GnRH analogues in the treatment of endometriosis

Modifications of the native gonadotropin-releasing hormone (GnRH) decapeptide have led to longer-acting compounds with increased binding ability. Pharmacologic doses of agonists result in suppression of ovarian estradiol production to levels similar to oophorectomized patients. The resultant hypoestrogenism is associated with regression in endometrial implant size. Both subjective and objective clinical improvement have been reported. Recent studies document that a reversible state of hypogonadism is effective treatment for endometriosis.     

Indications of GnRH analogues before and after surgery for endometriosis

Indications of GnRH analogues before and/or after surgery for endometriosis remain controversial. Although some studies have underlined a decrease in rAFS scores using GnRH analogues pre-operatively, data are insufficient to recommend their systematic use in routine. In the same way, despite an increase in symptom free period subsequent to the use of GnRH analogues post-operatively, no effect of this therapeutic on recurrence rate and fertility outcome has been proved. In addition to a meta-analysis on GnRH analogues in endometriotic women, further studies, especially in women with large endometriomas and with deep pelvic endometriosis, are required to clarify the indications of GnRH analogues associated with surgical management.     

Low-dose GnRH agonist therapy for the management of endometriosis.

OBJECTIVE: In order to examine whether treatment with a GnRH agonist alone can maintain estrogen levels within the "estrogen window" that inhibits endometriosis without influencing bone-mineral density, we studied the effects of GnRH agonist therapy and changes in bone-mineral density. METHODS: Buserelin acetate nasal spray was administered 3 times a day for 8 weeks (daily dose, 900 micrograms) to 21 women with endometriosis. The drug was then given twice a day for 16 weeks (daily dose, 600 micrograms). The total duration of treatment was 24 weeks. The bone-mineral density of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry before treatment (baseline), at the end of treatment, and 24 weeks after the end of treatment. RESULTS: The bone-mineral density of the lumbar vertebrae at the end of treatment was 2.44% +/- 0.46% (mean +/- standard error) lower than the baseline value. The value at 24 weeks after the end of treatment was 1.10% +/- 0.64% lower than the baseline value. More than 80% of the patients had serum-estradiol levels of 45 pg/ml or less. During treatment, more than 90% of the patients had serum-estradiol levels of 60 pg/ml or less. Genital bleeding was inhibited in 90% of the patients. After 8 weeks of treatment, the clinical symptoms improved in 75% of the patients; such improvement persisted for the duration of the treatment. CONCLUSION: Decreasing the dose of GnRH agonist during treatment can minimize the loss of bone-mineral density without lessening the beneficial effects on endometriosis. This technique might be useful in the management of endometriosis.     

CA-125 monitored therapy with GnRH analogue of pelvic endometriosis.

Thirteen patients affected by endometriosis have been treated with GnRH analogue Buserelin. CA-125 serum levels have been monitored before, during and after treatment. Analysis of data suggests the hypothesis of an individualized follow up by means of repeated assays of CA-125 and their reference to pre and post treatment graphs.     

GnRH analogues as an adjuvant therapy for ovarian cancer patients.

OBJECTIVES: Lowering gonadotropin levels with gonadotropin-releasing hormone (GnRH) analogues in patients with ovarian cancer remains open to debate. The aim of this study was to assess the results of treatment in stage III and stage IV ovarian cancer patients who had surgery supplemented with chemotherapy, radiotherapy, and GnRH analogues. Gonadotropin levels were monitored during treatment. METHODS: The study group comprised 69 patients aged 27-70 years, stratified according to the type of treatment. The overall disease-free, 5-year survival rates and the frequency of remissions were analyzed. Hormonal tests [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were performed in 58 patients. Associations were checked between gonadotropin levels, clinical findings, and survival. The results were statistically compared. RESULTS: Statistically significant differences were noted when chemotherapy was supplemented with GnRH analogues and/or radiotherapy. Administration of GnRH analogues resulted in significantly lower levels of LH than of FSH. Levels of FSH were significantly lower in patients surviving at least 5 years or in complete remission at the time of this study. CONCLUSIONS: Combined therapy can produce favorable results in late-stage ovarian cancer, and GnRH analogues have an important role in treatment strategy.     

GnRH agonists in the treatment of endometriosis

GnRH agonists, synthetic peptide analogs of GnRH, desensitize pituitary receptors for the native molecule, thus causing reversible hypogonadotropic hypogonadism. Numerous clinical studies have suggested that these compounds are efficacious in the treatment of endometriosis, but it is not clear whether they are superior to the other drugs used in treatment of this disease. The frequency of recurrence of pain symptoms at the end of treatment is high and the data on recovery of fertility are conflicting. Long-term administration of GnRH agonists is a safe and well tolerated treatment but its role in the management of endometriosis is still not well defined.     

Bone density in adolescents treated with a GnRH agonist and add-back therapy for endometriosis

STUDY OBJECTIVE: To evaluate the bone density of adolescents with endometriosis treated with a GnRH-agonist and "add-back" therapy with norethindrone acetate. DESIGN: Retrospective chart review. SETTING: Pediatric gynecology clinic at a tertiary care center. PARTICIPANTS: 36 adolescents, ages 13 to 21 years, with endometriosis. MAIN OUTCOME MEASURES: Bone mineral density (BMD, g/cm(2)) by dual energy x-ray absorptiometry (DXA); BMD Z-scores of hip and spine. RESULTS: The mean BMD Z-score at the total hip was -0.24 +/- 1.0, with a range of -2.4 to 1.7. At this site, 6 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 2 had a Z-score < or = -2.0 SD. The mean BMD Z-score at the lumbar spine was 0.55 +/- 1.1, with a range of -2.8 to 1.4. At the spine, 11 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 3 had a Z-score < or = -2.0 SD. There was no correlation noted between duration of therapy with the GnRH-agonist plus add-back and BMD at the hip or spine. CONCLUSION: BMD at the hip was normal in most adolescents with endometriosis who were receiving a GnRH-agonist plus add-back therapy with norethindrone acetate. Almost one third of subjects exhibited skeletal deficits at the spine. These data suggest that BMD should be carefully monitored in adolescents receiving treatment with GnRH agonists.     

Treatment of endometriosis with transvaginal ultrasound-guided drainage under GnRH analogues and recombinant interleukin-2 left in the cysts

BACKGROUND: To analyze the therapeutic results of one dose of 3 million IU of recombinant interleukin-2 (rIL-2) left intracyst (group I) versus two doses with a 1-month interval (group II) after transvaginal ultrasound (US)-guided drainage of endometriomas under the effect of GnRH analogues. METHODS: Prospective and randomized clinical trial (helped by a random number table) at a University Hospital. Twenty-four consecutive patients with endometriomas initially sent to us for laparotomy and conservative surgery for endometriosis were included. INTERVENTIONS: Treatment with GnRH analogues every 28 days, 3 doses. Under their effect, one or two transvaginal US-guided punctures were performed in order to aspirate the endometriomas, and 3 million IU of rIL-2 were left in the aspirated cysts each time. MAIN OUTCOME MEASURES: Clinical results: two menstruations after GnRH analogues. Other secondary outcome measures were: the time until recurrence of cysts, symptoms and CA-125 >35 U/ml, and the need for further medical or surgical treatment. RESULTS: They were moderate or good in >50% of cases with one drainage and one dose of 3 million IU of rIL-2 intracyst, but were better with a second drainage and two doses of rIL-2 (25 vs. 58.3% 'good results'). There were fewer recurrences and the interval before recurrence was longer after two doses but differences were not significant. Six patients from group I (50%) and 3 from group II (25%) needed laparotomy and conservative surgery at 17.5 +/- 8.7 months (total time of follow-up = 33 +/- 8.8 months). CONCLUSIONS: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts under endometrial suppressive therapy with GnRH analogues has beneficial effects, improving clinical manifestations and avoiding some surgical therapies. The use of a higher dose of rIL-2 does not produce better results, whereas drainage + rIL-2 twice does.     

GnRH analogues,transvaginal ultrasound-guided drainage and intracystic injection of recombinant interleukin-2 in the treatment of endometriosis

We performed a double-blind, randomised controlled trial to evaluate the results of ultrasound-guided aspiration of endometriomas under the effect of GnRH analogues and a possible additional beneficial effect by leaving 600000 IU of recombinant interleukin-2 (rIL-2) in the cysts. Twenty-four women with endometriosis-related symptoms, increased values of CA-125 and transvaginal ultrasonography showing endometriomas >3 cm who were initially sent to us for laparotomy and conservative surgery for endometriosis were included. Main outcome measures were severity of symptoms, size and percentage of echographical reduction of endometriomas and CA-125 levels after 2 menses post-GnRH analogues. Secondary outcome measures were the time until recurrence of abnormal parameters and the need for surgery after treatment. We found moderate clinical results after treatment with drainage plus GnRH analogues and significantly improved results in women having received rIL-2 intracystically. There were no side effects. Two out of 3 previously infertile patients became pregnant after therapy. Though the rates of recurrence of endometriomas >or=3 cm were similar in both groups, the period until recurrence was significantly greater when rIL-2 was used, and the rates of recurrence of symptoms and increased CA-125 values were also significantly lower in patients who received rIL-2. Surgery was finally performed on 10 patients (4 with and 6 without previous rIL-2 treatment) during follow-up (30 +/- 12.7 months). These findings led to the conclusion that transvaginal ultrasound-guided puncture and aspiration of endometriomas under endometrial suppressive therapy with GnRH analogues have some value for endometriosis treatment, improving the clinical manifestations and avoiding some surgical therapies, and that rIL-2 left in the cyst increases these beneficial effects significantly.     

Endometrial carcinoma in gonadal dysgenesis with and without estrogen therapy

Two phenotypically female patients with gonadal dysgenesis who developed endometrial carcinoma are described. One patient has not received exogenous estrogen therapy. No such patient has been reported previously. This patient developed the unusual mixed adenosquamous carcinoma. Both carcinomas were detected at an early age. It is postulated that the carcinomas developed essentially because of unopposed endogenous estrogen secretion due to anovulation.     

子宫内膜癌的病理分类

198 8年国际妇科病理协会 (ＩＳＧＰ) [1] 及 1994年ＰｏｕｌｓｅｎＨ .Ｅ .全新完善的分类 ,将子宫内膜癌分为①腺癌 ;②浆液性腺癌 ;③透明细胞腺癌 ;④粘液性腺癌 ;⑤鳞状细胞癌 ;⑥混合性癌 ;⑦未分化癌。其中 ,腺癌被称为“子宫内膜样”腺癌 ,而腺棘癌、腺鳞癌、分泌性癌、纤毛细胞癌被认为是普通腺癌的变异 ,另外 ,浆液性乳头状腺癌、透明细胞腺癌、粘液性腺癌 ,属于非子宫内膜样癌 ,但它们中的任意一种都可以与子宫膜样腺癌并存[2 ] 。现将其病理类型分述如下。1　巨检子宫内膜癌多见于子宫底部内膜 ,以子宫两角附近居多 ,依病变形态…     

Endometrial carcinoma associated with Sheehan's syndrome and stilbestrol therapy

At the age of 25, pregnant with her 2nd child, a woman was diagnosed as having pituitary necrosis resulting from hemorrhagic shock, in turn the result of a clotting defect caused by an amniotic fluid embolism. For the next 17 years, her daily replacement therapy included 50 mg ma of cortisone, 120 mg of thyroid, and .5-1 mg of diethylstilbestrol given cyclically (21 days). When an exploratory laparotomy was performed on her at age 42 because of abdominal mass,an endometrial adenocarcinoma and varying degrees of hyperplasia were found. A total abdominal hysterectomy was performed, but a year later it became clear that the patient had diffuse carcinomatosis, and 2 months later she died. Prolonged unopposed estrogen therapy is suggested as the cause of the endometrial cancer, rather than pituitary disturbance.     

Endometrial antigens involved in the autoimmunity of endometriosis

Serum and peritoneal fluid from five fertile women without endometriosis and serum (n = 23) and peritoneal fluid (n = 12) from infertile women with endometriosis were tested for the presence of antibodies against endometrial tissue antigens by a Western blot analysis. Antigens with molecular weights (MW) of 19, 31, 38, and 42 kd reacted with antibodies in the serum and peritoneal fluid from both fertile and infertile women. Antibodies in 20 of 23 (87%) sera and all 12 (100%) peritoneal fluid samples from endometriosis patients reacted against endometrial antigens with molecular weights (MW) of 26 kd and/or 34 kd. Serum from 10 patients (43%) and peritoneal fluid from 6 patients (50%) also had antibodies to an endometrial antigen with MW of 21.5 kd. Reactivity to other endometrial antigens with MW 16, 24, 48, and 75 kd was also noted in patients with endometriosis. Antibodies in the serum and peritoneal fluid from fertile women failed to react against these antigens. It is concluded that the humoral and local endometrial autoimmunity detected in patients with endometriosis is primarily directed against antigens with MW of 26 and 34 kd.