Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen deprivation treatment (ADT) significantly lowers testosterone. That, in turn, can decrease sexual drive, facilitating better self-control and lower recidivism rates among sexually disordered offenders. Potential side effects can include: decreases in bone density; development of a metabolic syndrome involving weight gain, accompanied by changes in glucose and lipid metabolism; and rarely, depression. In the presence of a proper treatment protocol designed either to prevent or to minimize side effects, particularly the development of osteoporosis, the risks associated with ADT are generally within the same range as those associated with many other commonly prescribed psychotropic interventions.
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PMID:Risk/benefit ratio of androgen deprivation treatment for sex offenders. 1929 34

The growing relevance of prostate carcinoma in the developed world requires serious attention to focus on the risk-benefit relationships of the treatments used. Given the increasingly complex therapeutic approach to prostate carcinoma, an extensive range of knowledge is required. Androgen deprivation plays a central role in this disease. The management of androgen deprivation-derived toxicity in the form of hot flashes, metabolic syndrome, osteoporosis, cognitive disorders, etc., is of growing interest. The drug treatment of hot flashes involves hormone management that is not without oncological risk and moreover generates considerable toxicity. Antidepressants in turn play an important role in the non-hormone treatment of this disorder. Trazodone, a serotonin reuptake inhibitor/5-HT2A receptor antagonist affording more selective action upon the receptors implicated in hot flashes, could be of great interest. Trazodone shows great affinity for the 5-HT2A receptors and moderate affinity for the 5-HT1A receptors. Serotonin (5-hydroxytryptamine, or 5-HT) levels are known to be lowered in postmenopausal women, and normalize when replacement therapy is provided. This suggests that abrupt sexual hormone deprivation gives rise to a reduction in blood serotonin - with a subsequent increase in its hypothalamic 5-HT2A receptors. These receptors would be implicated in the physiopathology of hot flashes; as a result, the blocking of such receptors is one of the principal therapeutic measures. The use of trazodone, increasing the serotonin concentrations and blocking the 5-HT2A and 5-HT1A receptors, could be viewed as a novel management approach more in line with the physiopathology of hot flashes. Well designed comparative studies are needed to establish the efficacy of such treatment. Other issues pending clarification would be the most effective dose and duration of treatment for controlling hot flashes.
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PMID:[Trazodone: a new selective approach to the treatment of hot flashes induced by androgen deprivation in prostate carcinoma?]. 1971 46

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

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

The incidence of metabolic syndrome is rapidly increasing. Metabolic syndrome is associated with elevated morbidity and mortality secondary to cardiovascular disease, insulin resistance, and hepatic dysfunction. A body of evidence has already implicated metabolic syndrome as a cancer risk factor; emerging evidence now suggests that cancer survivors themselves may be at risk for developing metabolic syndrome as a result of their anti-cancer therapy. Treatment of both breast cancer and prostate cancer often involves hormone-modifying agents that have been linked to features of metabolic syndrome. Androgen suppression 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. Similar findings have been noted in men with testicular cancer treated with chemotherapy. In addition, several emerging therapies, including mammalian target of rapamycin (mTOR) inhibitors and targeted kinase inhibitors, are increasingly associated with some features of metabolic syndrome. As the number of cancer survivors continues to grow, consideration of these factors and of the risk of metabolic syndrome will become increasingly important when choosing between therapy options and managing long-term follow-up.
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PMID:Metabolic syndrome after hormone-modifying therapy: risks associated with antineoplastic therapy. 2092 42

Prostate cancer is the most frequently diagnosed malignancy among UK men and accounts for 12% of male deaths. Androgen deprivation therapy (ADT) is commonly used as part of the treatment for prostate cancer. It is effective at suppressing prostate-specific antigen, stabilizing disease, alleviating symptoms in advanced disease, and potentially prolonging survival. However ADT, presumably at least in part owing to low testosterone levels is associated with insulin resistance, the development of metabolic syndrome plus increased overall and cardiovascular disease mortality. We have reviewed the relationship between prostate cancer, ADT, metabolic syndrome, type 2 diabetes, and cardiovascular disease. We have not reviewed other potential medical problems such as osteoporosis. We suggest that there should be a baseline assessment of patients' risk for cardiovascular disease before starting ADT. Consideration should be given to starting appropriate therapies including lifestyle advice, antihypertensive and lipid-lowering agents, insulin sensitizer, plus possibly aspirin. Having started ADT, the patients should have a regular (possibly annual) assessment of their cardiovascular risk factors.
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PMID:Prostate cancer, androgen deprivation therapy, obesity, the metabolic syndrome, type 2 diabetes, and cardiovascular disease: a review. 2129 30

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.
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PMID:Insulin increases de novo steroidogenesis in prostate cancer cells. 2174 18

Androgen deprivation therapy (ADT) is a major component of the contemporary management of prostate cancer. ADT's use is increasing rapidly. The side effects of this therapy include loss of bone mass and fractures, increase in fat mass, and worsening of insulin resistance, the metabolic syndrome, diabetes and cardiovascular risk, and anemia and loss of muscle. Neuropsychological and sexual symptoms are common. The impact of these side effects is often overlooked or underestimated in decisions about prostate cancer therapy. This review surveys the data relating to the side effects of ADT and provides recommendations regarding their minimization and management.
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PMID:Management of side effects of androgen deprivation therapy. 2188 27

Prostate cancer (PCa) is the most common malignancy in men. Androgen deprivation therapy (ADT) plays an important role in the management of locally advanced and metastatic PCa. Its use in combination with external beam radiation and as an adjuvant therapy has resulted in improved survival in a subset of patients with locally advanced disease. In men with metastatic disease, ADT results in improvement in pain and overall quality of life. In addition to these two clinical settings where ADT has proven benefits, it is also being increasingly used in patients experiencing biochemical recurrence and those with early stage localized disease, even though no survival advantage has been demonstrated. ADT has significant adverse effects such as sexual dysfunction, decreased lean mass, increased fat mass, decreased quality of life, anemia, and osteoporosis. Recently, insulin resistance, diabetes, and metabolic syndrome have emerged as complications of ADT. Some data also suggests that ADT might be responsible for incident cardiovascular disease. Since the majority of men with PCa die of conditions other than their malignancy, recognition and management of these adverse effects is important. This paper serves as a focused review of recent studies examining the metabolic abnormalities and cardiovascular disease related to ADT.
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PMID:Androgen deprivation therapy for prostate cancer: implications for cardiometabolic clinical care. 2239 Oct 14


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