Download PROSPECTIVE STUDY OF METABOLIC DISORDER, SEX HORM

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)
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