A comparison of goserelin and danazol as endometrial thinning agents prior to endometrial laser ablation. Depot goserelin and danazol pre-treatment before rollerball endometrial ablation for menorrhagia. Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study. Is endometrial pre-treatment of value in improving the outcome of transcervical resection of the endometrium? Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata. Treatment with a gonadotrophin releasing hormone agonist before endometrial resection: a multicentre, randomised controlled trial. Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery. Gonadotropin-releasing hormone agonist use before hysterectomy. Luteinizing hormone affects uterine receptivity independently of ovarian function.
To compare the effectiveness of goserelin and danazol prior to endometrial laser ablation and assess different dosage regimens.
                A prospective open randomised trial.
                Specialist unit in minimal access gynaecological surgery in a district general hospital.
                One hundred and sixty premenopausal women with dysfunctional uterine bleeding.
                Randomisation into four groups receiving either one or two injections of goserelin acetate (3.6 mg subcutaneously) or 28 or 56 days of danazol (four 200 mg tablets daily), followed by endometrial laser ablation.
                Endometrial thickness pretreatment and, immediately prior to endometrial laser ablation, assessed by vaginal ultrasound and full thickness endometrial biopsy; appearance of the endometrium at surgery; duration of the operation; the amount of fluid absorbed during surgery; and the clinical outcome at 24 weeks after surgery.
                The two drugs were equally effective in thinning the endometrium. Compared with danazol, goserelin was better tolerated and resulted in a more satisfactory endometrial appearance at hysteroscopy, a greater reduction in cavity length (0.5 cm compared with 0.3 cm, P = 0.002), a shorter operation (16.4 min compared with 21.6 min, P < 0.001), less fluid absorption (0 ml compared with 200 ml, P = 0.001), and a higher rate of amenorrhoea or oligoamenorrhoea (77% compared with 54%, P < 0.001) at the six month check. The administration of goserelin for 8 weeks compared with 4 weeks produced greater thinning of the endometrium on ultrasound and on histological examination, a greater reduction in cavity length on ultrasound and an increase in reported vasomotor symptoms. In both treatment regimens, 95% of women reported a satisfactory reduction in menstrual flow at the six month check.
                Goserelin appears to be more effective and better tolerated than danazol for treatment prior to endometrial laser ablation. Eight weeks treatment with goserelin resulted in better operating conditions and more vasomotor side effect, compared with four weeks treatment, although there was no difference in clinical outcome. To compare the safety and efficacy of a GnRH agonist, depot goserelin, and danazol as preoperative treatments before rollerball endometrial ablation.
                We performed an open, randomized study of women with clinically convincing histories of menorrhagia. Two treatment groups of equal size (goserelin acetate, 3.6 mg subcutaneous implant given monthly, n = 30; and danazol, 200 mg two times per day, n = 30) were treated for 2 months before undergoing endometrial ablation, which entailed using the rollerball with 80-100 watts of coagulating current.
                Measured menstrual blood loss decreased dramatically after ablation, with 74% of goserelin users and 62% of danazol users achieving complete amenorrhea by the end of the 6-month follow-up period. Among women who did not achieve complete amenorrhea, those in the danazol group were more likely to experience occasional episodes of moderate or heavy bleeding. Mean measured blood loss decreased from 94.8 to 1.1 mL at 3 months and 1.0 mL at 6 months after goserelin, and 97.9 to 15.0 mL and 7.4 mL after danazol. Menstrual pain also improved markedly. The median duration of surgery was 20 minutes (range 5-55) in both groups, median irrigation fluid deficit was 100 mL (range 0-800), and median operative blood loss was 20 mL (range 1-50). Endometrium was less than 2 mm thick in all goserelin and most danazol users. Side effects of goserelin and danazol therapy were all within the expected pattern for these drugs.
                Depot goserelin and danazol both provide adequate endometrial preparation before rollerball endometrial ablation for treatment of menorrhagia due to ovulatory dysfunctional uterine bleeding. To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery.
                Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2).
                Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%).
                Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery. The aim of this study was to determine whether or not the use of medical pre-treatment of the endometrium improves the outcome of transcervical resection of the endometrium with regards to long-term operative outcome, histological findings and patient satisfaction. A prospective randomized trial comparing three endometrial pre-treatment agents (danazol, medroxyprogesterone acetate or nafarelin) with no pre-treatment was conducted. The main outcome measures were: (i) thickness of the endometrium and myometrium resected; (ii) histological stage of the endometrium at the time of operation; (iii) the presence or absence of menses and (iv) patient satisfaction 1 year post-operatively. Of the three pre-treatments studied, danazol produced a lower median endometrial thickness than the control, showed the greatest ability to induce atrophy of the endometrial glands and stroma (not statistically significant) and produced the highest rate of amenorrhoea (not different to the control). Danazol and nafarelin produced significantly lower median endometrial thickness than no pre-treatment. There were, however, no significant differences in the rates of amenorrhoea in any of the pre-treatment groups compared with that in the control group. No improvement in clinical outcome or patient satisfaction is conferred by the use of medical pre-treatments if transcervical resection of the endometrium is performed in the proliferative phase of the menstrual cycle. 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. To ascertain whether treatment with a gonadotrophin releasing hormone agonist before endometrial resection reduces absorption of distension fluid and operating time and facilitates the procedure.
                A multicentre, prospective, randomised controlled study.
                Seventy-one premenopausal women with established menorrhagia.
                Eight weeks of goserelin depot treatment before endometrial resection of immediate surgery in the early proliferative phase of the cycle.
                Irrigation fluid deficit, operating time and degree or difficulty of the procedure.
                After randomisation eight women withdrew from the study, leaving 33 women in the goserelin arm and 30 in the immediate surgery arm. Mean (SD) operating time was 15.1 (9.0) min in the goserelin group versus 16.9 (9.5) min in the controls; mean difference + 1.8 min, 95% CI, -2.9 to + 6.4. Mean (SD) distension medium deficit was, respectively, 422 (287) ml versus 564 (291 ml); mean difference + 142 ml, 95% CI -4 to + 288. The goserelin effect was restricted to the 29 women with adenomyosis as the mean (SD) fluid deficit was considerably less in the 19 treated women than in the 10 controls (299 (206) ml versus 597 (135) ml; mean difference + 298 ml, 95% CI + 149 to + 447). The surgeons classified the intraoperative difficulties as none in 6, minimal in 20, moderate in 7, and severe in no cases in the goserelin group; corresponding figures in the group without pretreatment were 2, 14, 13, and 1.
                Goserelin administration before endometrial resection may reduce absorption of fluid at surgery in women with adenomyosis and may facilitate intrauterine operating conditions. To evaluate the clinical value of postoperative hormone therapy in endometriosis, 60 patients with advanced disease were randomized to receive in a double-blind study danazol (200 mg, 3 times daily), medroxyprogesterone acetate (MPA) (100 mg daily) or placebo post-operatively for 6 months. Treatment efficacy was evaluated clinically and at laparoscopy 6 months after medication. In relation to placebo, danazol and high-dose MPA treatments, which did not differ from each other in efficacy, significantly alleviated pelvic pain. In addition, the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group. Breakthrough bleeding, weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment. These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinically beneficial. Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy.
                Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist.
                All patients in the two groups with a pretreatment hemoglobin < 11.0 gm/dl randomized to agonist had a significant (p < 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p < 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms.
                The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin < 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity. Previous studies have suggested that LH, in addition to its well-known effects on the ovary, may exert direct effects on the uterus. This study evaluated the effects of mid-cycle administration of human chorionic gonadotrophin (HCG), which signals through the LH receptor, on endometrial thickness and uterine receptivity in two groups of women lacking ovarian activity and receiving embryos from an oocyte donation programme. Patients in one group still had ovulatory cycles, but their ovarian function was suppressed by pituitary down-regulation with a gonadotrophin-releasing hormone (GnRH) agonist in the embryo transfer cycle, resulting in low endogenous LH concentrations. Patients in the other group were menopausal women whose pituitary function was not down-regulated in the embryo transfer cycle and whose endogenous LH concentrations were thus high. Patients in each of the two groups were randomized into two subgroups. Patients in one subgroup were given 5000 IU of HCG 2 days before oocyte recovery in the corresponding donor. Patients in the other subgroup received placebo at the same time. Oocytes from each donor were randomly distributed between one patient from the HCG subgroup and one patient from the placebo subgroup in each patient group. Endometrial growth and secretory transformation were stimulated by sequential treatment with oestradiol valerate and progesterone. In women with low endogenous LH receiving placebo, endometrial thickness stopped increasing at the beginning of secretory transformation. Mid-cycle HCG administration resulted in a continuous increase in endometrial thickness through this period, improved the implantation rate after embryo transfer in these women (30.6 versus 20.7%) and augmented the number of multiple pregnancies. No similar stagnation of endometrial thickness and no effects of mid-cycle HCG administration on endometrial thickness, the implantation rate and the number of multiple pregnancies were found in women with high endogenous LH. It is concluded that endometrial maturation is disturbed in women with low endogenous LH but can be rescued by mid-cycle stimulation of LH receptor with exogenous HCG in the absence of ovarian activity.
Endometrial thinning prior to hysteroscopic surgery in the early proliferative phase of the menstrual cycle for menorrhagia improves both the operating conditions for the surgeon and short term post-operative outcome. Gonadotrophin-releasing hormone analogues produce slightly more consistent endometrial thinning than danazol, though both agents produce satisfactory results. The effect of these agents on longer term post-operative outcomes such as amenorrhoea and the need for further surgical intervention reduces with time.