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)

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

The metabolism of steroids at position 17 is catalysed by a growing number of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs). Several human diseases like breast or prostate cancer, endometriosis,metabolic syndrome and mental diseases were associated with dysfunctions of 17beta-HSDs, which consequently became drug targets. This review will focus on identities of 17beta-HSDs and recent advances in analyses of their physiological roles in steroid and lipid metabolism. It will also address the potential of metabolomics in drug development.
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PMID:Recent advances in 17beta-hydroxysteroid dehydrogenases. 1944 36

It has been long appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Since 1995, 14 studies have been identified that investigate the clinical relationship between exercise and BPH/LUTS. No randomized controlled trials have been performed, but useful prospective cohort data originating from recent publications on the medical treatment of BPH and prevention of prostate cancer are available. Most of the literature supports a clinically significant, independent, and strong inverse relationship between exercise and the development of BPH/LUTS. Several mechanisms for this relationship have been proposed, including decreased sympathetic tone, avoidance of metabolic syndrome, and reduced oxidative damage to the prostate.
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PMID:Review of exercise and the risk of benign prostatic hyperplasia. 2004 44

Abdominal obesity as a key cardiovascular risk factor as well as metabolic syndrome and type 2 diabetes mellitus are associated with low testosterone levels. In line with these facts, investigations of patients undergoing androgen ablation therapy for prostate cancer have shown a negative effect of this treatment approach on insulin sensitivity and body fat mass. The effects of physiological doses of testosterone seem to have less impact on the parameters of lipid metabolism. However, supraphysiological levels of testosterone can lower HDL levels. At present data on glycemic control in patients with type 2 diabetes are not yet uniform, but negative effects on glycemic control in type 2 diabetics have not been reported. In fact two studies were able to demonstrate a positive effect of testosterone on glycemic control in patients with type 2 diabetes. It is currently not yet possible to conclusively evaluate the significance of testosterone treatment in patients with metabolic syndrome and type 2 diabetes mellitus. Only larger, randomized prospective trials will show whether testosterone therapy is helpful in metabolic syndrome or type 2 diabetes. However, administration of testosterone in hypogonadal men with metabolic syndrome appears to be a promising treatment option to improve metabolic control.
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PMID:[Testosterone and the metabolic syndrome]. 2006 85

Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies might increase patients' risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones; thus, treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardiovascular disease, and insulin resistance. Anti-estrogen therapy in women with breast cancer can affect lipid profiles, cardiovascular risk, and liver function. As the number of cancer survivors continues to grow, treating physicians must be aware of the potential risks facing patients who have been treated with either androgen suppression therapy or anti-estrogen therapy so that early diagnosis and intervention can be achieved.
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PMID:Care of the cancer survivor: metabolic syndrome after hormone-modifying therapy. 2010 97

Prostate cancer (PCa) is the most common malignancy in men. Androgen deprivation therapy (ADT) is used in the treatment of locally advanced and metastatic PCa. Although its use has improved survival in a subset of patients, it also has negative consequences. Osteoporosis, sexual dysfunction, hot flashes and adverse changes in body composition are well-known and well-studied complications of ADT. Recent studies have also found metabolic complications in these men such as insulin resistance, diabetes and metabolic syndrome. In addition, these men might also experience higher cardiovascular mortality. Studies are needed to determine the mechanism behind these complications and to employ strategies to prevent them.
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PMID:Emerging cardiometabolic complications of androgen deprivation therapy. 2014 44

It is well-established that total testosterone (TT) in men decreases with age and that bioavailable testosterone (bio-T) falls to an even greater extent. The clinical relevance of declining androgens in the aging male and use of testosterone replacement therapy (TRT) in this situation is controversial. Most studies have been short term and there are no large randomized placebo-controlled trials. Testosterone has many physiological actions in: muscles, bones, hematopoietic system, brain, reproductive and sexual organs, adipose tissue. Within these areas it stimulates: muscle growth and maintenance, bone development while inhibiting bone resorption, the production of red blood cells to increase hemoglobin, libido, enhanced mood and cognition, erectile function and lipolysis. Anabolic deficits in aging men can induce: frailty, sarcopenia, poor muscle quality, muscle weakness, hypertrophy of adipose tissue and impaired neurotransmission. The aging male with reduced testosterone availability may present with a wide variety of symptoms which in addition to frailty and weakness include: fatigue, decreased energy, decreased motivation, cognitive impairment, decreased self-confidence, depression, irritability, osteoporotic pain and the lethargy of anemia. In addition, testosterone deficiency is also associated with type-2 diabetes, the metabolic syndrome, coronary artery disease, stroke and transient ischemic attacks, and cardiovascular disease in general. Furthermore, there are early studies to suggest that TRT in men with low testosterone levels may improve metabolic status by: lowering blood sugar and HbA1C in men with type-2 diabetes, reducing abdominal girth, ameliorating features of the metabolic syndrome, all of which may be protective of the cardiovascular system. The major safety issue is prostate cancer but there is no evidence that supports the idea that testosterone causes the development of a de novo cancer. So on balance in a man with symptoms of hygonadism and low or lowish levels of testosterone with no evidence of prostate cancer such as a normal PSA a therapeutic (4-6 months) trial of TRT is justified. Treatment and monitoring of this duration will determine whether the patient is responsive.
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PMID:Testosterone and the aging male: to treat or not to treat? 2015 46

Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment.
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PMID:Androgens and male aging: Current evidence of safety and efficacy. 2015 99

Although the role of metabolic syndrome (MS) and a high fat diet in prostate cancer (PCa) risk is still a matter of intense debate, it is becoming increasingly clear that obesity can cause perturbations in metabolic pathways that contribute to the pathogenesis and progression of PCa. Moreover, prostate epithelial cells per se undergo a series of metabolic changes, including an increase in de novo lipogenesis, during the process of tumor formation. These metabolic alterations, at both the cellular and organismal levels, are intertwined with genetic aberrations necessary for neoplastic transformation. Thus, altered metabolism is currently subject to intense research efforts and might provide preventative and therapeutic opportunities, as well as a platform for biomarker development. In this article, we review evidence that the metabolic sensor 5'-AMP-activated protein kinase (AMPK), which physiologically integrates nutritional and hormonal signals and regulates cell survival and growth-related metabolic pathways to preserve intracellular ATP levels, represents a link between energy homeostasis and cancer. Thus, when AMPK is not activated, as in the setting of MS and obesity, systemic metabolic alterations permissive to the development of PCa are allowed to proceed unchecked. Hence, the use of AMPK activators and inhibitors of key lipogenic enzymes may represent a promising therapeutic strategy for PCa.
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PMID:New strategies in prostate cancer: targeting lipogenic pathways and the energy sensor AMPK. 2042 84

Given the fundamental role of sex hormones in the regulation of body composition and homeostasis, in humans, more emphasis should be placed on the potential role of androgen dysregulation in the pathophysiology of different obesity phenotypes and the metabolic syndrome (MetS). Physicians must be mindful to evaluate MetS in all men diagnosed with hypogonadism and hypogonadism in all men diagnosed with MetS. Thus, clinical screening for obese patients should include the assessment of waist circumference, testosterone levels, body mass index and physical inactivity. The side effects of Androgen deprivation therapy (ADT) for prostate cancer patients may delay mortality from prostate cancer but, it is undeniable that the effects induced by this treatment have serious consequences. ADT should be considered and discussed between physicians and patients when making treatment decisions. If the decision is to initiate ADT, proper monitoring, preventive strategies and management of weight, insulin resistance, diabetes hyperlipidemia, sexual function and Osteopenia is essential.
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PMID:The relationship between sex hormones and the metabolic syndrome. 2051 95


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