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)

Androgens have been implicated in prostate tumourigenesis. However, no association between circulating levels of androgens and prostate cancer risk was found in a recent large pooled analysis of prospective studies. A decreased risk of prostate cancer among men treated with finasteride, a 5 alpha-reductase inhibitor which reduces levels of dihydrotestosterone, was observed in the Prostate Cancer Prevention Trial (PCPT), a large clinical trial. In the PCPT, a higher number of high-grade tumours was found in the finasteride group than in the control group; the reason for this finding is still unclear. Treatment of symptoms of late-onset hypogonadism - such as decreased muscle and bone mass and decreased cognition and libido - has become more prevalent with the advent of new forms of administration of testosterone replacement therapy. One small placebo-controlled study showed no increase in incidence of prostate cancer after 6 months of testosterone therapy, but data on the safety of testosterone replacement therapy remain limited.
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PMID:Androgens and prostate cancer risk. 1897 Nov 21

With aging, a significant percentage of men over the age of 60 years have serum testosterone levels below the lower limits of young adult men. Testosterone is not only pivotal for male reproductive/sexual functioning but plays also a significant role in the maintenance of bone and muscle mass and is a determinant of glucose homeostasis and lipid metabolism. The metabolic syndrome, erectile dysfunction and patterns of testosterone in aging men are intertwined. Testosterone is a factor in libido but also exerts essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. Treatment of testosterone deficiency is to become part of this approach. Recently, professional organizations have published guidelines in an attempt to define the condition and provide treatment. Despite this, much confusion still exists regarding the appropriate approach to diagnosing late-onset hypogonadism. Side effects concern mainly the prostate and erythropoeisis, but the currently available literature indicates that there is no increased risk of developing prostate cancer in men receiving testosterone treatment. Administration of testosterone to elderly men with testosterone deficiency is an acceptably safe practice.
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PMID:Late-onset hypogonadism. 1901 Dec 89

Testosterone levels are reduced in obesity, the metabolic syndrome and type 2 diabetes. Low testosterone levels are now being recognised as an independent risk factors for these conditions. Findings from men undergoing androgen suppression as treatment for prostate cancer confirm that the hypogonadal state increases body fat mass and serum insulin and there is a high rate of developing new diabetes in this population. Clinical trial data are consistent in showing reductions in body fat mass during testosterone replacement therapy. There are also trials showing improvements in insulin resistance and glycaemic control with testosterone. Most of the trials in this area to date have been of small size and the promising results require confirmation in larger trials, which are underway. In the longer term, large trials should be conducted to assess the potentially beneficial effects of testosterone on cardiovascular risk in this and other patient groups. In the meantime physicians involved in the care of men with diabetes should remain vigilant for the symptoms and signs of hypogonadism. Testosterone replacement therapy should be considered for those men with subsequently confirmed hypogonadism.
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PMID:Testosterone in obesity, metabolic syndrome and type 2 diabetes. 1901 Dec 90

Osteoporosis and osteoporotic fractures are generally considered to mainly affect older postmenopausal women, but up to 20% of symptomatic vertebral fractures and 30% of hip fractures occur in men. Osteoporotic fractures in men are associated with substantial morbidity, greater excess mortality than in women and account for almost 25% of the cost of osteoporotic fractures in the UK. One of the major secondary causes of osteoporosis in men is hypogonadism, which is found in up to 20% of men with symptomatic vertebral fractures and 50% of elderly men with hip fractures. This chapter outlines the pathogenesis of osteoporosis in men, placing particular emphasis on the importance of sex steroids in the maintenance of bone health. The effects of hypogonadism on the skeleton are described, as well as the consequences of androgen deprivation therapy in men with prostate cancer. Finally, we review the effects of testosterone replacement in hypogonadism and explore other options for the treatment of osteoporosis secondary to loss of sex steroids in men.
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PMID:Testosterone, bone and osteoporosis. 1901 Dec 93

Testosterone plays a critical role in male reproductive and metabolic functioning. Serum testosterone levels decrease with age, and low testosterone is associated with a variety of comorbidities, including insulin resistance, type 2 diabetes, obesity, metabolic syndrome, and cardiovascular disease. Men with type 2 diabetes have been shown to have significantly lower testosterone levels than men without diabetes. Several forms of testosterone replacement therapy (eg, oral, injectable, buccal, transdermal preparations) are available for use in the United States. The primary goals of testosterone therapy are to restore physiologic testosterone levels and reduce the symptoms of hypogonadism. Testosterone therapy may be a viable option in some men with diabetes and low testosterone; however, clinicians must be aware of contraindications to therapy (eg, prostate cancer and male breast cancer), implement appropriate monitoring procedures, and ensure that patient expectations are realistic regarding treatment outcome. Data suggest that testosterone therapy may have a positive effect on bones, muscles, erythropoiesis and anemia, libido, mood and cognition, penile erection, cholesterol, fasting blood glucose, glycated hemoglobin, insulin resistance, visceral adiposity, and quality of life. Sexual health may be a window into men's health; thus, more effective communication strategies are needed between clinicians and men with diabetes to ensure that sexual health topics are adequately addressed. Diabetes educators can play a key role in screening for low testosterone, providing relevant information to patients, and increasing clinician awareness of the need to address men's sexual health and implement appropriate strategies. Multidisciplinary care and individualized treatment are needed to optimize outcome.
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PMID:Men's health, low testosterone, and diabetes: individualized treatment and a multidisciplinary approach. 1902 Feb 65

Bone health may be impaired in many patients being treated for cancer. Primary tumors that reside in or form metastases to bone can result in compromised skeletal integrity. It has also been increasingly recognized that patients undergoing therapies for treatment of cancer are at higher risk of bone loss. These include androgen-deprivation therapy for prostate cancer and aromatase inhibitor therapy for breast cancer, among others. Hypogonadism induced by many of these cancer treatments results in bone loss and increases the risk of osteoporosis and fractures. Progress has been made in identifying the role of oral and intravenous bisphosphonates to prevent bone loss in these patients. This review discusses bone loss associated with cancer treatments, with a focus on breast cancer, prostate cancer, and survivors of childhood malignancies.
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PMID:Cancer treatment-related bone disease. 1919 56

Hypogonadism is highly prevalent in the elderly and in men with prostate cancer. Symptoms of hypogonadism, such as depression, lack of libido, and decreased bone mineral density, can significantly impair quality of life. In addition, testosterone plays an important role in erectile preservation and in growth and function of the cavernosal and penile nerves. There are compelling data showing that testosterone replacement therapy (TRT) does not increase the risk of prostate cancer. The literature (four published studies) concerning men treated with TRT after definitive therapy for prostate cancer reports only one biochemical recurrence. Based on these data, physicians cannot really justify withholding TRT from symptomatic patients after they have been successful treated for prostate cancer. This review gives the practising urologist an overview of the latest literature and useful advice on this controversial topic.
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PMID:[Testosterone replacement therapy and prostate cancer. The current position 67 years after the Huggins myth]. 1929 69

A considerable body of evidence exists suggesting that androgen deficiency contributes to the onset, progression, or both of cardiovascular disease (CVD). The aim of this review is to evaluate the relationships between testosterone (T) deficiency and risk factors of CVD and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. The relationship between androgen deficiency and endothelial function, lipid profiles, inflammatory responses, altered vascular smooth muscle reactivity, and hypertension are discussed with regard to CVD. A comprehensive literature search was carried out with the use of Pub Med from 1980 through 2009, and relevant articles pertinent to androgen deficiency and vascular disease were evaluated and discussed. Low T, whether attributed to hypogonadism or androgen deprivation therapy, in men with prostate carcinoma, produces adverse effects on cardiovascular health. Androgen deficiency is associated with increased levels of total cholesterol, low-density lipoprotein, increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction. Testosterone supplementation restores arterial vasoreactivity; reduces proinflammatory cytokines, total cholesterol, and triglyceride levels; and improves endothelial function but also might reduce high-density lipoprotein levels. Testosterone is an anabolic hormone with a wide range of beneficial effects on men's health. The therapeutic role of T in men's health, however, remains a hotly debated issue for a number of reasons, including the purported risk of prostate cancer. In view of the emerging evidence suggesting that androgen deficiency is a risk factor for CVD, androgen replacement therapy could potentially reduce CVD risk in hypogonadal men. It should be emphasized, however, that androgen replacement therapy should be done with very thorough and careful monitoring for prostate diseases.
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PMID:The dark side of testosterone deficiency: III. Cardiovascular disease. 1934 98

Testosterone deficiency syndrome (TDS) can be linked to premature mortality and to a number of co-morbidities (such as sexual disorders, diabetes, metabolic syndrome, ...). Testosterone deficiency occurs mainly in ageing men, at a time when prostate disease (benign or malign) start to emerge. New testosterone preparations via different route of administration appeared during the last decade allowing optimized treatment to these patients. One potential complication of this treatment is the increased risk of prostate and breast cancer. Consequently, the guidelines from the agencies and the institutions, the recommendations of the scientific expert committees and the attitude of the clinicians to who, when and how to treat hypogonadal patients, is very conservative, not to say, highly restrictive. To date, as documented in many reviews on the subject, nothing has been found to support the evidence that restoring testosterone levels within normal range increases the incidence of prostate cancer. In our experience, during a long-term clinical study including 200 hypogonadal patients receiving a patch of testosterone, 50 patients ended 5 years of treatment and no prostate cancer have been reported. In fact, the incidence of prostate cancer in primary or secondary testosterone treated hypogonadal men is lower than the incidence observed in the untreated eugonadal population. However, even if the number of patients treated in well-conducted clinical trials for whom cancer of the prostate has been reported is insignificant (a very few), the observed population is still too small to raise definite conclusions. Low testosterone levels have been reported in patients undergoing radical prostatectomy and the outcomes are of worse diagnostic in this population; at a later stage, testosterone deficiency can be induced by anti hormonal manipulation of patient with a prostate cancer, leading to the symptoms of hypogonadism. The question is to know whether it is justified, in case of profound symptoms, to supplement those patients with testosterone. Some attempts have been made and the results are encouraging: so it is time to re-examine our position and to question about the definite recommendation that patients with prostate cancer should never receive testosterone supplementation therapy; this is already the situation when intermittent androgen blockade is initiated if the biological response is satisfactory. Furthermore, it has been advocated that, under a rigorous surveillance, patients cured of prostate cancer can be treated with testosterone supplementation with beneficial results.
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PMID:Testosterone deficiency syndrome: treatment and cancer risk. 1942 38

Recent studies using genetically modified mice, such as FGF23-/- and Klotho-/- mice that exhibit altered mineral homeostasis due to a high vitamin D activity showed features of premature aging that include retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan. The phenotype reversed by normalizing vitamin D and/or mineral homeostasis. Thus, hypervitaminosis D due to an increased 1alpha-hydroxylase activity seems to be a cause of the premature aging. In several studies, we have described that a complete or partial lack of vitamin D action (VDR-/- mice and CYP27B1-/-) show almost similar phenotype as FGF23-/- or Klotho-/- mice. VDR mutant mice have growth retardation, osteoporosis, kyphosis, skin thickening and wrinkling, alopecia, ectopic calcification, progressive loss of hearing and balance as well as short lifespan. CYP27B1-/- mice do not show alopecia nor balance deficit, which might be apoVDR-dependent or calcidiol-dependent. The features are typical to premature aging. The phenotype is resistant to a normalization of the mineral homeostasis by a rescue diet containing high calcium and phosphate. Taken together, aging shows a U-shaped dependency on hormonal forms of vitamin D suggesting that there is an optimal concentration of vitamin D in delaying aging phenomena. Our recent study shows that calcidiol is an active hormone. Since serum calcidiol but not calcitriol is fluctuating in physiological situations, calcidiol might determine the biological output of vitamin D action. Due to its high serum concentration and better uptake of calcidiol-DBP by the target cells through the cubilin-megalin system, calcidiol seems to be an important circulating hormone. Therefore, serum calcidiol might be associated with an increased risk of aging-related chronic diseases more directly than calcitriol. Aging and cancer seem to be tightly associated phenomena. Accumulation of damage on DNA and telomeres cause both aging and cancer, moreover the signalling pathways seem to converge on tumour suppressor protein, p53, which seems to be regulated by vitamin D. Also, the insulin-like growth factor signalling pathway (IGF-1, IGFBPs, IGFR) and fibroblast growth factor-23 (FGF-23) regulate growth, aging and cancer. Vitamin D can regulate these signalling pathways, too. Also NF-kappaB and telomerase reverse transcriptase (TERT) might be molecular mechanisms mediating vitamin D action in aging and cancer. Calcidiol serum concentrations show a U-shaped risk of prostate cancer suggesting an optimal serum concentration of 40-60 nmol/L for the lowest cancer risk. Therefore, it is necessary to study several common aging-associated diseases such as osteoporosis, hypertension and diabetes known to be vitamin D-dependent before any recommendations of an optimal serum concentration of calcidiol are given.
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PMID:Vitamin D and aging. 1944 37


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