清除术及房间隔缺损修补术,结合术中及病理结果,确诊为子宫平滑肌瘤、血管内平滑肌瘤。好转出院,随访8个月,肿瘤未复发。子宫平滑肌瘤侵入血管长入右心室达肺动脉者极少,病情严重,早发现、早诊断、早治疗尤为重要。     

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.     

Adverse effects of phytoestrogens on reproductive health: a report of three cases

BACKGROUND: Phytoestrogens have been thought to have favorable effects on women's health and perhaps in offsetting cancers. The possible adverse effects of phytoestrogens have not been evaluated. CASES: Abnormal uterine bleeding with endometrial pathology in three women was found to be related to a high intake of soy products. The first woman had postmenopausal bleeding with uterine polyp, proliferative endometrium and a growing leiomyoma. The second woman presented with severe dysmenorrhea, abnormal uterine bleeding, endometriosis and uterine leiomyoma not responding to treatment. The third woman with severe dysmenorrhea, abnormal uterine bleeding, endometriosis and uterine leiomyomata presented with secondary infertility. All three women improved after withdrawal of soy from their diet. CONCLUSION: Additional information on phytoestrogens is necessary to ascertain their safety before they can be routinely used as supplements.     

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

Aims: To evaluate the effect of low-dose mifepristone on leiomyoma-related symptoms, uterine and leiomyoma in women with symptomatic leiomyomata.
Methods: 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.
Results: 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.
Conclusions: 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.     

Role of GnRH agonists prior to endoscopic surgical treatment of fibroids

Uterine fibroids are the most common benign tumors found in women of reproductive age and their treatment is mainly by surgery, especially if they are symptomatic. Since the boom in endoscopy, many reports conclude that treatment of fibroids can be performed safely by laparoscopy or hysteroscopy.The development of GnRH analogues is not only a breakthrough in the field of obstetrics and gynecology, but a major leap forward in the treatment of various hormone-dependent diseases in general medicine. Recently GnRH agonistic analogues have been applied to treat various gynecological conditions, such as uterine leiomyomas, endometriosis, dysfunctional uterine bleeding, hyperandrogenism (polycystic ovaries) and infertility, cancer and precocious puberty.GnRH agonist administration prior to the surgical approach to uterine fibroids has a positive role in the management of these tumors, because—despite the expense—they reduce fibroid and uterine volume and intraoperative blood loss and they increase hemoglobin levels prior to surgical intervention. GnRH agonists can be used preoperatively in the field of endoscopic surgery in selected cases, especially in hysteroscopic surgery. However, their exact role in the laparoscopic management of fibroids needs further evaluation.     

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.     

GnRH agonists

The development of GnRH agonists has had a major impact on the practice of gynecology and reproductive endocrinology. The clinical usefulness of GnRH agonists will increase as modes of administration are improved and indications become better defined. GnRH agonists and, potentially, antagonists will provide a prompt, effective, and reversible method of suppressing ovarian function. GnRH agonists may soon become a treatment of choice for many of the noncontraceptive uses of oral contraceptives. Current indications for GnRH agonist administration are best divided into two groups: short-term (less than 6 months) and long-term (greater than 6 months) suppression. Short-term administration of GnRH agonist include most of the current usage of GnRH agonists. Short-term administration avoids most of the side effects of GnRH agonist and offers the most potential for development of GnRH antagonists. Short-term therapy has been shown to be particularly effective in the preoperative treatment of fibroids, suppression of ovarian function before ovulation induction, for short-term suppression of endometriosis, and for diagnostic purposes to determine whether a medical illness is related to ovarian function. Chronic administration of GnRH agonist has produced varying degrees of success. The treatment of precocious puberty is probably the perfect indication for GnRH agonist suppression. The disease is completely reversed with a remarkable absence of side effects. Long-term administration for metastatic breast or prostatic cancer has been shown to be as efficacious as other forms of gonadal suppression and the potential benefits of suppression outweigh the potential side effects of long-term suppression. The risk-benefit ratio must be carefully analyzed for the other indications for long-term suppression. Long-term suppression could be used for medical illnesses exacerbated by the menstrual cycle, painful symptoms related to endometriosis, contraception, and suppression of hyperandrogynism. Although initial studies show the agonist to be quite effective in treating all of these disorders, long-term suppression also may result in potential serious side effects related to hypoestrogenism including hot flashes and osteoporosis. Long-term administration of GnRH agonist may become feasible by lowering the dose and degree of suppression or by combining GnRH agonist with estrogen or progestin replacement, or both.