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Table of Contents
REVIEW ARTICLE
Year : 2012  |  Volume : 16  |  Issue : 7  |  Page : 12-19

Testosterone and metabolic syndrome: The link


1 Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
2 Department of Endocrinology, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India
3 Department of Physiology, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication24-Mar-2012

Correspondence Address:
Ranabir Salam
Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur - 795 004
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2230-8210.94248

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   Abstract 

Metabolic syndrome (MetS) or "Syndrome X" which is a constellation of insulin resistance, hyperglycemia, hypertension, low high-density lipoprotein cholesterol (HDL-C), and increased very-low-density lipoprotein (VLDL) and triglyceride (TG) levels. It is one of the main threats for public health in the 21st century with its associated risk of cardiovascular disease. This condition affects a major chunk of mankind. International Diabetes Federation (IDF) estimated that around 20-25% of the adult population of the world has MetS. Several definitions have been put forward by different expert bodies leading to confusion. To overcome this, joint new statement of many expert group have been issued. Serum testosterone (T) has been shown to be associated with MetS. Several studies have shown a higher prevalence of MetS in subjects with low testosterone. There are also several studies showing a significant difference in serum T between those with MetS and those without. Serum T has also been shown to be associated with components of MetS and testosterone replacement therapy (TRT) improves various metabolic and anthropometric parameters in MetS. Patients with androgen deprivation for treatment of various cancers have also been reported to have higher prevalence of MetS. But the evidence of association is not sufficient evidence for the causation of MetS by low testosterone and long-term studies are needed to confirm whether T deficiency is the cause or is a feature of MetS.

Keywords: Androgen deprivation, insulin resistance, metabolic syndrome, testosterone, testosterone replacement therapy


How to cite this article:
Salam R, Kshetrimayum AS, Keisam R. Testosterone and metabolic syndrome: The link. Indian J Endocr Metab 2012;16, Suppl S1:12-9

How to cite this URL:
Salam R, Kshetrimayum AS, Keisam R. Testosterone and metabolic syndrome: The link. Indian J Endocr Metab [serial online] 2012 [cited 2017 Dec 18];16, Suppl S1:12-9. Available from: http://www.ijem.in/text.asp?2012/16/7/12/94248


   Introduction Top


The metabolic syndrome (MetS) was first described by Kylin, a Swedish physician, in 1923 as a clinical association between hypertension and gout. It was modified in 1947, to include upper body adiposity. In 1988 Reaven emphasized the importance of MetS. [1] He described it as "Syndrome X" which is a constellation of insulin resistance, hyperglycemia, hypertension, low high-density lipoprotein cholesterol (HDL-C), and increased very-low-density lipoprotein (VLDL) and triglyceride (TG) levels. [2]

It is considered the main threat for public health in the 21 st century with its associated risk of cardiovascular disease. [3]

Several definitions for MetS have been put forward by different expert bodies such as World Health Organization (WHO), [4] European Group for Study of Insulin Resistance (EGIR), [5] National Cholesterol Education program (NCEP), [6] American Association of Clinical Endocrinologist (AACE), [7] National Heart, Lung, and Blood Institute/American Heart Association, [8] and International Diabetes Federation (IDF). [9] In 2005 IDF has drafted a singly unifying definition. The main emphasis is on central obesity defined by waist circumference: waist circumference (WC) in Europids ≥94 cm and in Asians >90 cm. And there should be two or more of the following four factors: elevated TG ≥1.7 mmol/l (≥150 mg/dl), reduced HDL-C <1.03 mmol/l (<40 mg/dl), elevated blood pressure (BP) systolic ≥130 mmHg, diastolic ≥85 mmHg (or treatment), and dysglycemia (raised fasting plasma glucose, FBG ≥5.6 mmol/l (≥100 mg/dl) (or type 2 diabetes mellitus, DM). [10] A new joint statement from a number of professional organizations such as IDF, the National Heart, Lung, and Blood Institute (NHLBI), WHO, the International Atherosclerosis Society, and the American Heart Association (AHA) has identified specific criteria for the clinical diagnosis of the metabolic syndrome. Patients with three of the five criteria (elevated WC, elevated TGs, reduced HDL-C levels, elevated BP and elevated FBG levels) are considered to have MS. [11]

Prevalence of MetS: It is estimated that around 20-25% of the world's adult population have the metabolic syndrome. [12] In the United States the prevalence of MetS is 34.5% based on the NCEP definition and 39.0% based on IDF definition. [13] Even in children and adolescents it has been reported in up to 9%. [14] In North India the prevalence of MetS was reported to range from 31.6% to 49.2% of the urban population using NCEP ATP III/modified NCEP ATP III guidelines. [15],[16],[17],[18] Two studies from urban North India reported the prevalence of MetS ranging from 35.8% to 38.5% by NCEP ATP III criteria, 45.3% by modified NCEP ATP III criteria and 39.5% to 47.4% by IDF criteria. [19],[20] In South India the prevalence has been reported in the range of 18.3-41% using NCEP ATP III guidelines. [21],[22] In an urban population of South India the prevalence of MetS ranges from 18.3% by NCEP ATP III criteria, 23.2% by WHO criteria and 25.8% by IDF criteria. [22] Another two studies showed a prevalence of 29.7-41.3% using IDF guidelines. [23],[24] Using WHO criteria a higher prevalence of 46.4% was reported from South India. [25] In Mumbai, West India, the prevalence is reported in the range of 19.5-35.2% using different criteria. [26],[27] In a rural population of Central India it is seen in around 9% by modified ATP III criteria. [28] In Sub-Himalayan region of Eastern India, MetS ranges from 4% to 50%. [29]


   Testosterone and Metabolic Syndrome Mechanism Top


There is a strong inverse relationship between T and body fat in men. [30] Abdominal obesity has been associated with low T in both cross-sectional [31] and longitudinal studies, [32] and low T concentration correlates with greater visceral fat accumulation. [33] Central fat depots have high aromatase activity converting T to estradiol (E2). [34] Testosterone normally inhibit adipocyte development but in states of low T there is greater fat mass. [35] Testosterone promotes lipolysis and reduces fatty acid synthesis. [36] An animal model has shown that T deficiency decreases lipolysis. [37] Visceral obesity causes increased inflow of free fatty acids into the liver and perturbs metabolism. Liver fat is correlated with all components of MetS. [38]

Obesity is associated with increased inflammatory cytokine production, as well as increased aromatization of T to estradiol in peripheral fat tissue. Both of these factors then decrease the pituitary production of gonadotropins, which, in turn, decreases testicular production of T. [39],[40] The increased level of leptin in obese individuals may interfere with luteinizing hormone/human chorionic gonadotropin stimulation of androgen production, thereby decreasing T levels. [41]

Testosterone deficiency leads to increased fat deposition resulting in insulin resistance. In states of low T muscle biopsy showed impaired mitochondrial oxidative phosphorylation. And as up to 70% of the body's insulin sensitivity is accounted by muscle, low T leads to insulin resistance. [42]

Hyperinsulinemia, as encountered in insulin resistance, might impair T secretion by the Leydig cell may be directly since there are insulin receptors on the Leydig cell. [43] It has also been found in obese men that there is an attenuated pulse amplitude of luteinizing hormone (LH) while the LH pulse frequency is unaffected, thus producing a less strong stimulation of testicular T production. [44]


   Testosterone and Metabolic Syndrome Top


There are a number of epidemiological studies linking T and MetS. Although there are a number of publications showing the association of T and MetS in females, [45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56] in this review we will restrict to the association in males.

The frequency of MetS is increased with declining tertiles of total T (TT). [57] And an inverse relationship for circulating T, [58] bioavailable T, sex-hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEA-S) is also seen with MetS. [59] The Quebec Family study found higher levels of T reduced the risk of metabolic syndrome and increased insulin sensitivity. [60]

In a Finnish study of 1896 nondiabetic middle-aged men, free T and SHBG were 11% and 18% lower in men with MetS. [40] Men with metabolic syndrome at baseline are at an increased risk of developing hypogonadism based on an 11-year follow-up. [61] In another Finish study of 702 middle-aged men who had neither diabetes nor the metabolic syndrome, after 11 years of follow-up 147 men developed MetS using NCEP ATP III criteria and 57 men developed diabetes. After adjustment for age men with total T, calculated FT, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome and diabetes. [62]

In a population-based sample of 462 older Italian men with mean age of 75 years, participants with MetS had lower levels of TT and SHBG. After adjusting for multiple confounders, including age, smoking, alcohol intake, and physical activity, TT was found to be negatively associated with MetS. [63]

The Massachusetts Male Aging Study has demonstrated that low T levels in a nonobese population were found to predict the later onset of the metabolic syndrome particularly among men with a BMI < 25 kg/m 2 . [64]

In the Baltimore Longitudinal Study of Aging of 618 healthy Caucasian adult men with a mean age of 63 years alone did not predict the development of MetS. Total T and SHBG were inversely related to the development of MetS over a mean follow-up period of 5.8 years. [65]

A cross-sectional study from Australia involving 2502 community dwelling men aged 50-70 years without known diabetes reported that men with hypogonadotrophic hypogonadism have a high prevalence of metabolic syndrome. The risk of metabolic syndrome increased for total T<20 nmol/l, SHBG<50 nmol/l, and free T<300 pmol/l. [66]

In Study of Health in Pomerania (SHIP), which is a population-based prospective cohort of adults aged 20-79 years without baseline MetS, after a median follow-up time of 5.0 years 47.8% developed MetS. With increasing number of MetS components T levels decreased. Testosterone in the lowest quartile predicted MetS particularly among men aged 20-39 years. [67]

Data from the Third National Health and Nutrition Examination Survey showed that after adjustment for age, race/ethnicity, smoking status, alcohol intake, physical activity level, LDL -C, CRP, and insulin resistance, men with lower total testosterone were more likely to have metabolic syndrome than men with higher T (P<0.001 for linear trend). Similarly, men with lower SHBG were more likely to have metabolic syndrome than men with higher SHBG (P=0.02 for linear trend). [68]

In a study of 63 males with MetS total and calculated FT and SHBG were significantly lower in cases with MetS than controls. Hypogonadism was seen in 30% cases with MetS compared to 3.1% in controls [69] [Table 1].
Table 1: The various studies which reported the difference in the serum testosterone level in normal subjects and those with MetS

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In a meta-analysis of 20 studies, patients with MetS showed significantly lower T compared to healthy individuals. Separate analysis of subjects with and without erectile dysfunction yielded similar results. Comparison of data using NCEP ATP III criteria and other MetS classifications reveals the same. Lower baseline T was demonstrated among patients with incident MetS compared to controls in longitudinal studies. [72]

In another meta-analysis of 52 observational studies comprising 22,043 men and 7839 women, endogenous TT and FT levels were lower in men with MetS and higher in women with MetS. Similarly, men with higher TT levels had a lower MetS risk whereas higher TT levels increased the risk of MetS in women. In both sexes, higher SHBG levels were associated with a reduced risk. [73]

Although various studies have shown that lower T levels may be associated with MetS and type 2 DM, both conditions associated with cardiovascular disease, reverse causation has to be considered, as systemic illness may result in reduced T levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. [74]


   Testosterone and Components of MetS Top


In the Telecom Study, there appeared to be an association of T and cardiovascular risk factors in healthy, nondiseased adult men. Serum TG, TC, LDL-C, apolipoprotein B, fasting, and 2-hour plasma insulin were higher and serum HDL-C was lower in men with lower serum T levels. [75]

Total and FT and SHBG were inversely associated with concentrations of insulin, glucose, TG, C-reactive protein (CRP), and CRP-adjusted ferritin and positively associated with HDL-C. Low TT and FT levels were associated with high levels of insulin, glucose, and TG and low levels of HDL-C. [40]

In the Tromso Study, T levels were inversely associated with anthropometrical measurements with the lowest levels of total and free T found in men with the most pronounced central obesity. Total T was inversely associated with systolic blood pressure, and also men with hypertension had lower levels of both total and free T. Furthermore, men with DM had lower T levels compared to men without a history of DM, and an inverse association between T levels and HbA1c was found. [76]

A strong association of MetS with sex hormones was observed for TG higher than 150 mg/dl and WC more than 102 cm and a modest with hypertension. Total T and FT were associated with dysglycemia, but SHBG was not. Increased odds of low HDL-C <40 mg/dl were observed with lower TT levels and SHBG but not with FT. Further adjusting for BMI, observed associations of sex hormones and MetS were attenuated but remained statistically significant with the exception of the associations observed with hypertension. [64] Total T was positively associated with HDL-C but not with other components of MetS. Log SHBG is positively associated with HDL-C, negatively associated with TG and WC, but not associated either way with BP or BG levels. [63] Total T was significantly associated with abdominal obesity and high concentrations of TG. SHBG was also significantly associated with abdominal obesity and a high concentration of TG. Free T was not significantly associated with any MetS components. Bioavailable T was significantly associated with abdominal obesity and marginally associated with high blood pressure. TT was also shown to be associated with all except hypertension, and free T was associated only with WC and TG. [67]

In a study of middle-aged Japanese men, T was significantly related to the MetS parameters of obesity (WC and BMI), hypertension, dyslipidemia, insulin resistance, and adiponectin. [77]


   Androgen Suppression and Metabolic Syndrome Top


There are studies from special groups of patients where hypogonadism is a feature due to pharmacotherapy, which strengthens opinion that T deficiency is a risk factor for the development of MetS and type 2 DM, and is an independent cardiovascular risk factor.

A small study showed that initiation of GnRH agonist or antiandrogen therapy in 22 men with prostate cancer led to increases in serum insulin, arterial stiffness, and fat mass over the subsequent 3-month period. [78]

Braga-Basaria et al. evaluated 58 men, including 20 with prostate carcinoma undergoing androgen deprivation therapy for at least 12 months. The prevalence of MetS was higher in the androgen deprivation group compared with the nonandrogen deprivation group and control groups. Men in the androgen deprivation group had a higher prevalence of abdominal obesity and hyperglycemia. Androgen-deprived men also had elevated TG compared with controls but the prevalence of hypertension and low HDL levels were similar. [79]

A longitudinal study followed a large population of 73,196 men with loco-regional prostate cancer followed for a median of 4.55 years. Those treated with androgen suppression therapy were more likely to develop diabetes, ischemic heart disease, myocardial infarction, and sudden death from cardiovascular disease compared with those patients untreated or treated with other modalities. [80]

Similarly, a study of 396 men with prostate cancer undergoing androgen-deprivation therapy showed worsening glycemic control with an increase in HbA1c and an increased incidence of new onset of diabetes. [81]

Another study has shown increased risk of MetS with chemotherapy compared with radiotherapy for testicular cancer. Metabolic syndrome was positively associated with cumulative cisplatin, bleomycin, and etoposide doses but not with cumulative vinblastine dose. Logistic regression using a backward stepwise model with all four chemotherapy agents and age included, revealed cumulative cisplatin dose as significant variables. [82]

Effect of testosterone replacement on components of metabolic syndrome

One of the earliest studies reporting the effect of TRT on obesity was by Rebuffescrive et al. in 1991 in a small group of 11 men where it was found that waist-hip ratio decreased in 9 out of 11 men after 6 weeks of testosterone replacement. [83] Recently, there have been a number of studies published investigating the effect of TRT in men primarily with type 2 DM and MetS.

Marin and colleagues were the first to report a significant reduction in diastolic blood pressure after TRT in obese middle-aged men, along with a reduction in visceral fat, FBG, TG, and total cholesterol. In a study of 122 men receiving treatment with parenteral T undecanoate over 15 months, both systolic and diastolic blood pressure decreased. A single-blind randomized study of T administration to men with MetS and recent onset of DM established also beneficial effects of testosterone on blood pressure over and above the effects of diet and exercise. [84] In men with osteoporosis intramuscular T for 6 months showed significant reduction in diastolic blood pressure along with total cholesterol, TGs, and HDL-C. [85]

Boyanov et al. reported a study of 48 type 2 diabetic men with symptoms of androgen deficiency in an open-label, randomized treatment undertaken over 3 months. Testosterone treatment resulted in significant reductions in weight, WHR, and percentage body fat compared with no treatment. Fasting blood glucose and postprandial blood glucose levels were also reduced significantly, and HbA1c fell by 1.8% (P<0.05). No significant effects on lipid parameters were observed. This study provides the first evidence that testosterone treatment may offer clinical benefit to men with type 2 diabetes. [86]

In the first double-blind placebo-controlled study by Kapoor et al. with 24 patients of type 2 DM and clinical diagnosis of hypogonadism, T treatment resulted in a significant improvement in the HOMA-IR index in those patients not on insulin therapy and resulted in insulin dose reduction by an average of 7 units per day in those patients recieving insulin. Statistically significant reductions in both FBG (−28.4mg/dl) and fasting insulin were observed, with HbA1c falling by 0.4% (P=0.03). Testosterone treatment also resulted in statistically significant improvement in WC, WHR, and total cholesterol although there was no significant effect on HDL-C, LDL-C, TGs, or blood pressure. [87]

Heufelder et al. investigated the effects of TRT in 32 hypogonadal men with newly diagnosed, treatment-naive type 2 DM with MetS in a 52-week single-blind, randomized but not placebo-controlled study, with either diet and exercise advice alone, or diet and exercise advice in conjunction with 50 mg T gel once daily. Compared with diet and exercise alone, T treatment resulted in a statistically significant improvement in HbA1c of −0.8% (P<0.001), with all patients attaining an HbA1c of <7.0% and 87.5% of patients attaining an HbA1c <6.5%. There was also a statistically significant reduction in the HOMA-IR index, although the observed treatment-mediated reduction in FPG (−5.4 mg/dl) narrowly failed to achieve statistical significance (P=0.06). Significant improvement in WC was also observed. Testosterone treatment was associated with a statistically significant reduction in serum TG and a statistically significant increase in serum HDL-C. [88]

In another study, waist circumferences declined significantly over the first 9 months of T replacement. There were declines in plasma total cholesterol, LDL-C, and TG, whereas plasma HDL-C showed an increase. [89]

A large multicenter, randomized, double-blind, placebo-controlled study undertaken in eight European countries, the TIMES2 (Testosterone replacement In men with Metabolic Syndrome or type 2 diabetes), recruited 220 hypogonadal men diagnosed with either type 2 DM and/or MetS (defined according to the IDF criteria) with no TRT within the previous 6 months. Insulin resistance (HOMA-IR) improved after 6 and 12 months of therapy. Testosterone therapy was also associated with reductions in the percentage of body fat, TC, and LDL-C and lipoprotein (a) after 6 months but there was no significant effect on HDL-C or TG. HbA1c was 0.58% lower compared with placebo after 9 months treatment but not earlier. [90]


   Summary Top


There is a strong evidence of a high prevalence of MetS in patients with a low T level. Many components of MetS are adversely affected in the presence of hypogonadism. There are reports of high prevalence of T deficiency in patients with type 2 DM.

Early interventional studies have shown that TRT in hypogonadal men with MetS has beneficial effects on central adiposity, insulin resistance, and glycemic control. There are consistent data regarding beneficial effect on blood pressure, TG, or HDL-C. Furthermore testosterone replacement in several studies has been shown to have a small but significant effect in reducing cholesterol and LDL-C, also important cardiovascular risk factors. Whether low T is just a biomarker of the degree of illness or a contributory factor to the progression of atherosclerosis is unclear. Accumulating evidence now suggests that T deficiency is a risk factor for cardiovascular disease and intervention may ameliorate the process. Active systemic inflammatory disorders including chronic infections may accelerate atherosclerotic progression and destabilize plaques. There is a need for long-term interventional study to examine the effect of T on cardiovascular disease in men with MetS and/or type 2 DM.

 
   References Top

1.Muraleedharan V, Jones TH. Testosterone and the metabolic syndrome. Ther Adv Endocrinol Metab 2010;1:207-23.  Back to cited text no. 1
    
2.Reaven GM. Role of insulin resistance in human-disease. Diabetes 1988;37:1595-607.  Back to cited text no. 2
    
3.Taskinen MR. Is metabolic syndrome the main threat to human health in the twenty-first century? Arteioscler Thromb Vasc Biol 2007;27:2275.  Back to cited text no. 3
    
4.Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications, part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539-53.  Back to cited text no. 4
    
5.Balkau B, Charles MA. Comment on the provisional report from the WHO consultation: European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999;16:442-3.  Back to cited text no. 5
    
6.Executive summary of the Third Report of The National Cholesterol Education Program (NCEP). Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.  Back to cited text no. 6
    
7.Einhorn D, Reaven GM, Cobin RH, Ford E, Ganda OP, Handelsman Y, et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 2003;9:237-52.  Back to cited text no. 7
    
8.Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; for the Conference Participants. Definition of Metabolic Syndrome: Report of the national heart, lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:433-8.  Back to cited text no. 8
    
9.Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome: A new worldwide definition. Lancet 2005;366:1059-62.  Back to cited text no. 9
    
10.Alberti KG, Zimmet P, Shaw J. Metabolic syndrome: A new world-wide definition: A consensus statement from the International Diabetes Federation. Diabet Med 2006;23:469-80.  Back to cited text no. 10
    
11.Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation task force on epidemiology and prevention: National Heart, Lung, and Blood Institute: American Heart Association; World Heart Federation: International Atherosclerosis Society: and International Association for the Study of Obesity. Circulation 2009;120:1640-5.   Back to cited text no. 11
    
12.The IDF consensus worldwide definition of the metabolic syndrome. The metabolic syndrome. IDF Communications 2006. p. 1-23.  Back to cited text no. 12
    
13.ES Ford. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the US. Diabetes Care 2005;28:2745-9.  Back to cited text no. 13
    
14.Agirbasli M, Agaoglu NB, Orak N, Caglioz H, Ocek T, Poci N, et al. Sex hormones and metabolic syndrome in children and adolescents. Metab Clin Exp 2009;58:1256-62.  Back to cited text no. 14
    
15.Gupta R, Deedwania PC, Gupta A, Rastogi S, Panwar RB, Kothari K. Prevalence of metabolic syndrome in an Indian urban population. Int J Cardiol 2004;97:257-61.   Back to cited text no. 15
    
16.Misra A, Wasir JS, Pandey. An evaluation of candidate definitions of the metabolic syndrome in adult Asian Indians. Diabetes Care 2005;28:398-403.   Back to cited text no. 16
    
17.Wasir JS, Misra A, Vikram NK, Pandey RM, Gupta R. Comparison of definitions of the metabolic syndrome in adult Asian Indians. J Assoc Physicians India 2008;56:158-64.   Back to cited text no. 17
    
18.Sharma SK, Reddy EV, Sharma A, Kadhiravan T, Mishra HK, Sreenivas V, et al. Prevalence and risk factors of syndrome Z in urban Indians. Sleep Med 2010;11:562-8.  Back to cited text no. 18
    
19.Mangat C, Goel NK, Walia DK, Agarwal N, Sharma MK, Kaur J, et al. Metabolic syndrome: A challenging health Issue in highly urbanized Union Territory of North India. Diabetol Metab Syndrome 2010;2:19.  Back to cited text no. 19
    
20.Ravikiran M, Bhansali A, Ravikumar P, Bhansali S, Dutta P, Thakur JS, et al. Prevalence and risk factors of metabolic syndrome among Asian Indians: A community survey. Diabetes Res Clin Pract 2010;89:181-8.  Back to cited text no. 20
    
21.Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Metabolic syndrome in urban Asian Indian adults: A population study using modified ATP III criteria. Diabetes Res Clin Pract 2003;60:199-204.  Back to cited text no. 21
    
22.Deepa M, Farooq S, Datta M, Deepa R, Mohan V. Prevalence of metabolic syndrome using WHO, ATPIII and IDF definitions in Asian Indians: The Chennai Urban Rural Epidemiology Study (CURES-34). Diabetes Metab Res Rev 2007;23:127-34.  Back to cited text no. 22
    
23.Pemminati S, Prabha Adhikari MR, Pathak R, Pai MR. Prevalence of metabolic syndrome (METS) using IDF 2005 guidelines in a semi urban south Indian (Boloor Diabetes Study) population of Mangalore. J Assoc Physicians India 2010;58:674-7.  Back to cited text no. 23
    
24.Kaur P, Radhakrishnan E, Rao SR, Sankarasubbaiyan S, Rao TV, Gupte MD. The metabolic syndrome and associated risk factors in an urban industrial male population in South India. J Assoc Physicians India 2010;58:363-6,371.  Back to cited text no. 24
    
25.Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Metabolic syndrome does not increase the risk of conversion of impaired glucose tolerance to diabetes in Asian Indians-Result of Indian diabetes prevention programme. Diabetes Res Clin Pract 2007;76:215-8.  Back to cited text no. 25
    
26.Mahadik SR, Deo SS, Mehtalia SD. Increased prevalence of metabolic syndrome in non-obese Asian Indian-an urban-rural comparison. Metab Syndr Relat Disord 2007;5:142-52.  Back to cited text no. 26
    
27.Sawant A, Mankeshwar R, Shah S, Raghavan R, Dhongde G, Raje H, et al. Prevalence of metabolic syndrome in urban India. Cholesterol 2011;2011:920983.  Back to cited text no. 27
    
28.Kamble P, Deshmukh PR, Garg N. Metabolic syndrome in adult population of rural Wardha, central India. Indian J Med Res 2010;132:701-5.  Back to cited text no. 28
[PUBMED]  Medknow Journal  
29.Sarkar S, Das M, Mukhopadhyay B, Chakrabarti CS, Majumder PP. High prevalence of metabolic syndrome and its correlates in two tribal populations of India and the impact of urbanization. Indian J Med Res 2006;123:679-86.  Back to cited text no. 29
[PUBMED]  Medknow Journal  
30.Kapoor D, Malkin CJ, Channer, KS, Jones TH. Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf) 2005;63:239-50.  Back to cited text no. 30
    
31.Pasquali R, Casimirri F, Balestra V, Flamia R, Melchionda N, Fabbri R, et al. The relative contribution of androgens and insulin in determining abdominal body-fat distribution in premenopausal women. J Endocrinol Invest 1991;14:839-46.  Back to cited text no. 31
    
32.Barrettconnor E. Lower endogenous androgen levels and dyslipidemia in men with noninsulin- dependent diabetes-mellitus. Ann Intern Med 1992;117:807-11.  Back to cited text no. 32
    
33.Haffner SM, Valdez RA, Stern MP, Katz MS. Obesity, body-fat distribution and sex hormones in men. Int J Obesity 1993;17:643-9.  Back to cited text no. 33
    
34.Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly men. Aging Male 2002;5:98-102.  Back to cited text no. 34
    
35.Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 2003;144:5081-8.  Back to cited text no. 35
    
36.De Pergola G. The adipose tissue metabolism: Role of testosterone and dehydroepiandrosterone. Int J Obesity 2000;24:S59-63.  Back to cited text no. 36
    
37.Yanase T, Fan W, Kyoya K, Min L, Takayanagi R, Kato S, et al. Androgens and metabolic syndrome: Lessons from androgen receptor knock out (ARKO) mice. J Steroid Biochem Mol Biol 2008;109:254-7.  Back to cited text no. 37
    
38.Saad F. The role of testosterone in type 2 diabetes and metabolic syndrome in men. Arq Bras Endocrinol Metab 2009;53:901-7.  Back to cited text no. 38
    
39.Dobs AS, Bachorik PS, Arver S, Meikle AW, Sanders SW, Caramelli KE, et al. Interrelationships among lipoprotein levels, sex hormones, anthropometric parameters, and age in hypogonadal men treated for 1 year with a permeation-enhanced testosterone transdermal system. J Clin Endocrinol Metab 2001;86:1026-33.  Back to cited text no. 39
    
40.Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Salonen R, et al. Sex hormones, inflammation and the metabolic syndrome: A population-based study. Eur J Endocrinol 2003;149:601-8.  Back to cited text no. 40
    
41.Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, et al. Leptin and androgens in male obesity: Evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab 1999;84:3673-80.  Back to cited text no. 41
    
42.Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, et al. Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 2005;28:1636-42.  Back to cited text no. 42
    
43.Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 2005;90:2636-41.  Back to cited text no. 43
    
44.Vermeulen A, Kaufman JM, Deslypere JP, Thomas G. Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab 1993;76:1140-6.  Back to cited text no. 44
    
45.Sutton-Tyrrell K, Wildman RP, Matthews KA, Chae C, Lasley BL, Brockwell S, et al. Sex hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN). Circulation 2005;111:1242-9.  Back to cited text no. 45
    
46.Weinberg ME, Manson JA, Buring JE, Cook NR, Seely EW, Ridker PM, et al. Low sex-hormone binding globulin is associated with the metabolic syndrome in postmenopausal Women. Metabolism 2006;55:1473-80.  Back to cited text no. 46
    
47.Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen leveis independent of obesity and insulin resistance. J Clin Endocrinol Metab 2006;91:492-7.  Back to cited text no. 47
    
48.Zanolin ME, Tosi F, Zoppini G, Castello R, Spiazzi G, Dorizzi R, et al. Clustering of cardiovascular risk factors associated with the insulin resistance syndrome: Assessment by principal component analysis in young hyperandrogenic women. Diabetes Care 2006;29:372-8.  Back to cited text no. 48
    
49.Maggio M, Lauretani F, Ceda GP, Bandinelli S, Basaria S, Paolisso G, et al. Association of hormonal dysregulation with metabolic syndrome in older women: Data from the InCHIANTI study. Am J Physiol Endocrinol Metab 2007;292:E353-8.  Back to cited text no. 49
    
50.Kajaia N, Binder H, Dittrich R, Oppelt PG, Flor B, Cupisti S, et al. Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome. Eur J Endocrinol 2007;157:499-507.  Back to cited text no. 50
    
51.Phillips GB, Jing T, Heymsfield SB. Does insulin resistance, visceral adiposity, or a sex hormone alteration underlie the metabolic syndrome? Studies in women. Metabolism 2008;57:838-44.  Back to cited text no. 51
    
52.Tfayli H, Silva Arslanian S. Menstrual health and the metabolic syndrome in adolescents. Ann N Y Acad Sci 2008;1135:85-94.  Back to cited text no. 52
    
53.Torréns JI, Sutton-Tyrrell K, Zhao X, Matthews K, Brockwell S, Sowers MF, et al. Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in mid-life women: SWAN. Menopause 2009;16:257-64.  Back to cited text no. 53
    
54.Patel SM, Ratcliffe SJ, Reilly MP, Weinstein R, Bhasin S, Blackman MR, et al. Higher serum testosterone concentration in older women is associated with insulin resistance, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 2009;94:4776-84.  Back to cited text no. 54
    
55.Janssen I, Powell LH, Kazlauskaite R, Dugan SA. Testosterone and visceral fat in midlife women: The Study of Women's Health Across the Nation (SWAN) Fat Patterning Study. Obesity (Silver Spring) 2010;18:604-10.  Back to cited text no. 55
    
56.Perry A, Wang X, Goldberg R, Ross R, Jackson L. Racial disparities between the sex steroid milieu and the metabolic risk profile. J Obes 2010;2010:174652.  Back to cited text no. 56
    
57.Tong PC, Ho CS, Yeung VT, Ng MC, So WS, Ozaki R, et al. Association of testosterone, insulin-like growth factor- I, and C-reactive protein with metabolic syndrome in Chinese middle-aged men with a family history of type 2 diabetes. J Clin Endocrinol Metab 2005;90:6418-23.  Back to cited text no. 57
    
58.Kupelian V, Hayes FJ, Link CL, Rosen R, McKinlay JB. Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab 2008;93:3403-10.  Back to cited text no. 58
    
59.Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT. Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 2005;90:2618-23.  Back to cited text no. 59
    
60.Blouin K, Despres JP, Couillard C, Tremblay A, Prudhomme D, Bouchard C, et al. Contribution of age and declining androgen levels to features of the metabolic syndrome in men. Metab Clin Exp 2005;54:1034-40.  Back to cited text no. 60
    
61.Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, et al. The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: A prospective cohort study. J Clin Endocrinol Metab 2005;90:712-9.  Back to cited text no. 61
    
62.Laaksonen DE, Niskanen L, Punnonen K, Onen KN, Tuomainen TP, Valkonen VP, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004;27:1036-41.  Back to cited text no. 62
    
63.Maggio M, Lauretani F, Ceda GP, Bandinelli S, Basaria S, Ble A, et al. Association between hormones and metabolic syndrome in older Italian men. J Am Geriatr Soc 2006;54:1832-8.  Back to cited text no. 63
    
64.Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab 2006;91:843-50.  Back to cited text no. 64
    
65.Rodriguez A, Muller DC, Metter EJ, Maggio M, Harman SM, Blackman MR, et al. Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. J Clin Endocrinol Metab 2007;92:3568-72.  Back to cited text no. 65
    
66.Haring R, lzke HV, Felix SB, Schipf S, Dorr M, Rosskopf D, et al. Prediction of metabolic syndrome by low serum testosterone levels in men: Results from the Study of Health in Pomerania. Diabetes 2009;58:2027-31.  Back to cited text no. 66
    
67.Chubb SA, Yeap BB. Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: The Health in Men Study. Eur J Endocrinol 2008;158:785-92.  Back to cited text no. 67
    
68.Li C, Ford ES, Li B, Giles WH, Liu S. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insulin resistance in men. Diabetes Care 2010;33:1618-24.  Back to cited text no. 68
    
69.Singh SK, Goyal R, Pratyush DD. Is hypoandrogenemia a component of metabolic syndrome in males? Exp Clin Endocrinol Diabetes 2011;119:30-5.  Back to cited text no. 69
    
70.Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008;93:68-75.  Back to cited text no. 70
    
71.Katabami T, Kato H, Asahina T, Hinohara S, Shin T, Kawata T, et al. Serum free testosterone and metabolic syndrome in Japanese men. Endocr J 2010;57:533-9.  Back to cited text no. 71
    
72.Corona G, Monami M, Rastrelli G, Aversa A, Tishova Y, Saad F, et al. Testosterone and metabolic syndrome: A meta-analysis study. J Sex Med 2011;8:272-83.  Back to cited text no. 72
    
73.Brand JS, van der Tweel I, Grobbee DE, Emmelot-Vonk MH, van der Schouw YT. Testosterone, sex hormone-binding globulin and the metabolic syndrome: A systematic review and meta-analysis of observational studies. Int J Epidemiol 2011;40:189-207.  Back to cited text no. 73
    
74.Yeap BB. Are declining testosterone levels a major risk factor for ill-health in aging men? Int J Impotence Res 2009;21:24-36.  Back to cited text no. 74
    
75.Fontbonne A, Papoz L, Eschwege E, Roger M, Saint-Paul M, Simon D. Features of insulin-resistance syndrome in men from French Caribbean Islands: The Telecom Study. Diabetes 1992;41:1385-9.  Back to cited text no. 75
    
76.Svartberg J, Jenssen T, Sundsfjord J, Jorde R. The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men: The Tromsø Study. Diabetes Metab 2004;30:29-34.  Back to cited text no. 76
    
77.Akishita M, Fukai S, Hashimoto M, Kameyama Y, Nomura K, Nakamura T, et al. Association of low testosterone with metabolic syndrome and its components in middle-aged Japanese men. Hypertens Res 2010;33:587-91.  Back to cited text no. 77
    
78.Smith MR, Lee H, Fallon MA, Nathan DM. Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer: Evidence for a distinct hypogonadal metabolic syndrome? Urology 2008;71:318-22.  Back to cited text no. 78
    
79.Braga-Basaria M, Dobs AS, Muller DC, Carducci MA, John M, Egan J, et al. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol 2006;24:3979-83.  Back to cited text no. 79
    
80.Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006;24:4448-56.  Back to cited text no. 80
    
81.Derweesh IH, DiBlasio CJ, Kincade MC, Malcolm JB, Lamar KD, Patterson AL, et al. Risk of new-onset diabetes mellitus and worsening glycaemic variables for established diabetes in men undergoing androgen-deprivation therapy for prostate cancer. BJU Int 2007;100:1060-5.  Back to cited text no. 81
    
82.Haugnes HS, Aass N, Fossa SD, Dahl O, Klepp O, Wist EA, et al. Components of the metabolic syndrome in long-term survivors of testicular cancer. Ann Oncol 2007;18:241-8.  Back to cited text no. 82
    
83.Rebuffescrive M, Marin P, Bjorntorp P. Effect of testosterone on abdominal adipose-tissue in men. Int J Obesit 1991;15:791-5.  Back to cited text no. 83
    
84.Marin P, Holmang S, Gustafsson C, Jonsson L, Kvist H, Elander A. Androgen treatment of abdominally obese men. Obes Res 1993;1:245-51.  Back to cited text no. 84
    
85.Anderson FH, Francis RM, Faulkner K. Androgen supplementation in eugonadal men with osteoporosis: Effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Bone 1996;18:171-7.  Back to cited text no. 85
    
86.Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003;6:1-7.  Back to cited text no. 86
    
87.Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006;154:899-906.  Back to cited text no. 87
    
88.Saad F, Gooern LJ, Haider A, Yassin A. A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate. J Androl 2008;29:102-5.  Back to cited text no. 88
    
89.Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl 2009;30:726-33.  Back to cited text no. 89
    
90.Jones H, Howell J, Channer K. Testosterone improves glycaemic control, insulin resistance, body fat and sexual function in men with the metabolic syndrome and/or type 2 diabetes: A Multicentre European Clinical Trial: the TIMES2 Study. Endocrine Abstracts 2010;21:6.  Back to cited text no. 90
    



 
 
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