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

There is increasing evidence that androgen therapy in men may be effectively applied in several conditions to improve well being and health. Classical indications for androgen therapy in males are represented by primary or secondary hypogonadism, delayed puberty, aplastic anemia and that secondary to chronic renal failure, protein wasting diseases such as trauma, burns, tumors and infectious diseases. Androgen innovating applications in men are represented by aging and visceral obesity associated with the metabolic syndrome. In addition, it is clear that appropriate testosterone treatment can be adequately used in male contraception, provided spermatogenesis is abolished and tolerability is adequate. Due to unphysiological hormone levels achieved by currently available testosterone preparations, new delivery systems have been produced to achieve more physiological and sustained hormone levels and improve tolerability and action at the levels of target tissues. Some of them are now available in several countries and new formulas are under development.
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PMID:Testosterone therapy in men: clinical and pharmacological perspectives. 1080 80

We investigated the effects of oxandrolone on regional fat compartments and markers of metabolism. Thirty-two 60- to 87-yr-old men (body mass index, 28.1 +/- 3.4 kg/m(2)) were randomized to oxandrolone (20 mg/d; n = 20) or matching placebo (n = 12) treatment for 12 wk. Oxandrolone reduced total (-1.8 +/- 1.0 kg; P < 0.001), trunk (-1.2 +/- 0.6 kg; P < 0.001), and appendicular (-0.6 +/- 0.6 kg; P < 0.001) fat, as determined by dual energy x-ray absorptiometry. The changes in total and trunk fat were greater (P < 0.001) than the changes with placebo. By magnetic resonance imaging, visceral adipose tissue decreased (-20.9 +/- 12 cm(2); P < 0.001), abdominal sc adipose tissue (SAT) declined (-10.7 +/- 12.1 cm(2); P = 0.043), the ratio VAT/SAT declined from 0.57 +/- 0.23 to 0.49 +/- 0.19 (P = 0.002), and proximal and distal thigh SC fat declined [-8.3 +/- 6.7 cm(2) (P < 0.001) and -2.2 +/- 3.0 kg (P = 0.004), respectively]. Changes in proximal and distal thigh SC fat with oxandrolone were different than with placebo (P = 0.018 and P = 0.059). A marker of insulin sensitivity (quantitative insulin sensitivity check index) improved with oxandrolone by 0.0041 +/- 0.0071 (P = 0.018) at study wk 12. Changes in total fat, abdominal SAT, and proximal extremity SC fat were correlated with changes in fasting insulin from baseline to study wk 12 (r >or= 0.45; P < 0.05). Losses of total fat and SAT were greater in men with baseline testosterone of 10.4 nmol/liter or less (<or= 300 ng/dl) than in those with higher levels [-2.5 +/- 1.1 vs. -1.5 +/- 0.8 kg (P = 0.036) and -24.1 +/- 14.3 vs. -2.9 +/- 21.3 cm(2) (P = 0.03), respectively]. Twelve weeks after discontinuing oxandrolone, 83% of the reductions in total, trunk, and extremity fat by dual energy x-ray absorptiometry scanning were sustained (P < 0.02). Androgen therapy, therefore, produced significant and durable reductions in regional abdominal and peripheral adipose tissue that were associated with improvements in estimates of insulin sensitivity. However, high-density lipoprotein cholesterol decreased by -0.49 +/- 0.21 mmol/liter and directly measured low-density lipoprotein cholesterol increased by 0.57 +/- 0.67 mmol/liter and non-high-density lipoprotein cholesterol increased by 0.54 +/- 0.97 mmol/liter (P < 0.03 for each) during treatment with oxandrolone; these changes were largely reversible. Thus, therapy with an androgen that does not adversely affect lipids may be beneficial for some components of the metabolic syndrome in overweight older men with low testosterone levels.
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PMID:Effects of androgen therapy on adipose tissue and metabolism in older men. 1547 77

Prostate cancer is one of the most common cancers in men. Androgen-deprivation therapy (ADT) is often employed in the treatment of recurrent and metastatic prostate cancer. Although its use as an adjuvant therapy has resulted in improved survival in a subset of patients, ADT also results in a multitude of endocrine complications. These complications affect quality of life and sense of well-being in these men. Some of the endocrine complications of ADT such as osteoporosis, sexual dysfunction, hot flashes, gynecomastia, and adverse body composition are well-known. Recently, insulin resistance, hyperglycemia, and metabolic syndrome have emerged as metabolic complications of castration and may be responsible for increased cardiovascular mortality in this population. In this article, we provide a detailed review of the endocrine complications of ADT, touching upon management strategies where applicable.
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PMID:Endocrine complications of androgen-deprivation therapy in men with prostate cancer. 1709 26

Androgen exposure during intrauterine life in nonhuman primates and in sheep results in a phenocopy of the reproductive and metabolic features of polycystic ovary syndrome (PCOS). Such exposure also results in reproductive features of PCOS in rodents. We investigated whether transient prenatal androgen treatment produced metabolic abnormalities in adult female rats and the mechanisms of these changes. Pregnant dams received free testosterone or vehicle injections during late gestation, and their female offspring were fed regular or high-fat diet (HFD). At 60 days of age, prenatally androgenized (PA) rats exhibited significantly increased body weight; parametrial and subcutaneous fat; serum insulin, cholesterol and triglyceride levels; and hepatic triglyceride content (all P < 0.0125). There were no significant differences in insulin sensitivity by intraperitoneal insulin tolerance test or insulin signaling in liver or skeletal muscle. HFD had similar effects to PA on body weight and composition as well as on circulating triglyceride levels. HFD further increased hepatic triglyceride content to a similar extent in both PA and control rats. In PA rats, HFD did not further increase circulating insulin, triglyceride, or cholesterol levels. In control rats, HFD increased insulin levels, but to a lesser extent than PA alone ( approximately 2.5- vs. approximately 12-fold, respectively). We conclude that transient prenatal androgen exposure produces features of the metabolic syndrome in adult female rats. Dyslipidemia and hepatic steatosis appear to be mediated by PA-induced increases in adiposity, whereas hyperinsulinemia appears to be a direct result of PA.
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PMID:Transient prenatal androgen exposure produces metabolic syndrome in adult female rats. 1854 44

Prostate cancer (PCa) is the most common cancer in men. Androgen deprivation therapy (ADT) is used in the treatment of locally advanced and metastatic PCa. Although its use as an adjuvant therapy has resulted in improved survival in some patients, ADT has negative consequences. Complications like osteoporosis, sexual dysfunction, gynecomastia, and adverse body composition are well known. Recent studies have also found metabolic complications in these men. Studies show that short-term ADT (3-6 months) results in development of hyperinsulinemia without causing hyperglycemia. Studies of men undergoing long-term (>or=12 months) ADT reveal higher prevalence of diabetes and metabolic syndrome compared with controls. In addition, men undergoing ADT also experience higher cardiovascular mortality. Long-term prospective studies of ADT are needed to determine the timing of onset of these complications and to employ strategies to prevent them. In the meantime, baseline and serial screening for fasting glucose and other cardiac risk factors in men receiving ADT is prudent. In selected cases, glucose tolerance testing and cardiac evaluation may be required.
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PMID:Androgen deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth. 1856 42

Hyperinsulinemia as a consequence of insulin resistance causes hyperandrogenemia in women. The objective was to review evidence for the converse situation, i.e. whether androgens adversely influence insulin action. Androgen excess could potentially contribute to the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS), metabolic syndrome/type 2 diabetes, and in obese peripubertal girls. An Entrez-PubMed search was conducted to identify studies addressing the relationship of androgens with metabolic syndrome/type 2 diabetes in women. Studies reporting outcomes of androgen administration, interventions to reduce androgen effects in hyperandrogenemic women, and basic studies investigating androgen effects on insulin target tissues were reviewed. Multiple studies showed associations between serum testosterone and insulin resistance or metabolic syndrome/type 2 diabetes risk in women, but their cross-sectional nature did not allow conclusions about causality. Androgen administration to healthy women was associated with development of insulin resistance. Intervention studies in women with hyperandrogenism were limited by small subject numbers and use of indirect methods for assessing insulin sensitivity. However, in three of the seven studies using euglycemic hyperinsulinemic clamps, reduction of androgen levels or blockade of androgen action improved insulin sensitivity. Testosterone administration to female rats caused skeletal muscle insulin resistance. Testosterone induced insulin resistance in adipocytes of women in vitro. In conclusion, the metabolic consequences of androgen excess in women have been under-researched. Studies of long-term interventions that lower androgen levels or block androgen effects in young women with hyperandrogenism are needed to determine whether these might protect against metabolic syndrome/type 2 diabetes in later life.
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PMID:Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome? 1861 51

Prostate cancer is the most common gender-specific malignancy in men in the USA. Androgen-deprivation therapy (ADT) is commonly used in the treatment of metastatic or recurrent prostate cancer. The use of ADT is increasing with the advocacy of adjuvant and neoadjuvant ADT for treating asymptomatic patients with locally advanced prostate cancer. Although the use of ADT has resulted in improved survival in men with advanced prostate cancer, ADT, with its resulting severe hypogonadism, causes profound metabolic side-effects. We comprehensively reviewed previous reports using Medline searches of English-language literature (1950 to the present), with the keywords 'hypogonadism', 'testosterone', 'androgen deprivation therapy', 'hormonal treatment', 'prostate cancer', 'diabetes', 'metabolic syndrome', and 'cardiovascular disease'. Men with prostate cancer who undergo long-term ADT are at greater risk of developing dyslipidaemia, insulin resistance, hyperglycaemia and metabolic syndrome. These metabolic and physiological changes are a direct result of the induced severe hypogonadism and might predispose patients to a greater risk of cardiovascular morbidity and mortality. There is a need for prospective studies aimed and designed to investigate the metabolic and cardiovascular adverse effects of ADT, and assess the benefit/risk ratio, especially in special populations such as diabetics.
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PMID:Metabolic and cardiovascular effects of androgen deprivation therapy. 1872 14

A considerable body of evidence exists suggesting a link among reduced testosterone plasma levels, type 2 diabetes (T2D), and insulin resistance (IR). Hypogonadal men are at higher risk for T2D. Here we evaluate the relationships between testosterone, metabolic syndrome (MetS), T2D, and IR and discuss the relationships among androgen deficiency and these factors, especially as it ultimately relates to the development of cardiovascular disease and erectile dysfunction (ED). Thus, a comprehensive literature search was carried out using PubMed, and relevant articles pertinent to androgen deficiency, T2D, IR, MetS, and ED were reviewed and discussed. Low testosterone precedes elevated fasting insulin, glucose, and hemoglobin A1c (HbA1C) values and may even predict the onset of diabetes. Treatment of prostate cancer patients with surgical or medical castration exacerbates IR and glycemic control, strengthening the link between testosterone deficiency and onset of T2D and IR. Androgen therapy of hypogonadal men improves insulin sensitivity, fasting glucose, and HbA1c levels. We suggest that androgen deficiency is associated with IR, T2D, MetS, and with increased deposition of visceral fat, which serves as an endocrine organ, producing inflammatory cytokines and thus promoting endothelial dysfunction and vascular disease.
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PMID:The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. 1877 88

Androgen deprivation therapy is widely used in a number of different settings in the treatment of prostate cancer. This overview will look at the current evidence for the potential development of metabolic syndrome and cardiovascular disease as a consequence of this therapy, and highlight strategies aimed at their prevention. The relationship between metabolic syndrome and prostate cancer development will also be examined.
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PMID:Metabolic syndrome and prostate cancer: a review. 1911 51

Testosterone is an important hormone involved in sexual arousal, and, indeed, a profound reduction of testosterone levels may be helpful in controlling sexual impulses in sex offenders. Earlier thought of as a sex hormone only, testosterone has been increasingly shown to have manifold actions in the adult male. Normal adult levels of androgens are required for the health of bones, a large number of metabolic functions, mood, erythropoiesis, sebaceous gland activity of the skin, and several other functions. Severe androgen deficiency is associated with pathologies of these biological systems. Androgen deprivation therapy may result in osteoporosis, weight gain with an increased visceral adiposity, impaired glucose tolerance, dyslipidemia, and emotional disturbances. Some of these features combine in the metabolic syndrome that is also frequently associated with the use of psychotropic medication in general. It leads to a moderately increased risk of fractures and diabetes mellitus (by 40%-50%), and a small increased risk of cardiovascular morbidity and depression (by 10%-20%). It should be noted that small proportionate increases in risk may be of modest clinical significance when background risks are very low. Effective and safe management of sex offenders treated with testosterone-deprivation therapy should include careful monitoring of side effects and their prevention and treatment.
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PMID:Potential side effects of androgen deprivation treatment in sex offenders. 1929 35


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