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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy characterized by oligo/anovulatiaon and elevated circulating androgens or evidence of hyperandrogenism after all known potential causes have been excluded. In addition, insulin resistance and accompanying hyperinsulinemia commonly occur in women with PCOS. There is increasing evidence that the endocrinologic and metabolic abnormalities in PCOS may have complex effects on the endometrium, contributing to the infertility and endometrial disorders observed in women with this syndrome. Androgen receptors and steroid receptor co-activators are over-expressed in the endometrium of women with PCOS. Also, biomarkers of endometrial receptivity to embryonic implantation-such as alpha(v)beta3-integrin and glycodelin-are decreased, and epithelial expression of estrogen receptor alpha (ERalpha) abnormally persists in the window of implantation in endometrium in women with PCOS. In addition to being responsive to the steroid hormones estradiol, progesterone, and androgens, the endometrium is also a target for insulin, the receptor for which is cyclically regulated in normo-ovulatory women. In vitro, insulin inhibits the normal process of endometrial stromal differentiation (decidualization). In addition, insulin-like growth factors (IGFs) and their binding proteins are regulated in and act on endometrial cellular constituents, and hyperinsulinemia down-regulates hepatic IGFBP-1, resulting in elevated free IGF-I in the circulation. Thus, elevated estrogen (without the opposing effects of progesterone in the absence of ovulation), hyperinsulinemia, elevated free IGF-I and androgens, and obesity all likely contribute to endometrial dysfunction, infertility, increased miscarriage rate, endometrial hyperplasia, and endometrial cancer common in women with PCOS. The potential mechanisms underlying these disorders, specifically in women with PCOS, are complex and await additional transdisciplinary research for their complete elucidation.
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PMID:Endometrium in PCOS: Implantation and predisposition to endocrine CA. 1677 54

Pain following depot intramuscular (IM) injection of oil vehicle-based drugs has been little studied. This study aimed to determine prospectively the prevalence, determinants, severity and functional consequences of pain during the week after IM injection of 1 000 mg testosterone undecanoate (TU) in a 4-mL castor oil vehicle. Androgen-deficient men receiving regular T replacement therapy at an academic andrology clinic were recruited to report pain scores using a coloured visual linear analogue scale at seven times over the first day and daily for a week after a deep IM gluteal injection. The time course and covariables influencing pain scores were analysed by mixed model analysis of variance (ANOVA). Following 168 injections in 125 men, pain was reported by 80% of men, peaking immediately after injection, reaching only moderate severity, lasting 1-2 days and returning to baseline by day 4. The pain required little analgesic use and produced minimal interference in daily activities. The time course of pain scores was reproducible in the 43 men who underwent two consecutive injections. Pain was more severe in men who had an earlier painful injection, but less severe in older and more obese men. There were negligible differences in post-injection pain experience between experienced nurses administering injections. Deep IM gluteal injection of depot TU in 4-mL castor oil is well tolerated and post-injection pain is influenced by earlier painful injection experience, as well as age and obesity.
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PMID:Factors influencing time course of pain after depot oil intramuscular injection of testosterone undecanoate. 2011 50

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

Hirsutism represents a primary clinical indicator of androgen excess. The most common endocrine condition causing hirsutism is polycystic ovary syndrome (PCOS). Diagnosing PCOS is not easy as the signs and symptoms are heterogenous. The newest diagnostic guideline made by the Androgen Excess and PCOS Society in 2006, claims the presence of hyperandrogenism, and ovarian dysfunction (oligo / anovulation and / or polycystic ovaries). Obesity associated reproductive and metabolic dysfunctions may aggravate the symptoms of PCOS. PCOS might be underdiagnosed in non obese women because lean PCOS phenotypes might be underestimated for the syndrome. Effective medical treatment of PCOS and associated hirsutism depends on the endocrinological expertise and experience of the therapist in each individual case. An algorithm for the treatment has not been established yet.
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PMID:Endocrinology of hirsutism. 2118 21

Androgen deprivation therapy (ADT) is standard of care for patients with metastatic hormone-sensitive prostate cancer (HSPC), yet through its induction of a hypogonadal state leads to metabolic perturbations, including insulin resistance (IR) and obesity. IR and obesity have been associated with an increased risk of progression to castrate-resistant prostate cancer (CRPC) and ultimately increased prostate cancer-specific mortality. On a molecular level, this association between obesity/IR and prostate cancer progression may be mediated by alterations in the insulin-like growth factor (IGF) axis, which has been shown to be up-regulated upon disease progression to CRPC. Targeting the IGF axis, either by anti-IGF therapy or via enhancement of peripheral insulin sensitivity, represents a viable therapeutic target in patients with prostate cancer. Using the development of IR and/or obesity may represent a clinically available biomarker that may predict those patients most likely to respond to such therapy, and warrants testing in future prospective clinical trials.
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PMID:Insulin-like growth factor pathway: a link between androgen deprivation therapy (ADT), insulin resistance, and disease progression in patients with prostate cancer? 2165 78

Androgen deprivation therapy (ADT) is the most effective systemic treatment for prostate cancer. ADT has been shown to have a high rate of response and to improve overall survival in patients with metastatic prostate cancer. In addition, multiple studies have shown that adding ADT to external beam radiation therapy leads to improvement in cure rates and overall survival in prostate cancer patients. The most commonly used ADT is gonadotropin-releasing hormone (GnRH) agonist therapy. Although GnRH agonist therapy has significant benefits for patients with prostate cancer, it has also been shown to have significant side effects, including fatigue, hot flashes, decreased libido, decreased quality of life, obesity, diabetes mellitus, coronary artery disease, decreased bone mineral density, and increased risk of fractures. Therefore, it is crucial that the benefits of ADT be weighed against its potential adverse effects before its use.
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PMID:Efficacy and safety of gonadotropin-releasing hormone agonists used in the treatment of prostate cancer. 2227 15

Metabolic syndrome has become quite prevalent within our society. Over the past two decades, the prevalence of metabolic syndrome has sharply increased worldwide and it has become a major public health problem in several countries. It is associated with the global epidemic of obesity and diabetes mellitus and imposes numerous cardiovascular risks. Prostate cancer is the second most common cancer among men, surpassed only by non-melanoma skin cancer. A considerable body of evidence exists suggesting that some components of the metabolic syndrome have been associated with the risk of prostate cancer. These components include obesity, an abdominal fat distribution, and hyperinsulinemia. Androgen deprivation therapy (ADT) is the most widely used therapeutic modality in prostate cancer. It changed the body composition and lipid profile of men with prostate cancer. Androgen deficiency is associated with increased levels of total cholesterol, low-density lipoprotein (LDL)- cholesterol, increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction. The aim of this review is to evaluate the association between metabolic syndrome and prostate cancer and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. A comprehensive literature search was carried out with the use of PubMed from 1980 through 2012, and relevant articles pertinent to metabolic syndrome and prostate cancer are evaluated and discussed.
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PMID:Prostate cancer and metabolic syndrome: is there a link? 2250 49

The differential association of hypoandrogenism in men and hyperandrogenism in women with insulin resistance and obesity suggests that androgens may exert sex-specific effects on adipose and other tissues, although the underlying mechanisms remain poorly understood. Moreover, recent studies also suggest that rodents and humans may respond differently to androgen imbalance. To achieve better insight into clinically relevant sex-specific mechanisms of androgen action, we used nonhuman primates to investigate the direct effects of gonadectomy and hormone replacement on white adipose tissue. We also employed a novel ex vivo approach that provides a convenient framework for understanding of adipose tissue physiology under a controlled tissue culture environment. In vivo androgen deprivation of males did not result in overt obesity or insulin resistance but did induce the appearance of very small, multilocular white adipocytes. Testosterone replacement restored normal cell size and a unilocular phenotype and stimulated adipogenic gene transcription and improved insulin sensitivity of male adipose tissue. Ex vivo studies demonstrated sex-specific effects of androgens on adipocyte function. Female adipose tissue treated with androgens displayed elevated basal but reduced insulin-dependent fatty acid uptake. Androgen-stimulated basal uptake was greater in adipose tissue of ovariectomized females than in adipose tissue of intact females and ovariectomized females replaced with estrogen and progesterone in vivo. Collectively, these data demonstrate that androgens are essential for normal adipogenesis in males and can impair essential adipocyte functions in females, thus strengthening the experimental basis for sex-specific effects of androgens in adipose tissue.
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PMID:Androgen effects on adipose tissue architecture and function in nonhuman primates. 2254 68

Resistin is an obesity-related adipokine which has also been implicated in bone metabolism. Therefore, we designed a study to investigate the possible role of resistin gene variation in both obesity and bone mineral density. We included 1,155 individuals from the Odense Androgen Study (663 young subjects and 492 older subjects), a population-based, prospective, observational study on the inter-relationship between endocrine status, body composition, muscle function, and bone metabolism in men, in an association study with resistin (RETN) polymorphisms. Three RETN variants (rs1862513, rs3745367 and rs3745369) were genotyped with TaqMan Pre-Designed Genotyping assays. Linear regression was performed to investigate the possible association of these variants with several obesity- and bone-related parameters. After genotyping 1,155 Danish men, 663 young subjects and 492 older subjects, we found that rs3745367 was associated with several obesity-related measures in both the young and elderly cohort. Rs3745369 was only associated with obesity-phenotypes in the elderly cohort. When studying the combined cohorts, we could confirm the associations of rs3745367 with several obesity-related parameters. We were unable to identify any association between RETN polymorphisms and bone-related measurements. Together, these results illustrate resistin's role in the development of obesity. Rs3745367 gives the most consistent results in the current study and these should be confirmed in other populations. Research into its possible functional effect might also be required. A role for RETN variants in determining bone mineral density seems unlikely from our results.
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PMID:Resistin polymorphisms show associations with obesity, but not with bone parameters in men: results from the Odense Androgen Study. 2320 10

Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of "old players" for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer.
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PMID:New players for advanced prostate cancer and the rationalisation of insulin-sensitising medication. 2357 93


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