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)

Estrogen-related cardiovascular dysfunction was noted in 23 out of 30 patients with prostatic cancer (PC). Coronary subjects with PC suffered from cardiac pain evident on ECG necessitating correction by effective doses of coronary active drugs. PC patients with essential hypertension exhibited frequent headache, progressive edema of the legs, drastic hypertensive reactions. It is held that estrogen therapy for prostatic cancer should be preceded and monitored by therapeutic evaluation responsible for optimal conditions to prevent and early diagnose cardiovascular complications.
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PMID:[Diagnosis and therapeutic correction of changes in the cardiovascular system of patients with prostatic cancer treated with estrogens]. 208 39

Nafarelin, a synthetic agonist of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LH-RH); gonadorelin] appears likely to join the other GnRH analogues currently used in a range of conditions reliant on gonadotrophins or sex hormones. With repeated administration, the pituitary becomes desensitised, and gonadotrophin release, and therefore sex hormone synthesis, are inhibited. Nafarelin has proved to be comparable to danazol in the management of women with endometriosis, with fewer potentially harmful adverse effects. Nafarelin has also been used effectively in in vitro fertilisation programmes, and in hirsute women and those with uterine leiomyoma, particularly to induce preoperative fibroid shrinkage. The drug shrinks hypertrophic tissue in men with benign prostatic hyperplasia, although treatment would need to be maintained indefinitely and therefore should probably be reserved for those unsuitable for prostatectomy. Preliminary data suggest that nafarelin is equivalent to diethylstilbestrol (stilboestrol) in terms of disease-free survival in men with prostate cancer. As a reliable method of contraception, nafarelin gives unpredictable results in men and the promising results in women may be offset by hypoestrogenic side effects. Nafarelin may join other GnRH agonists which are now routinely used in the management of children with central or combined precocious puberty. Nafarelin is readily and rapidly absorbed following intranasal delivery, and is protected to some extent from enzymatic degradation. The resultant relatively long elimination half-life allows once- or twice-daily administration. Estrogen depletion accounts for the most common side effects associated with nafarelin, including hot flushes and vaginal dryness, which are mild and tolerable in most patients. Reversible resorption of trabecular bone can occur during nafarelin therapy, perhaps necessitating cyclical treatment to enable bone mass to recover. Nafarelin, therefore, looks likely to find a role in the treatment of women with endometriosis, and results achieved in other conditions dependent on the pituitary-gonadal axis are promising.
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PMID:Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions. 214 Sep 79

Basal serum levels and ACTH-induced increments ('delta-values') of dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and testosterone and serum albumin levels were studied in patients with prostatic cancer before treatment and after orchidectomy or during estrogen treatment (intramuscular polyestradiol phosphate during the first 3 months, followed by another 3 months with additional oral ethinyl estradiol). Orchidectomy as well as single drug intramuscular or oral + intramuscular estrogens exerted a similar suppressive effect on basal levels of A-4 and 17-OHP. Orchidectomy caused a slight decrease in basal DHAS, while combined oral + intramuscular estrogens caused a pronounced decrease in basal DHAS and also in DHA. Single drug intramuscular estrogens did not affect basal DHA or DHAS levels. Increased basal cortisol levels appeared during combined oral + intramuscular estrogen therapy. delta DHA and delta A-4 values were unaffected by endocrine treatment, but delta 17-OHP and delta cortisol increased slightly after orchidectomy and during estrogen therapy. Significantly decreased albumin levels were only observed during combined oral + intramuscular estrogen treatment. Determination of estriol, which is a major metabolite of estradiol originating from polyestradiol phosphate, revealed significantly higher estriol levels during combined oral + intramuscular estrogen treatment than during single drug intramuscular estrogen therapy, indicating an increased induction of hepatic 16 alpha-hydroxylase activity. The pronounced decreases in DHAS and also in DHA during combined oral + intramuscular estrogen treatment are probably another reflexion of the liver side effects of oral estrogens.
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PMID:Adrenocortical function in prostatic cancer patients: effects of orchidectomy or different modes of estrogen treatment on basal steroid levels and on the response to exogenous adrenocorticotropic hormone. 216 78

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.
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PMID:Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients. 235 Nov 92

Prostatic tissue removed at the time of cystoprostatectomy was separated into periurethral and peripheral zones. Homogenized tissue was incubated with [1,2,6,7(3)H] androstenedione in the presence or absence of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHAD) and a 5 alpha-reductase inhibitor 4-MA (N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane 17 beta-carboxamide). Estrogen formation was determined by reverse isotope dilution of [3H] estrone and [3H] estradiol and crystallization to constant specific activity. Control incubations were carried out in parallel utilizing heated prostatic tissue. Total estrogens produced in the periurethral zone in patients with benign prostatic hyperplasia (BPH) was 223 fmol/mg protein/hr (SE +/- 57) compared to 102 fmol (SE +/- 17) in patients without BPH. Estrogen formation in the peripheral zone was 175 fmol (SE +/- 69) and 105 fmol (SE +/- 26) in patients with and without BPH, respectively. The prostatic aromatase exhibits Michaelis-Menton kinetics with an apparent Km of 90 nM. 4-OHAD inhibited aromatization in the prostatic tissue by 57-93%. Aromatization was also strongly inhibited by 4-MA, indicating that 4-MA is a potent aromatase as well as a 5 alpha-reductase inhibitor in this tissue. These results suggest that aromatization of androgens to estrogens in the human prostate proceeds at a substantial rate and that local estrogen formation could preexist and be a factor in the etiology of BPH and prostatic cancer.
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PMID:Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia. 243 1

The effects of parenteral and parenteral plus oral estrogen therapy on the serum levels of sex hormone binding globulin (SHBG), pregnancy-associated alpha 2-macroglobulin (alpha 2-PAG), growth hormone (GH), and somatomedin C (SmC) were studied in 26 patients with prostatic cancer. Intramuscular polyestradiol phosphate treatment, yielding a mean serum level of estradiol-17 beta of 1,446 pM and a mean testosterone level of 4.5 nM, had no significant effects on alpha 2-PAG, GH, and SmC and increased SHBG levels only marginally. Combined treatment with intramuscular polyestradiol phosphate and oral ethinyl estradiol greatly increased SHBG and alpha 2-PAG levels and caused elevated GH and decreased SmC levels. The route of estrogen administration is probably of major importance for the hormonal effects on hepatic activity as reflected by SHBG and alpha 2-PAG levels. Bypassing the portal circulation might be advantageous with respect to liver-related side effects of estrogen therapy. GH and SmC might act as mediators of estrogen effects on the human liver.
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PMID:Steroid-sensitive proteins, growth hormone and somatomedin C in prostatic cancer: effects of parenteral and oral estrogen therapy. 244 14

To assess if and by which mechanisms pharmacological estrogen treatment induces gallstone disease, we examined patients with recently diagnosed prostatic cancer randomly allocated to estrogen therapy (n = 37) or orchidectomy (n = 35). According to gallbladder ultrasonography, after 1 yr new gallstones had developed in 5 of 28 estrogen-treated patients, compared with 0 of 26 orchidectomized patients (P = 0.03). Estrogen therapy for 3 mo increased the relative concentration of cholesterol and cholesterol saturation of bile by approximately 30% (n = 10). Serum LDL cholesterol was reduced by approximately 40%, and its relative change related inversely to that of bile cholesterol (Rs = -0.77). There were no changes in biliary or serum lipids after orchidectomy (n = 9). Secretion rates of biliary lipids were measured with a duodenal perfusion technique. Patients on chronic estrogen therapy (n = 5) had approximately 40% higher biliary excretion rates of cholesterol than age-matched controls (n = 7). Phospholipid secretion was also higher, but no difference in bile acid secretion was found. We conclude that an increased hepatic secretion of cholesterol results in increased cholesterol saturation of bile and an enhanced rate of gallstone formation during estrogen treatment. The changes in bile cholesterol seem to be related to the induced changes in serum lipoprotein metabolism.
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PMID:Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma. 276 Feb 14

We report 2 cases of true hypocalcemia (not caused by decreased binding proteins) associated with metastatic prostate cancer and review previously reported cases. Hypocalcemia is a common but frequently unrecognized complication of prostatic cancer. Estrogen therapy often is associated with the hypocalcemia, which may be asymptomatic. The hypocalcemia is always associated with osteoblastic metastases and usually it is associated with increased serum alkaline phosphatase activity, acid phosphatase activity and serum parathyroid hormone concentration. Serum concentrations of magnesium, phosphorus and vitamin D frequently are decreased. Patients are in a positive calcium balance. The osteoblastic metastases seem to act as a calcium sink, creating a "hungry tumor phenomenon". The role of estrogens may be to stop the resorption of normal bone resulting in lower serum calcium concentrations.
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PMID:Hypocalcemia associated with estrogen therapy for metastatic adenocarcinoma of the prostate. 317 54

Serum concentrations of testosterone (T) and estradiol-17 beta (E2) were analyzed in prostatic cancer patients treated with 160, 240, or 320 mg polyestradiol phosphate (PEP) i.m. every fourth week as single drug therapy during a 6 month period. Estrogen effects on the liver were studied by analyzing serum levels of sex hormone binding globulin (SHBG) in the 320 mg group and compared with values obtained in patients treated with 80 mg PEP i.m. every fourth week + oral ethinylestradiol (EE2) 150 micrograms daily, or by orchidectomy. Orchidectomy levels of T were reached within 3 weeks in the 320 and 3 months in the 240 mg group. In the 160 mg group, mean T levels reached the upper limit of orchidectomy values after 6 months. Accumulation of E2 occurred to mean levels 1,300-2,500 pmol/L at 6 months. At 6 months, SHBG levels had increased to 617% of pretreatment values in the oral EE2 group, to 166% in the 320 mg group, and were unaffected by orchidectomy. No cardiovascular side effects occurred during single-drug PEP treatment.
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PMID:Single drug polyestradiol phosphate therapy in prostatic cancer. 324 84

Cardiovascular complications are a well recognized side-effect of antihormonal therapy in men with prostatic carcinoma. We studied changes in plasma lipoproteins in patients with prostate cancer during treatment with several androgen suppression therapies. Estrogen, orchiectomy, and a combination of LHRH agonist and antiandrogen (flutamide) reduced plasma testosterone concentrations (89-92%) and plasma estradiol decreased by 85%, 44%, and 54%, respectively. Estrogen induced hypertriglyceridemia and elevation of plasma HDL cholesterol, phospholipid, and apolipoprotein A-I and A-II concentrations. Low density lipoprotein (LDL) cholesterol decreased but LDL apolipoprotein B did not. These results suggest that the cardiovascular complications that occur during estrogen administration are not mediated through changes in lipoprotein profile, other than the hypertriglyceridemic effect. Orchiectomy caused hypercholesterolemia and an increase in both total and LDL apolipoprotein B, all of which are strong determinants of cardiovascular disease. The high density lipoprotein (HDL) concentration was not affected despite a reduction in plasma testosterone, perhaps due to a simultaneous decrease in estradiol. Combination therapy had no effect on plasma lipid and apolipoprotein B concentrations, but very low density lipoprotein (VLDL) apolipoprotein B decreased, and LDL apolipoprotein B increased. The HDL cholesterol and apolipoprotein A-I concentrations increased but A-II and phospholipids did not. These results suggest enhanced lipoprotein lipase activity, consistent with the reciprocal changes in VLDL and LDL apolipoprotein B levels, apolipoprotein B enrichment of LDL particles, and increase in HDL cholesterol. The higher apolipoprotein A-I to A-II ratio indicates an increase in HDL2 subfraction due to inhibition of endothelial hepatic lipase, increased secretion of apolipoprotein A-I, or both. These effects are attributed to estradiol, which decreased less than after orchiectomy, and to additional adrenal androgen inhibition by flutamide. We conclude that estradiol plays an important role in determining plasma lipoprotein concentrations in men, and androgens exert an antagonist effect. The lipoprotein profile resulting from the combination treatment is more beneficial than that resulting from orchiectomy or estrogen administration.
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PMID:Changes in plasma lipoproteins during various androgen suppression therapies in men with prostatic carcinoma: effects of orchiectomy, estrogen, and combination treatment with luteinizing hormone-releasing hormone agonist and flutamide. 327 21


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