Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histologic changes induced in the mammary gland of male-to-female transsexuals have not yet been reported in the literature. We studied the histologic changes induced by chemical and surgical castration and estrogen therapy in the breasts of 14 such patients, with particular reference to acinar and lobular formation. To objectify the influence of cross-sex treatment, the histologic findings were compared with those in two men treated hormonally for prostate cancer. The slight increase in the plasma estrogen-to-androgen ratio seen in idiopathic gynecomastia usually does not induce acinar and lobular formation in the male breast. In men treated with nonprogestative antiandrogens for prostate cancer, only moderate acinar and lobular formation occurs. Only in male-to-female transsexuals in whom progestative chemical castration is combined with feminizing estrogen therapy will full acinar and lobular formation occur with hormonally stimulated nuclei and pseudolactational changes. Hence, combined progestative antiandrogens and estrogens are necessary for genetically male breast tissue to mimic the natural histology of the female breast. Orchidectomy does not contribute to this. Apocrine metaplasia may occur in breasts of male-to-female transsexuals, but so far, only four cases of breast cancer in male-to-female transsexuals have been documented.
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PMID:Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men. 1063 90

A phenomenon of the prostate gland, which is also shared by hair follicles, is that it is little influenced by testosterone (T) for androgenic stimulation, but instead by its metabolite 5alpha-dihydrotestosterone (DHT). By blocking the conversion of T to DHT, the circulating level of DHT is reduced by 80%, the size of the prostate gland is reduced by about 20% and the level of prostate-specific antigen (PSA) by about 50%. Treatment of patients with obstructive benign prostatic hypertrophy (BPH) with the drug Finasteride leads to a moderately improved urinary flow, symptomatic improvement and halts the natural progress of the disease. Since DHT potentiates the effect of testosterone on erectile function, the side-effects are impotence in 3% of patients, decreased ejaculatory volume, and gynaecomastia in 0.4% of patients. The drug could be regarded as a safe way to treat moderately symptomatic BPH. The efficacy of the drug is long-lasting (more than 7 years). It has also been tried in prostate cancer, but is less effective. It reduces PSA levels by 50% and, in combination therapy, therefore, PSA levels remain low for longer when Finasteride is added. An important finding is the efficacy of Finasteride treatment in haematuria from BPH. The drug interacts with vascular endothelium growth factor and efficiently prevents new bleeding. It could be regarded as a first-line therapy for this type of haematuria. Finasteride can also be used to stop male baldness. It seems particularly effective in men aged 20-40 years; 85% of patients stopped losing hair when given Finasteride. When the treatment was stopped hair loss continued, thus therapy may have to be "lifelong".
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PMID:Finasteride in the treatment of benign prostatic hypertrophy: an update. New indications for finasteride therapy. 1063 64

This paper reports on results of the EORTC protocol 30892, an open, prospective, randomized study of 310 patients with previously untreated metastatic prostate cancer with favourable prognostic factors who were treated by either flutamide (FLU) or cyproterone acetate (CPA) monotherapy. The final analysis with regard to the main end points, time to progression and survival are still pending. Final results related to the evaluation of sexual functioning prior to and under treatment are reported here. Of 310 randomized patients 294 were eligible for evaluation within this side study. The median age was 71 years (range 48-85). Potential risk factors related to age, general health and prostate cancer were evaluated. For evaluation of sexual functions a five-item questionnaire was used which was administered by the investigator. The protocol allowed time dependent observations at 3-monthly follow-up visits. Sexual functioning was dependent on age but not on prostate cancer-related parameters. Sexual functions at entry were similar within the two treatment groups, spontaneous (nightly) erections and sexual activity were seen in 43-51% and 29-35% of cases. Under treatment, sexual functions under FLU and CPA declined slowly with median times of 12.9 and 5.8 months versus 13.7 and 8.9 months respectively for spontaneous erections and sexual activity. Eventually, with an average observation time in excess of 2 years, loss of spontaneous erections and of sexual activity occurred in 80% versus 92% and in 78% versus 88% of men under FLU versus CPA treatment respectively. None of these differences reached statistical significance. Maintenance of potency under treatment with FLU as reported in the literature is not confirmed in this study. However, loss of sexual functions under monotherapy with both antiandrogens is slow and 10-20% of men retain sexual activity after 2-6 years of treatment. This observation can be exploited in new treatment schemes and is likely to lead to improved quality of life. The advantage of FLU in time and total preservation of sexual functions is statistically not significant and must be balanced against the side effects of FLU and other pure antiandrogens, which may exceed those of CPA especially with respect to gynaecomastia. Hepatic toxicity may limit the long-term use of both drugs.
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PMID:Prostate cancer treated by anti-androgens: is sexual function preserved? EORTC Genitourinary Group. European Organization for Research and Treatment of Cancer. 1064 78

Several health conditions specifically involve men, including impotence (erectile dysfunction), androgen deficiency syndrome, benign prostatic hypertrophy, prostate cancer, baldness, and gynecomastia. This article reviews the major features of these syndromes and highlights the specific nursing issues involved.
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PMID:Health issues unique to the aging man. 1103 4

Endocrine treatment of prostate cancer has been established for more than 5 decades. Focusing on immediate or short-term side effects, bilateral orchidectomy may cause psychological trauma, treatment with oral estrogens is combined with a high risk of severe cardiovascular complications, and the use of LH-RH agonists and antiandrogens as monotherapies or in combination may result in tumor flare, hot flashes, and gynecomastia. In recent years an increasing number of reports on anemia and/or osteoporosis related to endocrine treatment have been published. These side effects are regular and persistent after orchidectomy, or during treatment with LH-RH agonists, and are most often expressed with maximum androgen blockade. In contrast, anemia and/or osteoporosis are not reported with estrogen treatment or the use of nonsteroidal antiandrogens as a monotherapy regimen. Since many prostate cancer patients are treated hormonally for many years, control of Hb levels and bone mineral density before and after initiation of treatment at regular intervals is highly recommended as a standard of care.
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PMID:Potential side-effects of endocrine treatment of long duration in prostate cancer. 1105 92

Men with locally advanced prostate cancer face a high risk of disease progression and cancer-related death. The traditional active treatment options for locally advanced disease, either following failure of treatment of primary curative intent or newly diagnosed, are radiotherapy and castration. Radiotherapy alone has a high failure rate, although outcome can be improved by adjuvant hormonal therapy. Castration is associated with loss of libido, sexual dysfunction, osteoporosis and hot flushes, which are significant drawbacks when patients may receive treatment for several years. Monotherapy with a non-steroidal antiandrogen offers potential benefits with respect to quality of life. Studies in the adjuvant setting are in progress. In the setting of previously untreated locally advanced disease, pooled mature data (56% deaths) from two major studies indicate no significant difference in survival outcome between bicalutamide ('Casodex') 150 mg and castration. Bicalutamide 150 mg offers quality of life benefits with respect to sexual interest and physical capacity. Preliminary data suggest that bicalutamide maintains bone mineral density. Bicalutamide 150 mg is well tolerated; gynaecomastia and breast pain, common side effects of antiandrogen monotherapy, may be managed by prophylactic irradiation or surgery. Bicalutamide 150 mg monotherapy is an alternative to castration for locally advanced prostate cancer.
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PMID:Treatment of locally advanced prostate cancer--a new role for antiandrogen monotherapy? 1111 97

This article summarizes discussions of the importance of androgens and androgen antagonists in the genesis of prostate cancer. These discussions occurred at a recent symposium on prostate cancer chemoprevention sponsored by the National Cancer Institute. Considerable information exists indicating the importance of androgens in the development of prostate cancer. Trials in breast cancer indicate that estrogen antagonists prevent breast cancer-suggesting, by analogy, that the blockade of androgen action might prevent the emergence of prostate cancer. The 5alpha-reductase inhibitors block the intracellular metabolism of testosterone and inhibit the growth of the prostate. Limited data suggest that 5alpha-reductase inhibitors reduces prostate-specific antigen in men with localized and advanced, primary or recurrent prostate cancer. An ongoing national trial of 18,000 men over 50 years of age has completed accrual and will evaluate whether a standard dose of finasteride will prevent the development of prostate cancer. The toxicity profile of finasteride (Proscar, Merck & Co., West Point, PA), the only approved 5alpha-reductase inhibitor, is favorable leading to its evaluation as a potential chemopreventive agent for prostate cancer. Anti-androgens such as bicalutamide (Casodex, AstraZeneca, Wilmington, DE) are active in the treatment of prostate cancer and comparable, in some trials, to testicular androgen suppression. These data suggest that antiandrogens may be active in the prevention of prostate cancer; however, the toxicity of antiandrogens (gynecomastia, gastrointestinal toxicity) poses concerns for application in prevention studies. Opportunities for study of factors predictive or associated with the development of prostate cancer and new agents that may interrupt this process offer numerous leads that may reduce the incidence of prostate cancer.
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PMID:Androgen antagonists: Potential role in prostate cancer prevention. 1129 97

Androgens are important steroid hormones for expression of the male phenotype. They have characteristic roles during male sexual differentiation, during development and maintenance of secondary male characteristics, and during the initiation and maintenance of spermatogenesis. The two most important androgens in this respect are testosterone and 5 alpha-dihydrotestosterone. Each androgen has its own specific role during male sexual differentiation, testosterone is involved in the development and differentiation of Wolffian duct derived structures, whereas 5 alpha-dihydrotestosterone, a metabolite of testosterone, is the active ligand in the urogenital sinus and tubercle and their derived structures. The actions of androgens are mediated by the androgen receptor. This ligand dependent transcription factor belongs to the superfamily of nuclear receptors, including those for the other steroid hormones. The androgen receptor gene is located on the X-chromosome at Xq11--12 and codes for a protein with a molecular mass of approximately 110 kDa. Only one androgen receptor cDNA has been identified sofar, despite two different ligands. It is generally accepted that defects in the androgen receptor gene prevent the normal development of both internal and external male structures in 46, XY individuals. The end-organ resistance to androgens has been designated as androgen insensitivity syndrome (AIS) and is distinct from other forms of male pseudohermaphroditism like 17 beta-hydroxy-steroid dehydrogenase type 3 deficiency, leydig cell hypoplasia due to inactivating LH receptor mutations or 5 alpha-reductase type 2 deficiency. Furthermore, two additional pathological situations are associated with abnormal androgen receptor structure and function -- spinal and bulbar muscular atrophy (SBMA, or Kennedy's disease) and prostate cancer. In the AR gene, four different types of mutations have been detected in DNA from individuals with AIS -- (i) single point mutations resulting in amino acid substitutions or premature stopcodons; (ii) nucleotide insertions or deletions most often leading to a frame shift and premature termination; (iii) complete or partial gene deletions; and (iv) intronic mutations in either splice donor or acceptor sites, which affect the splicing of AR RNA. The main phenotypic characteristics of individuals with the complete androgen insensitivity syndrome (CAIS) are, female external genitalia, a short, blind ending vagina, the absence of Wolffian duct derived structures, the absence of a prostate, development of gynecomastia and the absence of pubic and axillary hair. Usually testosterone levels are elevated at the time of puberty, while also elevated LH levels are found. In the partial androgen insensitivity syndrome (PAIS) several different phenotypes are evident, ranging from individuals with predominantly a female appearance to persons with ambiguous genitalia, or individuals with a predominantly male phenotype. At puberty, elevated LH, testosterone and estradiol levels are observed. Individuals with mild symptoms of undervirilization (mild androgen insensitivity syndrome (MAIS)) and infertility have been described as well. Phenotypic variation between individuals in different families has been described for several mutations. However, in cases of CAIS no phenotypic variation has been described within one single family, in contrast to families with individuals with PAIS. In general AIS, can be routinely analyzed and more than 150 different mutations have been reported now. Differential diagnosis of AIS is possible with syndromes presenting with almost similar phenotypes but with a completely different molecular cause.
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PMID:Molecular basis of androgen insensitivity. 1142 Jan 35

Nonsteroidal antiandrogens are generally used in conjunction with castration as combined androgen blockade. However, the changing profile of patients with prostate cancer has made monotherapy with a nonsteroidal antiandrogen an attractive alternative therapeutic approach, offering potential quality-of-life benefits over conventional treatment modalities. Of available antiandrogens, monotherapy with bicalutamide has been most extensively evaluated. Combined data from 2 studies at a median follow-up time of 6.3 years revealed no statistically significant difference in overall survival between bicalutamide 150-mg monotherapy and castration in patients with nonmetastatic locally advanced disease. In patients with metastatic disease, there was a statistically significant difference (6 weeks) in overall survival in favor of castration. Bicalutamide monotherapy is associated with significant quality-of-life benefits (sexual interest and physical capacity), with preliminary data suggesting that the risk of osteoporosis may also be reduced by bicalutamide 150-mg monotherapy compared with castration. In general, bicalutamide is well tolerated, with a predictable adverse-effect profile. Breast pain (40%) and gynecomastia (49%) are the most common adverse events seen during monotherapy with this drug. In summary, the availability of bicalutamide 150-mg monotherapy broadens treatment options for men with locally advanced prostate cancer, offering a viable and attractive alternative to castration in this patient population. Ongoing studies will determine the role of bicalutamide in the treatment of localized disease.
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PMID:Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer. 1150 39

The advent of prostate-specific antigen (PSA) testing and increased patient awareness has led to patients being diagnosed with prostate cancer at an earlier stage and a younger age than previously. Adjuvant hormonal therapy to radiotherapy or prostatectomy has been shown to reduce the risk of tumour progression, and in some studies survival benefits have been demonstrated. The non-steroidal antiandrogen bicalutamide ('Casodex') has undergone extensive evaluation and is currently undergoing clinical trials as immediate therapy, either alone or as adjuvant to treatment of curative intent in patients with localized or locally advanced disease. Data from the first analysis of one of the studies in the Early Prostate Cancer (EPC) programme involving 3,603 patients have shown that, after a median follow-up of 2.6 years, the risk of prostate cancer progression was significantly reduced (by 43%) in patients receiving bicalutamide 150 mg compared with those receiving standard care alone (HR 0.57; 95% CI 0.48, 0.69; p << 0.0001). The risk of PSA progression was also significantly reduced (by 63%). At this stage the survival data are still immature. Side effects of bicalutamide were mostly gynaecomastia and breast pain, which is consistent with its pharmacology. Overall withdrawal rates were similar in the bicalutamide 150 mg and standard care alone groups. In the bicalutamide 150 mg group, withdrawals were mainly due to side effects, whereas in the group receiving standard care alone, withdrawals were mainly due to disease progression. The programme is ongoing, and survival data are awaited.
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PMID:Delaying/reducing the risk of clinical tumour progression after primary curative procedures. 1168 60


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