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PROSPECTIVE STUDY OF METABOLIC DISORDER, SEX HORMONE AND RISK OF PROSTRATE DISORDER IN PATIENT ATTENDING GENERAL HOSPITAL ONITSHA BY ONUORA IFEOMA JOY (B.MLS, M.SC) Abstract Background Diabetes, obesity and prostate cancer (PCa) are the major, growing health problems that affect millions of men worldwide (Mathis, et al 2012). Several mechanisms could explain the association of obesity and metabolic syndrome with prostate cancer risk, including the sex steroid hormone, insulin and IGF signaling, and inflammation pathway. The relation of prostate cancer with sex steroids and obesity is complex, and the underlying biological mechanisms are unclear. (Ann et al, 2007) .The current dogma regarding androgens and prostate cancer is that higher concentrations of androgens increase the risk of prostate cancer. Despite this fact, one wonders why older men tend to be at more risk of developing prostate cancer since androgen level decreases with age. Early in their development, prostate cancers need relatively high levels of androgens to grow. Such prostate cancers are referred to as androgen dependent or androgen sensitive because treatments that decrease androgen levels or block androgen activity can inhibit their growth. Most prostate cancers eventually become "castration resistant," which means that they can continue to grow even when androgen levels in the body are extremely low or undetectable. (Hååg et al 2005) . Hormone therapy for prostate cancer—also called androgen suppression therapy or androgen deprivation therapy—can block the production and use of androgens. Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate cancer. Metabolic disorders such as diabetes, obesity and the metabolic syndrome have been shown to modulate prostate cancer (PCa) risk and aggressiveness in population-based and experimental studies. Metabolic syndrome, also called insulin resistance syndrome, is defined as a constellation of metabolic abnormalities, including glucose intolerance (fasting plasma concentrations > 110 mg/dL), dyslipidemia (serum triacylglycerol concentration ≥ 150 mg/dL, serum HDL concentration < 40 mg/dL), hypertension (blood pressure ≥ 130/85 mm Hg), and obesity (a waist circumference of >102 cm). (Ann, et al 2007). As shown, obese men have an increased risk of high-grade prostate cancer and a lower concentration of serum testosterone, which has been shown to be associated with increased risk of high-grade tumors (Platz et al 2005).. Whether low concentrations of serum testosterone reflect the insulin-resistant state in these patients and whether insulin alone, in the absence of high serum testosterone, is sufficient to trigger progression of prostate cancer to higher-grade tumors need to be clarified. PURPOSE/AIMS Given the rising epidemic of obesity and metabolic syndrome worldwide, especially in developing countries, and the potential links among obesity, androgen metabolism, diabetes, and inflammation, it is critical to understand better the complex relations between overall and abdominal obesity and prostate cancer risk and the pathogenesis of prostate cancer. OBJECTIVE 1) Assessment of abdominal obesity, biochemical measures, such as insulin concentrations, sex steroids, and IGFs in patient with prostrate disorder. 2) To compare sex hormones level( testosterone and estradiol) among patient with benign prostrate hypertrophy, normal and prostate cancer ie comparing circulating hormone levels in men with and without prostate cancer 3) association between metabolic conditions, sex steroids and Prostrate cancer risk and management Methodology Among patient undergoing treatment in Onitsha hospitals, a total of 300 subjects between the age of 45 and 80yrs will be randomly selected of which involves 100 apparently normal individual ( control), 100 benign prostrate hyperplasia and 100 prostate cancer patient. Ethical clearance will be obtained from Ministry of Health, Anambra State Nigeria. Data collection involves using self administered close ended questionnaire with socio-demographic characteristics, lifestyle and dietary habits, medical and family history, prostrate cancer drugs. Anthropometric measurements weight, height and BP will be made according to WHO procedure. Blood sample is to be collected from fasting subjects using standard procedure. Serum lipid profile, fasting blood glucose estimation will be analysed by automation using LANDWIND 100 PLUS analyser whereas testosterone, estradiol , total PSA, free PSA and insulin will be done by Enzyme-linked Immunosorbent Assay (ELISA) method using AIA 360 immunoassay analyser (TOSOH). Statistical analyses are to be done using software SPSS 17.0. Student’s t test will used to compare independent sample means; correlations between individual hormone levels and between hormone level and prostrate disorder, will be assessed by use of Spearman correlation coefficients (r). Odds ratios (ORs) specifying the prostate cancer risk associated with quartile levels of individual hormones, is to be calculated by use of conditional logistic regression modeling. Statistical significant is set at p < 0.05. EXPECTED OUTCOMES Previous studies show that there are no associations of serum estrogen with prostate cancer risk in untreated men (Song Yao). Low levels of circulating estradiol may represent an additional risk factor (Peter at al, 1996). A man's odds of developing prostate cancer don't appear to be influenced by his blood levels of testosterone and other sex hormones.( Miranda Hitti 2008). Obesity and associated insulin excess are linked to increased prostrate cancer aggressiveness and worse outcomes. Secondly and somewhat paradoxically, long-standing diabetes may be protective against prostrate cancer development. This apparent paradox may be due to the fact that long-standing diabetes is associated with insulin depletion and decreased IGF1 signalling. (Hsing, et al 2007). Metabolic factors and androgens may promote prostate carcinogenesis (Mathis et al 2012) REFERENCE Ann W Hsing, Lori C Sakoda, Streamson C Chua Jr ( 2007) Obesity, metabolic syndrome, and prostate cancer. America Journal of Clinical Nutrition September vol. 86 no. 3 843S-857S Goldstein BJ. (2003) Insulin resistance: from benign to type 2 diabetes mellitus. Revolution Cardiovascular Medicine; 4(suppl 6):S3–10. Hååg P, Bektic J, Bartsch G, Klocker H, Eder IE. (2005); Androgen receptor down regulation by small interference RNA induces cell growth inhibition in androgen sensitive as well as in androgen independent prostate cancer cells. Journal of Steroid Biochemistry and Molecular Biology 96(3-4):251-258. Hsing AW, Sakoda LC & Chua S Jr (2007). Obesity, metabolic syndrome, and prostate cancer. American Journal of Clinical Nutrition 86s 843–s857 Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB. (2006 ) Low sex hormonebinding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in non obese men. Journal of Clinical Endocrinology and Metabolism 91:843–50 Lee RJ, Smith MR. Hormone Therapy for Prostate Cancer. In: Chabner BA, Longo DL, (2011) eds. Cancer Chemotherapy and Biotherapy: Principles and Practice. 5th ed: Wolters Kluwer: Lippincott Williams & Wilkins. Mathis Grossmann and Gary Wittert. (2012) Androgens, diabetes and prostate cancer Endocrine-Related Cancer 19F47–F62 Miranda Hitti Louise Chang, MD (2008) Sex Hormones Not a Prostate Cancer Risk;Men's Blood Levels of Testosterone and Other Sex Hormones Don't Affect Their Odds of Developing Prostate Cancer, Report Shows WebMD Health News Peter H. Gann, Charles H. Hennekens, Jing Ma, Christopher Longcope Meir J. Stampfer (1996) Prospective Study of Sex Hormone Levels and Risk of Prostate Cancer ,Journal of the National Cancer Institute 88 (16): 1118-1126 Platz EA, Leitzmann MF, Rifai N, et al.( 2005). Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiologic Biomarkers Prev;14:1262–9. Song Yao, Cathee Till, Alan R. Kristal, Phyllis J. Goodman, Ann W. Hsing, Catherine M. Tangen, (2011) Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case– control study .Cancer Causes Control. ; 22(8): 1121–1131 .