trelstar and Uterine-Neoplasms

Uterine fibroids, also called uterine leiomyomas or myomas, are the most common benign tumours in women of reproductive age. Albeit generally benign, uterine fi broids can have a major impact on women's health and quality of life by contributing to abnormal uterine bleeding and causing pelvic pressure symptoms (such as increased urinary frequency, pelvic pain and constipation). Traditional treatments for symptomatic fi broids include a variety of surgical techniques. However, because of the high recurrence rate, as well as possible pain and infertility caused by the formation of postoperative adhesions, this approach may not be advisable. Safer and more effective medical therapy has long been awaited. Both in vitro studies and clinical trials have suggested that use of the aromatase inhibitors (AIs), a class of anti-oestrogens, might inhibit fi broid growth, thereby eliminating the need for surgery.. To evaluate the effectiveness and safety of aromatase Inhibitors (AIs) in women with uterine fibroids.. We searched the following databases (from inception to August 21, 2013): Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL and PsycINFO. In addition, the reference lists of included trials were searched, and experts in the field were contacted.. Randomised controlled trials (RCTs) in women of reproductive age comparing the effects of any AI versus placebo, no treatment or any medical treatment/surgery were included.. Selection of eligible trials, assessment of trial quality and data extraction were performed independently by two review authors. If data were available, we planned to calculate odds ratios (ORs) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CIs).. Only one trial involving 70 participants was included. This trial did not report our primary review outcome (relief of symptoms of fibroids). The only secondary review outcomes reported by this trial were adverse effects (hot flushes) and reduction in fibroid size. Significantly fewer women reported hot flushes in the letrozole group than in the GnRHa group (0/33 vs 26/27, P < 0.05). Use of letrozole reduced fibroid volume by 46% and use of a gonadotrophin-releasing hormone (GnRH) agonist (GnRHa) by 32% after 12 weeks of treatment; these proportions were not significantly different. The included trial did not report data on fibroid volume in a form that permitted calcuation of an odds ratio. Morevoer it was unblinded and included only 60/70 women in analysis.. Evidence is insufficient to support the use of AI drugs in the treatment of women with uterine fibroids.

Topics: Antineoplastic Agents; Aromatase Inhibitors; Female; Hot Flashes; Humans; Leiomyoma; Letrozole; Nitriles; Triazoles; Triptorelin Pamoate; Uterine Neoplasms

Uterine leiomyomata are the commonest neoplasms of the female reproductive system in the procreative age. In these cases operation is still a treatment of choice. The procedure's range depends on: number, size and localisation of the myomas, patient's age and possession of children. Currently uterine leiomyomata are removed more frequent by endoscopic operations. We present the technique of laparoscopic myomectomy taking into consideration very important problem--patients' qualification this procedure. We pay attention to necessity of precise closing the wound in layers after removed myoma, which seems to prevent uterine rupture during pregnancy and labour. We also present some controversial aspects of using GnRH analogues. In summary we emphasise benefits of laparoscopic myomectomy particularly for women in the procreative age, who are planning pregnancy.

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Female; Humans; Hysterectomy; Laparoscopy; Leiomyoma; Neoadjuvant Therapy; Risk Factors; Triptorelin Pamoate; Uterine Neoplasms

We report a case of a 37-year-old woman who had received five courses of gonadotropin-releasing hormone (GnRH) agonist (Decapeptyl) for presumed uterine leiomyomata associated with episodes of uterine bleeding. Submucous myoma (histologically proven) was partially removed on the first visit. After a period of significant reduction in the tumor size and cessation of uterine bleeding, the symptoms recurred along with rapid re-growth of the uterus. Total abdominal hysterectomy was performed and the pathologic evaluation revealed leiomyosarcoma with a high mitotic rate. This case and the literature review emphasize the problems encountered with the early diagnosis of uterine leiomyosarcoma during GnRH agonist therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Female; Humans; Hysterectomy; Leiomyoma; Leiomyosarcoma; Mitosis; Triptorelin Pamoate; Uterine Hemorrhage; Uterine Neoplasms

To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas.. Multicenter, randomized, controlled clinical trial.. University hospitals.. A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B).. Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks.. Measurement of myoma volume and E(2), FSH, LH, and T levels.. Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment.. Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma.

Topics: Adult; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Estradiol; Female; Follicle Stimulating Hormone, Human; Germany; Gonadotropin-Releasing Hormone; Hormones; Hospitals, University; Hot Flashes; Humans; Iran; Leiomyoma; Letrozole; Luteinizing Hormone; Nitriles; Prospective Studies; Testosterone; Time Factors; Treatment Outcome; Triazoles; Triptorelin Pamoate; Tumor Burden; Uterine Neoplasms

To evaluate the efficacy of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients with abnormal uterine bleeding.. Multicenter, prospective, randomized, clinical study.. Tertiary-care university hospitals.. Thirty-nine consecutive patients with submucous myomas graded as G0 or G1 according to the European Society for Gynecological Endoscopy classification (myoma size 10-35 mm).. Patients were randomized to either direct surgery or 2 months of GnRH analogues before undergoing hysteroscopic resection of the submucous myoma.. Operating times, fluid absorption, difficulty of the operation, surgeon satisfaction with the procedure, intra- and postoperative complications, postoperative pain, and patient satisfaction were recorded.. Patients treated with GnRH analogue had significantly shorter operative times (15.9+/-3.1 minutes vs. 21.3+/-4.0 minutes) and significantly reduced fluid absorption (378+/-137 mL vs. 566+/-199 mL) compared with no preoperative medical treatment. Operative difficulty and overall surgeon satisfaction were significantly better in the GnRH analogue group. Patient satisfaction was similar in the two groups.. GnRH analogue treatment before hysteroscopic resection of G0-G1 10-35 mm submucous myomas was effective in reducing operative times, fluid absorption, and difficulty of the procedure.

Topics: Adult; Algorithms; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Humans; Hysteroscopy; Leiomyoma; Luteolytic Agents; Middle Aged; Mucous Membrane; Neoadjuvant Therapy; Postoperative Complications; Triptorelin Pamoate; Uterine Hemorrhage; Uterine Neoplasms

To evaluate if pre-operative GnRH-a modify uterine leiomyoma pseudocapsule and the possible clinical effects of these changes.. The study was performed at the University Federico II of Naples on 33 premenopausal patients submitted to laparotomic myomectomy after treatment with triptorelin depot. 29 untreated patients formed the control group. The operating time, the intraoperative bleeding and the prompt identification of the cleavage plan between myoma and myometrium were evaluated. The pseudocapsule features and the immunoexpression of PCNA and CD34 in this area were studied.. Treated patients showed lower blood loss and not clearly identifiable cleavage plan, but without any significant increase in the operating time. Treated lesions showed less evident border between myoma and myometrium and lower PCNA and CD34 pseudocapsule immunoexpression than untreated ones.. We propose the changes of leiomyoma pseudocapsule as partial explanations of the reported clinical and surgical findings after pre-operative GnRH-a.

Topics: Adult; Antigens, CD34; Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Cell Proliferation; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Myometrium; Neovascularization, Pathologic; Preoperative Care; Proliferating Cell Nuclear Antigen; Triptorelin Pamoate; Uterine Neoplasms

To evaluate the effectiveness and safety of triptorelin in the treatment of uterine leiomyoma.. A multi-center, prospective, randomly controlled clinical trial was carried out from Dec. 2002 to Mar. 2004 in three university hospitals. A total of 125 qualified patients with uterine leiomyoma were randomly divided into either triptorelin group (63 cases) treated with 3.75 mg triptorelin injected intramuscularly or leuprorelin group (62 cases) treated with 3.75 mg leuprorelin injected subcutaneously. Both drugs were injected every 28 days for a total of 3 months.. All 125 patients finished the trial. The uterine volumes were similar before treatment between the triptorelin group and the leuprorelin group and were decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 51% and 49%, respectively, without significant difference between two groups (P > 0.05). The volumes of the largest leiomyoma decreased significantly after drug therapy (P < 0.01) in both groups, with a median decrease rate of 50% and 48% in the triptorelin and leuprorelin groups, respectively, without significant difference between them (P > 0.05). Patients with serum level of 17beta-estradiol < 183 pmol/L accounted for 94% in both groups. The hemoglobin and serum ferrum levels were both significantly increased in the two groups after treatment (P < 0.05). The amenorrhea rates after 3 months of treatment were 97% in the triptorelin group and 95% in the leuprorelin group (P > 0.05). Dysmenorrhea, noncyclic pelvic pain and pressure-like symptoms were relieved quickly and remarkably in both groups after treatment. The rates of adverse event occurred in 71% of patients in both groups. The main side effects included flare-up effects and hypoestrogenic symptoms. Nine patients in the triptorelin group and 6 in the leuprorelin group received add-back therapy with tibolone 1.25-2.50 mg/d because of remarkable climacteric-like symptoms.. Treatment of uterine leiomyoma with triptorelin for 3 months is both effective and safe in Chinese women.

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Leiomyoma; Leuprolide; Prospective Studies; Treatment Outcome; Triptorelin Pamoate; Uterine Neoplasms

To ascertain whether adjuvant gonadotropin-releasing hormone (GnRH) agonist therapy decreases blood loss during abdominal myomectomy.. Randomized controlled trial.. Academic reproductive surgery center.. One hundred premenopausal women requiring first-line conservative surgery for symptomatic intramural or subserous fibroids.. Eight weeks of treatment with depot triptorelin before myomectomy or immediate surgery.. Intraoperative blood loss, operating time, degree of difficulty of the procedure, and short-term rate of fibroid recurrence.. Mean (+/-SD) intraoperative blood loss was 265 +/- 181 mL in triptorelin recipients and 296 +/- 204 in patients who had immediate surgery (mean difference, -31 mL [95% CI, -108 to 46 mL]). No significant differences were observed in blood loss according to uterine volume, number of fibroids removed, or total length of myometrial incisions. Most procedures in either group were of routine difficulty. On ultrasonography 6 months after myomectomy, four women in the GnRH agonist group and one in the immediate surgery group had tumor recurrence.. Treatment with a GnRH agonist before abdominal myomectomy has no significant effect on intraoperative blood loss. Thus, systematic use of medical therapy before abdominal myomectomy does not seem to be justified.

Topics: Adult; Antineoplastic Agents, Hormonal; Blood Loss, Surgical; Female; Hemoglobins; Humans; Leiomyoma; Triptorelin Pamoate; Uterine Neoplasms

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

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Hysterectomy; Laparoscopy; Leiomyoma; Middle Aged; Preoperative Care; Prospective Studies; Time Factors; Triptorelin Pamoate; Uterine Neoplasms; Uterus

In this prospective, randomized, double-blind study, we evaluated the effects of tibolone therapy in association with preoperative gonadotropin releasing hormone agonist (GnRHa) therapy on the reduction of myoma volume. Twenty patients with myoma uteri were divided into two groups. Group I was given monthly triptoreline (3.75 mg every 28 days IM) treatment for six months. As for group II, tibolone was added on to this treatment. For all of the patients, physical examinations, pelvic ultrasonography, and hormone analyses were carried out and the myoma volume was measured by ultrasonography. The patients were called every month and physical examination, ultrasonography and hormone analyses were repeated. Side-effects were recorded. The SPSS/PC 6.0 program was used for statistical analysis. Statistical significance was defined as a p < 0.05. The results are expressed as means +/- SD. While the average volume of myoma was 72.97 +/- 68.5 cm3 in group I, 78.83 +/- 74.1 cm3 in group II before treatment; it was reduced to 29.91 +/- 27.8 cm3 in group I at the end of six months of treatment. Reductions of 59.6% in group I and 63.9% in group II were determined, however the difference was not statistically significant (p > 0.05). At the beginning the level of serum estradiol was 65.4 +/- 22.3 pg/ml in group I which decreased to 37.2 +/- 4.2 pg/ml by the end of the first month. Amenorrhea occurred in six patients after the second injection and four patients after the third injection in group I. Whereas the level of estradiol was 60.9 +/- 19.5 pg/ml in group II at the beginning, it was reduced to 40.5 +/- 6.2 pg/ml by the end of the first month. Amenorrhea occurred in four patients after the second injection and four patients after the third injection in group II. In group I the patients had the problem of flushing (80%), vaginal dryness (50%), and night sweats (30%). In group II these rates were 30%, 20%, and 20%, respectively. Triptoreline is a GnRHa which has been found to be effective in reducing myoma volume, but this effect could not be deactivated with tibolone. However, a decrease was observed in the side-effects resulting from hypoestrogenism.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Double-Blind Method; Drug Therapy, Combination; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Norpregnenes; Prospective Studies; Treatment Outcome; Triptorelin Pamoate; Ultrasonography; 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 ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure.. A multicentre, prospective, randomised, controlled study.. One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks.. Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery.. Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment.. After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P < 0.0001; OR 6.06; 95% CI, 2.60 to 14.10). Pre- and post-operative serum haemoglobin and haematocrit levels were significantly higher in the GnRH agonist than in the immediate surgery arm. No appreciable difference was observed between the groups in the other intra- and post-operative variables, including patients' satisfaction.. Pre-operative GnRH agonist therapy increased the rate of vaginal hysterectomy in selected women with fibroids and uterine volume of 12 to 16 gestational weeks.

Topics: Adult; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Delayed-Action Preparations; Female; Humans; Hysterectomy; Leiomyomatosis; Middle Aged; Prospective Studies; Treatment Outcome; Triptorelin Pamoate; Ultrasonography; Uterine Neoplasms

To assess whether tibolone can prevent the bone loss and symptomatic side effects normally associated with GnRH agonist (GnRH-a) use and whether tibolone modifies the effect of GnRH-a on endometriosis.. Prospective, double-blind, placebo-controlled, group comparative study.. Gynecological research unit in a London teaching hospital.. Twenty-nine patients with endometriosis and two with fibroids.. Six months of treatment with 3.75 mg/mo IM triptorelin combined with daily tablets of either placebo or 2.5 mg tibolone.. Daily symptom diary for hot flushes and bleeding episodes, laparoscopic scoring of endometriosis, endocrine and biochemical changes, and bone mineral density scans.. Lumbar spine bone mineral density decreased significantly from baseline in the placebo group (-5.1%) but not in the tibolone group (-1.1%). The frequency of hot flushes and sweating episodes was reduced significantly by tibolone. There was no difference between the two treatment groups with regard to the endometriosis scores.. The addition of tibolone to GnRH-a treatment reduces the bone loss and vasomotor symptoms that normally occur with GnRH-a, thus making long-term treatment with GnRH-a safer and more acceptable. It does not negate the therapeutic effect of GnRH-a on endometriosis.

Topics: Adult; Anabolic Agents; Bone Density; Double-Blind Method; Drug Interactions; Endometriosis; Female; Humans; Leiomyoma; Luteolytic Agents; Norpregnenes; Prospective Studies; Triptorelin Pamoate; Uterine Neoplasms

Gonadotropin-releasing hormone agonist-induced partial pituitary suppression with low-grade estrogen production may be useful in long-term treatment of uterine leiomyomas.. Twenty-seven women with uterine leiomyomas were treated with a standard dose of triptorelin for 8 weeks. Patients were then randomized to use 100, 20, or 5 micrograms of triptorelin until week 26. Uterine and myoma size, pituitary-ovarian function, bone metabolism, and bone mineral density were monitored.. During standard treatment uterine size was reduced to 67.1% of baseline. During randomized treatment uterine size was further reduced to 57.8% of baseline. There were no differences in overall volume reduction among the groups. Luteinizing hormone and estradiol levels were restored in a dose-dependent way. Bone mineral density decreased significantly in the highest-dose group at week 26.. This study shows that the beneficial effects of initial high-dose agonist treatment on uterine leiomyomas can be preserved by continued low-dose treatment. Bone mineral density does not seem to change during reduced-dose agonist treatment.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Female; Follicle Stimulating Hormone; Humans; Leiomyoma; Luteinizing Hormone; Triptorelin Pamoate; Uterine Neoplasms

To investigate the usefulness of a routine short term treatment with gonadotropin releasing hormone agonist (D-Trp-6-LHRH depot) before abdominal hysterectomy for leiomyoma.. Prospective, comparative, randomized study.. A teaching hospital of Barcelona University.. Fifty premenopausal women requiring hysterectomy as treatment for symptomatic leiomyomas. Twenty-three patients were randomized to receive gonadotropin releasing hormone agonist treatment before hysterectomy (cases), and 27 patients were randomized to immediate hysterectomy (controls).. Type of abdominal incision, operating time, operative hemoglobin and hematocrit decrease, postoperative morbidity, and days in hospital.. In the agonist treated group mean uterine volume decreased and mean hemoglobin and hematocrit significantly rose after 8 weeks of treatment. Operative time was similar in both groups of patients but the number of women having Pfannenstiel incision was significantly higher in the cases. Mean operative hemoglobin and hematocrit decrease and postoperative morbidity were lower in the cases. There was a trend for shorter postoperative hospital stays in the agonist treated group.. Our results favor the routine use of a short term gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma in order to decrease operative blood loss and postoperative morbidity.

Topics: Adult; Combined Modality Therapy; Female; Humans; Hysterectomy; Leiomyoma; Length of Stay; Middle Aged; Postoperative Complications; Prospective Studies; Single-Blind Method; Triptorelin Pamoate; Uterine Neoplasms

Topics: Adult; Combined Modality Therapy; Female; Humans; Hysteroscopes; Hysteroscopy; Leiomyoma; Middle Aged; Premedication; Triptorelin Pamoate; Uterine Neoplasms

To determine whether pre-operative treatment with gonadotrophin-releasing hormone (GnRH) analogue may have a beneficial effect on surgery outcome, 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy (TAH), were randomly divided into a study group (n = 29) and a control group (n = 24). The study group of patients were treated by an i.m. injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery. The control group had no pre-operative treatment. Haemoglobin concentration and oestradiol, follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery, and at surgery. The duration of surgery was shorter in the study group (49 versus 70 min in the hysterectomy group) and intra-operative blood loss was less (208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies). Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery, and diminishing the intra-operative blood loss in surgery for fibroid uteri. Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri.

Topics: Adult; Estradiol; Female; Follicle Stimulating Hormone; Hemoglobins; Humans; Hysterectomy; Leiomyoma; Luteinizing Hormone; Postoperative Complications; Preoperative Care; Triptorelin Pamoate; Uterine Neoplasms

The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/day) in either the first (protocol A) or last (protocol B) 12-week period along with a 6-month course of the GnRH analog (GnRH-a; leuprolide acetate; 1 mg/day, sc) on uterine and leiomyomata volumes and hormone (estradiol, LH, and FSH) and serum lipid (total cholesterol, triglycerides, and high and low density lipoprotein) levels. Sixteen women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, respectively, and were then crossed over at 12 weeks to placebo or MPA, respectively, for the final 12-week interval of GnRH-a therapy. Total, myoma, and nonmyoma uterine volumes were determined by magnetic resonance imaging, and serum studies were performed at the beginning of the study and at 12 and 24 weeks. In both protocols, LH and estradiol levels declined by 80-90% (P < 0.03) and 55-72% (P < 0.02) of the baseline, respectively, at 12 weeks and remained at this level at 24 weeks. There were no significant changes in the other laboratory tests between protocols or longitudinally over time. Total uterine volume decreased to 73% of the baseline at 12 weeks in protocol B (P < 0.04), but did not change in protocol A. After crossover at 12 weeks, the total uterine volume of women in protocol A decreased to 74% of the baseline (P < 0.02) at 24 weeks. Between-protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks, but after cross-over, MPA addition was associated with a significant increase in total uterine volume (protocol B) compared to a decrease in protocol A at 24 weeks (P < 0.005). In contrast, although myoma volume declined in both protocols, no significant changes in myoma volume were detected within or between groups over the treatment period. Nonmyoma volume changes in protocols A and B roughly paralleled total uterine volume changes, with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Double-Blind Method; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Luteinizing Hormone; Magnetic Resonance Imaging; Medroxyprogesterone Acetate; Middle Aged; Placebos; Prospective Studies; Triptorelin Pamoate; Uterine Neoplasms

Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen-progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen-progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed.

Topics: Adult; Bone Density; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Leuprolide; Middle Aged; Progestins; Prospective Studies; Spine; Triptorelin Pamoate; Ultrasonography; Uterine Neoplasms; Uterus

Following the introduction of GnRH analogue drugs the medical treatment of uterine myomatosis has been proposed. The use of these compounds in fact causes a reduction in mean plasma levels of 17-beta-estradiol which is reflected in the target tissue of myomas. Using this hormone-dependence as a starting Tryptoreline point, the study examined the volumetric changes induced by LH-RH agonist analogue, Tryptoreline, administered to a group of 15 selected patients. The results are encouraging: in all cases there was a marked reduction of tumour volume ranging between 30 and 40%. The therapeutic effect, however, gradually wore off following the suspension of treatment. For this reason, the use of this analogue should be reserved for premenopausal or younger patients for the treatment of menometrorrhagic episodes, or as a preoperative therapy in order to limit blood loss during surgery.

Topics: Adolescent; Adult; Age Factors; Blood Loss, Surgical; Drug Evaluation; Female; Humans; Leiomyoma; Middle Aged; Preoperative Care; Remission Induction; Triptorelin Pamoate; Uterine Neoplasms

Uterine fibroids are the commonest tumors of the female genital tract. Hysterectomy is the typical therapy in patients whose families are complete. In women desirous of children GnRH-analogues can effect a shrinkage of leiomyomata before a myomectomy. Furthermore, GnRH-A treatment can be an alternative to hysterectomy in inoperable patients or in premenopausal women with symptoms of uterine fibroids. In this study eleven patients were treated with 3.2 mg triptorelin monthly and ten patients with 900 micrograms buserelin daily for 6 months. With triptorelin, a 50% reduction of the uterus volume can be observed after 3 months. A further treatment has no benefit. With buserelin, a regression in the same range as with triptorelin can be reached only after 6 months. In contrast, fibroid volumes revealed a regression of 28% with triptorelin and 21% with buserelin in the same time. In this period all fibroid-associated symptoms disappeared. Less bleeding resulted in an increase of hemoglobin. Therefore, treatment with GnRH analogues can be an important factor in the management of uterine fibroids patients in at-risk.

Topics: Adult; Antineoplastic Agents; Buserelin; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms

To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas.. Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas.. All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p<.005).. Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas.

Topics: Adult; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Attitude of Health Personnel; Contraceptive Agents; Female; Humans; Hysteroscopy; Leiomyoma; Letrozole; Nitriles; Norpregnadienes; Operative Time; Pain, Postoperative; Patient Satisfaction; Pilot Projects; Prospective Studies; Triazoles; Triptorelin Pamoate; Tumor Burden; Uterine Neoplasms

The study investigated the impact of gonadotropin-releasing hormone analogue (GnRH-a) on coagulation and fibrinolytic activities and its effectiveness in the prevention of pelvic adhesion after myomectomy. Thirty-two infertile women underwent myomectomy followed by adhesion evaluation surgery with a second-look laparoscopy. Before myomectomy, 15 women were treated with triptorelin acetate for 3 months and 17 received no treatment. Plasminogen activator inhibitor (PAI), thrombin activatable fibrinolysis inhibitor (TAFI), protein C (PC), plasminogen, α2-antiplasmin were determined by enzyme-linked immunosorbent assays and the activity of coagulation factors V and VIII by coagulometric methods. Patients treated with GnRH-a showed significant decrease in PAI, TAFI, factors V, and VIII (P < .05) and increased PC (P < .05), but no significant change in plasminogen and α2-antiplasmin levels compared with control group. The incidence, extent, and severity of adhesions were significantly lower in GnRH-a-treated patients compared with control group (P < .05), suggesting a possible critical role of the GnRH-a therapy in preventing postoperative adhesion development.

Topics: Adult; Blood Coagulation; Female; Fibrinolysis; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Postoperative Complications; Preoperative Care; Tissue Adhesions; Triptorelin Pamoate; Uterine Neoplasms

To study the role of triptorelin in the treatment of patients with endometriosis, adenomyoma and fibromyoma and the effect of an extended-interval dosing regimen.. Seventy patients suffering from endometriosis, adenomyoma and fibromyoma were divided into two groups: extended-interval dosing (group E) and conventional dosing (group C). There were treated with injection of triptorelin 3.75 mg intramuscularly either every 6 weeks of totally four dose regimen (group E) or every 4 weeks of six dose regimen (group C). Comparison was made in improvement of symptoms, size of uterus and volume of tumor, as well as in serum levels of 17beta-estradiol, luteinizing hormone, and follicle-stimulating hormone.. In each group, symptoms and tumor growth significantly improved after treatment (P < 0.05). For the patients of both groups E and C, the levels of gonadotropins and gonadal steroids were obviously reduced throughout the treatment period and up to 8 - 10 weeks after the injection of the last dose (P < 0.05). The hormonal profile of group E was similar to group C (P > 0.05).. Gonadotropin-releasing hormone agonist is efficacious in the treatment of endometriosis and adenomyoma through reducing the serum levels of follicle-stimulating hormone, luteinizing hormone and 17beta-estradiol. The curative effect is satisfactory in most patients receiving an extended interval dosing regimen. To reduce the cost of treatment, the extended-interval dosing regimen of triptorelin should be adopted in well-equipped hospitals.

Topics: Adenomyoma; Adult; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Dysmenorrhea; Endometriosis; Female; Humans; Treatment Outcome; Triptorelin Pamoate; Uterine Neoplasms

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Leiomyoma; Middle Aged; Ovarian Hyperstimulation Syndrome; Pleural Effusion; Triptorelin Pamoate; Uterine Neoplasms

The objective was to test the hypothesis that uterine sarcomatous cells are hormone-sensitive. We included 2-methoxyestradiol, an endogenous metabolite of estradiol with antiproliferative properties.. Proliferation assays assessed the effects of estradiol, progesterone, tamoxifen, raloxifen, [D-Trp(6)]leuteinizing hormone-releasing hormone (LHRH), ICI 182,780 (faslodex or fulvestrant), and 2-methoxyestradiol on cell growth of a cell line derived from uterine carcinosarcoma, but consisting solely of mesenchymal cells (SK-UT-1). Morphological changes of SK-UT-1 cells after exposure to 2-methoxyestradiol were evaluated and fluorescence immunohistochemistry for tubulin was used to detect changes in the mitotic spindle. Flow cytometry was used to assess the influence of 2-methoxyestradiol on the SK-UT-1 cell cycle as well as the role of p53 in apoptosis.. Cell proliferation analysis revealed that SK-UT-1 cells were stimulated by progesterone, tamoxifen, and [D-Trp(6)]LHRH. Cells were insensitive to estradiol, raloxifen, and ICI 182,780. Inhibition occurred after exposure to 2-methoxyestradiol and was accompanied by a threefold increase in the G2/M population, with a concomitant decrease in the G1 population, as shown by cell cycle analysis. SK-UT-1 cells exposed to 2-methoxyestradiol showed morphological changes indicative of apoptosis. Examination of signaling pathways that mediate 2-methoxyestradiol-induced apoptosis showed p53-independent growth inhibition. The inhibition of SK-UT-1 cell growth by arresting the cells during G2/M progression could be attributed to interference with the microtubule system, as determined by fluorescence immunohistochemistry.. The stimulatory effect of progesterone, tamoxifen, and [D-Trp(6)]LHRH suggests that uterine sarcomatous cells are hormone-sensitive. Our finding that 2-methoxyestradiol-mediated growth inhibition of uterine sarcomatous cells occurred in a p53-independent manner may have considerable clinical significance. The inadequate armature against uterine sarcomas and the limited toxicity of 2-methoxyestradiol may render these observations especially important.

Topics: Antineoplastic Agents, Hormonal; Carcinosarcoma; Cell Cycle; Cell Division; Cell Line, Tumor; Estradiol; Estrogen Antagonists; Female; Fulvestrant; Humans; Neoplasms, Hormone-Dependent; Progesterone; Raloxifene Hydrochloride; Tamoxifen; Triptorelin Pamoate; Uterine Neoplasms

Topics: Antineoplastic Agents, Hormonal; Diagnosis, Differential; Fallopian Tubes; Female; Humans; Hysterectomy; Injections, Intramuscular; Leiomyoma; Magnetic Resonance Imaging; Middle Aged; Ovariectomy; Prolapse; Triptorelin Pamoate; Ultrasonography; Uterine Hemorrhage; Uterine Neoplasms

Topics: Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Triptorelin Pamoate; Uterine Neoplasms

We report endometrial adenocarcinoma in two patients shortly after suspending GnRH-agonist treatment for menometrorrhagia and uterine fibromata.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Female; Humans; Injections, Intramuscular; Leiomyoma; Leuprolide; Metrorrhagia; Middle Aged; Myometrium; Neoplasms, Second Primary; Triptorelin Pamoate; Uterine Neoplasms

Topics: Blood Loss, Surgical; Female; Gonadotropin-Releasing Hormone; Gynecologic Surgical Procedures; Humans; Leiomyoma; Lypressin; Terlipressin; Triptorelin Pamoate; Uterine Neoplasms; Vasoconstrictor Agents

To investigate the clinical characteristics of uterine myomas with cytogenetic rearrangements.. Comparative study of myomas with normal and abnormal karyotype.. University hospital.. Premenopausal, GnRH-agonist (GnRH-a) treated and menopausal patients.. Myomectomy or hysterectomy.. Karyotype analysis and clinical characteristics.. Clonal abnormalities occurred in 29% of uterine myomas but were not related to the age of the patient or, in untreated menopausal patients, to the size of the myoma. In GnRH-a treated and menopausal women, 48% of the myomas larger than 4 cm were associated with clonal abnormalities. Submucous myomas had significantly fewer clonal abnormalities (12%) than subserosal (29%) or intramural myomas (35%).. The data support the hypothesis that cytogenetic rearrangements in uterine myomas are associated with loss of steroid hormones dependency and alter the growth potential of the tumor.

Topics: Adult; Age Factors; Aged; Antineoplastic Agents, Hormonal; Chromosome Aberrations; Chromosome Disorders; Cohort Studies; Female; Humans; Karyotyping; Leiomyomatosis; Middle Aged; Prevalence; Retrospective Studies; Triptorelin Pamoate; Uterine Neoplasms

Our objective was to determine whether long GnRH agonists induce effective and persistent shrinkage of uterine myomas in perimenopausal women, as well as to determine the usefulness of Doppler sonography study in evaluating the therapy benefit. The study covers 30 patients with symptomatic myomas in perimenopausal period. We used long GnRH agonist-Decapeptyl (Ferring) at 28 days intervals in the course of 4 months. After discontinuing the application of Decapeptyl, medroxyprogesterone acetate was introduced for 6 months. The GnRH/gestagens therapy is useful and effective in treatment of symptomatic myomas in perimenopausal patients, and may be a valid alternative to hysterectomy. Doppler sonography is reliable in monitoring of uterine circulation in patients under GnRH therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Leiomyoma; Premenopause; Triptorelin Pamoate; Ultrasonography; Uterine Neoplasms; Vascular Resistance

To study the effects of pretreatment with triptorelin on uterine fibroid before abdominal hysterectomy.. Fifteen premenopausal Chinese women with symptomatic uterine fibroids requiring hysterectomy were recruited in the study. All patients received monthly intramuscular injections of 3.75 mg triptorelin for three months prior to abdominal hysterectomy.. There was significant reduction in the serum levels of oestradiol (68.6%), progesterone (95.6%) and luteinizing hormone (73.9%) and in uterine (45.0%) and fibroid (68.0%) volumes. The serum level of follicle-stimulating hormone and haemoglobin concentration were not significantly different.. Shrinkage of uterine fibroids can be achieved in women who are rendered hypoestrogenic with monthly injections of triptorelin for three months. This treatment modality may be of value prior to hysterectomy or myomectomy especially when the fibroid is large.

Topics: Adult; Chemotherapy, Adjuvant; Female; Humans; Hysterectomy; Injections, Intramuscular; Leiomyoma; Luteolytic Agents; Middle Aged; Preoperative Care; Triptorelin Pamoate; Uterine Neoplasms

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

The increasing use of analogs of Gn-RH during treatment of some benign gynaecological diseases, has induced the authors to investigate the principal collateral effects, fixing one's attention on the loss of bony mass.. This perspective research has considered 38 patients selected for two diseases "endometriosis" and "uterine fibromyomatosis". The therapy has been effected with triptorelin intramuscularly in a dose of 3.75 mg every 28 days for six months, in all six phials.. After a half-yearly cycle of therapy, the loss of bony mass was valued about 3% medium.. In the light of other studies too, it was decided to confirm the necessity of associating other medicines able to prevent the side effects caused by their analogs of Gn-RH.

Topics: Adult; Bone Density; Endometriosis; Female; Fibroma; Genital Diseases, Female; Genital Neoplasms, Female; Growth Hormone-Releasing Hormone; Humans; Leiomyoma; Middle Aged; Osteoporosis; Triptorelin Pamoate; Uterine Neoplasms

Our purpose was to investigate the histopathologic changes in uterine leiomyomas in cell proliferation, proliferating cell nuclear antigen expression, angiogenesis, and apoptosis after treatment with gonadotropin-releasing hormone agonist.. Fifteen consecutive patients who had undergone gonadotropin-releasing hormone agonist treatment before surgery and 44 patients who did not were studied. The volumes of myomas were determined ultrasonographically, and in patients receiving gonadotropin-releasing hormone agonist therapy measurements were done again after administration of the gonadotropin-releasing hormone agonist to evaluate the response to treatment. Paraffin sections were stained with hematoxylin and eosin, PC 10 for proliferating cell nuclear antigen expression, MIB 1 for measurement of cell proliferation, ApopTag for apoptosis, and factor VIII for quantitation of microvessel density. A deoxyribonucleic acid fragmentation test was also done on nine cases with available frozen tissues.. Most of the leiomyomas showed substantial expression of proliferating cell nuclear antigen. Gonadotropin-releasing hormone agonist therapy further induced significant overexpression of proliferating cell nuclear antigen (p = 0.0004, chi 2 test). All three leiomyomas that failed to respond to therapy showed less proliferating cell nuclear antigen staining compared with the good responders. In contrast, data from MIB 1 immunostaining showed that < 0.3% of leiomyoma cells were proliferating. However, positive-staining cells were more frequently detected in the treatment group (0.075% +/- 0.091% vs 0.002% +/- 0.010%, p = 0.0002, Mann-Whitney U test). Apoptosis developed spontaneously in leiomyoma cells independent of gonadotropin-releasing hormone agonist therapy. No significant change in apoptosis but a significant increase in microvessel density was observed in the treatment group compared with the control group.. Enhanced deoxyribonucleic acid damage or repair with cell growth arrest may be responsible for the action of gonadotropin-releasing hormone agonist in shrinking uterine leiomyomas. Moreover, the extent of proliferating cell nuclear antigen expression seems to be associated with the response to gonadotropin-releasing hormone agonist therapy.

Topics: Adult; Antibodies, Monoclonal; Apoptosis; DNA Damage; DNA Fragmentation; DNA Repair; Factor VIII; Female; Histocytochemistry; Humans; Immunohistochemistry; Ki-67 Antigen; Leiomyoma; Middle Aged; Proliferating Cell Nuclear Antigen; Triptorelin Pamoate; Uterine Neoplasms

Topics: Adult; Antineoplastic Agents, Hormonal; Estradiol; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leiomyoma; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms

To correlate the cytogenetics and the DNA content in uterine myomas.. Prospective study in treated and untreated females.. Tertiary University Center.. Premenopausal, menopausal, and GnRH-agonist (GnRH-a)-treated patients.. Myomectomy or hysterectomy.. Karyotype analysis and the DNA content measured by microfluorescence technique and expressed in fluorescence units.. The mean DNA content in cells from karyotypically normal and karyotypically abnormal myomas, respectively, was 37.4 +/- 6.9 and 30.4 +/- 1.8 fluorescence units in premenopausal females, 30.3 +/- 5.3 and 28.7 +/- 0.9 fluorescence units in menopausal females, and 31.6 +/- 2.7 and 32.9 +/- 5.8 fluorescence units in GnRH-a-treated females.. Forty percent of the myomas evaluated demonstrated an abnormal karyotype and had a significantly lower DNA content than the chromosomally normal myomas. After GnRH-agonist treatment, the DNA content was decreased in the euploid myoma group only.

Topics: Biopsy; DNA, Neoplasm; Female; Fluorescence; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Karyotyping; Leiomyoma; Menopause; Premenopause; Prospective Studies; Triptorelin Pamoate; Uterine Neoplasms

The results of hormonal examinations, measurements of dimensions of the uterus and leiomyomas, body weight, and also frequency of incurred climacteric signs in patients treated with Decapeptyl Depot 3.75 mg for three months are reported. Subjects consisted of 12 women, among whom nine were treated for leiomyomas and four for endometriosis (one patient also had leiomyomas). Based on examinations carried out, the biggest decrease of the uterus and leiomyomas was 13-17% observed just after two doses of analog, though after the end of treatment the dimensions of the uterus slowly increased. Therefore, 2-month therapy could be used successfully as preparation for further conservative surgical treatment. Significant increase of body weight in treated patients was not observed. In women with endometriosis pain symptoms in the hypogastric area and dyspareunia regressed during treatment and at the end were not observed. The disadvantages of therapy with Decapeptyl Depot 3.75 was the rapid occurrence of symptoms--climacteric signs, especially hot flashes--which were badly tolerated by patients. All these symptoms almost totally regressed one month after ending therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Body Weight; Delayed-Action Preparations; Endometriosis; Female; Humans; Leiomyomatosis; Middle Aged; Triptorelin Pamoate; Uterine Diseases; Uterine Neoplasms

Magnetic resonance (MR) imaging is increasingly applied for the quantitative evaluation of uterine leiomyomas. MR is thought to be more accurate in comparison to ultrasound (US) techniques. MR signal intensity (SI) may prove to be predictive of myoma response to GnRH agonist treatment. This study aimed to evaluate the precision of uterine volume assessment by a parallel planimetric MR method and the accuracy of the ellipsoid formula based calculations from MR and US images. It was also attempted to analyze the precision of MR leiomyoma volume measurements and examine the relation between pretreatment myoma SI patterns and the response to agonist therapy. Twenty-seven women with a myomatous uterus were scanned three times during GnRH agonist treatment for 6 months. T1- and T2-weighted, as well as T1 contrast-enhanced sequences of the uterus were obtained in the transverse and sagittal plane. Abdominal US of the uterus was performed with a conventional sector scanner. By the use of a software system for analysis of three-dimensional images obtained by MR, uterine volume was measured by a parallel planimetric method (MR-ROI) as well as the use of the ellipsoid formula (MR-ELL). Myoma volume was assessed by the MR-ROI method. SI of the myomas was estimated from selected tissue samples as well as from the integral myoma region of interest. By abdominal US, volume was assessed by the ellipsoid equation (US-ELL). Within- and between-observer and method reliability (Rw/Rb) was calculated from mean squares obtained by analysis of variance. For uterine volume assessment, reliability between observers and between methods when the MR-ROI and MR-ELL methods were analyzed was excellent. For the US-ELL measurements, the between-observer reliability was limited. Moreover, the reliability of the US-ELL was low when the MR-ROI method was used as the standard. Myoma volume assessment with the MR-ROI method showed high between-observer and between-method agreement. The myoma/fat SI ratio and the mean SI coefficient of variation failed to show a correlation with the degree of response to triptorelin treatment of individual myomas. In MR uterine volume assessment the MR-ELL method is very accurate compared with the more complicated MR-ROI method. The agreement between MR and US is limited. Therefore, the ellipsoid method on MR images is to be regarded as the method of choice for quantitative assessment of uterine volume response to hormonal treatment. Myoma SI patterns were sh

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Image Processing, Computer-Assisted; Leiomyoma; Magnetic Resonance Imaging; Observer Variation; Reproducibility of Results; Triptorelin Pamoate; Ultrasonography; Uterine Neoplasms; Uterus

In literature there have been only 8 cases of unavoidable laparotomy due to uterine leiomyomas performed in patients with breast cancer on Tamoxifen (TAM). Our article describes two cases of rapidly growing leiomyomas in patients treated with TAM: one of these underwent abdominal hysterectomy while the second stopped taking TAM and began therapy with Triptorelin. This therapeutical alternative could be a useful choice.

Topics: Adult; Breast Neoplasms; Female; Humans; Leiomyoma; Middle Aged; Tamoxifen; Triptorelin Pamoate; Uterine Neoplasms

A less bulky uterine myoma is technically easier to deal with during surgery. Recently gonadotropin-releasing hormone agonists (GnRH-a) have been used for the purpose of medical hypophysectomy, thereby reducing the size of uterine myomas. Ten premenopausal women with infertility and intramural-submucous myoma manifesting with menorrhagia and obstruction of the tubal ostia were recruited for this study. A long-acting depot GnRH-a, Decapeptyl, was given intramuscularly every four weeks for three months as an adjunct prior to myomectomy. Luteinizing hormone, follicular stimulating hormone and estradiol declined to the menopausal range following treatment. The size of the myoma decreased to a mean of 32.3 +/- 13.3% of the original volume. Myomectomy was performed in eight patients at the end of the study. Remarkably little blood loss was observed during the surgery. All of the patients had their uteri preserved, and six out of eight patients achieved pregnancy within 12 months after surgery. Our results indicate that monthly administration of long-acting GnRH-a significantly reduces the myoma volume and makes myomectomy technically easier to perform with the possibility of reduced complication rates and better preservation of future fertility.

Topics: Adult; Combined Modality Therapy; Delayed-Action Preparations; Female; Humans; Leiomyoma; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms; Uterus

Several studies have shown that gonadotrophin-releasing hormone analogue (GnRHa) offers a promising medical approach in the treatment of uterine leiomyomas. Medical management is very important especially when fertility is desired. We report on a case with mechanical infertility, in which the right tube was obstructed by cornual myoma and the left tube was resected due to a ruptured ectopic pregnancy. The myoma was reduced in size by GnRHa treatment and the patient subsequently conceived.

Topics: Adult; Chorionic Gonadotropin; Fallopian Tubes; Female; Humans; Leiomyoma; Menotropins; Pregnancy; Triptorelin Pamoate; Ultrasonography, Prenatal; Uterine Neoplasms

Three pre-menopausal women with uterine myomas were treated with leuprolide acetate depot and experienced profuse vaginal bleeding 7-11 weeks after initiation of treatment, despite profound oestradiol suppression. In each case, leuprolide therapy was discontinued and the women were treated with combination oral contraceptives and ferrous sulphate. Vaginal bleeding ceased within 24-48 h of oral contraceptive treatment in all women. Haemoglobin concentrations were restored to normal values and all women underwent definitive surgical treatments after 4-6 weeks of oral contraceptive treatment without the need for homologous blood transfusion. The final pathology report revealed focal necrosis of submucous myomas in all cases.

Topics: Adult; Contraceptives, Oral; Delayed-Action Preparations; Drug Therapy, Combination; Estrogens; Female; Ferrous Compounds; Gonadotropin-Releasing Hormone; Hemorrhage; Humans; Leiomyoma; Leuprolide; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms; Vaginal Diseases

Thirty-five women with symptomatic fibroids were treated with monthly injections of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17 beta-oestradiol levels decreased, falling to castration levels associated with a reduction in the volume of the fibroids. In 16 patients a complete calcium homeostasis and bone metabolism work-up was carried out during treatment and subsequently for a 6-month follow-up period. Bone mineral content (BMC) and Compton bone densitometry readings remained unchanged. There were significant increases in serum calcium phosphate and alkaline phosphatase concentrations. A slight although not significant increase was observed in osteocalcin and parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and calcium/creatinine ratios as well as 24-h urinary calcium values increased significantly during the treatment period but decreased rapidly to pretreatment values after 3 months in the follow-up period. The endocrine changes induced by the GnRH-agonist treatment were associated with reversible biochemical signs of increased bone turnover and no significant changes in bone mass, suggesting that the treatment can be administered safely for a period of 6 months in patients with oestrogen-dependent diseases.

Topics: Adult; Bone and Bones; Bone Density; Calcium; Female; Gonadotropin-Releasing Hormone; Homeostasis; Humans; Leiomyoma; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms

An increasing number of publications document regression of fibroids under treatment with gonadotropin releasing hormone (GnRH) agonists. However, recurrence after stopping treatment regularly counterbalances its benefit. We now report on 28 patients with intramural myomas, treated with triptorelin for 4-6 months and followed for 42-56 months. During or shortly after treatment, six patients entered menopause. In this group, a volume reduction of 71% was achieved and no surgery was needed thereafter. In 22 premenopausal women, a 64% decrease of uterine volumes was obtained at the end of treatment; the long-term reductive effect was 31%. When compared with initial values, a significant decrease was observed at the end of treatment (p = 0.0001) and of follow-up (p < 0.0005). In 13 (of 22) premenopausal patients, surgery was needed after triptorelin treatment for permanent control of fibroids. The remaining nine patients were free of symptoms after 42-56 months, having uteri in situ. These two groups differ significantly in pretreatment uterine volume (p < 0.001) and in reduction rate after therapy (p < 0.01), both parameters being higher in patients who finally needed surgery. In conclusion, triptorelin treatment is definitely beneficial in perimenopausal women and in nearly half of premenopausal women, in whom hysterectomy can be prevented. In the other half, surgery is necessary, despite significant volume reduction. These results need to be corroborated on larger groups of patients. More research is needed to explain different responses to treatment in premenopausal patients.

Topics: Adult; Erythrocyte Count; Estradiol; Female; Hemoglobins; Humans; Leiomyoma; Menopause; Middle Aged; Osteocalcin; Triptorelin Pamoate; Uterine Neoplasms; Uterus

In the case reported here, an injection of DTRP6 GnRh microcapsules was given in the 5th, 9th and 13th week of a spontaneous unsuspected multiple pregnancy. No deleterious effect of the embryo could be demonstrated at birth or six months later.

Topics: Adult; Delayed-Action Preparations; Female; Fetus; Humans; Infant, Newborn; Injections, Intramuscular; Leiomyoma; Pregnancy; Pregnancy Complications; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy, Multiple; Triptorelin Pamoate; Ultrasonography, Prenatal; Uterine Neoplasms

CA 125, a marker of ovarian cancer, is also increased in otherwise normal women suffering from, for example, pelvic inflammatory disease, endometriosis and adenomyosis. The tissues suspected of producing CA 125 in normal women include the endometrium, the ovary and the peritoneum. This study was based on the hypothesis that uterine myomata would distend the peritoneum covering the uterus and thereby increase the peripheral levels of CA 125. To verify this hypothesis we measured CA 125 by an immunoradiometric assay in eight normal women every second day throughout the cycle and in 26 women with uterine fibroids before and after hysterectomy and at 8 and 12 weeks during gonadotrophin releasing hormone (GnRH) analogue therapy. In normal women no difference was observed between CA 125 levels in the follicular phase or in the luteal phase of the cycle. Over one-third (10/26) of the patients with uterine fibroids had increased (greater than 90th centile of the controls) levels of CA 125 before GnRH therapy or hysterectomy. Removal of the uterus or administration of GnRH significantly decreased peripheral concentrations of CA 125 to levels below those observed in normal women. Furthermore, a significant positive correlation was observed between the levels of CA 125 and the volume of myomata as assessed by ultrasound. We conclude that in those cases of uterine fibroids where CA 125 is increased, monitoring this parameter during GnRH therapy is a good indirect measurement of regression of myomata.

Topics: Adult; Antigens, Tumor-Associated, Carbohydrate; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Menstrual Cycle; Middle Aged; Organ Size; Postoperative Period; Triptorelin Pamoate; Uterine Neoplasms

The indications for operative laparoscopy have expanded greatly over the past decades, as its many advantages over laparotomy have been recognized. We report our techniques and short-term results concerning myomectomy by laparoscopy. From January 1, 1990 to October 1, 1991, 147 intraperitoneal myomectomies were performed in 70 patients: 46 of 70 were treated preoperatively with a depot gonadotrophin-releasing hormone agonist. No complications were observed. In selected cases, with the advantages of laparoscopic surgery, laparoscopic myomectomy appears to be a safe technique.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Leiomyoma; Leuprolide; Premedication; Suture Techniques; Triptorelin Pamoate; Uterine Neoplasms

Twenty-five non-menopausal women with uterine myomas were treated with LHRH-analogues for 3-6 months. An average reduction of 40% in uterine volume was observed. One patient refused to complete her therapy, three had no more menses after the interruption of treatment, nine underwent myomectomy within four weeks of their final administration, while in 12 cases hysterectomy was performed. In all cases the decrease in uterine volume induced by the analogue allowed a more limited intervention and prevented excessive blood loss.

Topics: Administration, Inhalation; Adult; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Chemotherapy, Adjuvant; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Injections, Intramuscular; Leiomyoma; Leuprolide; Luteinizing Hormone; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms

Topics: Adult; Buserelin; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Receptors, LHRH; Triptorelin Pamoate; Uterine Neoplasms

Gonadotropin-releasing hormone (GnRH) analogue was used to reduce large leiomyomas in three young women who were scheduled to have an abdominal hysterectomy and vaginal plastic repair. Significant size decrease due to the hormonal treatment enabled safe vaginal hysterectomy and repair.

Topics: Adult; Antineoplastic Agents; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy, Vaginal; Leiomyoma; Preoperative Care; Triptorelin Pamoate; Uterine Neoplasms; Vagina

The value of CA-125 for the diagnosis and management of endometriosis (EN) was investigated by assaying the marker in the serum and peritoneal fluid (PF) from patients with the disease in comparison with control subjects. Of women who underwent 270 consecutive laparoscopies, 81 with various stages of EN (18 stage I, 13 stage II, 35 stage III and 15 stage IV) and 38 with normal pelvic findings were studied. CA-125 serum values increased progressively in relation to the severity of the disease. The levels in stages III and IV EN were significantly higher (P less than .01) than in stages I and II or control patients. The latter two groups did not differ from each other. High CA-125 PF values were found in all the patients investigated. Twenty-two patients with EN were treated with a gonadotropin releasing hormone agonist for six months before second-look laparoscopy or laparotomy. CA-125 values decreased significantly after one month of medical treatment and remained unchanged during the course of therapy. No significant relationship was found in the outcome after therapy.

Topics: Adult; Antigens, Tumor-Associated, Carbohydrate; Ascitic Fluid; Endometriosis; Evaluation Studies as Topic; Female; Gonadotropin-Releasing Hormone; Humans; Laparoscopy; Middle Aged; Neoplasm Staging; Prognosis; Reoperation; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome; Triptorelin Pamoate; 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

Sixty-six patients with fibrocystic mastopathy were enrolled in the trial after being selected according to clinical, radioultrasonographic, and histologic criteria. No characteristic hormonal profile was noted in most patients (52%). Estrogen receptors or progesterone receptors, or both, were found in 57% of patients. Hormone receptor levels were correlated with atypical proliferative mastopathy (87.5%). Mastopathy was associated with a uterine fibroma or a fibromatous uterus in 73% of cases. All patients received intramuscular injections of a sustained delivery system (microcapsules) of luteinizing hormone releasing hormone agonist [D-Trp6]-LHRH, Ipsen-Biotech, Paris) for 3 to 6 months. In case of partial response at 3 months, an antiestrogen (tamoxifen, 40 mg/day, for estrogen receptor-predominant lesions) or a progestin (cyproterone acetate, 50 mg/day, for progesterone receptor-predominant lesions) was added to the luteinizing hormone releasing hormone agonist. A complete response was observed in more than half of the patients (n = 35, 53%) treated by [D-Trp6]-LHRH alone (n = 29) or associated with tamoxifen (n = 4) or cyproterone acetate (n = 2). A significant partial response was observed in 30 other patients (45%). Additionally, half of them received inhibitory drugs. The best responses were seen with cyst reformation (complete response, 100%) and fibrous block. Clinical responses to treatment with [D-Trp6]-LHRH alone were independent of hormone receptor status, but synergistic effects occurred with concomitant use of the corresponding inhibitory drugs. We conclude that chronic mastopathy, particularly when associated with uterine fibroma, can be successfully treated by luteinizing hormone releasing hormone analogs in premenopausal women.

Topics: Adult; Cyproterone; Cyproterone Acetate; Drug Synergism; Drug Therapy, Combination; Female; Fibrocystic Breast Disease; Fibroma; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Luteolytic Agents; Middle Aged; Receptors, Estradiol; Receptors, LHRH; Receptors, Progesterone; Tamoxifen; Triptorelin Pamoate; Uterine Neoplasms

Estrogens (estrone [E1] and estradiol [E2]), their sulfates and progesterone receptor (PR) were evaluated in patients with uterine leiomyomata nontreated and treated with Decapeptyl (D-Trp6-gonadotropin-releasing hormone [GnRH]; Ipsen Biotech, Paris, France). Estrogen concentrations are very high in the leiomyoma (secretory phase, pg/g tissue [mean +/- SEM]: n = 10; E1: 147 +/- 24; E2: 850 +/- 116; E1-sulfate: 1,668 +/- 808; E2-sulfate: 718 +/- 126). Decapeptyl treatment provokes a significant decrease in E2 and particularly in E1 and E2 sulfates. Progesterone receptors were higher in the leiomyoma than in the myometrium; after a long treatment (3 to 4 months) a significant decrease in both tissues is observed. The decrease provoked by D-Trp6-GnRH on estrogens (unconjugated and sulfates) and in PR in the leiomyoma after long treatment, supports the hypothesis that estrogens are implicated in the cause of these tumors.

Topics: Adult; Antineoplastic Agents; Estradiol; Estrogens; Estrone; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Middle Aged; Myometrium; Receptors, Progesterone; Triptorelin Pamoate; Uterine Neoplasms

Fourteen patients with large uterine fibroids and urinary symptoms were treated with monthly injections of [D-Trp6]-luteinizing hormone-releasing hormone microcapsules. The average uterine size before treatment was 728 ml; it dropped to 323 ml (a drop of 55%) after treatment. Urinary symptoms of diurnal frequency disappeared in 11 of 12 patients (p less than 0.005) after the reduction of uterine size. Urgency decreased in 11 of 13 (p less than 0.005) and nocturia in eight of 10 (p less than 0.02). No differences were found before and after treatment in the symptoms of urge incontinence and stress incontinence in the cystometric and urethral pressure profile measurements. Urinary symptoms of frequency, urgency, and nocturia may be caused by the direct pressure exerted on the bladder by the enlarged uterus. Symptoms of urge incontinence and stress incontinence deserve a more specific treatment as they are not related to uterine size.

Topics: Adult; Antineoplastic Agents; Female; Fibroma; Gonadotropin-Releasing Hormone; Humans; Luteolytic Agents; Middle Aged; Triptorelin Pamoate; Urinary Bladder; Urinary Incontinence; Urinary Incontinence, Stress; Urination Disorders; Uterine Neoplasms

Concentrations of estrogen receptors, progesterone receptors, unconjugated estrogens (estradiol and estrone) and sulfate-conjugated estrogens (estradiol sulfate and estrone sulfate) were determined in patients treated with Decapeptyl and in controls. After prolonged Decapeptyl therapy, a highly significant fall in progesterone receptors was evidenced; estrogen receptors were found to be decreased in the myoma as compared with the secretory phase in controls and in the myometrium as compared with the proliferative phase in controls. Tissue levels of estrone sulfate and estradiol sulfate decreased very substantially. In conclusion, Decapeptyl emerges as a very promising agent for the treatment of uterine myomas.

Topics: Antineoplastic Agents; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Myometrium; Receptors, Estradiol; Receptors, Progesterone; Triptorelin Pamoate; Uterine Neoplasms

In view of advancements in treatment of certain hormone-dependent cancers with analogues of luteinizing hormone-releasing hormone (LH-RH), this study was undertaken to establish the presence and characteristics of receptors for [D-Trp6]LH-RH on the membranes of human endometrial cancer. Specific binding of [125I,D-Trp6]LH-RH was demonstrated in membrane preparations from 24 of 31 (77%) endometrial carcinomas and from 3 of 13 (23.1%) nonmalignant human endometrial specimens. Ligand binding was dependent on temperature, time, and plasma membrane concentration in a fashion expected of a peptide hormone. Mathematical analysis of the binding data showed that interaction of [125I,D-Trp6]LH-RH with the binding sites was consistent with the presence of a single class of high affinity, noncooperative receptors (Kd 9.88 +/- 4.59 x 10(-9) M; Bmax 0.70 +/- 0.14 x 10(-12) mol/mg membrane protein). The rates of association and dissociation were calculated to be 6.5 x 10(6) M-1 min-1 and 0.021 min-1, respectively. [125I,D-Trp6]LH-RH binding was not displaced by either unlabeled somatostatin or epidermal growth factor, but was displaced completely by native LH-RH. Using 125I-epidermal growth factor, specific, high-affinity receptors were also detected in membranes from 22 of 26 (85%) endometrial cancers and in all of 6 nonmalignant endometrial specimens (Kd 0.42 +/- 0.12 x 10(-9) M; Bmax 0.30 +/- 0.15 x 10(-12) mol/mg membrane protein). The potential functional role of the receptors for [D-Trp6]LH-RH in human endometrial carcinoma is not clear, but this finding provides a rationale for the use of therapeutic approaches based on LH-RH analogues in this malignancy.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Biomarkers, Tumor; Cell Membrane; ErbB Receptors; Female; Gonadotropin-Releasing Hormone; Humans; Kinetics; Middle Aged; Receptors, LHRH; Triptorelin Pamoate; Uterine Neoplasms

A long-acting GnRHa (D-Trp-6 microcapsules) proved capable of lowering serum PRL levels in a young hyperprolactinemic patient treated for a large myomatous uterus. No similar inhibitory effect was found in normoprolactinemia. Chronic GnRHa therapy may constitute an alternative to the existing forms of treatment for hyperprolactinemia and pituitary adenomas.

Topics: Adult; Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Hyperprolactinemia; Leiomyoma; Triptorelin Pamoate; Uterine Neoplasms

Oestrogen deficiency at the menopause is associated with changes in calcium and bone metabolism. Hypo-oestrogenism induced by the use of GnRH-agonists is clinically useful in the treatment of oestrogen-dependent diseases. This study was done to investigate calcium homeostasis and bone metabolism of pre-menopausal women in a GnRH-agonist-induced pseudo-menopause. Eighteen patients with endometriosis or uterine leiomyoma received monthly i.m. injections of 3.2 mg of long-acting D-Trp-6-LHRH over a 6-month period. Plasma oestradiol-17 beta and progesterone levels under treatment were significantly decreased to the levels of the early follicular phase. Plasma total calcium, serum osteocalcin and plasma alkaline phosphatase concentrations increased, while plasma phosphate levels did not change. Levels of 1,25-dihydroxyvitamin D3 decreased significantly, but 25-hydroxyvitamin D3 values remained constant. Trabecular bone mineral density of lumbar spine decreased continuously during the 6-month period. Nine women completed 6-9 months follow-up. In these women bone loss was reversible. Cortical bone measurements at the proximal radius showed no change during oestrogen deficiency. In conclusion, our findings demonstrate that GnRH-agonist-induced bone loss is reversible. Furthermore, they suggest that the state of pseudo-menopause induced by GnRH-agonist may serve as a model for further pathophysiological studies on calcium homeostasis and bone metabolism in the post-menopause.

Topics: Adult; Alkaline Phosphatase; Antineoplastic Agents; Bone and Bones; Calcifediol; Calcitriol; Calcium; Calcium-Binding Proteins; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Minerals; Osteocalcin; Osteoporosis; Progesterone; Triptorelin Pamoate; Uterine Neoplasms

Long acting D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) microcapsules, 3.2 mg were given monthly, intramuscularly for a period of 6 months to 26 menstruating patients with symptomatic leiomyomas. The patients ages were 22 to 52 years. Five patients (20%) were infertile. Patient evaluation before initiation of treatment included endometrial biopsy, ultrasonic measurements of uterine and tumor volumes, and bone-mineral density. The patients were periodically followed hormonally and ultrasonographically. A statistically significant reduction in uterine and tumor volumes (maximal after 4 months of treatment) was observed in all the patients except one. Two patients discontinued the treatment after 2 months, preferring surgery. A nonsignificant decrease in the mean bone-mineral density was noted after completion of therapy. Minor side effects such as hot flushes, vaginal dryness, backache, vaginal spotting, and nervousness, were encountered frequently, disappearing within 6 weeks after the last injection. A significant increase in uterine and myoma volume was noted in all the patients at 3 months after treatment.

Topics: Adult; Antineoplastic Agents; Capsules; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Leiomyoma; Luteinizing Hormone; Middle Aged; Time Factors; Triptorelin Pamoate; Uterine Neoplasms

Seven women with endometriosis and three women with uterine myomas were treated for six months with tryptoreline (Decapeptyl, Decapeptyl Depot, Ferring). In six patients with endometriosis improvement was achieved according to the AFS classification and the finding on palpation and ultrasonic examination. In three patients with uterine myoma a reduction by 25-100% was recorded. Dysmenorrhoea and pain in the hypogastrium disappeared completely in all patients except one. The LH and FSH levels declined and E2 levels were similar as in the menopause. The menstrual cycle disappeared in the course of treatment and all women experienced flushes. Daily s. c. and monthly depot doses gave similar results. Four months after treatment the hormonal levels and the menstrual cycle were normal. Endometriosis disappeared twice, four times minor endometriotic nodes persisted, once a uterine myoma of half the size reappeared. Treatment with LH-RH agonists in endometriosis matches danazole treatment in uterine myomas it is suitable for special cases.

Topics: Adult; Antineoplastic Agents; Delayed-Action Preparations; Drug Administration Schedule; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Injections, Subcutaneous; Leiomyoma; Middle Aged; Pelvic Neoplasms; Triptorelin Pamoate; Uterine Neoplasms

Topics: Adult; Escherichia coli Infections; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Triptorelin Pamoate; Uterine Cervicitis; Uterine Neoplasms

Gonadotropin-releasing hormone (GnRH) analogs can cause regression of uterine leiomyomata. This effect is thought to be mediated by the inhibition of gonadotropin release and steroid synthesis. In the present study we examined the possibility that these analogs may also act directly on uterine leiomyomata. Specific binding sites for GnRH are present in myoma membranes, as 125I-Buserelin binding was displaced with equal efficiency by the superagonists, Buserelin and D-Trp6-GnRH, and by the antagonist Organon 30276, but not by unrelated peptides such as thyrotropin releasing hormone and oxytocin. A nonlinear Scatchard curve obtained for Buserelin specific binding suggests the presence of at least two binding sites, one of which exhibits a relatively high affinity for GnRH analogs (Kd of approximately 10(-8) M). Western blotting with a specific GnRH receptor antibody revealed the presence of a 60 kDa protein in myoma membranes. This protein has a similar molecular weight to the purified pituitary GnRH receptor. These results indicate, for the first time, the presence of specific binding sites for GnRH in uterine leiomyomata, suggesting a direct effect of GnRH analogs on this tissue.

Topics: Adult; Buserelin; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Middle Aged; Molecular Weight; Receptors, LHRH; Thyrotropin-Releasing Hormone; Triptorelin Pamoate; Uterine Neoplasms; Uterus

Topics: Adult; Antineoplastic Agents; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms

Pituitary desensitization following infusion of gonadotropin-releasing hormone (GnRH) is measurable if bioactivity instead of immunoreactivity is considered. We hypothesized that GnRH agonist therapy induces the same kind of desensitization, but that radioimmunoassays (RIA) for gonadotropins based on polyclonal antibodies cannot show this effect because they recognize inactive fragments of gondadotropins. To test this hypothesis we measured luteinizing hormone (LH) with two different assays: one RIA was based on a polyclonal rabbit anti-hLH, while the other one was an immunoradiometric assay (IRMA) based on 2 different mouse monoclonal anti-hLH. LH measurements were performed on plasma samples obtained from 13 women with laparoscopically proven endometriosis and treated with microcapsules of the GnRH agonist D-Trp6-GnRH (Ferring) once a month. The correlation between LH measurements with both assays in 36 control plasma samples and in another 13 samples obtained before treatment in women with endometriosis was excellent (r = 0.959). In contrast, in women treated with GnRH agonist, the RIA yielded values ranging from undetectable to 12 mIU/ml, whereas 60 out of 66 values were undetectable with the IRMA. We conclude that the monoclonal anti-hLH antibodies in the IRMA either recognize an epitope close to the active site and/or do not recognize the biologically inactive LH fragments which are known to be produced during GnRH agonist therapy. Thus, monoclonal-antibody-based IRMA provide a new and interesting clinical tool to follow the effects of therapies which desensitize the gonadotropic function of the pituitary.

Topics: Antibodies, Monoclonal; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Radioimmunoassay; Triptorelin Pamoate; Uterine Neoplasms

Ten women with intramural leiomyomas were treated with the microencapsulated GnRH analogue Decapeptyl for 24 weeks. Four (4) mg Decapeptyl was injected, starting on day 21 of the menstrual cycle, and injections were repeated every 4 weeks for a total of 24 weeks. All patients showed a marked reduction in uterine size: before treatment it measured 284 +/- 57 cm3, after 8 weeks 122 +/- 33 cm3, and after 24 weeks 89 +/- 14 cm3. LH and estradiol decreased significantly; FSH decreased but not significantly; prolactin remained almost unaltered. Serum calcium, phosphate, alkaline phosphatase and osteocalcin increased, but, since calcium excretion (and hydroxyproline excretion) remained unaltered, these changes were considered to reflect increased bone turnover rather than bone loss. From these data it is concluded that Decapeptyl is very effective in reducing uterine fibroids, that treatment can be shorter than 6 months and that measurable bone loss did not occur.

Topics: Adult; Bone and Bones; Calcium; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Luteinizing Hormone; Middle Aged; Prolactin; Triptorelin Pamoate; Uterine Neoplasms

Agonist analogs of GnRH were used to effect a "medical castration" in 14 patients with uterine fibroids, presenting with either an enlarged uterus, recurrent menometrorrhagia, and/or infertility. This study confirms prior reports of a reduction in uterine size and cessation of menometrorrhagia in patients with fibroids following treatment with GnRHa. Of interest, however, was the successful use of GnRHa as either the sole treatment for uterine fibroid-associated infertility, or as a preoperative adjunct in infertility patients scheduled for myomectomy. Three of the five infertility patients in this study achieved intrauterine pregnancies. Further study of the role of GnRHa treatment in infertility patients with uterine fibroids appears warranted.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Triptorelin Pamoate; Uterine Neoplasms

Suppression of the secretion of gonadal steroids by chronic administration of a superactive agonist of luteinizing hormone-releasing hormone (LH-RH) was used for treatment of leiomyomata uteri. Ten menstruating women, presenting with a total of 20 uterine leiomyomas, were treated for 3 months with daily subcutaneous injections of D-Trp6-LH-RH. Serum estradiol (E2) levels were suppressed rapidly in five patients and were decreased in other patients. At the end of therapy, leiomyomas regressed completely in three patients, while five patients showed a decrease of more than 40% in the volume of leiomyomas. The reduction in tumor size was correlated with the rapidity of the fall in serum E2 levels. In one patient, the leiomyomata increased in size during treatment, and one woman had a poor clinical response. The agonist was well tolerated and few side effects were observed. Therapy with LH-RH agonists offers an alternative in the management of some uterine leiomyomas.

Topics: Adult; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Luteinizing Hormone; Middle Aged; Triptorelin Pamoate; Ultrasonics; Uterine Neoplasms

Topics: Adult; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Middle Aged; Triptorelin Pamoate; Uterine Neoplasms

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hematocrit; Humans; Leiomyoma; Menorrhagia; Triptorelin Pamoate; Ultrasonics; Uterine Neoplasms