Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue which, during continuous administration, down-regulates the pituitary-ovarian gonadal axis and reduces levels of the gonadotrophins, luteinising hormone and follicle-stimulating hormone. In women, this results in suppression of ovarian steroidogenesis and a decline in estrogen to levels similar to those observed after menopause or following surgical oophorectomy. Thus, goserelin has a useful role in the management of some benign estrogen-dependent gynaecological disorders. Goserelin is available as a biodegradable sustained release depot 3.6mg injection which is administered every 28 days. In women with endometriosis, monthly injections of depot goserelin were effective in achieving resolution of endometriotic implants and in improving pelvic symptoms, including pain and dyspareunia. Randomised clinical comparisons of depot goserelin with danazol indicate that goserelin is at least as effective as danazol and is better tolerated in the treatment of endometriosis. In the management of uterine leiomyomata (fibroids), goserelin depot injections reduce uterine size and the size of uterine leiomyomata, with maximum clinical benefit achieved approximately 3 to 4 months after initiation of treatment. When used as an adjunctive pretreatment for women undergoing surgical removal of uterine leiomyomata, goserelin was associated with technically easier surgical procedures, reduced intraoperative blood loss and reduced transfusion requirements around the time of surgery. As an alternative to surgery, therapeutic use of goserelin is limited by the rapid regrowth of leiomyomata following cessation of treatment. However, goserelin may be a useful treatment for women approaching menopause, in whom uterine leiomyomata shrink naturally as endogenous estrogen levels decline. In women with dysfunctional uterine bleeding, treatment with depot goserelin before surgery facilitates resection and ablative procedures by suppressing endometrial growth and thinning the endometrial mucosa. Goserelin is also an effective alternative to surgery in this patient group. As adjuvant therapy for women undergoing assisted reproduction procedures, goserelin is associated with reduced cycle cancellation rates and with an increase in the rate of oocyte retrieval. The tolerability profile of goserelin is characterised by adverse effects typical of hypoestrogenism, including hot flushes, loss of libido and loss of bone mineral density. However, concomitant 'add-back' hormone replacement therapy appears to effectively reduce these hypoestrogenic symptoms. In summary, the availability of depot goserelin has broadened the spectrum of effective treatments for benign estrogen-dependent gynaecological disorders. As goserelin is effective as a sustained release depot formulation suitable for administration on a monthly basis, it is also a convenient and practical treatment choice.
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PMID:Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in benign gynaecological disorders. 880 70

A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.
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PMID:A prospective, randomised study to compare goserelin acetate (Zoladex) versus cyproterone acetate (Cyprostat) versus a combination of the two in the treatment of metastatic prostatic carcinoma. 882 90

Add-back hormone replacement therapy has been shown to alleviate some of the hypo-oestrogenic side effects associated with gonadotrophin-releasing hormone agonists, including demineralisation of bone. Studies on patients with uterine fibroids have shown that concomitant add-back therapy reduced the efficacy of these agents, but that deferred administration was less detrimental. This trial set out to investigate if deferred add-back therapy could offer any advantages to patients with endometriosis compared with immediate therapy. Zoladex [goserelin acetate (3.6 mg every 4 weeks)] was given for 24 weeks either with placebo, with medrogestone (10 mg/day) for 24 weeks (immediate add-back therapy), or with placebo for 12 weeks followed by medrogestone (10 mg/day) for 12 weeks (deferred add-back therapy) to 123 patients. The number of responders measured using the Revised American Fertility Society score (decrease in this score of > or = 50%) was greatest in the immediate add-back therapy group, although there were no significant differences between groups. All three treatment groups showed significant decreases in bone mineral density compared with baseline but smaller losses were generally observed in the add-back groups. A significantly smaller number of patients in the immediate add-back group reported hot flushes during the first 12 weeks of treatment compared with the deferred add-back group. In conclusion, it appears that there is no extra advantage to patients with endometriosis being treated with goserelin in delaying the start of add-back therapy.
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PMID:Should add-back therapy for endometriosis be deferred for optimal results? 891 82

Goserelin acetate is a LH-RH agonist developed by AstraZeneca (formerly ICI, UK), and has been used clinically for the treatment of prostate cancer as a 4-week controlled-release formulation (Zoladex 3.6 mg depot). Recently, a new drug (Zoladex LA 10.8 mg depot) with 3-month controlled-release formulation was developed and became commercially available in Japan. In the randomized comparative phase III studies carried out with global bases, single administration of the new drug yielded almost equivalent anti-testosterone effect and the same serum level of the previous 3.6 mg depot formulation in 3-times continuous administration. In these studies, adverse drug reactions, which were mainly due to pharmacological effects of the new drug and minimal, were found in 52.6% (41/78) compared with 54.8% (46/84) with the previous 3.6 mg depot formulation. In the phase III studies, there were no significant differences in average serum testosterone levels between the two formulations at 12 and 13 weeks after administration. In the Japanese late phase II study with untreated patients, castration effect was observed in all 20 cases entered in the trial. In 20 cases in which treatment was switched from 3.6 mg depot to the new formulation, there were no significant changes in serum testosterone levels at castration level of the untreated patients, 90% (18/20) responded to the treatment, and normalization of PSA level was found in 75.0% (15/20). The adverse drug reactions were mainly increased triglyceride level and hot flushes. In the retrospective evaluation of untreated patients in this trial and the post-marketing clinical trial data for 3.6 mg depot, it was concluded that the new drug had almost the same efficacy and safety profile as 3.6 mg depot in Japanese people. These results indicate that Zoladex LA 10.8 mg depot has the same efficacy and safety as 3.6 mg depot with administration every three months, the burden of injection of LH-RH agonist can be reduced. This new medication can be considered a new standard for treatment of prostate cancer.
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PMID:[A new LH-RH agonist for treatment of prostate cancer, 3-month controlled-release formulation of goserelin acetate (Zoladex LA 10.8 mg depot)--outline of pre-clinical and clinical studies]. 1235 59

The use of the luteinising hormone releasing hormone (LHRH) analogues--goserelin (Zoladex, AstraZeneca) and leuprorelin (Prostap, Wyeth)--is well established and forms the backbone of the treatment of locally advanced and metastatic prostate cancer. Comparable efficacy with orchidectomy and, historically, diethylstilbestrol (DES) is accepted, with the advantages of reversibility and limited thromboembolic and cardiovascular toxicity, respectively. Side effects such as hot flushes, loss of libido, lethargy and decreased bone mineral density have recently stimulated more interest in the use of non-steroidal anti-androgens such as bicalutamide (Casodex, AstraZeneca) in locally advanced disease. Although better tolerated, bicalutamide has significant problems with gynaecomastia and breast pain. Maximal androgen blockade using LHRH analogues and their adjuvant use with radiotherapy are discussed, as well as their experimental application in intermittent androgen suppression therapy. Similar side effect profiles are reported for the LHRH analogues but injection tolerability differs with the smaller 23G needle for Prostap 3 compared to the 16G needle for Zoladex LA. There is no evidence to suggest a difference in the efficacy between the LHRH analogues goserelin and leuprorelin, although no direct comparison has yet been undertaken.
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PMID:Luteinising hormone releasing hormone analogues in the treatment of prostate cancer. 1247 66


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