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)

Genitourinary problems, including neurogenic dysfunction, impotence, prostatism, urinary tract infections, and prostate cancer, are common in the elderly, and most of the symptoms can be alleviated through pharmacological management. Patients with neurogenic dysfunction who present with symptoms such as incontinence and urinary retention can be appropriately managed with bladder and sphincter relaxants or stimulants. Anticholinergic agents in the form of oxybutynin, flavoxate, and propantheline are effective bladder relaxants, and phenoxybenzamine, prazosin, and terazosin are commonly used as sphincter relaxants. Bethanechol chloride is the agent most commonly used to stimulate bladder contraction, but physicians should be careful when prescribing it for elderly patients with cardiovascular problems. Organic and psychogenic causes of impotence usually overlap, and oral agents have limited use in the treatment process. The use of yohimbine has increased recently, but its value and rate of success remains questionable. Testosterone is being used widely to treat impotence, but it is only helpful to patients with hypogonadism and should be used with discretion in the elderly, who have a high incidence of prostate cancer. Vasoactive intracavernous pharmacotherapy, on the other hand, is a recently discovered alternative to testosterone with promising results. Although the treatment of choice for benign prostatic hypertrophy is surgery, there have been important pharmacological advances in treating this disorder. alpha-Adrenergic antagonists and anti-androgenic agents have been found to relieve the symptoms of prostatic enlargement. The use of chemotherapeutic and antibiotic agents to treat and suppress acute and chronic urinary tract infections is reviewed; these are second only to pulmonary infections as the most frequent cause of febrile episodes in patients over the age of 65. Lower urinary tract infections can be treated with almost any antibacterial agent. Upper urinary tract infections require full genitourinary evaluation and appropriate antibiotics should be used according to the urine culture sensitivity studies. With the advent of new hormonal agents, more choices are now available for the management of prostate cancer, which is the second most common malignancy in men. Diethylstilbestrol (stilboestrol), an oral estrogen, remains a commonly used agent to achieve castrate levels of androgens in advanced prostatic carcinoma. Agonist analogues, such as goserelin and leuprorelin, of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] achieve the same results as diethylstilbestrol but without the cardiovascular side effects. Antiandrogens are also being used in combination with GnRH agonists to produce complete androgen blockage, with mixed results.
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PMID:Current concepts in the treatment of genitourinary tract disorders in the older individual. 172 98

The antiandrogen cyproterone acetate (CA), as well as oestrogens have been reported to influence pituitary-adrenal function in prostate cancer patients, but the clinical relevance of these findings is unknown. We therefore investigated serum cortisol (F), dehydro-epiandrosterone sulphate (DS), testosterone (T) and prolactin (Prl) levels in patients treated with CA or oestradiol undecylate for at least 6 months. Hypothalamic-pituitary-adrenal function was further assessed by analysis of diurnal hormone variation and by ACTH stimulation and dexamethasone suppression tests. To differentiate between direct CA or oestrogen effects and secondary effects resulting from therapy-induced hypogonadism, we performed similar tests in untreated normogonadal and hypogonadal patients. CA treatment effected a significant decrease in serum F (-40%), DS (-73%) and T (-58%) levels and an increase in serum Prl (+118%). Oestrogen treatment resulted in markedly lowered T levels (-89%), slightly elevated serum F (+24%) and significantly increased serum Prl (+192%). Corresponding changes of F, DS and Prl could not be found in the untreated hypogonadal controls, thus indicating a direct drug-related effect. Neither diurnal rhythmicity of serum F nor adrenal response to ACTH stimulation or sensitivity to dexamethasone suppression significantly changed under CA or oestrogen treatment. We conclude that, although serum F levels may decrease under CA or increase slightly under oestrogen therapy for prostate carcinoma, these findings do not justify specific treatment, since neither clinical side effects nor an impairment of hypothalamic-pituitary-adrenal feedback occurs.
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PMID:Effect of oestrogen or cyproterone acetate treatment on adrenocortical function in prostate carcinoma patients. 242 11

The authors describe the abnormalities of gonadal function developing in a patient with prostate cancer who had received estrogen therapy continuously for 6 years. The pretreatment prostate biopsy showed well developed acini consistent with normal androgenization and adenocarcinoma. Twelve years later, 6 years after discontinuation of estrogen treatment, the patient presented with severe hypogonadism, gynecomastia, and primary hypothyroidism. Testicular biopsies showed ghosts of seminiferous tubules with absence of Leydig cells, and prostatic biopsies showed atrophic acini without evidence of malignancy. Despite undetectable serum testosterone levels, serum gonadotropins were inappropriately normal and responded minimally to gonadotropin-releasing hormone (GnRH) administration. Replacement therapy with levothyroxine did not correct gonadal dysfunction. Thus, prolonged estrogen therapy may result in irreversible testicular destruction and loss of the feed-back response of the hypothalamic pituitary gonadal axis.
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PMID:Hypogonadism following long-term treatment with diethylstilbestrol. 250 19

LHRH physiology is now well known. This decapeptide is released every 60 to 120 minutes by the hypothalamic pulse generator. Dopamine, noradrenaline, prostaglandins and endogenous morphinomimetics play a role in its regulation. Testosterone exerts its feed back exclusively at the hypothalamic level. LHRH action at the pituitary level is mediated through high affinity receptors. LHRH internalization is not necessary for its action which is calcium-dependent. At the testicular level, LHRH receptors are identical to those on the pituitary. Acute administration of LHRH increases both receptors on the pituitary and the testis. The synthesis of LHRH analogs with prolonged effects has produced agonist and antagonist substances which both inhibit gonadotropins. This gonadotrope inhibition is explained, in the case of agonists by both pituitary and gonadal desensitization in animal experiments. This last action is linked to LH increase. In the rat, LHRH has also led to a parallel impairment of steroidogenesis by 17 hydroxylase and 17-20 desmolase deficiency. The physiological effect of LHRH is produced exclusively by pulsatile administration. It can now be considered for the treatment of hypogonadotrophic hypogonadism. Moreover, the gonadotrope inhibition induced by LHRH agonist with prolonged action can be of therapeutic use in idiopathic precocious puberty, prostatic cancer and inhibition of spermatogenesis (an association with androgens being necessary in this last case).
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PMID:[LHRH in man. Current data]. 613 Jul 41

Obesity is a product of welfare. About 1/3 of our population has got excessive weight, 6 to 8% is truly obese and in 0.1% we may speak of pathologic obesity. Obesity is not only an esthetic problem, but is goes together with higher morbidity and mortality. In men with a body mass index (BMI = W (kg)/L2 (m)) of more than 35, the glucose metabolism was disturbed in 70%, the lipid spectrum had a clearly atherogenic profile, the average (free) testosterone level was significantly diminished and there was also a certain degree of hypogonadism. A short term treatment (4 to 6 weeks) based on a hypocaloric diet (400) and rich in proteins normalized the glucose metabolism in a very great number of patients, while the insulinemia fell with 40% and the lipidogram always became normal, but for the HDL-C, which showed a slight drop, while the testosterone levels became normal with a strong rise of the sex hormone binding globulin. And yet, at that very moment the patients were still definitely obese: this suggests that the metabolic disturbances are not the consequence of obesity in itself, but may be related to the dietary habits of the patients. Concerning the mechanism of hypogonadism, the cause of its disturbance seems to be situated in the hypothalamo-hypophyseal area and be characterized by a lower amplitude of LH-pulses, which are correlated with the testosterone levels. This hypothalamic disorder is however not limited to the LH-secretion, but the amplitude of growth hormone- and of ACTH-pulses is also reduced. Our study suggests that not obesity itself, but dietary factors might be responsible for the detected abnormalities. This might have important implications. Indeed, it is well known that in population groups, whose diet contains fewer calories and less fat--such as the Chinese and the Japanese--sex hormone binding globulin exists in far higher concentrations whereas free testosterone is found in a lower concentration. In these populations the prevalence of clinically obvious prostate cancer--which is androgen-sensitive--is much lower than in Western countries: it seems obvious to look for a correlation between both observations. Another remarkable phenomenon is the difference in testosterone metabolism between the Eastern and Western people; this leads us to the remarkable findings that in Asian people the same amount of androgens nearly always produces azoospermia and infertility, whereas this appears in only 2/3 of the cases among Western people.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Metabolic effects of obesity in men]. 812 79

Androgens are needed in male fertility control methods to impede gonadotropin secretion. Large and frequent doses of testosterone esters are used to induce this effect, but these large and frequent doses are linked to wide fluctuations of plasma testosterone levels. Thus, men need a contraceptive that supplies effective, appropriate, continuous replacement doses over long periods. The synthetic androgen 7alpha-methyl-19-nortestosterone (MENT) can likely address this problem. Studies in primates, rats, and adult men show that it is much more potent than testosterone and can be administered via subdermal implants in effective amounts, which mimic physiologic doses and effects of testosterone, for 12 months. There will most likely be 2 subdermal implants, 1 releasing MENT and the other releasing a luteinizing hormone releasing hormone. Unlike testosterone, MENT is not reduced (5alpha-reduction) to a 5alpha-dihydrosteroid in the prostate. If MENT is administered in a dose sufficient to not disturb normal muscle mass and gonadotropin secretion, it will not hyperstimulate the prostate. Thus, it is less apt to cause benign prostatic hypertrophy and, possibly, prostate cancer than is testosterone. MENT is the first androgen to promote health (i.e., reduction of the incidence of prostate disease). Clinicians may also be able to use MENT to treat hypogonadism, prostatic hyperplasia, and muscle wasting.
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PMID:7 alpha-methyl-nortestosterone (MENT): the optimal androgen for male contraception. 848 61

Erectile dysfunction associated to low circulating androgens is characterized by a low testosterone due to hypogonadism of hypothalamic-pituitary or testicular origin. Long term androgen administration is unacceptable unless biology has demonstrated hypogonadism with a low testosterone level not related to hyperpolactinemia. Intramuscular testosterone or transdermal dihydrotestosterone can be used with a similar clinical effect but a different biological impact regarding aromatase activity. Whatever may be the type of androgen supplementation, one should use low dosage with frequent administration in order to obtain stable and physiologic plasmatic values. On account of androgen impact on prostate and cardiovascular system, careful pretreatment screening should eliminate an occult prostate cancer and a vascular thrombosis risk in a complaining and informed patient. Clinical and biological parameters should be periodically followed throughout androgen therapy.
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PMID:[Treatment of erectile disorders with androgens: When? How?]. 926 78

The role of insulin-like growth factor I (IGF-I) in prostate development is currently under thorough investigation because it has been claimed that IGF-I is a positive predictor of prostate cancer. To assess the effect of GH and IGF-I levels on prostate pathophysiology, 46 acromegalic (30 in active disease, 10 cured from acromegaly, and 6 affected from GH deficiency) and 30 age-matched male controls, free from previous or concomitant prostate disorders, underwent pituitary, androgen, and prostate hormonal assessments and transrectal ultrasonography. Compared to control values, GH (P < 0.0001), IGF-I (P < 0.0001), and IGFBP-3 (P < 0.001) levels were increased, whereas testosterone (P < 0.0001) and dihydrotestosterone levels (P < 0.0001) were reduced in active acromegalic patients. Hypogonadism was present in 28 of the 46 acromegalic patients (60.8%). The anteroposterior (P < 0.05), and transverse (P < 0.0001) prostate diameters and the transitional zone volume (P < 0.05) were increased in acromegalic patients compared to those in controls. Prostate volume (PV) was significantly higher in untreated acromegalic patients than in controls (41.7 +/- 3.2 vs. 21.9 +/- 1.4 mL; P < 0.0001), cured patients (23.6 +/- 1.6 mL; P < 0.0001), and GH-deficient patients (17.5 +/- 1.1 mL; P < 0.0001). In the patients, PV was correlated with disease duration (r = 0.606; P < 0.0001) and age (r = 0.496; P < 0.0001), whereas in controls it was correlated with age (r = 0.476; P < 0.01) and IGF-I levels (r = -0.448; P < 0.05). Benign prostate hyperplasia (PV > or = 30 mL) was found in 58% of the acromegalics and 26.6% of the controls. When grouped by age (<40, 40-60, and >60 yr), PV was increased in elderly patients compared to younger patients (P < 0.05) and to controls (P < 0.01). The prevalence of structural abnormalities, including calcifications, nodules, cysts, and vesicle inflammation, was significantly increased in patients compared to controls (78.2% vs. 23.3%; chi2 = 5.856; P < 0.05). No clinical, transrectal ultrasonography, or cytological evidence of prostate cancer was detected in acromegalic or control subjects. In conclusion, chronic excess of GH and IGF-I cause prostate overgrowth and further phenomena of rearrangement, but not prostate cancer.
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PMID:Effect of growth hormone (GH) and insulin-like growth factor I on prostate diseases: an ultrasonographic and endocrine study in acromegaly, GH deficiency, and healthy subjects. 1037 98

'Andropause', like menopause, has received significant attention in recent years. It results in a variety of symptoms experienced by the elderly. Many of these symptoms are nonspecific and vague. For this reason, many authors have questioned the value of androgen replacement in this population. Also in dispute is the normal cutoff level for testosterone beyond which therapy should be initiated, and whether to measure free or total testosterone. Testosterone levels decline with age, with the lowest level seen in men older than 70 years. This age-related decline in testosterone levels is both central (pituitary) and peripheral (testes) in origin. With aging, there is also a loss of circadian rhythm of testosterone secretion and a rise in sex hormone binding globulin (SHBG) levels. Total testosterone level is the best screening test for patients with suspected hypogonadism. If the total testosterone concentration is low, free testosterone levels should be obtained. Prostate cancer remains an absolute contraindication to androgen therapy. Testosterone replacement results in an improvement in muscle strength and bone mineral density. Similar effects are observed on the haematopoietic system. Data on cognition and lipoprotein profiles are conflicting. Androgen therapy can result in polycythemia and sleep apnoea. These adverse effects can be deleterious in men with compromised cardiac reserve. We recommend that elderly men with symptoms of hypogonadism and a total testosterone level <300 ng/dl should be started on testosterone replacement. This review discusses the pros and cons of testosterone replacement in hypogonadal elderly men and attempts to answer some of the unanswered questions. Furthermore, emphasis is made on the regular follow-up of these patients to prevent the development of therapy-related complications.
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PMID:Risks versus benefits of testosterone therapy in elderly men. 1049 72

Prostate cancer is the most common visceral malignancy in men. As the tumor is testosterone dependent, a frequent treatment modality involves therapy with GnRH agonists (GnRH-a) resulting in hypogonadism. Because testosterone is essential for the maintenance of bone mass in men, we postulated that GnRH-a therapy would negatively impact skeletal integrity. We compared bone mineral density (BMD), biochemical markers of bone turnover, and body composition in 60 men with prostate cancer (19 men receiving GnRH-a therapy and 41 eugonadal men) and BMD in 197 community-living healthy controls of similar age. BMD was assessed by dual energy x-ray absorptiometry and ultrasound. Biochemical markers of bone turnover, included markers of bone resorption (urinary N-telopeptide) and bone formation markers (bone-specific alkaline phosphatase and osteocalcin). Body composition (total body fat and lean body mass) was assessed by dual energy x-ray absorptiometry. Significantly lower BMD was found at the lateral spine (0.69 +/- 0.17 vs. 0.83 +/- 0.20 g/cm(2); P < 0.01), total hip (0.94 +/- 0.14 vs. 1.05 +/- 0.16 g/cm(2); P < 0.05), and forearm (0.67 +/- 0.11 vs. 0.78 +/- 0.07 g/cm(2); P < 0.01) in men receiving GnRH-a compared with the eugonadal men with prostate cancer. Significant differences were also seen at the total body, finger, and calcaneus (all P < 0.01). BMD values in eugonadal men with prostate cancer and healthy controls were similar. Markers of bone resorption (urinary N-telopeptide) and bone formation (bone-specific alkaline phosphatase) were elevated in men receiving GnRH-a therapy compared with those in eugonadal men with prostate cancer. Men receiving GnRH-a also had a higher percent total body fat (29 +/- 5% vs. 25 +/- 5%; P < 0.01) and lower percent lean body weight (71 +/- 5% vs. 75 +/- 5%; P < 0.01) compared with eugonadal men with prostate cancer. In conclusion, men with prostate cancer receiving androgen deprivation therapy have a significant decrease in bone mass and increase in bone turnover, thus placing them at increased risk of fracture.
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PMID:Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. 1139 88


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