goserelin and Leiomyoma

Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013.. To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials.. All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.. Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach.. This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report. Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.

Topics: Adult; Antineoplastic Agents, Hormonal; Bias; Contraceptives, Oral; Desogestrel; Female; Goserelin; Humans; Intrauterine Devices, Medicated; Leiomyoma; Leuprolide; Levonorgestrel; Lynestrenol; Medroxyprogesterone Acetate; Menstruation; Middle Aged; Nandrolone; Norethindrone Acetate; Premenopause; Progestins; Randomized Controlled Trials as Topic; Tumor Burden; Uterine Neoplasms

Fibroids, the most common gynecologic condition in women of reproductive age, have traditionally been treated with hysterectomy. As more women delay childbearing, myomectomy becomes an essential component of the gynecologist's armamentarium. Minimally invasive approaches to myomectomy have been shown to decrease morbidity and reduce care-related costs, while improving reproductive outcomes. Hysteroscopic myomectomy is a reproducible and easily learned technique for the treatment of submucosal fibroids. Robot-assisted laparoscopic myomectomy overcomes most of the technical challenges of laparoscopic myomectomy for intramural and subserosal fibroids. The combined adoption of these technologies will allow more patients with fibroids to benefit from a minimally invasive approach.

Topics: Antineoplastic Agents, Hormonal; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysteroscopy; Infertility, Female; Laparoscopy; Leiomyoma; Neoadjuvant Therapy; Robotic Surgical Procedures; Uterine Myomectomy; Uterine Neoplasms

Topics: Adjuvants, Pharmaceutic; Adult; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Premenstrual Syndrome; Uterine Hemorrhage

Topics: Adult; Antineoplastic Agents, Hormonal; Catheterization; Combined Modality Therapy; Female; Goserelin; Humans; Leiomyoma; Preoperative Care; Uterine Neoplasms; Uterus

Topics: Antineoplastic Agents, Hormonal; Endometriosis; Female; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

To clarify whether preoperative treatment with gonadotropin-releasing hormone (GnRH) agonists offers substantial advantages to patients undergoing conservative or definitive surgery for uterine leiomyomas.. A review of data from the most recent English-language literature.. Inducing amenorrhea in patients with heavy menorrhagia and severe sideropenic anemia before both conservative and definitive surgery for uterine fibroids raises hemoglobin and hematocrit values to within the normal range, limits homologous blood transfusions and enables operations to be scheduled with the patients in better condition. A temporary 30-50% reduction in mean uterine volume theoretically may convert an abdominal into a vaginal hysterectomy in "borderline" cases or sometimes allow a transverse instead of longitudinal abdominal incision. No trial has yet demonstrated "clinically" significant reductions in operating time, operative blood loss or postoperative morbidity in patients undergoing myomectomy or hysterectomy after a course of GnRH agonists as compared with those operated on immediately. There seems insufficient scientific evidence to justify the routine use of GnRH agonists before myomectomy at laparotomy, except possibly in the case of extremely bulky uteri. GnRH agonist treatment before hysteroscopic myomectomy induces endometrial thinning, reduces bleeding and mucous debris, and decreases the diameter of submucous leiomyomas, improving visibility and limiting operating time and fluid intravasation.. The available data seem to support the use of GnRH agonist treatment before surgery for uterine leiomyomas in selected circumstances. Administration of GnRH agonist for only two or three months preoperatively seems to achieve all the advantages of this treatment, limiting side effects and cost.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysterectomy; Leiomyoma; Leuprolide; Preoperative Care; Treatment Outcome; Uterine Neoplasms

This review addresses the question of whether the different gonadotropin releasing hormone (GnRH) agonists in clinical use might have different impacts, related to their chemical structure, delivery system and dose. Impact was investigated in benign gynecological disorders, i.e. endometriosis and leiomyoma. Arguments are presented indicating that a difference in impact of different analogs can be expected. All currently used intranasal, daily subcutaneous and depot preparations finally give rise to low levels of serum estradiol. The number of days before the first ovulatory menstruation after discontinuation of GnRH agonist treatment is remarkably constant. Four weeks after the last impact of the agonist, there is resumption of follicle growth. This phenomenon is independent of chemical structure, delivery system and dose. One should realize, however, that it generally takes about 30 days before the impact of a depot preparation disappears. Consequently, the impact of a depot preparation lasts 4 weeks longer than that of an otherwise applied agonist. Thus resumption of pituitary activity after discontinuation of a depot formulation takes 4 weeks longer than after discontinuation of non-depot formulations. All agonists have an impressive effect on endometriosis, independent of their chemical structure and delivery system. However, there are no studies comparing different agonists with the same delivery system in comparable endometriosis groups. Similarly, all agonists considerably reduce myoma volume, independently of their chemical structure and delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Buserelin; Dose-Response Relationship, Drug; Drug Delivery Systems; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Leuprolide; Menstrual Cycle; Nafarelin; Structure-Activity Relationship; Triptorelin Pamoate

Topics: Anemia; Female; Goserelin; Humans; Leiomyoma; Menorrhagia; Uterine Neoplasms

Topics: Buserelin; Combined Modality Therapy; Drug Therapy, Combination; Female; Goserelin; Humans; Leiomyoma; Medroxyprogesterone; Medroxyprogesterone Acetate; Receptors, Estradiol; Tamoxifen; Uterine Neoplasms

Topics: Buserelin; Endometriosis; Female; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

This review covers literature published between December 1990 and November 1991. It shows a continuous outpouring of publications on the use of gonadotropin-releasing hormone agonists and operative hysteroscopy as part of the background of alternatives to hysterectomy. The new technologies question traditional management of fibroids, which may vary considerably in different areas. Abdominal myomectomy, which never received adequate recognition as an alternative in the past, is also discussed. The review concludes with a section on abdominal hysterectomy.

Topics: Buserelin; Female; Goserelin; Humans; Hysteroscopy; Leiomyoma; Leuprolide; Methods; Uterine Neoplasms

Goserelin is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] which stimulates gonadotrophin and sex hormone release in the short term, and then causes suppression with continued administration. Goserelin is given as a subcutaneous biodegradable depot incorporating 3.6 mg of the drug, which is released continuously at an average rate of 120 micrograms/day over 4 weeks. Monthly goserelin depot therapy produces partial disease remission or stabilisation in about 75% of men with previously untreated prostatic cancer, a rate equivalent to that achieved with orchidectomy or diethylstilbestrol (stilboestrol). The response to goserelin is more rapid than to diethylstilbestrol, and goserelin is better tolerated. About 30 to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy. In benign hormone-dependent conditions, preoperative goserelin aids surgical removal of uterine leiomyoma (fibroids) and reduces blood loss, and 6 months of therapy relieves the signs and symptoms of endometriosis. The elevation in testosterone at the beginning of goserelin therapy can result in disease 'flare' in men with prostate cancer, and sex steroid suppression with continued treatment results in hot flushes and loss of libido in most patients. Thus, goserelin is an effective alternative to surgery or estrogen therapy in prostatic cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Other gynaecological conditions reliant on the pituitary-gonadal axis also appear amenable to hormone manipulation with goserelin.

Topics: Animals; Breast Neoplasms; Buserelin; Drug Evaluation; Endometriosis; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Goserelin; Humans; Leiomyoma; Male; Menstruation Disturbances; Polycystic Ovary Syndrome; Prostatic Neoplasms; Uterine Neoplasms

Topics: Adult; Buserelin; Drug Evaluation; Female; Goserelin; Humans; Hysterectomy; Leiomyoma; Middle Aged; Uterine Neoplasms

The aim of this randomised prospective study was to investigate the impact of preoperative gonadotrophin-releasing hormone agonist (GnRHa) compared with a control group with myomectomy. A total of 36 women (n = 36, group 1) with fibroids were randomised to receive either two monthly doses (n = 18/36, group 1a) or three monthly doses of goserelin (n = 18/36, group 1b) prior to myomectomy. The 32 women who received no treatment (group 2) comprised the controls. All patients had similar demographic features. There were no significant differences among the three groups with respect to: (1) mean intraoperative blood loss; (2) preoperative and postoperative blood transfusion or (3) length of hospital stay. The only advantage of administering GnRHa prior to myomectomy for symptomatic fibroids in our population was a higher haemoglobin level prior to surgery among the women who received three doses of the drug.

Topics: Adult; Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Blood Transfusion; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Goserelin; Hemoglobins; Humans; Leiomyoma; Length of Stay; Preoperative Care; Prospective Studies; Uterine Myomectomy; Uterine Neoplasms

To evaluate the role of three-monthly pre-treatment with gonadothropin releasing hormone (GnRH) analogues prior to myomectomy for women in comparison with control group of patients with no application. Analysis is focused on peroperative and postoperative results of surgery treatment for women with clinically symptomatic uterine fibroids in reproductive age with interest in getting pregnant.. Prospective clinical study.. Gynecological and Obstetric Clinic of Medical Faculty of Masaryk University and the University Hospital Brno.. The group of 212 patients with symptomatic uterine fibroids detected by ultrasound. 90 patients (42.5%) underwent laparoscopic myomectomy (LM) and 122 patients (57.5%) underwent open laparotomic myomectomy (OM). In the selected group we were observing the common number of exstirpated uterine fibroids, their size, anatomical localisation, depth of invasion of dominant exstirpated uterine fibroid in relation to uterine wall.. Both groups of patients were randomised into two parts. The group LM with GnRH pretreatment contained 42 patients (19,8 %) and control group with no pre-treatment 48 patients (22.7%). Laparotomic part of study was divided into two groups with preoperative application of GnRH analogues 44 patients (36,7 %) and control group OM with no application 44 patients (20.8%). The main outcome measures were peroperative blood loss, duration of surgery, the length of hospital stay, evidence of per- and postoperative complications and the final results by second look laparoscopy (SLL).. In the observed group LM with pre-treatment of GnRh analogues there was significantly higher volume of blood loss (p = 0.0003), significantly longer duration of surgery (p = 0.0063) and significantly higher lenght of hospital stay (p = 0.0025) compared with control group. We have not found a significant difference in the incidence of peroperational converse to laparotomy, final result of neoformation of uterus wall and occurrence of postoperative adhesions by SLL in observed LM group compared with control group. In the observed OM group with pre-treatment of GnRH analogues there was no significant difference in: peroperative blood loss (p = 0.5324), duration of surgery (p = 0.3927) neither average length of hospital stay compared with control group. In the OM group, there was significantly lower incidence of recidives of uterine fibroids observed by SLL (p = 0.0025) and no significant difference of occurrence of postoperative adhesions compared with control group. We have not found significant difference in the incidence of peroperative complications, early and late postoperative complications in group of LM and OM in comparison with control groups.. Application of GnRH analogues in observed group of patients before LM and OM have not lead to improvement of peroperative results in comparison with control group. Pre-treatment of GnRh analogues before OM have lead to significant drop in recidives of uterine fibroids observed by SLL (p = 0.0025) compared with control group.

Topics: Adult; Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Laparoscopy; Laparotomy; Leiomyoma; Length of Stay; Neoadjuvant Therapy; Postoperative Hemorrhage; Preoperative Care; Uterine Neoplasms

Submucous fibroids are common benign tumours responsible for menorrhagia, subfertility and miscarriage. They can be readily removed by hysteroscopic transcervical resection of myoma (TCRM). To facilitate resection, pre-operative GnRH analogues have been suggested, but the value of this treatment is uncertain. Our aim was to assess the value of pre-operative GnRH analogues for the resection of submucous fibroids.. This was a prospective, double-blind, placebo-controlled, randomized trial. Women found to have submucous fibroids on three-dimensional saline infusion sonohysterography (3D SIS) were randomized to receive GnRH or placebo. Following treatment patients underwent TCRM by a single operator blinded to the group allocation. Women were followed up 6 weeks after their operation to ascertain resolution of symptoms. The primary outcome measure of the study was completeness of fibroid resection. Secondary outcome measures included the duration of the TCRM, the fluid deficit recorded at TCRM, the resolution of symptoms post-operatively and the number of subsequent fibroid related operations.. Forty-seven women were randomized to GnRH or placebo. On the basis of intention-to-treat analysis, there was no significant difference in the number of complete fibroid resections between women who received GnRH analogues [14/24, 58.3% (95% CI 38.6-78.1)] and those who received placebo [16/23, 69.6% (50.8-88.4)] (RR 0.84, 95% CI 0.54-1.29; P = 0.43). Similarly there was no significant difference between the groups in any of the secondary outcome measures.. Our study does not support routine administration of GnRH analogues before transcervical resection of fibroid as we did not identify any benefit in such treatment.

Topics: Adult; Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Blood Volume; Body Fluids; Combined Modality Therapy; Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Middle Aged; Postoperative Complications; Premedication; Reoperation; Statistics as Topic; Time Factors; Uterine Neoplasms

To compare intra-operative blood loss with triple tourniquets to occlude uterine blood supply against preoperative treatment with gonadotrophin-releasing hormone (GnRH) analogues at open myomectomy.. A prospective randomised controlled trial.. University teaching hospital.. Forty women undergoing open myomectomy for symptomatic fibroids.. Women due to undergo open myomectomy were randomised to either 3 months pre-treatment with a GnRH analogue or the intra-operative application of triple tourniquets (number 1 polyglactin suture [Vicryl Ethicon Inc., Somerville, NJ, USA] tied around the cervix and a size 10 polythene suction catheter tied around the infundibulo-pelvic ligaments) to occlude the uterine blood supply.. The primary outcome measure was intra-operative blood loss. Secondary outcome measures included postoperative blood loss, blood transfusion rate and postoperative morbidity.. The two groups were similar in baseline characteristics. An average of 15 and 22 fibroids were removed from the GnRH analogue and tourniquet groups respectively. Intra-operative estimated blood loss was significantly higher in the GnRH analogue group (median 2482 ml, 75% percentile 1744-3151) than when triple tourniquets were used (median 640 ml, 75% percentile 418-881), giving a difference between means of 1842 ml (P<0.001). Similarly, significantly more women required blood transfusion in the GnRH analogue group (70 versus 30%, P<0.025). Postoperative morbidity was similar between the two groups. There were two serious complications in the tourniquet group, but they were not considered to be directly related to occlusion of the uterine blood supply.. Triple tourniquets are significantly more effective than preoperative treatment with GnRH analogues at reducing intra-operative blood loss at open myomectomy.

Topics: Adult; Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Blood Transfusion; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Middle Aged; Morbidity; Nafarelin; Postoperative Hemorrhage; Premedication; Prospective Studies; Statistics, Nonparametric; Suture Techniques; Tourniquets; Treatment Outcome; Uterine Neoplasms; Uterus

To assess the efficacy of tibolone add-back therapy with Goserelin treatment of uterine fibroids.. Randomized placebo-controlled study.. Gynecology department of an inner-city teaching hospital.. Seventy-five women of reproductive age with uterine fibroids.. All women were given monthly SC implants of 3.6 mg goserelin and were randomized to take 3 months of placebo followed by 3 months of tibolone 2.5 mg daily (delayed administration), tibolone 2.5 mg daily for 6 months, or placebo for 6 months.. Changes in bone mineral density (BMD) at the hip and spine, fibroid and uterine size, and patient symptomatology.. In the tibolone group, 2% loss of BMD at the spine was observed compared with 5.5% loss in the placebo group. For total hip, tibolone led to a 0.7% gain in BMD compared with a loss of 1.7% in the placebo group. Tibolone did not affect GnRH analogue-induced fibroid shrinkage. Vasomotor symptom scores in women taking tibolone were 2.2 and were significantly lower than those taking placebo or in the delayed administration groups (mean scores 2.9 and 2.7, respectively).. Tibolone appears to be a safe and effective add-back therapy which can be given from the commencement of GnRH analogue treatment for fibroids.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone and Bones; Bone Density; Chemotherapy, Adjuvant; Cross-Over Studies; Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Middle Aged; Norpregnenes; Patient Compliance; Placebos; Treatment Outcome; Uterine Hemorrhage; Uterine Neoplasms

To compare goserelin and leuprolide given before hysterectomy for symptomatic large fibroid uteri.. A randomized study of 66 premenopausal women with fibroid uteri at least 14 weeks of gestation in a gravid uterus. Women were randomized to receive either subcutaneous depot 3.6 mg goserelin or 3.75 mg leuprolide every 4 weeks for a total of 3 doses. Hysterectomy was performed within 1 month of the last dose.. A total of 34 women randomized to the goserelin group and 31 women to the leuprolide group were available for analysis. Preoperative hemoglobin level (P=0.89), operative blood loss (P=0.72), and operating time (P=0.39) were not different between the 2 groups. Postoperative hemoglobin was higher in the leuprolide group (P=0.003), but blood transfusion requirement was not different between the groups (P=1.0). Other outcomes and side effects of the drugs were similar.. Goserelin and leuprolide administered before hysterectomy for uterine fibroids have similar perioperative outcomes.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Female; Goserelin; Humans; Hysterectomy; Leiomyoma; Leuprolide; Middle Aged; Treatment Outcome; Uterine Neoplasms

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.. 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.. 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).. 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.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Genes, bcl-2; Goserelin; Humans; Leiomyoma; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Raloxifene Hydrochloride; Receptors, Estrogen; Receptors, Progesterone; Selective Estrogen Receptor Modulators; Tumor Suppressor Protein p53; Uterine Neoplasms

Women with symptomatic uterine leiomyomas (fibroids) may have iron-deficiency anemia (IDA); therefore, surgery places them at risk of blood-borne morbidity from perioperative transfusions. Such women might benefit from a preoperative treatment that restores hematologic normality and alleviates fibroid symptoms.. The purpose of this study was to examine the effects of a single preoperative depot injection of goserelin acetate plus iron treatment compared with iron monotherapy, in premenopausal women with IDA due to uterine leiomyomas.. This Phase III, randomized, multicenter, double-blind, controlled trial (12 weeks of treatment plus a 24-week follow-up period) was conducted from October 1997 to August 1999. Patients received an injection of goserelin acetate 10.8 mg (3-month formulation) or a sham, with both groups receiving PO iron (ferrous sulfate) 325-mg tablets TID during the 12-week treatment period. Surgery (hysterectomy or myomectomy) was planned for week 12. Hemoglobin (Hb) level, symptoms of uterine leiomyomas, requirement for blood transfusion throughout, ability to donate blood for autologous transfusion, and leiomyoma and uterine volume were assessed for efficacy. The tolerability assessment included bone mineral density measurements and subjective symptomatology (ie, menstrual bleeding [uterine hemorrhage], fatigue, pelvic pain, and pelvic pressure).. A total of 110 women received treatment (n = 54, goserelin acetate 10.8 mg; n = 56, sham). The majority of patients (69.1%) were black and the mean age at study entry was 39.9 years, with a mean weight of 80.1 kg. At approximately 12 weeks, Hb levels were significantly higher in the goserelin group compared with the sham group (difference of least squares mean, 1.17 g/dL; 95% CI, 0.68-1.66; P < 0.001), and significantly more patients in the goserelin group had an increase in Hb concentration of >or=2 g/dL (odds ratio 6.36; 95% CI, 2.00-20.18; P < 0.001). A nonsignificant decrease in both uterine and leiomyoma volume was experienced by patients who administered goserelin compared with increases in the sham group. Uterine hemorrhage was also experienced numerically less often by goserelin-treated patients compared with those given the sham injection (9.3% vs 28.6%, respectively). One or more adverse events (AEs) were reported by 89% of patients in each treatment group. Goserelin acetate 10.8 mg was generally well tolerated by patients, with no serious drug-related AEs reported during this 36-week trial.. A single, preoperative injection of goserelin acetate 10.8 mg in addition to PO iron 325 mg TID was associated with improved Hb levels in these premenopausal women with IDA due to uterine leiomyomas.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Antineoplastic Agents, Hormonal; Double-Blind Method; Drug Therapy, Combination; Female; Ferrous Compounds; Goserelin; Gynecologic Surgical Procedures; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Leiomyoma; North America; Premedication; Premenopause; Time Factors; Treatment Outcome; Uterine Neoplasms

To determine if goserelin immediately after uterine artery embolization (UAE) affected myoma reduction.. Randomized pilot study (level 1).. Teaching hospital.. Twenty-six women.. All patients underwent UAE, and then 12 patients received 10.8 mg of goserelin 24 hours later. The treatment group was 5 years older: 43 versus 37.7 years. Uterine and myoma volumes were measured by ultrasound 2 weeks before UAE and at 3, 6, and 12 months.. Uterine and fibroid volumes.. Pretreatment uterine volume was 477 versus 556 cm3, and dominant fibroid volume was 257 versus 225 cm3 in the control versus goserelin groups. Analysis of variance measurements indicated that the change over time did not significantly differ between the two groups. By 12 months, the control group had a mean uterine volume reduction of 58%, while the goserelin group had a reduction of 45%. Dominant fibroid changes over time did not differ between the two groups. At 12 months, the mean fibroid volume had decreased by 86% and 58% in the control and goserelin groups, respectively.. The addition of goserelin therapy to UAE did not alter the reduction rate or volume of uterine myomas.

Topics: Adult; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Embolization, Therapeutic; Female; Goserelin; Humans; Leiomyoma; Ontario; Pilot Projects; Severity of Illness Index; Treatment Outcome; Uterine Neoplasms

The early and heavy clinical symptoms of the submucous myomas demand early surgical intervention. The new alternative to the classical abdominal operation is the transcervical hysteroresection which is miniinvasive and organ-preserving procedure.. to assess the effect of the preoperative treatment of the patients with Goserelin acetate (Zoladex) on the intraoperative measures (operation time, intraoperative complications, difficulty of the procedure).. prospective. PATIENT(S) AND METHODS: Total of 50 women with submucous myomas underwent hysteroresection. Ten of them were treated with Zoladex for two months preoperatively.. In the treated group a mean decrease of 10.16 mm of the myoma diameter was achieved. This is especially important for myomas above 30 mm in diameter because 10 mm decrease in diameter leads to significant reduction of the tissue volume which has to be resected. In the treated group the mean operation time was decreased by 17.08 min. and the operation was assessed as "easier" in 90% of the cases. The authors assessed that the positive effect of Zoladex consists not only of the decreasing of the myoma diameter but also of achieving an endometrial atrophy which significantly improves the conditions for performing the intrauterine operation.. Hysteroscopic resection of submucous myomas after pretreatment with Zoladex is faster, easier and with less intraoperative complications.

Topics: Adult; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Hysteroscopy; Leiomyoma; Prospective Studies; Treatment Outcome; Uterine Neoplasms

To compare the use of a new antiestrogen fulvestrant with goserelin in reducing uterine fibroid growth before hysterectomy.. An international, multicenter, randomized, placebo-controlled study.. Departments of obstetrics and gynecology.. Premenopausal women (n = 307) diagnosed with uterine fibroids requiring hysterectomy.. Over a 12-week period, patients received fulvestrant (50 mg, 125 mg, or 250 mg) as an i.m. injection, goserelin (3.6 mg) as a s.c. injection, or an injection-matched placebo once every 4 weeks. Patients underwent a hysterectomy at week 13.. Efficacy endpoints included changes in fibroid growth, endometrial thickness, and uterine volume. The excretion of urinary markers of bone resorption was also examined.. Goserelin significantly reduced fibroid growth and endometrial thickness compared with placebos. Fulvestrant did not significantly alter fibroid volume or endometrial thickness or change endpoints such as endometrial histology or vaginal bleeding. Fulvestrant was associated with fewer postmenopause-related adverse events than goserelin. Goserelin, but not fulvestrant, significantly increased markers of bone resorption.. At doses equivalent to those used for the treatment of breast cancer in postmenopausal women, fulvestrant did not significantly inhibit fibroid growth and, of particular note, did not lead to bone resorption.

Topics: Adult; Biopsy; Bone Resorption; Endometrium; Estradiol; Estrogen Antagonists; Estrogen Receptor Modulators; Female; Fulvestrant; Goserelin; Humans; Hysterectomy; Leiomyoma; Middle Aged; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Uterine Neoplasms

To investigate the effect of GnRH treatment on estrogen levels and sulfatase activity in leiomyoma and myometrium tissue.. Retrospective analyses of tissue obtained in a prospective randomized clinical study.. Gynecology departments of eight hospitals in the Netherlands.. Thirty-two patients scheduled for leiomyoma surgery.. Patients were randomized to receive either GnRHa (3.75 mg/4 weeks of triptorelin or 3.6 mg/4 weeks of goserelin) or no GnRHa for 4 months. At subsequent surgery, leiomyoma and myometrium samples were collected.. Estrone, estradiol, and sulfatase activity levels in leiomyoma and myometrium.. In myometrium, levels of estrone, estradiol, and sulfatase activity were significantly lower in the treated group (to median values of 46%, 21%, and 61%, respectively). In leiomyomas of treated patients, the reduction in median estrone level (to 65% of untreated value) was comparable to that in myometrium. The reduction in estradiol level in leiomyoma, however, was significantly less than in myometrium (median to 58% vs. 21%), and no significantly lower sulfatase activity was found.. Estradiol and sulfatase results show that the effect of GnRHa treatment on leiomyoma differs from the effect on myometrium, suggesting a continuing estrogenic stimulus in leiomyoma tissue despite treatment.

Topics: Antineoplastic Agents, Hormonal; Estradiol; Female; Goserelin; Humans; Leiomyoma; Myometrium; Randomized Controlled Trials as Topic; Retrospective Studies; Sulfatases; Triptorelin Pamoate; Uterine Neoplasms

Gonadotropin releasing hormone (GnRH) agonists are successfully used in the treatment of uterine leiomyomas. Different GnRH agonists may have different local effects on steroid receptors. This study was designed to evaluate potential differences in this respect between triptorelin (Decapeptyl) and goserelin (Zoladex) in a randomized controlled multicenter study using untreated patients during the luteal phase of their menstrual cycle as controls. Estrogen receptors (ERs) and progestin receptors (PRs) were measured by ligand binding assay in myoma and myometrium tissue following a 4-month treatment course with one of the GnRH analogs. In 18 untreated patients median values of ER and PR contents were comparable in myoma and myometrium: for ER at median levels of 56 and 43 fmol/mg protein, respectively; and for PR, median binding capacities were 690 and 730 fmol/mg protein, respectively. Both types of GnRH treatment (total number of patients 34) were associated with significant rises in ER in myoma (to a median level of 279 fmol/mg protein, p<0.001) and myometrium (to a median level of 109 fmol/mg protein, p<0.01). The increase in ER in myomas was significantly (p<0.001) greater than in myometria of the same patients (n=30). After treatment, PR in myomas (median level 520 fmol/mg protein) did not change significantly, but a significant (p<0.05) decrease was found for myometria (median level of 320 fmol/mg protein). Thus, ER and PR concentrations in myoma and myometrium are comparable before treatment, but estrogen suppression with GnRH analogs leads to a larger increase of ER level in leiomyomas than in myometrium, without an effect on PR, whereas myometria had lower PR levels. Therefore, leiomyoma reacts differently from myometrium towards lowered steroid concentrations in the circulation. Since the PR is considered to be a marker of estrogenic stimulation, this indicates remaining estrogenic effects on leiomyomas despite the large decrease of plasma estrogen concentrations.

Topics: Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Luteal Phase; Myometrium; Receptors, Estrogen; Receptors, Progesterone; Triptorelin Pamoate; Uterine Neoplasms

To obtain information on the efficacy of repeated short cycles of GNRH agonist treatment in order to avoid hysterectomy in near-menopausal women with symptomatic fibroids.. 72 pre-menopausal women (mean age 50 years) with one or more uterine fibroids >10 cm in diameter, symptomatic menorrhagia lasting three months or more and haemoglobin=9 g/dl entered the study. The patients were randomized with ratio of approximately 1:4 to: (a) immediate surgery; or (b) treatment with goserelin acetate. Patients randomized to goserelin acetate received a first cycle of 3.6 mg depot once every 28 days for four months. They were followed-up for three years. If menorrhagia was observed during the follow-up the woman was given goserelin acetate 3.6 mg depot for another three months. In case of further menorrhagia, a third cycle of goserelin acetate 3.6 mg depot for three months was given. After the third cycle of therapy if there was still menorrhagia, the patient underwent hysterectomy plus bilateral oophorectomy.. A total of 13 women were assigned to the immediate surgery group and 59 to goserelin. Three years after trial entry a total of 23 women allocated to goserelin acetate treatment had undergone hysterectomy.. This study suggests that GNRH agonists are efficacious for avoiding hysterectomy in women near menopause with uterine fibroids.

Topics: Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysterectomy; Leiomyoma; Menorrhagia; Middle Aged; Ovariectomy; Premenopause

Cell proliferation in uterine leiomyomas treated preoperatively with either nafarelin (400 microg/day) for 3 months (7 patients) or nafarelin plus hormone (oestradiol + norethisterone) add-back therapy (6 patients) was investigated by automatic image analysis of frozen tissue sections using immunohistochemistry with anti-proliferating cell nuclear antigen antibody. GnRHa therapy decreased cell proliferation in leiomyomas to a level corresponding to the situation previously seen in postmenopausal leiomyomas. However, there was no consistent correlation between cell proliferation and shrinkage of leiomyomal size. The hormone add-back therapy moderated the influence of GnRHa on cell proliferation and completely blocked a decrease in size of leiomyomas in our patients.

Topics: Adult; Antineoplastic Agents; Cell Division; Estradiol; Female; Goserelin; Hormones; Humans; Hysterectomy; Leiomyoma; Middle Aged; Nafarelin; Norethindrone; Premedication; Preoperative Care; Uterine Neoplasms

The aim of the study is to establish the efficacy of preoperative use of GnRH agonists in women with uterine fibromyomas. The study is a randomized prospective one and includes 34 patients, divided in two groups: group I--with preoperative application of GnRH agonists--Zoladex and group II--without medication. In Zoladex group amenorrhea was achieved in 76% of patients after 7-8 weeks of treatment. After a 3-months treatment with Zoladex Hb levels increased from 8.9 +/- 0.9 gl/l to 11.7 +/- 1.2 g/l; levels of serum Fe--from 7.3 +/- 4 mumol/l to 18.5 +/- 5 mumol/l. Total uterine volume decreased by 30% before surgery (from 328 +/- 85 ml to 233 +/- 61 ml), while myoma volume decreased by 39% (from 178 +/- 62 ml to 109 +/- 44 ml). Mean blood loss during surgery (hysterectomy) is definitely less in patients, treated with Zoladex--194 +/- 75 ml., compared to 287 +/- 102 ml in control group. The significant reduction in myoma volume in 6 patients due to presurgical treatment with Zoladex made smaller operation--myomectomy, possible. Side effects, related to GnRH agonist Zoladex, are well tolerated and transitory and did not lead to retreatment from the trial.

Topics: Adult; Analysis of Variance; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Middle Aged; Preoperative Care; Prospective Studies; Time Factors; Uterine Neoplasms

A randomized trial was carried out to investigate the effect of 12 months administration of the gonadotrophin-releasing hormone agonist (GnRHa) Zoladex in combination with either placebo or medroxyprogesterone acetate (MPA) from the third month. Bone density, markers of bone resorption, symptoms and uterine volume were monitored in 24 women with symptomatic fibroids or menstrual problems. A total of 21 women were recruited to act as controls for the assessment of bone parameters. Vasomotor side-effects were reduced significantly in the MPA-treated group. The reduction in uterine volume in women with fibroids was not impaired by the addition of MPA. The bone markers osteocalcin and alkaline phosphatase were assessed in plasma, and the cross-links pyridinoline and deoxypyridinoline measured in urine. Changes in these markers are reported which suggest increases in bone resorption during the period of observation. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at the spine and forearm. The net reduction in BMD at the spine in the treated groups was 4.30 +/- 0.59% at 6 months and 7.50 +/- 0.78% at 1 year, with no change in the control group. No change was seen in forearm BMD. No protective effect was observed when MPA was added. At 1 year after the completion of treatment, BMD remained significantly below baseline, and this has implications for the prolonged use of GnRHa.

Topics: Adult; Amino Acids; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone Density; Female; Goserelin; Humans; Leiomyoma; Medroxyprogesterone Acetate; Middle Aged; Uterine Neoplasms; Uterus

To assess the utility of urinary cross-linked N-telopeptides in monitoring bone resorption and predicting bone loss during GnRH agonist administration.. Ninety patients who were prescribed GnRH agonist therapy for 3-6 months for treatment of endometriosis, leiomyomas or other gynecologic disorders participated in this prospective multicenter study. N-telopeptides, serum estradiol (E2), and bone mineral density were monitored before, during and up to 3 months after the course of GnRH agonist therapy.. N-telopeptide levels increased significantly throughout GnRH agonist therapy and returned to baseline levels by 3 months after treatment was completed. A significant negative correlation was seen between N-telopeptide and E2 measurements after 3 months (r=-0.23, P<.05), 4 months (r=-0.32, P < .05), and 5 months (r=-0.41, P<.005) of GnRH agonist therapy. The percent change in bone mineral density at L1-L4 at 6 months of GnRH agonist treatment correlated inversely with the percent change in N-telopeptides from baseline to 2,3,4, and 5 months of treatment; the percent change of bone mineral density at the femoral neck at 6 months correlated inversely with the percent change of N-telopeptides from baseline to month 4.. Urinary N-telopeptide determinations provide a quantitative measure of bone resorption, due to GnRH agonist-induced hypoestrogenism. Increases in resorption as measured by N-telopeptides parallel decreases in in E2 levels. Increases in N-telopeptides on GnRH agonist therapy may provide a tool to predict decreases in bone mineral density.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Bone Resorption; Collagen; Collagen Type I; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Genital Neoplasms, Female; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Leiomyoma; Leuprolide; Middle Aged; Nafarelin; Peptides; Prospective Studies; Uterine Neoplasms

To compare the effects of goserelin acetate treatment with or without iron with iron alone.. Multinational, multicenter, prospective, randomized, double-blind study.. Premenopausal women with menorrhagia or metrorrhagia and anemia associated with uterine leiomyomata awaiting hysterectomy.. Patients were randomized to one of three 12-week treatment groups namely goserelin acetate 3.6 mg once monthly plus placebo iron; 3.6 mg goserelin acetate once monthly plus 600 mg/d iron; or sham injection once monthly plus 600 mg/d iron.. Preoperative hemoglobin concentration; preoperative uterine and fibroid volumes and operative blood loss.. Considering the entry and preoperative hemoglobin concentrations, there was a difference in least square means of just over 1 g/dL between the goserelin acetate plus iron and iron only groups and 2.6 g/dL between the goserelin acetate plus iron and goserelin acetate only group. These differences were both statistically significant. Uterine and fibroid volumes were decreased in the goserelin acetate-treated patients by between 37% and 40% and 44% and 47%, respectively, compared with 7% decreases for both in the iron only group. The differences in absolute changes were statistically significant for both the goserelin acetate-treated groups versus the iron-treated group. The least square geometric mean operative blood loss was greatest in the iron only group.. In the patient with uterine leiomyomata and anemia, goserelin acetate in combination with iron therapy has shown significant advantages over the iron alone in restoring hematologic normality, decreasing uterine and fibroid volumes, and reducing operative blood loss.

Topics: Adult; Anemia, Iron-Deficiency; Antineoplastic Agents, Hormonal; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Goserelin; Hemoglobins; Humans; Iron; Leiomyoma; Menorrhagia; Middle Aged; Outcome Assessment, Health Care; Prospective Studies; Uterine Neoplasms

Two hundred and forty-seven patients with uterine fibroids were randomized to surgery alone or 3 months' Zoladex (Zeneca, Macclesfield, Ches., UK) followed by surgery. Zoladex significantly reduced uterine and fibroid volumes (p = 0.0001). There was a significantly (p = 0.002) greater mean rise in haemoglobin from entry to preoperation in the Zoladex group (1 g/dl) compared with the surgery-alone group (0.3 g/dl) as well as a tendency towards easier surgery, and reduced operative blood loss. Zoladex-treated patients had a significantly (p = 0.016) shorter hospital stay and pelvic pain and abdominal pressure symptoms were significantly (p < 0.0001) reduced in this group. Zoladex was well tolerated.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Female; Goserelin; Hemoglobins; Humans; Leiomyoma; Length of Stay; Premedication; Prospective Studies; Uterine Neoplasms; Uterus

The objective of this study was to evaluate the effect on vertebral and femural bone density of the gonadotropin-releasing hormone (GnRH) analog administration. The changes in mineral bone density after 6 months discontinuation of the GnRH analog treatment were also measured. Forty-three premenopausal women with regular cycles and suffering from uterine myomatosis have been selected for the study. Twenty-eight women (group A) were treated with Goserelin 3.2 mg given as a depot every 28 days for 6 months. Fifteen women were treated with 10 mg of medroxyprogesterone acetate (MPA) from day 16 to day 25 of each month for 6 months. Vertebral and femural bone density was measured (by Hologic QDR-X 1000) just before the start of the study, at 6 months of treatment and at 12 months (after 6 months of discontinuation treatment). Significant loss of vertebral bone density was demonstrated in women treated with GnRH analog. After six months of treatment discontinuation bone mineral density did not recover the pretreatment values. Bone femural density showed a not significant decrease in the GnRH analog group. In our experience, the treatment with GnRH analog in premenopausal women induces a reduction in lumbar bone density that is not reversible after the treatment withdrawal; for this reason it would be safe to add at the GnRH analog a therapy which can prevent the bone loss.

Topics: Adult; Age Factors; Antineoplastic Agents, Hormonal; Bone Density; Female; Femur; Femur Neck; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Lumbar Vertebrae; Medroxyprogesterone; Menstrual Cycle; Premenopause; Progesterone Congeners; Uterine Neoplasms

On 30 women suffering from uterine fibroids, the monthly subcutaneous administration of goserelin depot (3.6 mg) for 6 (n = 22) or 12 months (n = 8) induced an about 50% shrinkage of uterus and fibroid volume, and within 3 months, an increase in the haematocrit value, with no metabolic side effects or detectable bone demineralization, evaluated by single photon absortiometry at distal radius. Both uterine and fibroid volumes reversed to pretreatment values after 3 months of goserelin depot withdrawal. In comparison with untreated subjects, on another 10 patients a three month administration of goserelin depot reduced the loss of blood during the surgical removal of the uterus or fibroids. Present data indicate that goserelin depot is effective and relatively safe in the medical management of uterine fibroids. Although, goserelin depot cannot yet be proposed as a definite medical therapy, it may represent a useful instrument in the presurgical management of uterine fibroids.

Topics: Adult; Blood Loss, Surgical; Delayed-Action Preparations; Female; Follicle Stimulating Hormone; Goserelin; Humans; Leiomyoma; Lipids; Luteinizing Hormone; Middle Aged; Treatment Outcome; Uterine Neoplasms

To investigate the effect of the gonadotrophin releasing hormone (GnRH)-agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre-operative symptoms, difficulty of operation and operative blood loss.. Randomised placebo-controlled study.. Patients were recruited from the gynaecological outpatient departments from hospitals in Edinburgh, Glasgow and Newcastle.. Seventy-one premenopausal women with uterine leiomyomata who were on the waiting list for hysterectomy.. After the presence of leiomyomata was confirmed using ultrasonography, the women were randomised to receive either the GnRH-agonist goserelin by monthly subcutaneous injection or a sham injection for three months prior to operation. At the monthly visits, patients were asked about treatment related symptoms, fibroid related symptoms, and their bleeding patterns. Blood was taken for haematological assessment.. Haemoglobin concentrations at recruitment, at operation and post-operatively, pre-operative symptoms, operative difficulty and blood loss and post-operative complications.. Treatment with goserelin induced amenorrhoea in over 80% of the women, and this was associated with a significant rise in haemoglobin level. At the time of operation, fibroid related symptoms were less in the goserelin group than in the placebo group. The hysterectomy was technically easier and the median (range) operative blood loss was significantly lower in the goserelin group compared with the placebo group (187 (60-600) ml vs 308 (118-1000) ml respectively; P < 0.05, Wilcoxon signed rank test). There was no difference between the two groups in the duration of hospital stay or the frequency of post-operative complications. The fibroids were smaller at the time of operation in the goserelin group, and more women treated with goserelin were able to have their operations through a transverse incision.. This study demonstrates the benefits of goserelin in women having total abdominal hysterectomy for uterine leiomyomata.

Topics: Adult; Blood Loss, Surgical; Double-Blind Method; Female; Goserelin; Hemoglobins; Humans; Hysterectomy; Leiomyoma; Length of Stay; Postoperative Complications; Preoperative Care; Uterine Neoplasms; Uterus

Topics: Adult; Blood Loss, Surgical; Combined Modality Therapy; Female; Goserelin; Hemoglobins; Humans; Leiomyoma; Time Factors; Uterine Neoplasms; Uterus

To determine the effect of hysteroscopic resection and goserelin in the treatment of submucous fibroids, and their significance in assisted conception.. Patients with history of subfertility and previous failed attempts at assisted conception were examined by transvaginal sonography before further attempts at assisted conception. Those diagnosed as having submucous fibroids were treated with goserelin injections, hysteroscopic resection, or a combination of both. Saline sonohysterography was performed whenever the submucous nature of the fibroid was unclear.. The Churchill Clinic Fertility and IVF Centre, London, United Kingdom. One hundred women being treated for subfertility over a period of 2 years. Twenty-seven had submucous fibroids diagnosed by transvaginal sonography, and a comparable group of 73 had a normal uterine cavity.. Three doses of goserelin 3.6 mg subcutaneously at 4-week intervals were given, followed by hysteroscopic resection of the submucous part of fibroids if the fibroids remained submucous. Three patients had hysteroscopic resection without goserelin, as the fibroids were resectable when they were diagnosed. All patients underwent assisted conception within 3 months unless they conceived spontaneously in the interim.. The pregnancy rate in patients with normal uterine cavity was 26%/embryo transfer, and 15.8% of these ended in a miscarriage. The pregnancy rate was significantly higher (p >0.02) in the study group after treatment of submucous fibroids (48.2%/embryo transfer), and the miscarriage rate of 23.1% was not significantly different.. Submucous fibroids are a significant cause of subfertility. A combination of goserelin injections and hysteroscopic resection significantly improves pregnancy rates without increasing the miscarriage rate.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Confidence Intervals; Female; Fertilization; Goserelin; Humans; Hysteroscopy; Infertility, Female; Injections, Subcutaneous; Leiomyoma; Pregnancy; Pregnancy Outcome; Ultrasonography; Uterine Neoplasms

Uterine myomas and endometriosis are benign pathologies frequently encountered in women. Myomas are often associated with infertility and/or menorrhagia particularly if they are sub-mucosal. Endometriosis is diagnosed in more than 35% of infertile patients. These two common pathologies are oestrogen-dependent and the administration of a GnRH agonist has been proposed as a non-surgical approach to the treatment of myomas and endometriosis. GnRH agonists cannot, however, be considered as definitive medical therapy because most myomas and endometriotic cysts return to their initial size within 4 months following the cessation of treatment. Moreover, because of the menopausal-like state that they induce, GnRH agonists provoke bone demineralization and for this reason, their long-term use is not recommended. These agents should, therefore, be considered as an adjuvant preoperative therapy. The aim is, above all, to achieve a preoperative reduction of tumour size, thus facilitating the endoscopic surgery: either hysteroscopic resection in the case of sub-mucosal myomas, or vaporization of ovarian cysts in the case of cystic endometriotic lesions.

Topics: Adult; Biopsy; Combined Modality Therapy; Endometriosis; Female; Goserelin; Humans; Hysteroscopy; Infertility, Female; Laparoscopy; Leiomyoma; Menorrhagia; Ovarian Cysts; Preoperative Care; Prospective Studies; Treatment Outcome; Uterine Neoplasms

From January 1987 to February 1988 patients affected by uterine fibroid were offered medical treatment with luteinizing hormone-releasing hormone analogs as an alternative to surgery. The aim was to compare results obtained with two different analog formulations. 42 patients were randomly assigned to receive either intranasal buserelin, preceded by a short period of subcutaneous injections (500 micrograms thrice daily for 10 days) or subcutaneous goserelin. Treatment was always started in the luteal phase. Response to therapy was evaluated through periodic clinic, endocrine and echotomographic controls. There were no significative differences in fibroid reduction between the two treatment groups. After 6 months of treatment, a fibroid reduction of more than 30% of the initial volume was observed in 16 patients in the buserelin group and in 18 patients in the goserelin group. The fibroid regrowth observed in all patients during the follow-up period severely limits the usefulness of this medical approach to selected clinical cases.

Topics: Administration, Cutaneous; Administration, Intranasal; Adult; Buserelin; Chi-Square Distribution; Delayed-Action Preparations; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Leiomyoma; Luteinizing Hormone; Random Allocation; Ultrasonography; Uterine Neoplasms

Gonadotropin-releasing hormone agonists induce a reversible hypogonadotropic hypogonadal environment. Leiomyomas are common, estrogen-sensitive, benign neoplasms that decrease in size by 40% to 50% during gonadotropin-releasing hormone agonist treatment. During gonadotropin-releasing hormone agonist therapy most women are amenorrheic. After discontinuation of gonadotropin-releasing hormone agonist treatment, uterine and myoma size increase and a return to pretreatment menstrual patterns often occurs. Concerns about the safety of long-term hypoestrogenism have made long-term gonadotropin-releasing hormone agonist administration an undesirable treatment strategy. This article focuses on the use of gonadotropin-releasing hormone agonists as preoperative therapy in selected women undergoing hysterectomy or myomectomy and the combination of a gonadotropin-releasing hormone agonist with estrogen-progestin "add-back" treatment as a potential long-term medical therapy for women with symptomatic leiomyomas. Finally, an estrogen threshold hypothesis to assess the effects of circulating estrogen concentrations on different tissues, is presented.

Topics: Buserelin; Estradiol; Estrogens; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Leuprolide; Middle Aged; Pilot Projects; Preoperative Care; Progestins; Time Factors; Uterine Neoplasms; Uterus

Menorrhagia is the most frequent symptom in women with leiomyomata uteri. We induced transient hypoestrogenism with a gonadotropin-releasing hormone agonist, goserelin (Zoladex, I.C.I.), in a depot formulation, to resolve severe anemia in 16 women with uterine myomas. Subcutaneous administration of goserelin 3.6 mg was repeated every 28 days for 6 months. Thirteen patients became amenorrheic in 5 weeks and 3 reported scanty bleeding. Estradiol fell to postmenopausal levels after one month's treatment with hormonal surges on only three occasions. Uterine volume decreased by 49% after 3 months' treatment but subsequent reduction was not achieved. Mean hemoglobin rose from 7.4 g/dl pretreatment to 13.2 g/dl at 3 months (+78.3%) and mean hematocrit from 26.1% to 39.8% (+52.4%) without any further improvement. Serum ferritin increased constantly during the 6 months. Goserelin depot therapy in severely anemic patients with leiomyomas and menorrhagia is practical, safe and may avoid the need for preoperative transfusion.

Topics: Adult; Anemia, Hypochromic; Buserelin; Delayed-Action Preparations; Female; Goserelin; Humans; Leiomyoma; Menorrhagia; Middle Aged; Uterine Neoplasms

Topics: Adult; Buserelin; Drug Evaluation; Female; Goserelin; Humans; Leiomyoma; Middle Aged; Pilot Projects; Premedication; Uterine Neoplasms

A woman in her early 20s presented with cough and fever. She had undergone an abdominal myomectomy 3 years ago for uterine leiomyoma. Chest CT and positron emission tomography-CT revealed multiple round nodules in both lungs, suggesting metastatic lesions. A CT-guided lung biopsy was performed, and the tumour was diagnosed as pulmonary benign metastasising leiomyoma (PBML) based on pathological analyses. Whole exon capture sequencing of uterine leiomyoma and PBML sections revealed that 13 genes (MCM10, SLC16A9, RAG1, BAZ1A, NLRP2, TRMT61B, CPXM1, NGLY1, SUCLG2, FAM13A, CAGE1, PHTF2 and ZDHHC2) were concurrently present in the two tumours. The patient was prescribed goserelin injections every 4 weeks. The symptoms improved 2 weeks after starting the treatment. The lung nodules considerably decreased in size after three courses of goserelin treatment. The nodular size continues to decrease with the treatment.

Topics: Chromosomal Proteins, Non-Histone; Exons; Female; Goserelin; GTPase-Activating Proteins; Humans; Leiomyoma; Lung; Lung Neoplasms; Mutation; Uterine Neoplasms

To investigate the outcome of total laparoscopic hysterectomy (TLH) and postoperative pain characteristics and compare the pain severity after TLH for adenomyosis or uterine fibroids.. This prospective observational study collected 101 patients received TLH for adenomyosis (AD group) including 41 patients were injected goserelin (3.6 mg) 28 days before TLH, while other adenomyosis patients received TLH without preoperative treatment, and 113 patients received TLH for uterine fibroids (UF group). Pain scores were evaluated at different time sites from operation day to postoperative 72 h using the numeric rating scale. Clinical data were collected from clinical record.. Operative time and anaesthetic time were longer in the AD group than those in the UF group (66.88 ± 8.65 vs. 64.46 ± 7.21,. Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids. While patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.. Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids.Patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

Topics: Adenomyosis; Female; Goserelin; Humans; Hysterectomy; Laparoscopy; Leiomyoma; Pain, Postoperative; Visceral Pain

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

Topics: Adult; Antineoplastic Agents, Hormonal; Chemokine CCL2; Cytokines; Female; Goserelin; Humans; Inflammation Mediators; Leiomyoma; Longitudinal Studies; Prospective Studies; Severity of Illness Index; Tumor Necrosis Factor-alpha; Uterine Neoplasms

Benign metastasising leiomyoma (BML) is a rare entity characterised by uterine leiomyoma that, later on, develops slow-growing metastasis mainly to the lung. In general, these lung metastases are incidentally discovered, but sometimes can become symptomatic with dyspnoea, cough and chest pain. The expression of oestrogen and progesterone receptors by these tumours supports the idea that they respond to hormone therapy (chemical, with oestrogen receptor modulators, aromatase inhibitors or luteinising hormone releasing hormone analogues and surgical, with bilateral adnexectomy). The authors present a case report of BML with two peculiarities: a less common pattern of metastisation (soft tissue), in addition to lung; and disease progression despite treatment with chemical and surgical castration.

Topics: Antineoplastic Agents, Hormonal; Back; Biopsy; Diagnosis, Differential; Disease Progression; Female; Forearm; Goserelin; Humans; Leiomyoma; Lung Neoplasms; Middle Aged; Radiography, Thoracic; Soft Tissue Neoplasms; Thorax; Tomography, X-Ray Computed; Uterine Neoplasms

To identify the genes presenting different expression in uterine leiomyomas after goserelin treatment.. Retrospective analyses of tissue obtained in a prospective clinical study.. School of Medicine of the University of São Paulo.. 30 nulliparous black women aged 20 to 45 years with symptoms of uterine leiomyoma, uterine volume over 300 mL, and surgical indications for myomectomy.. Fifteen patients were given a monthly dose of 3.6 mg of goserelin over 3 months before surgery (group A), and 15 patients underwent surgery without any previous treatment (group B). Five random samples from each group were analyzed using the microarray technique with the Affymetrix platform (GeneChip Rat Genome 230 2.0 Array).. Quantification of transcript expression levels of uterine fibroids in patients treated or not treated with goserelin.. Of the total of 47,000 sequences that were analyzed, representing approximately 38,500 human genes already characterized, we found a differential expression of 174 genes. Of these, 70 were up-regulated (33 genes with known function) and 104 were down-regulated (65 genes with known function) in samples from group A (treated) when compared with group B (nontreated).. The genic expression of uterine leiomyomas changes in women who have had goserelin treatment when compared with nontreated patients.

Topics: Adult; Age Factors; Antineoplastic Agents, Hormonal; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Goserelin; Humans; Leiomyoma; Middle Aged; Reproduction; Retrospective Studies; Tissue Array Analysis; Uterine Neoplasms; Young Adult

Topics: Abdomen, Acute; Adult; Antineoplastic Agents, Hormonal; Female; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

To describe the successful hormone treatment of noncircumscribed orbital leiomyoma.. Case report.. A 66-year-old woman with histologically proven orbital leiomyoma.. Because surgical excision of the tumor was impossible, therapy with the gonadotropin-releasing hormone (GnRH) analog goserelin was performed.. Hormone treatment was well tolerated and no side effects were noted. The tumor regressed significantly during treatment. No recurrence occurred during a 5-year follow-up period.. This report describes for the first time successful hormone treatment of a noncircumscribed orbital leiomyoma. Goserelin may have an antiproliferative effect on leiomyoma cells via membrane receptors for GnRH.

Topics: Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Female; Goserelin; Humans; Leiomyoma; Magnetic Resonance Imaging; Orbital Neoplasms

Our aim was to study the effects of the gonadotropin releasing hormone agonist on the uterine leiomyoma of infertile women.. 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.. 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.. 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.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Goserelin; Humans; Leiomyoma; Myometrium; Parity; Receptors, Estrogen; Receptors, Progesterone; Uterine Neoplasms; Uterus

The content of RNA and DNA in human myometrium and fibroids obtained at different endocrine conditions varied, with the highest RNA/DNA ratio in tissues from pregnant patients, intermediate ratios in women during the menstrual cycle and the lowest in tissues from postmenopausal and GnRHa-treated patients. mRNA expression of two house-keeping genes, gamma-actin and GAPDH, was highest in myometrium from pregnant women, intermediate in untreated women of fertile age and lowest in tissues from GnRHa-treated and postmenopausal women. To control for degradation of nucleic acids when measuring mRNA expression, we suggest additional analysis of gene(s), where the expression pattern is known, and that expression, whenever possible, is related to DNA, which is a more stable parameter than RNA and total nucleic acids, when there are differences in proliferation between tissues and/or groups of patients.

Topics: Actins; Adult; Aged; DNA; Female; Gene Expression; Glyceraldehyde-3-Phosphate Dehydrogenases; Goserelin; Humans; Leiomyoma; Menstrual Cycle; Middle Aged; Myometrium; Postmenopause; Pregnancy; Pregnancy Complications, Neoplastic; RNA, Messenger; Uterine Neoplasms

Topics: Antineoplastic Agents, Hormonal; Female; Goserelin; Homocysteine; Humans; Leiomyoma; Preoperative Care; Uterine Neoplasms

This report describes 2 unusual morphologic features of leiomyomas in patients who had been treated preoperatively with gonadotropin-releasing hormone (GnRH) agonists. In 1 case there was extensive and widespread infiltration of the leiomyoma by numerous small mature lymphocytes, in keeping with a leiomyoma with massive lymphoid infiltration. In the other leiomyoma there were fibrin and foamy histiocytes within the walls of many arterioles, in keeping with a vasculitis. These 2 features, massive lymphoid infiltration and vasculitis, have rarely been described in association with GnRH agonists. Since GnRH agonists are increasingly being used in the management of uterine leiomyomas, pathologists should be aware of these unusual morphologic features in order to avoid diagnostic confusion.

Topics: Adult; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Female; Goserelin; Humans; Leiomyoma; Lymphocytes; Lymphoma; Middle Aged; Preoperative Care; Uterine Neoplasms; Vasculitis

To determine mRNA and protein expression of the progesterone receptor (PR) and insulin-like growth factor-I (IGF-I) in myometrium and fibroids.. Retrospective clinical study.. Hospital-based and university-affiliated research laboratories.. Twelve women in the proliferative phase and six women treated with GnRH analogue (GnRH-a).. Blood sampling and collection of myometrium and fibroids.. PR and IGF-I mRNA levels in fibroids and myometrium were analyzed by solution hybridization and in situ hybridization whereas the proteins were localized by immunohistochemistry.. Fibroids and myometrium from women in the proliferative phase showed significantly higher PR mRNA than the corresponding tissues from GnRH-a-treated women. The amount of cells positively stained for PR-AB and PR-B in fibroids and myometrium decreased after GnRH-a treatment compared with in the proliferative phase. The IGF-I mRNA in both fibroids and myometrium in the proliferative phase was significantly higher than those after GnRH-a treatment. The immunostaining of IGF-I showed no difference between the two tissues. There was weaker immunostaining in the GnRH-a-treated group compared with in the proliferative phase group.. The shrinkage of fibroids after steroid deprivation is associated with alterations in PR and IGF-I expression.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Follicular Phase; Gonadotropin-Releasing Hormone; Goserelin; Humans; Immunohistochemistry; Insulin-Like Growth Factor I; Leiomyoma; Middle Aged; Myometrium; Receptors, Progesterone; RNA, Messenger

The purpose of this study was to examine the influence of luteinizing hormone-releasing hormone analog goserelin on serum leptin and body composition in women with solitary uterine myoma.. Fifteen women who were regularly menstruating and not obese were included. In all subjects, serum concentrations of leptin, insulin, testosterone, progesterone, and estradiol and body mass index and waist-to-hip ratio were measured before and after 4, 8, and 12 weeks of treatment with goserelin (3.6 mg every 4 weeks). Fat mass and lean body mass were measured by dual energy radiographic densitometry at baseline and after 12 weeks of therapy. Data were analyzed by multiple way analysis of variance and both simple and multiple regression.. The treatment caused a significant regression of myoma. Body weight, fat, and lean mass were unchanged. No changes in plasma leptin (even after correction for fat mass) were noted during the treatment. Plasma estradiol decreased below castrate levels. Plasma progesterone decreased significantly, and testosterone tended to decline during the study. At baseline a highly significant positive correlation was found between serum leptin and fat mass. In a multiple regression analysis, neither the change in fat mass nor any of the hormonal parameters explained the significant portion of variance of plasma leptin during the treatment.. Pharmacologic gonadectomy does not influence plasma leptin concentrations in women if body fat mass is unchanged.

Topics: Adipose Tissue; Adult; Antineoplastic Agents, Hormonal; Body Composition; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Leptin; Middle Aged; Progesterone; Testosterone; Uterine Neoplasms

Topics: Adult; Antineoplastic Agents, Hormonal; Deoxyglucose; Female; Goserelin; Humans; Leiomyoma; Radionuclide Imaging; Uterine Neoplasms

A 40-year-old primigravida presented with acute urine retention. Ultrasound examination revealed a large uterine submucosal leiomyoma and GnRH-a was administered. The leiomyoma grew to over twice its original size and protruded through the introitus. After 10 days, it was expelled completely and removed by resectohysteroscopy. The expulsion of the leiomyoma was most likely a result of GnRH-a's flare-up effect.

Topics: Adult; Female; Goserelin; Humans; Leiomyoma; Magnetic Resonance Imaging; Ultrasonography; Urinary Retention; Uterine Neoplasms

Although uterine leiomyomas constitute the commonest benign tumour in women, the regulation of their growth is poorly understood. It is believed that angiogenesis, the process by which new capillaries develop from pre-existing blood vessels, may be involved. We therefore investigated the expression of vascular endothelial growth factor-A (VEGF-A), a primary regulator of angiogenesis, in leiomyoma tissue and the adjacent myometrium in 36 pre-menopausal women undergoing hysterectomy for leiomyomas, with or without prior treatment with gonadotrophin-releasing hormone analogue (GnRHa). In 5 microm sections prepared from archival paraffin-wax blocks, VEGF-A was demonstrated by standard immunohistochemistry using a monoclonal antibody. VEGF-A was expressed in 14 of 18 (77.8%) leiomyoma sections from women without GnRHa pretreatment, and in 15 of 18 (83%) of those from women with prior treatment. VEGF-A expression in the adjacent myometrium was much lower, being noted in two of 18 (11.1%) sections from women without prior GnRHa treatment and in one of 18 (5.5%) sections from tissue that had been subject to prior down-regulation. Moreover, when VEGF-A expression was present, expression was strong in leiomyomas (> or =20 focal areas/cm(2)), but not in adjacent myometrium. The differential expression of VEGF-A antigen in leiomyomas compared with the adjacent myometrium indicates that local angiogenesis may be important in the development and growth of these tumours. GnRHa therapy does not appear to alter this pattern of VEGF-A expression.

Topics: Adult; Antineoplastic Agents, Hormonal; Endothelial Growth Factors; Female; Goserelin; Humans; Leiomyoma; Middle Aged; Myometrium; Neovascularization, Pathologic; Uterine Neoplasms; Vascular Endothelial Growth Factor A

Uterine leiomyomas (uterine fibroids) are sex-steroid dependent benign tumors. Limited knowledge is available regarding the role of estrogen and their receptors in the regulation of fibroids in premenopausal women, and in their shrinkage after treatment with a gonadotropin-releasing hormone analogue (GnRHa). The expression of the two subtypes of the estrogen receptor (ER), ER alpha and ER beta, was studied in leiomyoma and homologous myometrium from women in the proliferative phase of the menstrual cycle and from women treated with GnRHa. The mRNA levels of ER alpha and ER beta were monitored by solution hybridization and in situ hybridization, and receptor proteins were detected and localized by immunohistochemistry. Both ER alpha and ER beta were present in the leiomyomas and homologous myometrium. The ER alpha mRNA level in the leiomyomas was higher than in the surrounding myometrium. The ER beta mRNA level was lower than that of ER alpha in both groups. ER beta immunoreactivity was lower in leiomyomas when compared with the myometrium after GnRHa treatment, while ER alpha was higher in the leiomyomas. The present results imply that the increased ratio of ER alpha/ER beta observed in the fibroids after GnRHa treatment could reflect or be the cause of the shrinkage of the leiomyoma, which is the clinical outcome of this treatment.

Topics: Adult; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression; Goserelin; Humans; Immunohistochemistry; In Situ Hybridization; Leiomyoma; Menstrual Cycle; Middle Aged; Myometrium; Receptors, Estrogen; RNA, Messenger; Uterine Neoplasms

Gonadotropin releasing hormone agonist (GnRH-agonist) therapy has been useful as an adjunct before myomectomy or hysterectomy for uterine myoma but the concealed risk is often overlooked. We report an extremely rare clinical presentation of a patient with multiple submucosal myomata during the treatment of long-acting gonadotropin-releasing hormone agonist (GnRH-agonist) in a 23-year-old, virgin woman. This patient exhibited heavy menstruation and severe anemia for half of a year. Ultrasound demonstrated multiple submucous myomata and intramural myomata. She received a conservative medical treatment by GnRH-agonist. The patient showed marked suppression of serum estradiol concentrations throughout treatment (< 20 pg/ml since first dose injection). The volume of the uterus decreased 21% and the total volume of the uterine myomata decreased 27% at the end of the second dose injection. However, a sudden onset of major hemorrhage occurred at the 65th day without "add-back" hormonal replacement therapy after initial therapy of GnRH-agonist. Hypovolemic shock followed soon and immediately resuscitation was performed. After resuscitation, the patient was treated with hysteroscopic myomectomy, followed by 30 ml balloon Foley catheter placement for compressing the intrauterine rough surface and hormonal replacement therapy. When uterus returned to the normal size at the end of the first week, intrauterine device was positioned and maintained for three months. The patient married four months later and got pregnant soon. Now she has a pregnancy of 22 gestational weeks. The phenomenon suggests presence of concealed and potential risk of GnRH-agonist for managing a patient with multiple submucous myomata, even though GnRH-agonist is a well-documented transient treatment for uterine myomata not only by its effect on tumor shrinkage and decreasing blood loss during the myomectomy but also by providing a time for hematological recovery. This unexpected and unwanted clinical presentation should be alerted.

Topics: Adult; Female; Goserelin; Humans; Leiomyoma; Uterine Hemorrhage; Uterine Neoplasms

The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and fibroids from women with and without preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, from post-menopausal women, from pregnant women and in myometrium from women without fibroid disease. Women with menstrual periods were classified according to the phase of the cycle. In tissues from non-treated premenopausal women, IGF-I mRNA expression was significantly higher in fibroids than in myometrium, with no differences related to phase of the menstrual cycle. In post-menopausal women and in GnRH agonist-treated women responding to treatment, similar mRNA expression was seen in myometrium and fibroids but the concentrations were lower than in untreated premenopausal women. The IGF-I mRNA value in fibroids from pregnant women was higher than in any other group and myometrium from pregnant women exhibited higher mRNA expression than myometrium from non-treated premenopausal women. The IGF-I protein was more abundant in fibroids than in myometrium of non-treated premenopausal and of pregnant women and in both tissues the concentration was significantly higher in the group of pregnant women. The IGF-I protein concentrations in fibroids and myometrium from GnRH agonist-treated and post-menopausal women were similar to those from premenopausal non-treated women. High sex steroid concentrations in pregnant and non-pregnant women of fertile age seem to be associated with a higher expression of IGF-I in fibroids than in myometrium, suggesting that IGF-I contributes to the selective growth advantage of these tumours.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Estradiol; Female; Follicle Stimulating Hormone; Gene Expression; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin-Like Growth Factor I; Leiomyoma; Menopause; Menstrual Cycle; Middle Aged; Myometrium; Pregnancy; Progesterone; RNA, Messenger

Topics: Adult; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Endometrial Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

Topics: Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Middle Aged; T-Lymphocytes; Uterine Neoplasms

Uterine myomas are benign tumors of the uterus, occurring in up to 25% of women of reproductive age. We examined the possible causes for different degrees of volume reduction in patients with uterine myomas who received gonadotropin-releasing hormone agonist (GnRHa) treatment by investigating the hormone receptors at the end of GnRHa treatment.. This trial was designed as a prospective study of five premenopausal women presenting with symptomatic uterine myoma. All patients were treated with a subcutaneous injection of goserelin depot 3.6 mg every four weeks for 16 weeks. Clinical examinations, hormonal evaluation and ultrasound determinations were performed before, during and after treatment. At the end of the treatment period, all patients underwent myomectomy. The concentrations of the unbound progesterone receptors and estrogen receptors were evaluated.. The volume of the uterine myoma decreased by 21% to 65%. The percentage of decrease in volume of treated uterine myomas was found to negatively correlate with the concentration of unbound progesterone receptors (r2 = 0.92, p = 0.008). This percentage was not significantly correlated with the concentration of unbound estrogen receptors (r2 = 0.02, p = 0.84).. The limited data available suggested that the volume decrease of uterine myomas in GnRHa-treated patients is partly dependent on the concentrations of unbound sex-hormone receptors in the uterine myomas.

Topics: Antineoplastic Agents, Hormonal; Female; Goserelin; Humans; Leiomyoma; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; Ultrasonography; Uterine Neoplasms

To evaluate the clinical utility of recently developed biochemical markers in the assessment of bone metabolism during GnRH agonist (GnRHa) treatment, we compared five bone resorption markers [C-telopeptide (CTX) and N-telopeptide (NTX) of type I collagen, hydroxyproline (Hpr), pyridinoline (Pyr), and deoxypyridinoline (Dpyr)] and two bone formation markers [total alkaline phosphatase (Alp) and osteocalcin (OC)]. Sixty-eight normally menstruating women were injected with a long-acting GnRHa once a month for 24 weeks for the treatment of endometriosis or leiomyoma. The mean percentage bone loss at the lumbar spine was 3.79% at the end of treatment. Although levels of all markers increased significantly as the treatment progressed, CTX and NTX exhibited the highest correlation coefficients between bone loss at 24 weeks and the seven markers measured at 0, 4, 12, 16, and 24 weeks of treatment. Serum estradiol levels were similarly suppressed during the treatment in both fast losers (whose bone loss was more than the mean) and slow losers (whose bone loss was less than the mean). However, significantly higher z-scores of bone resorption markers, but not of bone formation markers, were observed in the fast losers at 24 weeks of treatment, suggesting a more accelerated bone resorption in this group. Whereas the three highest z-scores at 24 weeks of treatment were CTX, NTX, and Dpyr (in that order), the highest z-score (P < 0.05) was observed for CTX in the fast losers. The subjects in the highest quartile of CTX, the highest, and second highest quartiles of NTX at 24 weeks of treatment experienced 2.1, 2.2, and 1.7 times more bone loss (P < 0.001), respectively, than those in the lowest quartiles. Furthermore, the subjects in the highest quartile of both CTX and NTX experienced 3.6 times more bone loss (P < 0.001) than those in the lowest quartile of both markers. These results indicate that both CTX and NTX are useful and sensitive markers for bone resorption in a hypoestrogenic state induced by GnRHa.

Topics: Adult; Alkaline Phosphatase; Amino Acids; Antineoplastic Agents, Hormonal; Biomarkers; Bone Remodeling; Buserelin; Collagen; Collagen Type I; Endometriosis; Estradiol; Female; Goserelin; Humans; Hydroxyproline; Leiomyoma; Osteocalcin; Peptides; Retrospective Studies

We report a case with menorrhagia due to uterine fibroids who was admitted following an episode of unstable angina. Her coronary angiogram showed a tight proximal left anterior descending artery lesion for which stenting was deemed necessary. She was successfully anticoagulated in spite of her menorrhagia under cover of a gonadotrophin hormone releasing agonist; goserilin.

Topics: Angina, Unstable; Antineoplastic Agents, Hormonal; Coronary Angiography; Electrocardiography; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Hemoglobins; Humans; Injections, Subcutaneous; Leiomyoma; Menorrhagia; Middle Aged; Stents; Uterine Neoplasms

To report two unusual cases of massive lymphocytic infiltration of uterine leiomyomas, following GnRH agonist treatment. Previous reports have described a variety of alterations in leiomyoma histology following such therapy.. These cases were studied using haematoxylin and eosin stains, and immunohistochemistry for B and T-cell markers (CD20/CD79a and CD3/UCHL-1) was performed. Leiomyomas were heavily infiltrated predominantly by mature lymphocytes of T-cell phenotype. Associated myocyte degenerative changes were present.. Massive lymphocytic infiltration of leiomyomas may occur as a result of GnRH agonist treatment, although the mechanism is unclear.

Topics: Antineoplastic Agents, Hormonal; Combined Modality Therapy; Female; Goserelin; Humans; Leiomyoma; Lymphocytes; Middle Aged; Uterine Neoplasms

This study attempted to search for the possible mechanism of regrowth of uterine myoma after cessation of gonadotropin-releasing hormone agonist (GnRHa) therapy.. Five premenopausal women presenting with symptomatic uterine myoma were prospectively studied in this trial. All patients were treated with a subcutaneous injection of goserelin depot 3.6 mg every four weeks for 16 weeks. Clinical examinations as well as hormonal and ultrasound determinations were performed before, during and after treatment to monitor the efficacy of therapy. At the end of the treatment period, all patients underwent myomectomy. The ultrastructural change of the myoma was evaluated postoperatively.. The volume of the uterus decreased 21-57% and the volume of the uterine myoma decreased 21-65% after therapy. There was no significant change in resistance index of the uterine vessels or major vessels supplying the uterine myoma between pretreatment and post-treatment values. The morphologic features of the treated myoma showed marked cellular shrinkage and loss of myofibrillar structure.. There is no significant cellular damage to the cellular structure that contributes to regrowth of treated intramural uterine myoma following cessation of treatment.

Topics: Antineoplastic Agents, Hormonal; Female; Goserelin; Humans; Leiomyoma; Middle Aged; Prospective Studies; Ultrasonography; Uterine Neoplasms; Uterus

The aim of this study was to obtain data about the pregnancy rate in patients with uterine leiomyomata after treatment with gonadotropin-releasing hormone (GnRH) agonists followed by myomectomy. Between 1987 and 1993, 61 patients with uterine leiomyomata and sterility underwent 6 months' GnRH agonist treatment, in part with a surgical intervention. Sixty-two per cent of the patients suffered from concomitant endometriosis. After hormonal therapy 41 patients underwent a myomectomy. According to sonographic and clinical criteria, there was no indication for the enucleation of the leiomyomata for the remaining 20 patients. Owing to the combined therapy, consisting of primary treatment of uterine leiomyomata with GnRH agonists, followed by surgical intervention, 25 patients (41%) suffering from long-term sterility (average 4 years) became pregnant. An early abortion occurred in only three cases (12%). No patient who underwent a myomectomy developed new myomata during the following pregnancy. Four patients suffering from a single leiomyoma became pregnant within the first 3 months after myomectomy, all of them conceiving spontaneously. Considering the high rate of spontaneous conceptions and the low abortion and complication rates during pregnancy, the combined therapy of GnRH agonists followed by myomectomy represents a major step forwards in the effective treatment of sterility in patients with uterine leiomyomata.

Topics: Administration, Intranasal; Adult; Antineoplastic Agents, Hormonal; Buserelin; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Infertility, Female; Injections, Intramuscular; Leiomyoma; Leuprolide; Nafarelin; Pregnancy; Pregnancy Rate; Retrospective Studies; Time Factors; Triptorelin Pamoate; Uterine Neoplasms

Nineteen patients with fibromyomas who had been recommended to have a hysterectomy or abdominal myomectomy were referred as they wished to avoid a hysterectomy (14) or laparotomy incision for a myomectomy (5). Following administration of the GnRH analogue goserelin, laparoscopic surgery was performed on all these patients. Hysterectomy was avoided in all but 1 of the 14 patients and laparotomy myomectomy was avoided in 4 of the 5 patients recommended to have these procedures. The combination of a GnRH analogue and laparoscopic-based surgery may be an acceptable alternative to both laparotomy myomectomy and hysterectomy in women with fibromyomas requiring surgery.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Goserelin; Humans; Hysterectomy; Laparoscopy; Leiomyoma; Middle Aged; Treatment Outcome; Uterine Neoplasms

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Drug Therapy, Combination; Estradiol; Estrogen Replacement Therapy; Female; Follow-Up Studies; Goserelin; Humans; Leiomyoma; Lipid Metabolism; Lipids; Middle Aged; Time Factors; Uterine Hemorrhage; Uterine Neoplasms

We evaluated the effects on bone mineral density (BMD) of a 12-month treatment with goserelin depot, a gonadotropin-releasing hormone agonist, in a group of women with symptomatic uterine myomas requiring hysterectomy. Sixteen women, mean age 45.6 +/- 5.0, reporting menorrhagia associated with uterine myomas, candidates for hysterectomy, were scheduled to be treated with goserelin depot for 12 months. BMD was measured at the vertebral (L2-L4) and proximal femur level (femoral neck and trochanter) at the start of therapy and 6, 12, and 18 months later using dual energy X-ray absorptiometry (Hologic QDR 1000/W). The patients were followed for a minimum of 6 months after the end of treatment. Thirteen of the 16 women enrolled completed the treatment and three suspended it after 5, 6, and 7 months, respectively, because of side effects (hot flashes, insomnia, depression). Of the 13 women who completed the treatment, three underwent hysterectomy because of myoma regrowth and the recurrence of symptoms 3-18 months later; four reached the menopause 5-16 months later, and six were all menstruating normally with a follow-up varying from 6 to 18 months. After 12 months of therapy we observed a bone loss at vertebral, femoral neck, and trochanter of 4.4% (P < 0.05 versus baseline; P = not significant versus 6 months), 7.5% (P < 0.01 versus baseline, P < 0.01 versus 6 months), and 7.6% (P < 0.001 versus baseline, P < 0.05 versus 6 months), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Bone Density; Delayed-Action Preparations; Female; Goserelin; Humans; Hysterectomy; Leiomyoma; Middle Aged; Osteoporosis, Postmenopausal; Uterine Neoplasms

Topics: Adult; Combined Modality Therapy; Female; Goserelin; Humans; Hysterectomy, Vaginal; Leiomyoma

Topics: Adult; Female; Goserelin; Humans; Hysterectomy; Leiomyoma; Uterine Hemorrhage

To elucidate the mechanisms of action of GnRH agonists on uterine leiomyomas, morphometric and ultrastructural studies have been carried out on leiomyomas from patients treated with goserelin, and comparisons made with untreated tumors. The treated cases showed a variable degree of reduction of uterine size associated with leiomyoma shrinkage, and there was a correlation between the volume loss and the original size of the uterus. The morphological features of the treated lesions were very variable, with some showing evidence of marked cellular shrinkage and ultrastructural cytoplasmic changes, some having a lymphoid cell infiltrate, and others being indistinguishable from untreated control cases apart from having an increased number of compound lysosomes in the myoma cell cytoplasm. The degree of cellular shrinkage, measured by nuclear crowding, showed an inverse relationship to the proportion of collagen in the sections but none of the histological variables measured correlated with the degree of uterine shrinkage. It is concluded that the proportion of collagen in the lesions and other factors such as density of estrogen receptors, vascularity, cell proliferation rates, and degree of inflammatory cell infiltration affect the response to GnRH agonist therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Female; Goserelin; Humans; Leiomyoma; Microscopy, Electron; Middle Aged; Ultrasonography; Uterine Neoplasms

Uterine leiomyoma is the most common female benign pelvic tumor, affecting 20-25% of women during their reproductive years. There is strong clinical evidence that these tumors are estrogen-dependent for their growth, as also supported by their clear regression after the menopause. Although large clinical trials have not yet been reported, according to the estrogen dependency of uterine fibroids, LHRH agonists have been shown to be effective in the treatment of these conditions because they produce a condition of temporary hypoestrogenism secondary to the specific hypogonadotrophinism. This study was designed to evaluate if specific binding sites for LHRH are present in human uterine leiomyomata, myometrium and endometrial tissue. These tissues were taken from the fresh operative specimens of 14 patients who had undergone total hysterectomy for uterine leiomyomata. The results of this study demonstrate the presence of a LHRH specific binding site in uterine leiomyomata in 26% of cases; this specific binding site is also present both in myometrium and in endometrial tissue in 71% of cases. Moreover our study shows, for the first time, the high specificity of binding between LHRH agonist (goserelin) and natural LHRH receptor. In accordance with our results, a direct effect of LHRH agonists on fibroid tissue can be stressed.

Topics: Adult; Analysis of Variance; Endometrium; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysterectomy; Leiomyoma; Middle Aged; Myometrium; Radioligand Assay; Receptors, LHRH; Uterine Neoplasms

The authors discuss the usefulness of GnRH analogues inducing, through pituitary desensitization, a transient block of gonadal steroidogenesis--before hysterectomy for uterine leiomyomas. In patients with severe anemia these drugs proved to be very effective in improving the haematologic parameters; they also cause a significant reduction of uterine volume, thus allowing, in selected cases, vaginal hysterectomy in selected cases.

Topics: Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysterectomy; Hysterectomy, Vaginal; Leiomyoma; Multicenter Studies as Topic; Preoperative Care; Randomized Controlled Trials as Topic; Uterine Neoplasms

Topics: Danazol; Endometriosis; Endometrium; Female; Follow-Up Studies; Goserelin; Hemostasis, Endoscopic; Humans; Hysteroscopy; Laser Therapy; Leiomyoma; Menorrhagia; Preoperative Care; Treatment Outcome; Uterine Neoplasms

Topics: Adult; Ascites; Female; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

To investigate the effect of gonadotropin releasing hormone agonist (goserelin) treatment before hysterectomy for leiomyomata-associated menorrhagia.. Prospective, comparative, nonrandomized study.. A teaching hospital of Milano University.. Anemic women requiring hysterectomy for myoma-associated menorrhagia.. Six months' preoperative goserelin treatment (41 cases) or immediate surgery (92 controls).. Abdominal/vaginal hysterectomy rate, number of transfusions, operating time, blood loss, complications, febrile morbidity, and days in hospital.. In the goserelin group mean hemoglobin rose (8.5 versus 13.3 g/dl) and mean uterine volume decreased (528 versus 251 ml). At preoperative pelvic exploration abdominal hysterectomy was indicated in 22 (54%) cases and 74 (80%) controls and vaginal hysterectomy in 19 (46%) and 18 (20%) (relative risk 3.6, 95% confidence interval 1.6 to 7.7; p = 0.001). No case required a transfusion whereas 51% of controls needed a total of 127 packed red cell units.. In anemic women with menorrhagia and leiomyomas, gonadotropin releasing hormone agonist treatment before hysterectomy limited transfusion requirements and increased the vaginal procedure rate.

Topics: Adult; Anemia, Hypochromic; Female; Goserelin; Humans; Hysterectomy; Leiomyoma; Menorrhagia; Middle Aged; Premedication; Prospective Studies; Treatment Outcome; Uterine Neoplasms

GnRH analogues are widely used for the reduction of uterine fibroids. This case report describes the therapy of a 27-year-old woman, whose uterus had a diameter of about 13 cm. After 7 injections of Zoladex Depot (ICI Pharma, Heidelberg, Germany), the uterus was reduced to normal size carrying dorsally a myoma of the same size. After only 7 weeks of medroxyprogesterone acetate (5 mg twice daily, Clinofem, Upjohn, Heppenheim, Germany) the uterus had grown again, so that therapy was changed to Zoladex Depot for another 3 months. On the 27th day of the first spontaneous cycle, the patient ovulated and conceived. Up to the 29th week of gestation (Aug '91), the foetal growth and development was normal, the uterus was normal in size, a childhead sized myoma being situated unproblematically behind the foetus.

Topics: Adult; Antineoplastic Agents; Buserelin; Delayed-Action Preparations; Dose-Response Relationship, Drug; Down-Regulation; Drug Administration Schedule; Female; Goserelin; Humans; Leiomyoma; Medroxyprogesterone; Medroxyprogesterone Acetate; Pregnancy; Pregnancy Complications, Neoplastic; Receptors, LHRH; Uterine Neoplasms

Twenty-seven patients with uterine fibroids were treated for 3 months with the GnRH-agonist goserelin prior to surgical myomectomy. Ovarian function was suppressed reliably in all patients. After three applications, 15 fibroids were reduced in volume by more than 50%, and one complete remission was achieved. Seven patients showed a decrease of 10-50% in volume. However, in 5 cases there was no significant reduction. Analysing the time course of the fibroid reduction, the response can be predicted in most cases as early as four weeks after the first injection. Retrospective statistical analysis showed that a 50% reduction in fibroid size due to GnRH treatment is preceded by a 35% reduction after 4 weeks in 81% of cases, and after 8 weeks in all cases. Only 2 of 12 fibroids, which showed a smaller response (less than 50%) to GnRH therapy, were reduced by more than 35% after 4 and 8 weeks. In most cases it seems to be possible to estimate the individual response to GnRH-application after the first injection, so that it is possible to stop therapy in non-responding patients.

Topics: Buserelin; Estradiol; Female; Goserelin; Humans; Leiomyoma; Remission Induction; Retrospective Studies; Time Factors; Uterine Neoplasms

Topics: Adult; Bone Density; Buserelin; Climacteric; Delayed-Action Preparations; Drug Therapy, Combination; Estrogen Replacement Therapy; Female; Follow-Up Studies; Goserelin; Humans; Leiomyoma; Middle Aged; Uterine Neoplasms

Topics: Adult; Buserelin; Combined Modality Therapy; Endometriosis; Female; Goserelin; Humans; Hysteroscopy; Leiomyoma; Myometrium; Ovarian Neoplasms; Prospective Studies; Uterine Neoplasms

Six patients with large uterine fibroids were given a single subcutaneous implant of an LHRH analogue (goserelin 3.5 mg) prior to elective hysterectomy. Overall fibroid volume decreased by 30-47% within six weeks of implantation. All patients reported improvement in their symptoms of pressure and pain, and were rendered amenorrhoeic prior to surgery.

Topics: Adult; Buserelin; Combined Modality Therapy; Female; Goserelin; Humans; Leiomyoma; Middle Aged; Preoperative Care; Uterine Neoplasms

Ten pre-menopausal women with uterine leiomyoma were treated for 1 year with a monthly depot of luteinizing hormone-releasing hormone agonist (LHRA-a), goserelin, combined after the initial 3 months of treatment with conjugated oestrogens 0.3 mg (days 1-25) and medroxy-progesterone acetate 5 mg (days 16-25). Mean leiomyoma volume decreased by 49.3% during the first 3 months when goserelin alone was administered but did not change significantly during the 9 months of combination therapy. There were no significant changes in bone mass or high-density lipoprotein cholesterol during the study whereas hot flushes and menstrual blood loss were well controlled. These results indicate that ovarian suppression with a monthly depot of the LHRH-a, goserelin, combined after 3 months with low-dose hormonal replacement therapy reduced the size and the symptomatology of leiomyoma while preserving the bone mass.

Topics: Adult; Antineoplastic Agents; Bone Density; Buserelin; Cholesterol; Contraceptive Agents, Female; Drug Therapy, Combination; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Goserelin; Humans; Leiomyoma; Medroxyprogesterone; Medroxyprogesterone Acetate; Menstruation; Middle Aged; Pilot Projects; Triglycerides; Uterine Neoplasms

Topics: Buserelin; Female; Goserelin; Humans; Hysterectomy; Leiomyoma; Premedication; Uterine Neoplasms

Therapy with GnRH analogs is the first medical solution to be really effective in treating uterine fibromas, even if with limited and temporary benefits. Out of the 12 patients treated the Authors observed that a 60% reduction of the volume of the uterus can be achieved after 3-6 months therapy, with rapid recuperation of the initial volume after interruption of the treatment. It is therefore preferable to use GnRH analogs as a propedeutic therapy rather than surgery.

Topics: Adult; Buserelin; Delayed-Action Preparations; Female; Goserelin; Hemoglobins; Humans; Leiomyoma; Middle Aged; Pregnancy; Remission Induction; Ultrasonography; Uterine Neoplasms

Epidermal growth factor receptors (EGFr) were studied by immunohistochemistry in human myometrium and leiomyomas from women treated with the GnRH agonist (GnRH-a) goserelin. The results were compared with those obtained from women not treated. Vessel cells of leiomyomas and myometrium were always more immunoreactive than fibrocytes and myocites. In fibroids from treated patients the histochemical score (HSCORE) of vessel cells was always significantly lower (p less than 0.001) than in control patients. Our data confirm a role of EGF also in fibroid growth and suggest that, the blood supply reduction associated with the volume reduction of these tumours, consequent to the GnRH-a treatment, could be EGF mediated.

Topics: Adult; Buserelin; Delayed-Action Preparations; ErbB Receptors; Female; Goserelin; Humans; Immunohistochemistry; Leiomyoma; Middle Aged; Myometrium; Ultrasonography; Uterine Neoplasms

Topics: Adult; Androgens; Antineoplastic Agents; Buserelin; Drug Implants; Endometriosis; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Intramuscular; Leiomyoma; Luteinizing Hormone; Triptorelin Pamoate; Uterine Neoplasms

The administration of GnRH analogues is expected to improve treatment by avoiding hysterectomy, since problems connected with the surgical removal of leiomyomata are correlated with their size. In this study the GnRH analogue goserelin in its depot formulation (Zoladex, ICI, Plankstadt) was used for treating isolated leiomyomata of the uterus. All patients were treated for 3 months before myomectomy was performed. The complete regression of a large myoma (206 cm3) was observed in 1 of 11 patients. In 5 cases a reduction in volume of more than 50% was achieved. Ovarian function was suppressed by goserelin, after a short-term stimulation, within 7 +/- 3 days. Serum levels of 17 beta-oestradiol were found to be generally less than 25 pg/ml. All patients reported climacteric complaints, but in no case had therapy to be discontinued. After cessation of goserelin, restoration of ovarian function was observed in all patients.

Topics: Adult; Buserelin; Combined Modality Therapy; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Leiomyoma; Luteinizing Hormone; Progesterone; Ultrasonography; Uterine Neoplasms; Uterus

In a 28-year-old patient with a large uterine leiomyoma, complete tumor regression was achieved by the LHRH agonist Zoladex (ICI 118.630) when administered three times. During the follow-up period of three months, new myoma growth did not occur. On the basis of this case study, it is necessary to discuss a new therapy concept for the differentiated treatment of uterine leiomyomata in young women with a desire for pregnancy.

Topics: Adult; Buserelin; Delayed-Action Preparations; Female; Goserelin; Humans; Injections, Subcutaneous; Leiomyoma; Neoplasms, Hormone-Dependent; Ultrasonography; Uterine Neoplasms; Uterus

Since uterine leiomyomata (fibroids) are not found in conditions where oestradiol is either absent or present only in low concentrations, oestradiol is considered to be an important factor in the control of fibroid growth. To investigate whether this is due to a direct effect on the tissue, oestradiol and progestogen receptors were measured in tissue removed at hysterectomy from 12 normally cycling women and 13 women who had received the gonadotrophin-releasing hormone (GnRH) agonist Zoladex (ICI 118630) as a subcutaneous depot given at monthly intervals for 3 months preoperatively and a third group of three women who had received the antioestrogen tamoxifen (20 mg daily) for 3 months before surgery. Both unoccupied oestradiol receptors (measured by separating bound from free hormone with dextran-coated charcoal; DCC) and 'total' receptor populations (as measured by an enzyme immunoassay) were measured in each fibroid and adjoining myometrium. There was significantly more binding of both oestradiol and progestogen to fibroid than to myometrium in both the control (P less than 0.01) and agonist-treated groups (P less than 0.05). Oestradiol binding to fibroids in women treated with Zoladex exceeded that in the normally cycling women (P less than 0.05) which in turn exceeded that in the tamoxifen-treated group (P less than 0.05). However, the binding of progestogen, measured by DCC showed the reverse trend. These results may be explained by the low circulating oestradiol concentration in the GnRH agonist-treated women leading to low receptor occupancy.

Topics: Buserelin; Estradiol; Female; Goserelin; Humans; Leiomyoma; Menstrual Cycle; Myometrium; Progesterone; Receptors, Estradiol; Receptors, Progesterone; Uterine Neoplasms; Uterus

Twelve patients with uterine fibroids, who were due to undergo myomectomy, were treated preoperatively with the luteinising hormone-releasing hormone analogue, Zoladex. This resulted in a marked reduction in uterine and fibroid volume and surgery was facilitated.

Topics: Buserelin; Female; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

Luteinising hormone-releasing hormone analogues have been found to reduce the size of uterine fibroids. Further studies are required to determine their exact mechanism of action. However, they are known to induce hypo-oestrogenism, which leads to reduction in uterine arterial blood flow, one mechanism by which reduction of fibroid size is thought to occur.

Topics: Buserelin; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Nafarelin; Uterine Neoplasms

Treatment of patients with fibromyomata by Zoladex produces suppression of ovarian function. Receptor changes also occur in fibroids of women treated with Zoladex. The concentration of oestradiol receptors is significantly higher, whilst that of epidermal growth factor and progesterone is significantly lower.

Topics: Buserelin; ErbB Receptors; Female; Goserelin; Humans; Leiomyoma; Receptors, Estradiol; Receptors, Progesterone; Uterine Neoplasms

We know that there is a wide range of clinical applications for GnRH analogues in the field of benign gynaecological disorders. As we understand more of the physiology and mechanism of these GnRH agonists, and there appear more varied and perhaps efficient delivery systems, and antagonists become available, it may be possible to develop a graded approach in suppression of the hypothalamic pituitary axis. The true potential of these agents is then yet to be fully realized. There can be no doubt they are going to influence practice dramatically over the next decade. The potency of these agents, perhaps specifically their effects of oestrogen deficiency and calcium bone metabolism, suggests that limitation of duration of use and timing of recurrent administration to individuals is likely to be necessary.

Topics: Buserelin; Danazol; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Nafarelin; Osteolysis; Polycystic Ovary Syndrome; Uterine Neoplasms

The binding of epidermal growth factor (EGF) to human myometrium and leiomyomata was assessed in a group of women rendered hypo-oestrogenic with the LHRH agonist Zoladex (ICI 118630). The results were compared with those obtained with tissues from women with normal cycles. In normal women, the specific binding of radiolabelled [125I] EGF to both myometrial and fibroid homogenates did not vary during the menstrual cycle, but the specific binding of [125I] EGF to fibroid in women treated with LHRH agonist was significantly less than in the untreated group. Since the hypo-oestrogenic state induced by the agonist is associated with a decrease in fibroid size, the results suggest that the effect of oestrogen on fibroid tissue may partly be mediated by EGF.

Topics: Adult; Buserelin; Epidermal Growth Factor; Estradiol; Female; Goserelin; Humans; Leiomyoma; Menstrual Cycle; Myometrium; Uterine Neoplasms

Topics: Buserelin; Delayed-Action Preparations; Endometriosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Uterine Neoplasms

Thirteen premenopausal women with uterine fibroids were treated for a maximum of 6 months with a long-acting agonist of luteinizing hormone-releasing hormone (LH-RH), goserelin (Zoladex depot, ICI Pharmaceuticals, Macclesfield, UK) 3.6 mg, administered subcutaneously every 28 days. A 55% reduction (range, 38% to 84%) in uterine volume assessed by ultrasound was obtained. The greatest reduction (30%) was apparent within the first treatment cycle regardless of whether treatment was started in the early follicular or the luteal phase. Fibroid regression was inversely correlated with urinary estrogen concentration. Treatment was well tolerated and only one subject withdrew from the study before its scheduled completion. Following cessation of therapy, ovulatory menstruation returned within 3 months in the majority of the subjects, but this was accompanied by a rapid regrowth of the fibroids. This medical approach to the management of fibroids merits further investigation but as yet cannot be regarded as an alternative to surgery.

Topics: Adult; Buserelin; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Menstruation; Middle Aged; Ovulation; Time Factors; Uterine Neoplasms