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)

Luteinizing hormone-releasing hormone (LHRH) agonist, when administered in a continuous, nonpulsatile manner, causes desensitization of the LHRH receptor complex on the gonadotroph cells in the anterior pituitary gland. Biosynthesis and secretion of luteinizing hormone cease, and testicular androgenic production is inhibited. When used in this capacity, LHRH agonists can be an effective treatment for benign prostatic hyperplasia. After 4 to 6 months of therapy, prostatic volume decreases by 25% to 30%, voiding symptoms improve significantly in approximately 25% to 33% of patients, and the peak urinary flow rate increases substantially (more than 15 ml/second) in approximately 25% to 33% of patients. During the first month of treatment, serum luteinizing hormone, follicle-stimulating hormone, testosterone, dihydrotestosterone, 17 beta-estradiol, and prostate-specific antigen decline to low values and remain low throughout treatment. Prostatic 5 alpha-reductase activity and androgen receptor content also decrease with treatment. Side effects are significant: impotence, decreased libido, and hot flushes are the most common. Because the effect of LHRH agonist therapy on the serum testosterone concentration is reversible, treatment of benign prostatic hyperplasia with an LHRH agonist must be considered life-long therapy. Thus, this therapy should be reserved for patients who are impotent or who are poor surgical risks.
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PMID:LHRH agonists. A nonsurgical treatment for benign prostatic hyperplasia. 172 94

Cyproterone acetate is a progestational antiandrogen with potent antigonadotropic activity that results in rapid suppression of serum testosterone. Used as a single agent, cyproterone acetate yields a total androgen blockade. It may be combined with low-dose diethylstilbestrol, orchiectomy, or LHRH agonists to improve, in theory, the results of such therapy. In clinical testing, cyproterone acetate has proved equivalent to diethylstilbestrol with markedly less toxicity. It is useful in conjunction with LHRH agonists, either transiently to block the flare phenomenon, or continuously to block peripheral androgen receptors; the necessity for this latter action has not yet been proved. Cyproterone acetate may afford transient objective improvement in patients not responding to other forms of hormone deprivation. Experience in this role is limited. The drug may be used to suppress the hot flushes associated with orchiectomy or LHRH agonist therapy. Cyproterone acetate induces local tumor regression; owing to its reversible effects, it is useful as neoadjuvant or adjuvant androgen withdrawal therapy in patients with lower-stage disease undergoing radical surgery or radiotherapy. Adverse effects are mostly those related to hormone withdrawal, namely, impotence, infertility, and lassitude. Gynecomastia and breast tenderness occur in less than 18% and cardiovascular complications in approximately 10% of treated men.
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PMID:Use of cyproterone acetate in prostate cancer. 182 43

Prolonged administration of a luteinizing hormone releasing hormone agonist causes a transient increase in serum testosterone concentrations, lasting a few days, followed by a long-lasting decrease in the serum testosterone concentrations, luteinizing hormone releasing hormone agonists inducing a chemical castration equivalent to surgical castration. The effect is observed whatever the agonist employed, side-effects being limited to loss of libido, impotence and hot flushes. Moreover, chemical castration is reversible and may be repeated; therefore, this new therapy appears to be of considerable interest in the treatment of prostatic cancer. The indications for luteinizing hormone releasing hormone analogues, however, are limited to metastasized adenocarcinomas which represent the stage of the disease most frequently encountered (about 75% of the cancers treated). They constitute a method of treatment that is only palliative. The use of agonists competes directly with orchidectomy but it is costly and demanding, and it derives its indications from the fact that it is reversible, does not mutilate and is devoid of toxicity.
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PMID:Place of luteinizing hormone releasing hormone agonists in the treatment of prostatic cancer. 218 54

Buserelin is a synthetic gonadotropin-releasing hormone (GnRH) analog which is more potent than natural GnRH. Prolonged administration of the drug produces, after a short phase of stimulation, a selective and durable inhibition of secretion of pituitary gonadotropins, resulting in medical castration. In pilot and controlled studies buserelin shows a response rate that is similar to that of diethylstilbestrol or orchiectomy in the palliative treatment of advanced prostatic cancer, but larger and better designed studies are needed before reaching definitive conclusions about the duration of response and survival. The most common adverse effects of buserelin are loss of libido and/or impotence, hot flushes and possible flare-up of prostatic carcinoma symptoms in the first week of therapy. The combination of buserelin with an antiandrogen could avoid the flare syndrome; whether the combination has advantages compared to administration of buserelin alone requires confirmation from the large randomized studies still in progress.
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PMID:Buserelin in the treatment of prostatic cancer. 250 41

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.
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PMID:Zoladex as primary therapy in advanced prostatic cancer. A French cooperative trial. 297 63

Ten men with advanced breast cancer were evaluated for response to treatment with the luteinizing hormone-releasing hormone (LH-RH) analogue, buserelin, alone or in combination with the antiandrogen, flutamide. One of five patients receiving buserelin as a single agent had a partial remission lasting 12 months, and with the addition of flutamide, this lasted over 24 additional months. Three patients had stable disease with a median duration of 6 months (range, two to 14). One patient had progressive disease. Of five patients receiving the combination of buserelin and flutamide from the beginning of therapy, four patients had a partial remission with a median duration of over 15 months (range, over five to 16). One patient's disease remained stable for 12 months. Major side effects were hot flushes, loss of libido, and impotence. Buserelin initiates a castration-like endocrine response and has potential in the treatment of men with disseminated breast cancer when used either alone or in combination with flutamide.
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PMID:Advanced male breast cancer treatment with the LH-RH analogue buserelin alone or in combination with the antiandrogen flutamide. 313 19

The efficacy and tolerability of Casodex, a new non-steroidal antiandrogen, were studied in 267 patients with advanced prostate cancer. All patients received Casodex, 50 mg daily, as monotherapy. The objective response rate was 55.5% and the subjective response rate was 56.1%. The most common adverse events were the expected pharmacological effects of breast tenderness, gynecomastia and hot flushes. No other adverse events were reported in more than 5% of patients. There was minimal occurrence of impotence, loss of libido and diarrhea. The results show that Casodex 50 mg is effective and well tolerated in the treatment of advanced prostate cancer.
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PMID:Efficacy and tolerability of Casodex in patients with advanced prostate cancer. International Casodex Study Group. 757 54

Castration, whether surgical (orchiectomy) or pharmacological (androgen blockade), used in the management of advanced prostatic carcinoma, induces as a secondary effect, immediately following impotence, the onset of a vasomotor syndrome characterized by hot flushes and sweating. This syndrome which may present with such intensity and frequency as to severely affect the quality of life and even the psychological equilibrium of the patient. Treatment with progestinic agents leads to the release of opioid peptides at hypothalamic level, thus decreasing the level of catecholamines responsible for the vasomotor syndrome. In the 37 cases treated with progestogens, a therapeutic efficacy of 80% was observed following cyproterone acetate and of 70% following medroxyprogesterone acetate.
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PMID:[Therapy of vasomotor syndrome in the treatment of advanced prostatic cancer: apropos of 37 cases]. 954 67

Androgen suppressive maneuvers still represent the gold standard for prostate cancer patients. However, they are associated with side effects (fatigue, sexual impotence, hot flushes, anemia, anxiety, depression and osteoporosis) all of which have a negative impact on quality of life. Nonsteroidal antiandrogens compete with dihydrotestosterone for the linkage of its own receptors. These compounds are commonly used in combination with suppressive maneuvers. However, there is a growing experience with them as monotherapy, based on the possibility to spare gonadal function and therefore prevent the effects related to its suppression. Many studies have demonstrated the feasibility and safety of this approach, which can represent a valuable alternative to suppressive maneuvers for patients wishing to retain sexual function, especially for those without distant metastases. Unfortunately, none of the comparative studies performed so far had the power to detect the equivalence between monotherapy and castration.
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PMID:Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy? 1093 69

Prostate cancer represents the most common noncutaneous malignancy in men. With the widespread use of prostate-specific antigen screening, as many as one in six men in the USA will be diagnosed with prostate cancer. Significant healthcare resources are currently devoted to the treatment of this disease, specifically aimed at improving the side effects of successful treatment. Surgery or radiation therapy provides the best chance of cure from this disease. However, as many as 50% of patients treated with curative intent will develop a recurrence 10-15 years following treatment. Hormonal ablation via medical or surgical castration provides disease control, but is associated with significant hot flushes, loss of libido and impotence. Selective, apoptotic antineoplastic drugs, such as exisulind, may provide an alternative method to treating or preventing prostate cancer. This drug profile reviews the evidence for the use of exisulind in the treatment of prostate cancer.
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PMID:Exisulind in the treatment of prostate cancer. 1633 86


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