Use Of GnRH Analogues Research Articles

Evaluation of perioperative morbidity associated with single and multiple myomectomy

SummaryThe aim of the study was to evaluate the risk of intraoperative and postoperative complications associated with single and multiple myomectomy. The sample was a retrospective cohort study of 206 women undergoing abdominal myomectomy at a teaching hospital in the UK between 1999 and 2003. Means of continuous variables were compared using t-tests with Satterthwaite's correction for unequal variance. It was found that menorrhagia was the presenting symptom in 72% of the women. Estimated blood loss was significantly more in multiple myomectomy compared with single myomectomy. Preoperative use of GnRH analogue and intraoperative tourniquet was used in both groups at the surgeon's discretion. Major complications were rare and three patients needed hysterectomy. There was no significant difference in hospital stay: 5.73 vs 5.98 days. It was concluded that myomectomy is a relatively safe operation with low incidence of serious morbidity. Haemorrhage is the commonest complication and more likely during multiple myomectomy.

GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy

For preserving fertility in women during chemotherapy, the character of invasive techniques, such as ovarian cryopreservation and other techniques, await further experience. Meanwhile, non-invasive techniques have attempted to minimize the gonadotoxic effect of chemotherapy, by using gonadotrophin-releasing hormone-analogues (GnRH-a) or oral contraceptives (OC). We performed a computerized MEDLINE search to identify articles published on fertility preservation using GnRH-a or OCs. Nine human-controlled studies reported the use of GnRH-a and four reported the use of OCs in parallel to chemotherapy. All nine studies analysing the effect of GnRH-a found lower rates of premature ovarian failure (POF) in patients receiving GnRH-a compared with the controls. Summarizing the studies resulted in 11.1% incidence of POF in patients who received GnRH-a compared with 55.5% incidence in the controls. Evidence using the fertility preserving effect of OC is limited. Two studies showed lower POF rates in OC-treated patients. The summarized data revealed a POF rate of 13.2% in patients who received OCs compared with that of 29.8% in the controls. The published clinical studies provide evidence, but do not prove statistically, that GnRH-a co-treatment reduces gonadotoxicity. Owing to the retrospective and non-randomized nature of most of the studies, definite conclusions concerning the reduction of POF by GnRH-a can still not be unequivocally drawn. As GnRH-a and OC have no serious side effects and as GnRH-a can even reduce chemotherapy-induced complications, such as severe menometrorrhagia, GnRH-a are considered by many clinicians as a clinically useful co-treatment in chemotherapy. The published clinical studies on OC also suggest a possible effect on the reduction of POF under certain conditions.

Chemotherapy and amenorrhea: risks and treatment options

The purpose of this study is to review the impact of chemotherapy on fertility and to update the reader on the current state of fertility preservation techniques. Chemotherapy results in irreversible damage to ovarian follicles and stromal function, and alkylating agents cause the most significant damage to ovarian reserve. Options for fertility preservation range from well established techniques such as embryo cryopreservation to experimental ones such as ovarian tissue freezing. The safety and effectiveness of concomitant use of gonadotropin-releasing hormone analogues to prevent chemotherapy-induced follicle death is still debated. In-vitro maturation of germinal vesicle oocytes can be an option in patients who do not have sufficient time for ovarian stimulation. The impact of chemotherapy on future fertility is much more significant than is widely believed. Because of this, young females should be counseled about fertility preservation options. Fertility preservation requires an individualized approach. If possible these patients should be encouraged to utilize the most established assisted reproductive techniques. Although success of IVF with frozen-thawed embryos now approaches that of using fresh embryos, success rates with oocyte freezing are lower but these rates are on the rise. Even though ovarian tissue cryopreservation is still an experimental technique, currently it is the only fertility preservation option in children.

The use of gonadotropin-releasing hormone analog in preservation of ovarian function in women undergoing chemotherapy: a systematic review and meta-analysis

ObjectiveTo evaluate the efficacy and safety of gonadotrophic-releasing hormone analog (GnRHa) co-treatment in preservation of ovarian function during gonadotoxic chemotherapy.DesignMeta-analysis.Materials and methodsA Medline, Embase, Scopus and Web of Science databases literature search from inception up to March 2007 was performed to identify published clinical trials and cohort studies comparing chemotherapy with GnRHa to chemotherapy alone in premenopaual women without restriction to language of publication. The methodological quality was evaluated using validated scales and the outcome-data was extracted. Agreement was evaluated using K statistics. Funnel blot was used for the assessment of publication bias. POF was considered the primary outcome. Secondary outcomes included; post-treatment pregnancy and treatment related complications. Random effect models were used to calculate the pooled relative risk (RR) for different outcomes. Subgroups were specified a priori and test for interaction was used for evaluation of difference in efficacy among subgroups.ResultsConclusionsCurrent evidence from observational studies suggests a beneficial value of the use of GnRH along with chemotherapy in premenopusal women. This hypothesis should be tested in the context of a well designed RCT with objective timely endpoints and including all indications and types of chemotherapy. ObjectiveTo evaluate the efficacy and safety of gonadotrophic-releasing hormone analog (GnRHa) co-treatment in preservation of ovarian function during gonadotoxic chemotherapy. To evaluate the efficacy and safety of gonadotrophic-releasing hormone analog (GnRHa) co-treatment in preservation of ovarian function during gonadotoxic chemotherapy. DesignMeta-analysis. Meta-analysis. Materials and methodsA Medline, Embase, Scopus and Web of Science databases literature search from inception up to March 2007 was performed to identify published clinical trials and cohort studies comparing chemotherapy with GnRHa to chemotherapy alone in premenopaual women without restriction to language of publication. The methodological quality was evaluated using validated scales and the outcome-data was extracted. Agreement was evaluated using K statistics. Funnel blot was used for the assessment of publication bias. POF was considered the primary outcome. Secondary outcomes included; post-treatment pregnancy and treatment related complications. Random effect models were used to calculate the pooled relative risk (RR) for different outcomes. Subgroups were specified a priori and test for interaction was used for evaluation of difference in efficacy among subgroups. A Medline, Embase, Scopus and Web of Science databases literature search from inception up to March 2007 was performed to identify published clinical trials and cohort studies comparing chemotherapy with GnRHa to chemotherapy alone in premenopaual women without restriction to language of publication. The methodological quality was evaluated using validated scales and the outcome-data was extracted. Agreement was evaluated using K statistics. Funnel blot was used for the assessment of publication bias. POF was considered the primary outcome. Secondary outcomes included; post-treatment pregnancy and treatment related complications. Random effect models were used to calculate the pooled relative risk (RR) for different outcomes. Subgroups were specified a priori and test for interaction was used for evaluation of difference in efficacy among subgroups. Results ConclusionsCurrent evidence from observational studies suggests a beneficial value of the use of GnRH along with chemotherapy in premenopusal women. This hypothesis should be tested in the context of a well designed RCT with objective timely endpoints and including all indications and types of chemotherapy. Current evidence from observational studies suggests a beneficial value of the use of GnRH along with chemotherapy in premenopusal women. This hypothesis should be tested in the context of a well designed RCT with objective timely endpoints and including all indications and types of chemotherapy.

Diagnosis and laparoscopic treatment of an unusual case of advanced extragenital endometriosis

Endometriosis is considered to be a benign gynaecological disorder, although several pathophysiological aspects of endometrial lesions resemble the behaviour of malignant tissue: similar to carcinomas, endometriotic cells are able to invade and destroy surrounding anatomical structures. Although the medical treatment of endometriotic lesions, including the use of GnRH analogues or gestagens, show temporary effectiveness and have been reported to cause a regression of disease, they rarely provide long-term relief of symptoms in advanced stages of endometriosis involving extragenital organs, such as the rectum or the urinary system. We here describe the diagnosis and minimally invasive surgical treatment of an unusually advanced case of endometriosis involving the rectosigmoid, the urinary bladder and the ureter, leading to secondary hydronephrosis and loss of renal function.

Long-term use of gonadotropin-releasing hormone analogues before IVF in women with endometriosis

To discuss the relationship between endometriosis and infertility, the impact of endometriosis on assisted reproductive techniques and also the benefits of prolonged use of gonadotropin-releasing hormone analogue before IVF in women with endometriosis. The available evidence suggests that endometriosis is strongly associated with infertility. Many studies indicate lower pregnancy and implantation rates even in assisted reproductive cycles in women with endometriosis. It is well known that medical suppression of endometriosis does not appear to be warranted for endometriosis-associated infertility. Prolonged pretreatment with gonadotropin-releasing hormone analogue before IVF has been reported to improve clinical pregnancy rates in infertile women with endometriosis. Based on the recently published data, infertile women with endometriosis may benefit from long-term pretreatment of gonadotropin-releasing hormone analogue prior to IVF.

Pathophysiology of radiation-induced growth hormone deficiency: Efficacy and safety of GH replacement

Radiation-induced growth hormone deficiency (GHD) is primarily due to hypothalamic damage. GH secretion by the pituitary may be affected either secondary to some degree of quantitative deprivation of hypothalamic input or, if the radiation dose is high enough, by direct pituitary damage. As a consequence, the neurosecretory profile of GH secretion in an irradiated patient remains pulsatile and qualitatively intact. The frequency of pulse generation is unaffected, but the amplitude of the GH pulses is markedly reduced. Over the last 25 years, the final heights achieved by children receiving GH replacement for radiation-induced GHD have improved; these improvements are attributable to refinements in GH dosing schedules, increased use of GnRH analogues for radiation-induced precocious puberty, and a reduced time interval between completion of irradiation and initiation of GH therapy. When retested at the completion of growth, 80–90% of these teenagers are likely to prove severely GH deficient and, therefore, will potentially benefit from GH replacement in adult life. Such long-term GH treatment in patients treated previously for a brain tumor means that critical and continuous surveillance must be devoted to the risk of tumor recurrence and the possibility of second neoplasms.

Indications des analogues de la GnRH en pré- et postchirurgie pour endométriose

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

125 Guidelines for the use of GnRH-analogues in the management of endometriosis — results on an international consensus (Salzburg 2005)

125 Guidelines for the use of GnRH-analogues in the management of endometriosis — results on an international consensus (Salzburg 2005)

Gonadotropin-releasing hormone induces apoptosis of prostate cancer cells: role of c-Jun NH2-terminal kinase, protein kinase B, and extracellular signal-regulated kinase pathways.

A standard therapy used today for prostate cancer is androgen ablation by gonadotropin-releasing hormone analogs (GnRH-a). Although most patients respond to androgen ablation as an initial systemic therapy, nearly all cases will develop androgen resistance, the management of which is still a major challenge. Here, we report that GnRH-a can directly induce apoptosis of the androgen-independent prostate cancer-derived DU145 and PC3 cell lines. Using specific inhibitors, we found that the apoptotic effect of GnRH-a is mediated by c-Jun NH2-terminal kinase (JNK) and inhibited by the phosphatidylinositol 3'-kinase (PI3K)-protein kinase B (PKB) pathway. Indeed, in DU145 cells, GnRH-a activates the JNK cascade in a c-Src- and MLK3-dependent manner but does not involve protein kinase C and epidermal growth factor receptor. Concomitantly, GnRH-a reduces the activity of the PI3K-PKB pathway, which results in the dephosphorylation of PKB mainly in the nucleus. The reduction of PKB activity releases PKB-induced inhibition of MLK3 and thus further stimulates JNK activity and accelerates the apoptotic effect of GnRH-a. Interestingly, extracellular signal-regulated kinase is also activated by GnRH-a, and this occurs via a pathway that involves matrix metalloproteinases and epidermal growth factor receptor, but its activation does not affect JNK activation and the GnRH-a-induced apoptosis. Our results support a potential use of GnRH-a for the treatment of advanced prostate cancer and suggest that the outcome of this treatment can be amplified by using PI3K-PKB inhibitors.

Goserelin versus CMF as adjuvant therapy for node-negative, hormone receptor-positive breast cancer in premenopausal patients. The GABG IV-A-93 trial

534 Background: Increasing evidence supports the use of GnRH analogues as adjuvant treatment in hormone sensitive, premenopausal breast cancer. However, only limited information is available in patients with node-negative disease. Methods: We randomised 771 patients to either goserelin (3.6 mg every 28 days for 2 years; n=393) or 3 cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (500 mg/m2, 40 mg/m2 and 600 mg/m2, days 1,8 q 29; n=378). Patients' characteristics were well balanced with 26% of the patients being 40 years or younger, 64% having a tumor size below 21mm, 79% having grade 1 or 2 tumors, and 72% receiving breast conserving surgery. 123 events were observed during a median follow up of 4.9 years. Results: The first event of failure (goserelin vs CMF) was an isolated locoregional recurrence (20 vs 18), a distant failure (35 vs 46), and death without recurrence (2 vs 2). Five-year event-free survival rates were 84.4% (95% confidence interval (CI): 80.4% to 88.5%) and 81.0% (95% CI: 76.3% to 85.7%) in the goserelin and in the CMF group, respectively. The estimated hazard ratio (intention-to-treat analysis) of goserelin vs CMF was 0.81 (95% CI: 0.56 to 1.17, P=0.24). Conclusions: Although the results of the trial are still based on relatively few observed events, they add important information to the current attempts of defining the role of medical ovarian ablation with goserelin in premenopausal patients with node-negative, hormonsensitive breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca Germany

The effectiveness of GnRHa with and without 'add-back' therapy in treating premenstrual syndrome: a meta analysis.

To determine the effectiveness of gonadotrophin-releasing hormone analogues (GnRHa) with and without hormonal add-back therapy in the management of premenstrual syndrome. Randomised controlled trials were identified by searching multiple databases. Exeter and North Devon Research and Development Support Unit and Keele University Academic Unit of Obstetrics and Gynaecology. Women with pre-diagnosed premenstrual syndrome and/or premenstrual dysphoric disorder. A meta-analysis of published randomised placebo-controlled trials assessing the use of GnRHa in the management of premenstrual syndrome. The standardised mean difference for each individual study and subsequently an overall standardised mean difference were calculated after demonstrating the consistency or homogeneity of the study results. Overall improvement in premenstrual symptomatology and effectiveness of GnRHa with additional hormonal add-back therapy were the main outcome measures assessed in this analysis. A secondary analysis was performed to assess the effectiveness of GnRHa in treating physical and emotional symptoms. Overall standardised mean difference for all trials that assessed the efficacy of GnRHa was -1.19 (95% confidence interval [CI] -1.88 to -0.51). The equivalent odds ratio was 8.66 (95% CI 2.52 to 30.26) in favour of GnRHa. GnRHa were more efficacious for physical than behavioural symptoms, although the difference was not statistically significant. The addition of hormonal add-back therapy to GnRHa did not appear to reduce the efficacy of GnRHa alone; standardised mean difference 0.12 (95% CI -0.35 to 0.58). GnRHa appear to be an effective treatment in the management of premenstrual syndrome. The addition of hormonal add-back therapy to reduce side effects does not reduce efficacy.

Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement.

Final height (FH) outcome is important in survivors of childhood brain tumors. GH replacement is indicated in those found to be GH deficient (GHD). More recently, GnRH analogs (GnRHa) have been introduced to delay early or rapidly progressing puberty to allow more time for linear growth. Studies to FH are important to determine the effectiveness of growth-promoting strategies. Our aim was to assess whether evolving endocrine strategies have improved FH outcome and to determine whether GnRHa therapy has contributed auxologically. FH data were examined in 58 children (31 males and 27 females) with radiation-induced GHD who had been treated with GH. All had received a combination of cranial (CI; n = 17) or craniospinal (CSI; n = 41) irradiation with or without chemotherapy for a brain tumor. Eleven patients received GnRHa therapy. Throughout the 25 yr of the study patients came closer to achieving target height (i.e. a reduction in height loss), both those receiving CI (r = 0.5; P = 0.03) and those receiving CSI (r = 0.6; P < 0.001). The patients receiving GH therapy before 1988 compared with from 1988 onward had a similar age at irradiation [mean (+/-SD), 5.8 (3.0) vs. 6.2 (2.9) yr; P = 0.6], but experienced a more prolonged time interval from completing irradiation to starting GH [5.4 (2.4) vs. 3.3 (1.6) yr; P < 0.001]. Forward stepwise regression analysis revealed that height loss is affected by age at irradiation (P < 0.001), previous spinal irradiation (P = 0.02), chemotherapy (P < 0.001), and exposure to GnRHa therapy (P < 0.001). In the 11 patients treated with GnRHa therapy FH SD scores were improved compared with FH predictions calculated from a model derived from the patients not treated with GnRHa [-0.8 (1.6) vs. -2.4 (0.8) SD score; P < 0.001]. We have demonstrated an overall improvement in FH in children treated with GH for GHD after therapy for brain tumors over the last 25 yr. In the subset of children in whom the growth prognosis was adversely affected by early puberty, the combination of GnRHa and GH improved their prospects of achieving target height. The improved auxological outcome may reflect 1) the use of more standardized GH schedules and better dosing regimens, 2) a reduction in the time interval between finishing radiotherapy and receiving GH replacement, and 3) the use of GnRHa in addition to GH replacement in carefully selected patients.

Technological changes in the management of prostate cancer result in increased healthcare costs--a retrospective study in a defined Swedish population.

In two previous studies we calculated direct costs for men with prostate cancer who died in 1984-85 and 1992-93, respectively. We have now performed a third cost analysis to enable a longitudinal cost comparison. The aim was to calculate direct costs for the management of prostate cancer, describe the economic consequences of technological changes over time and estimate total direct costs for prostate cancer in Sweden. A total of 204 men in a defined population with a diagnosis of prostate cancer and who died in 1997-98 were included. Data on utilization of health services were extracted from clinical records from time of diagnosis to death from a university hospital and from one county hospital in the county of Ostergötland. The average direct cost per patient has been nearly stable over time (1984-85: 143 000 SEK; 1992-93: 150 000 SEK; 1997-98: 146 000 SEK). The share of costs for drugs increased from 7% in 1992-93 to 17% in 1997-98. The total direct costs for prostate cancer in Sweden have increased over time (1994-85: 610 MSEK; 1992-93: 860 MSEK; 1997-98: 970 MSEK). Two-thirds of the total cost is incurred by inpatient care. The share of the total costs for drugs is increasing due to increased use of gonadotrophin-releasing hormone analogues. Small changes in average direct costs per patient despite greater use of technology are explained by the fact that more prostate cancers are detected at the early stages.

Oocyte donor satisfaction with the use of GnRH analogues in ART cycles

Oocyte donor satisfaction with the use of GnRH analogues in ART cycles

Efficacy of pre-operative gonadotrophin hormone releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy: a systematic review.

To evaluate the role of pretreatment with gonadotrophin releasing hormone (GnRH) analogues (GnRHa) prior to surgery for women with uterine fibroids. A systematic review was undertaken of all randomised controlled trials assessing the efficacy of GnRHa treatment prior to surgery (myomectomy or hysterectomy) in women with fibroids. Secondary care. Sample Premenopausal women with fibroids awaiting surgery attending hospitals or clinics. Electronic searches of Medline, EmBase, Current Contents, the Cochrane Library, National Research Register, NLM's Clinical Trials Register and the Cochrane group's Trials Register were performed, between 1980 and 2000. Twenty-six randomised controlled trials were identified that compared GnRHa with no treatment, placebo or other medical treatment. The quality of the trials was assessed and data were extracted independently by two of the reviewers. Statistical analysis was performed in Revman according to Cochrane guidelines and where possible outcomes were pooled in a meta-analysis. Pre-operative assessment (reduction in uterine and fibroid volume, change in haemoglobin and haematocrit, change in patient's symptoms), intra-operative assessment (duration of operation, blood loss, proportion with vertical incision, proportion undergoing vaginal rather than abdominal procedure, frequency of blood transfusions), post-operative assessment (complications, duration of hospital stay, recurrence of fibroids). Pre- and post-operative haemoglobin and haematocrit were significantly improved by GnRHa therapy prior to surgery, and uterine volume, uterine gestational size and fibroid volume were all reduced. Pelvic symptoms were also reduced but some adverse events were more likely during GnRHa therapy. Hysterectomy appeared to be easier after pretreatment with GnRHa therapy; there was reduced operating time and a greater proportion of hysterectomy patients was able to have a vaginal rather than an abdominal procedure. Duration of hospital stay was also reduced. Blood loss and rate of vertical incisions were reduced for both myomectomy and hysterectomy. Evidence of increased risk of fibroid recurrence after GnRHa pretreatment in myomectomy patients was equivocal and few data were available to assess change in postoperative fertility. The use of GnRHa for three to four months prior to fibroid surgery reduces both uterine volume and fibroid size. They are beneficial in the correction of pre-operative iron deficiency anaemia, if present, and reduce intra-operative blood loss. If uterine size is such that a midline incision is planned, this can be avoided in many women with the use of GnRHa. For women undergoing hysterectomy, a vaginal procedure is more likely following the use of these agents.

Efficacy of pre-operative gonadotrophin hormone releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy: a systematic review

Objective To evaluate the role of pretreatment with gonadotrophin releasing hormone (GnRH) analogues (GnRHa) prior to surgery for women with uterine fibroids. Design A systematic review was undertaken of all randomised controlled trials assessing the efficacy of GnRHa treatment prior to surgery (myomectomy or hysterectomy) in women with fibroids. Setting Secondary care. Sample Premenopausal women with fibroids awaiting surgery attending hospitals or clinics. Methods Electronic searches of Medline, EmBase, Current Contents, the Cochrane Library, National Research Register, NLM's Clinical Trials Register and the Cochrane group's Trials Register were performed, between 1980 and 2000. Twenty-six randomised controlled trials were identified that compared GnRHa with no treatment, placebo or other medical treatment. The quality of the trials was assessed and data were extracted independently by two of the reviewers. Statistical analysis was performed in Revman according to Cochrane guidelines and where possible outcomes were pooled in a meta-analysis. Main outcome measures Pre-operative assessment (reduction in uterine and fibroid volume, change in haemoglobin and haematocrit, change in patient's symptoms), intra-operative assessment (duration of operation, blood loss, proportion with vertical incision, proportion undergoing vaginal rather than abdominal procedure, frequency of blood transfusions), post-operative assessment (complications, duration of hospital stay, recurrence of fibroids). Results Pre- and post-operative haemoglobin and haematocrit were significantly improved by GnRHa therapy prior to surgery, and uterine volume, uterine gestational size and fibroid volume were all reduced. Pelvic symptoms were also reduced but some adverse events were more likely during GnRHa therapy. Hysterectomy appeared to be easier after pretreatment with GnRHa therapy; there was reduced operating time and a greater proportion of hysterectomy patients was able to have a vaginal rather than an abdominal procedure. Duration of hospital stay was also reduced. Blood loss and rate of vertical incisions were reduced for both myomectomy and hysterectomy. Evidence of increased risk of fibroid recurrence after GnRHa pretreatment in myomectomy patients was equivocal and few data were available to assess change in post-operative fertility. Conclusions The use of GnRHa for three to four months prior to fibroid surgery reduces both uterine volume and fibroid size. They are beneficial in the correction of pre-operative iron deficiency anaemia, if present, and reduce intra-operative blood loss. If uterine size is such that a midline incision is planned, this can be avoided in many women with the use of GnRHa. For women undergoing hysterectomy, a vaginal procedure is more likely following the use of these agents.

Combined use of GnRH analog and antagonist: redundancy vs. complementary action

Objective: It was found that GnRH has receptors in the whole male and female reproductive tract: testis, cumulus complex, oocytes, fallopian tubes, endometrium, etc. The GnRH Analogue (GnRHA) has a beneficial effect at all levels while the GnRH Antagonist opposes it with an apparent trend toward lower pregnancy rates. However, the GnRH Antagonist is becoming more accepted because of a lesser incidence of O.H.S.S. and less cycle cancellations especially, in the challenging P.C.O.S. cases (multiple smaller than 12mm follicles with high Estradiol (E2)). Our pilot study attempts to determine if the beneficial effects of the GnRHA can be maintained and further enhanced by the timely addition of the GnRH Antagonist.

Pre-operative endometrial thinning agents before hysteroscopic surgery for heavy menstrual bleeding.

Menorrhagia is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Although medical therapy is generally the first approach, many will eventually require or request a hysterectomy. Hysterectomy is associated with a significant in-patient hospital stay and a period of convalescence that makes it an unattractive and unnecessarily invasive option for many women. Hysteroscopic endometrial ablation or resection offers a day-case surgical alternative to hysterectomy for these women. It is also a cheaper procedure than hysterectomy. Complete endometrial removal or destruction is one of the most important determinants of treatment success. Therefore surgery will be most effective if undertaken when endometrial thickness is less than 4mm, in the immediate post-menstrual phase, however there are often difficulties in reliably arranging surgery for this time. The other option is the use of hormonal agents which induce endometrial thinning or atrophy prior to surgery. The most commonly evaluated agents have been goserelin (a GnRH analogue) and danazol. Progestogens and other GnRH analogues have also been studied although less data are available. It has been suggested that the use of these agents, particularly GnRH analogues, will reduce operating time, improve the intra-uterine operating environment, and reduce distension medium absorption (this is the fluid used to distend the uterine cavity during surgery). To investigate the effectiveness of gonadotrophin-releasing hormone (GnRH) analogues, danazol, and progestogens, when used for endometrial thinning prior to hysteroscopic surgery for menorrhagia, in improving the intra-uterine operating environment and treatment outcome after surgery. The Menstrual Disorders and Subfertility Group search strategy (see Review Group details) was used to identify randomised trials that had compared the use of these drugs with either each other, or placebo, or no pre-operative treatment. Trials were included if they compared the effects of these agents with each other, or with placebo or no treatment on relevant intra-operative and post-operative treatment outcomes. Only randomised studies were included in this review. Eight studies met the inclusion criteria for this review. Four studies compared goserelin (a GnRH analogue) with no treatment or placebo. Three studies compared goserelin with danazol. One study compared progestogens, danazol and triptorelin (a GnRH analogue) with no treatment. Data was extracted independently by two reviewers. A third reviewer checked data extraction for accuracy and wrote to authors where relevant data was missing or unclear. Intra-operative parameters included endometrial thickness, duration of surgery, ease of surgery, distension medium absorption and complication rate. Post-operative outcomes compared were the proportion of women with amenorrhoea, post-operative menstrual loss and dysmenorrhoea, and the need for further surgery. Data on side-effects were also recorded. When compared with no treatment GnRH analogues are associated with a shorter duration of surgery, greater ease of surgery and a higher rate of post-operative amenorrhoea. Post-operative dysmenorrhoea also appears to be reduced. The use of GnRH analogues has no effect on intra-operative complication rates and patient satisfaction with this surgery is high irrespective of the use of any pre-operative endometrial thinning agent. GnRH analogues produce more consistent endometrial atrophy than danazol. For other intra-operative and post-operative outcomes any differences are minimal. Both GnRH analogues and danazol produce side-effects in a significant proportion of women, though few studies have reported these in detail. Little randomised data is available to assess the effectiveness of progestogens as endometrial thinning agents and the effect of any thinning agent

Clinical use of GnRH analogues.

Clinical use of GnRH analogues.