|Year : 2017 | Volume
| Issue : 1 | Page : 31-37
Prevalence of hypogonadism in male Type 2 diabetes mellitus patients with and without coronary artery disease
SV Madhu, M Aslam, AJ Aiman, A Siddiqui, S Dwivedi
Department of Medicine, Centre for Diabetes Endocrinology and Metabolism, University College of Medical Sciences (University of Delhi) and GTB Hospital, New Delhi, India
|Date of Web Publication||19-Dec-2016|
S V Madhu
Department of Medicine, Centre for Diabetes Endocrinology and Metabolism, University College of Medical Sciences (University of Delhi) and GTB Hospital, Dilshad Garden, New Delhi - 110 095
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: The present study is carried out to investigate hypogonadism using serum testosterone levels in male Type 2 diabetes mellitus (T2DM) subjects with and without coronary artery disease (CAD). Subjects and Methods: A total of 150 age and body mass index-matched male subjects in the age group of 30–70 years were recruited in three groups; Group A - subjects with normal glucose tolerance, Group B - T2DM subjects without CAD, and Group C - T2DM subjects with CAD (n = 50 each group). Subjects with CAD were diagnosed on the basis of electrocardiogram, treadmill testing, stress echocardiography, or coronary angiography. Total testosterone (TT), free testosterone (FT), bioavailable testosterone, calculated FT and glycemic parameters were measured and compared between all the three study groups. One-way ANOVA followed by post hoc Tukey's test and Pearson's coefficient of correlation tests were used for analysis. Results: Hypogonadism (TT <3 ng/ml) was observed in 40% (20/50) of subjects in Group C and 32% (16/50) of subjects in Group B as compared to only 14% (7/50) of subjects in Group A (Groups A vs. B; P = 0.055, Groups A vs. C; P = 0.006 and Groups B vs. C; P = 0.53). Group C subjects had significantly lower levels of TT (3.55 ± 1.46 ng/ml vs. 4.73 ± 2.17 ng/ml, P = 0.005), calculated FT (0.062 ± 0.0255 pg/ml vs. 0.0951 ± 0.0508 pg/ml, P≤ 0.001), and bioavailable testosterone (1.48 ± 0.65 ng/ml vs. 2.18 ± 1.20 ng/ml, P ≤ 0.001) compared to control Group A subjects. There was no significant difference in any of the testosterone parameters between Groups A and B. Furthermore, an overall positive correlation was found between hypogonadism and CAD (r = 0.177, P = 0.030, n = 150). Conclusion: We observed hypogonadism as indicated by low testosterone levels in a significant proportion of male T2DM subjects with CAD.
Keywords: Cardiovascular risk, coronary artery disease, diabetes, hypogonadism, testosterone
|How to cite this article:|
Madhu S V, Aslam M, Aiman A J, Siddiqui A, Dwivedi S. Prevalence of hypogonadism in male Type 2 diabetes mellitus patients with and without coronary artery disease. Indian J Endocr Metab 2017;21:31-7
|How to cite this URL:|
Madhu S V, Aslam M, Aiman A J, Siddiqui A, Dwivedi S. Prevalence of hypogonadism in male Type 2 diabetes mellitus patients with and without coronary artery disease. Indian J Endocr Metab [serial online] 2017 [cited 2017 Jan 16];21:31-7. Available from: http://www.ijem.in/text.asp?2017/21/1/31/195999
| Introduction|| |
In recent years, low testosterone levels have been recognized to be closely associated with increased cardiovascular (CV) risk., Studies in the past have reported that testosterone deficiency is inversely associated with coronary intima-media thickness (CIMT),, a surrogate marker for atherosclerosis which leads to the development of coronary artery disease (CAD). Furthermore, it has been found that testosterone induces endothelium-independent relaxation of isolated rabbit aorta. Studies have also reported that testosterone has beneficial effects on coronary blood flow in men with CAD.
Decrease in testosterone levels is also influenced by age, obesity, and insulin resistance (IR). Subjects with diabetes have been reported to have low serum testosterone levels as compared with the healthy individuals. Subjects with diabetes also possess a greater CV risk , and demonstrate CV risk biomarkers such as atherogenic dyslipidemia,, increased high-sensitivity C-reactive protein  levels, leptin, adiponectin levels, and leptin/adiponectin ratio. An inverse relationship between serum free testosterone (FT) levels and plaque score has also been found in men with diabetes. However, it is not clear if there is any association of hypogonadism and increased CV risk in subjects with diabetes. The present study was therefore carried out to find out the prevalence of hypogonadism in Indian male diabetes subjects with CAD.
| Subjects and Methods|| |
This study was approved by Institutional Ethics Committee-Human Research, University College of Medical Sciences, Delhi, India. All the investigations were performed as per the International Declaration of Helsinki and Tokyo. All the guidelines of the Ethics Committee were followed during the study. A total of 150 age and body mass index (BMI) matched male subjects in the age group of 30–70 years were recruited in three different groups; Group A - subjects with normal glucose tolerance (NGT), Group B - Type 2 diabetes mellitus (T2DM) subjects without CAD, and Group C - T2DM subjects with CAD (n = 50 each group).
Subjects who had fasting plasma glucose <100 mg/dl and 2 h postprandial plasma glucose <140 mg/dl (oral glucose tolerance test with 75 g anhydrous glucose) were labeled as NGTs in Group A. subjects with diabetes in Group B were recruited from the diabetic clinic of the institute/hospital. Diabetic subjects with CAD in Group C were recruited from preventive cardiology clinic of the institute/hospital under the supervision of subject specialists. A baseline 12 lead electrocardiogram, treadmill testing, stress echocardiography, or coronary angiography were used to look for any evidence of CAD.
Subjects suffering from any acute stress, coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery, or coronary angioplasty) in the previous 4 weeks, liver disease, serum creatinine levels >1.5 mg/dl, systemic disorders such as cancer, epilepsy, hypothyroidism, and evidence of any active infection including osteomyelitis, ulcers, and upper respiratory infection or any known history of hypogonadism or panhypopituitarism, and night shift workers were excluded from the study. History of mumps and alcohol consumption were also taken, and both were negative. All the subjects participated in the study were explained about the study and a written informed consent was obtained.
Informed consent was followed by a detailed medical history and clinical examination. BMI, systolic and diastolic blood pressure (supine and standing both) were recorded of all the recruited subjects. Fasting blood samples were collected for the estimation of plasma glucose, HbA1c, serum insulin, lipid profile, total testosterone (TT), FT, sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH).
Commercially available kits were used for estimation of biochemical parameters, namely, plasma glucose (Accurex Biomedicals, India), total cholesterol and triglyceride (Merck-Labkit, Spain), high-density lipoprotein cholesterol (HDL-c) third generation direct homogeneous assay (Auto Pure, Accurex Biomedicals, India). Each time Quality Control Sera (Bio-Rad, USA) were run along with the samples. Results of the unknown samples and quality control sera were in range and reproducible. Serum TT, FT, insulin, SHBG, LH, and FSH were measured using radioimmunoassay kits (Immunotech, Beckman Coulter Inc., Czech Republic). HbA1c was measured by high-performance liquid chromatography method (Bio-Rad D10 instrument).
The normal value for TT was 3–12 ng/ml (sensitivity - 0.04 ng/ml), for FT: 8.69–54.69 pg/ml (sensitivity - 0.18 pg/ml), for SHBG 20–70 nmol/L (sensitivity - 0.2 nmol/L), for LH: 1.8–10 IU/L (sensitivity - 0.2 IU/L), and for FSH was 1.3–11.5 IU/L (sensitivity - 0.2 IU/L). Calculated FT (cFT) was calculated from SHBG, serum albumin, and TT using the method of Vermeulen et al.
Hypogonadism was defined as TT values <3 ng/ml. Hypogonadotropic hypogonadism (HH) was defined as TT levels <3 ng/ml and LH values <10 IU/L. Primary hypogonadism was defined as TT levels <3 ng/ml and LH levels >10 IU/L.
Measurements of adiposity, namely, waist, subcutaneous body fat - biceps, triceps, subscapular, and suprailiac, were also recorded. Body fat percent was calculated by applying the four skinfold measurements into the Durnin and Womersley formula.
One-way ANOVA followed by post hoc Tukey's test was applied for comparison of parameters between the groups. Pearson's coefficient of correlation was calculated for all the three groups together and separately for all the above-mentioned parameters. Data were considered significantly different if P < 0.05.
| Results|| |
Subjects in all the three groups (n = 50 each) were matched for age and BMI. Anthropometric and hemodynamic measures have been presented in [Table 1] and [Table 2]. There was no significant difference in the measure of central obesity (waist circumference) between any of the three groups. Fasting plasma glucose and HbA1c were found to be significantly higher in Groups B and C compared to control Group A [Table 2]. There was no significant difference in fasting plasma glucose and HbA1c between Groups B and C.
Lowest levels of TT, cFT, and bioavailable testosterone were found in Group C subjects, i.e. T2DM with CAD. Group B subjects, i.e. T2DM without CAD showed intermediate levels of these indices whereas control Group A subjects had highest levels of all of these testosterone parameters [Figure 1].
|Figure 1: Various testosterone indices among the three study groups. (a) Group A versus Group B (P = 0.29), Group A versus Group C (P = 0.005), Group B versus Group C (P = 0.21); (b) Group A versus Group B (P = 0.14), Group A versus Group C (P ≤ 0.001), Group B versus Group C (P = 0.12); (c) Group A versus Group B (P = 0.12), Group A versus Group C (P ≤ 0.001), Group B versus Group C (P = 0.06); (d) Group A versus Group B (P = 0.13), Group A versus Group C (P = 0.49), Group B versus C (P = 0.71)|
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Serum levels of TT, cFT, and bioavailable testosterone were found to be significantly lower in Group C subjects compared to Group A subjects [Figure 1]a,[Figure 1]b,[Figure 1]c. FT levels were also found to be lower in Group C compared to Group A though this difference was not statistically significant [Figure 1]d. There was no significant difference in any of the testosterone indices between Group A and Group B [Figure 1].
Hypogonadism as indicated by low testosterone levels was found to be highest in Group C subjects (40%, 20/50) followed by Group B subjects (32%, 16/50) whereas only 14% (7/50) of the subjects in Group A had hypogonadism (Groups A vs. B; P = 0.055, Groups A vs. C; P = 0.006, and Groups B vs. C; P = 0.53). The majority of the subjects with hypogonadism in all the three groups had HH (19/20 in Group C, 11/16 in Group B and 6/7 in Group A). We did not observe any statistically significant difference in serum levels of SHBG, LH, and FSH between the three study groups [Table 2].
Subcutaneous body fat measurements, i.e. triceps, biceps, and subscapular were found to be significantly higher in Group B subjects compared to control Group A [Table 1]. Triceps and biceps were also found to be significantly higher in Group B subjects compared to Group C [Table 1]. However, fat percent, fat mass and suprailiac fat measurements were not significantly different between the three study groups [Table 1].
We observed an overall (n = 150) negative correlation of TT, FT, cFT, and bioavailable testosterone with body fat percent suggesting an inverse relationship between testosterone levels and obesity [Figure 2]. In addition, an overall positive correlation was found between hypogonadism and CAD (r = 0.177, P = 0.030, n = 150).
|Figure 2: Correlation of testosterone indices with body fat percent (n = 150). (a) Total testosterone with body fat %, (b) Free testosterone with body fat %, (c) Bioavailable testosterone with body fat %, (d) Calculated free testosterone with body fat %|
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IR, as indicated by homeostatic model assessment (HOMA-IR), was found to be significantly higher in Groups B and C subjects compared to Group A subjects [Table 2]. Beta cell function (HOMA-β) was found to be significantly lower in both Groups B and C subjects compared to Group A subjects [Table 2]. No significant difference was found between serum triglyceride, total cholesterol and HDL-c between the three study groups except in Groups C and B where Group C showed significantly lower levels of HDL-c compared to Group B. Serum insulin levels were also found to similar between the three study groups.
| Discussion|| |
In this study, we compared testosterone profiles of diabetes subjects with and without CAD with nondiabetic healthy controls. We found the highest prevalence of hypogonadism as indicated by low testosterone levels in diabetic subjects with CAD followed by diabetic subjects without CAD and then in controls. There was a significant difference in the prevalence of hypogonadism in diabetic subjects with CAD compared to controls whereas the difference fell just short of significance levels between diabetic subjects without CAD and controls.
We analyzed complete testosterone profile, namely, TT, FT, cFT bioavailable testosterone and SHBG in all the study subjects which allowed a comprehensive interpretation of testosterone status and provided a better understanding of internal validation. All testosterone measurements were carried out at 8 am which was fixed. This precaution was not taken in earlier studies. Hence, in our study, we also avoided any fluctuations in testosterone levels due to variability in blood sampling timings. Body fat measurements were also included in our study to see if the effects of testosterone deficiency were related to its effects on lean body mass or fat content. However, we used single point sampling for testosterone examination and not repeated sampling which could have provided more accurate assessment of hypogonadism in males and it remains a limitation of the present study.
We found HH in the majority of subjects detected with testosterone deficiency (95% in diabetic with CAD group, 68 in diabetics without CAD group and 85% in NGTs). In previous studies, both higher  as well as lower  proportion of HH in hypogonadal diabetic males has been reported. It has been hypothesized that increased body fat content secondary to testosterone deficiency leads to increased conversion of testosterone to estradiol. This results in enhanced suppression of hypothalamic GnRh ,, and LH  and consequent HH. Primary hypogonadism which has been reported less often is believed to occur secondary to microvascular damage in the testis.,
Testosterone indices (TT, bioavailable testosterone, and cFT) correlated negatively with the measure of central obesity, namely, waist circumference and body fat percent. TT levels also showed similar correlation with BMI and fat mass. These effects of testosterone deficiency may be contributing significantly to the associated CV risk in male T2DM subjects. Association of central obesity, higher adiposity and lower lean body mass with testosterone deficiency has been reported in earlier studies.,, It has been hypothesized that low testosterone levels promote increased fat deposition and increase in adiposity.
Several earlier studies have shown that deficiency in male sex hormones is associated with increased risk for CAD ,, besides its effects on lean body mass and adiposity. It has been reported that low testosterone levels are associated with markers of atherosclerosis such as increased CIMT., A meta-analysis study showed that low testosterone levels are associated with increased CV risk and mortality. This analysis also showed that testosterone replacement therapy in subjects with hypogonadism moderates metabolic components associated with CV risk. Significant testosterone deficiency observed in diabetes subjects with CAD raises the important issue whether these subjects should be given testosterone replacement therapy in an attempt to reduce CV risk. This notion is also based on the findings of a recent retrospective study involving over 83,000 veterans. Results of this study showed that normalization of TT levels with testosterone replacement therapy leads to a significant lowering of all causes of mortality, MI risk, and stroke. Several other studies have also reported improved glycemic control, reduced IR and increased insulin sensitivity in subjects of T2DM receiving testosterone replacement therapy ,,, which may subsequently lead to reduced CV risk in diabetes subjects. Further, it has been found that testosterone therapy reduces central obesity and consequent visceral fat mass and waist-hip ratio. Effect of testosterone therapy on IR and insulin sensitivity is thought to be androgen receptor-mediated as androgen receptors are found in much higher concentration in visceral fat depots than subcutaneous fat depots.
| Conclusion|| |
The present study finds testosterone deficiency in a significant proportion of male T2DM subjects particularly those with evidence of CV disease. Low testosterone levels could contribute to a significantly higher CV risk in subjects with T2DM.
Authors are thankful to Indian Council of Medical Research for providing financial assistance for the study and Department of Biomedical Informatics, University College of Medical Sciences, New Delhi for assistance in data analysis.
Financial support and sponsorship
Research grant for this study was provided by Indian Council of Medical Research (Grant ID: 5/3/8/50/2007-RHN), New Delhi, India.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Krysiak R, Gilowski W, Okopien B. The effect of testosterone on cardiovascular risk factors in men with type 2 diabetes and late-onset hypogonadism treated with metformin or glimepiride. Pharmacol Rep 2016;68:75-9.
Martínez-Jabaloyas JM; DE-SDT Study Group. Testosterone deficiency in patients with erectile dysfunction: When should a higher cardiovascular risk be considered? J Sex Med 2014;11:2083-91.
Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 2004;109:2074-9.
Svartberg J, von Mühlen D, Mathiesen E, Joakimsen O, Bønaa KH, Stensland-Bugge E. Low testosterone levels are associated with carotid atherosclerosis in men. J Intern Med 2006;259:576-82.
Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P. Testosterone relaxes rabbit coronary arteries and aorta. Circulation 1995;91:1154-60.
Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 1999;100:1690-6.
Ferrini RL, Barrett-Connor E. Sex hormones and age: A cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 1998;147:750-4.
Wang C, Jackson G, Jones TH, Matsumoto AM, Nehra A, Perelman MA, et al.
Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care 2011;34:1669-75.
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.
Kapoor D, Aldred H, Clark S, Channer KS, Jones TH. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: Correlations with bioavailable testosterone and visceral adiposity. Diabetes Care 2007;30:911-7.
Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes 2014;5:444-70.
Tan CE, Chew LS, Chio LF, Tai ES, Lim HS, Lim SC, et al.
Cardiovascular risk factors and LDL subfraction profile in type 2 diabetes mellitus subjects with good glycaemic control. Diabetes Res Clin Pract 2001;51:107-14.
Kalofoutis C, Piperi C, Kalofoutis A, Harris F, Phoenix D, Singh J. Type II diabetes mellitus and cardiovascular risk factors: Current therapeutic approaches. Exp Clin Cardiol 2007;12:17-28.
Bhatia V, Tomar R, Dhindsa S, Chandel A, Chaudhuri A, Ghanim H, et al
. Elevation of C-reactive protein concentrations in patients with hypogonadotrophic hypogonadism and type 2 diabetes. Diabetes Care 2006;29:2289-94.
Shanker J, Rao VS, Ravindran V, Dhanalakshmi B, Hebbagodi S, Kakkar VV. Relationship of adiponectin and leptin to coronary artery disease, classical cardiovascular risk factors and atherothrombotic biomarkers in the IARS cohort. Thromb Haemost 2012;108:769-80.
Satoh N, Naruse M, Usui T, Tagami T, Suganami T, Yamada K, et al.
Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 2004;27:2488-90.
Fukui M, Kitagawa Y, Nakamura N, Kadono M, Mogami S, Hirata C, et al.
Association between serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes. Diabetes Care 2003;26:1869-73.
Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666-72.
Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: The HIM study. Int J Clin Pract 2006;60:762-9.
Durnin JV, Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness: Measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 1974;32:77-97.
Rabijewski M, Papierska L, Zgliczynski W, Piatkiewicz P. The incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population. Biomed Res Int 2013;2013:767496. doi: 10.1155/2013/767496.
Corona G, Mannucci E, Petrone L, Ricca V, Balercia G, Mansani R, et al.
Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. Int J Impot Res 2006;18:190-7.
Cohen PG. The hypogonadal-obesity cycle: Role of aromatase in modulating the testosterone-estradiol shunt – A major factor in the genesis of morbid obesity. Med Hypotheses 1999;52:49-51.
Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 2000;85:3027-35.
Hayes FJ, DeCruz S, Seminara SB, Boepple PA, Crowley WF Jr. Differential regulation of gonadotropin secretion by testosterone in the human male: Absence of a negative feedback effect of testosterone on follicle-stimulating hormone secretion. J Clin Endocrinol Metab 2001;86:53-8.
Pitteloud N, Dwyer AA, DeCruz S, Lee H, Boepple PA, Crowley WF Jr., et al.
The relative role of gonadal sex steroids and gonadotropin-releasing hormone pulse frequency in the regulation of follicle-stimulating hormone secretion in men. J Clin Endocrinol Metab 2008;93:2686-92.
Jones TH. Testosterone associations with erectile dysfunction, diabetes and the metabolic syndrome. Eur Urol Suppl 2007;6:847-57.
Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients – 2002 update. Endocr Pract 2002;8:440-56.
Seftel A. Male hypogonadism. Part II: Etiology, pathophysiology, and diagnosis. Int J Impot Res 2006;18:223-8.
Seidell JC, Björntorp P, Sjöström L, Kvist H, Sannerstedt R. Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism 1990;39:897-901.
Haffner SM, Mykkänen L, Valdez RA, Katz MS. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab 1993;77:1610-5.
Phillips GB. Relationship between serum sex hormones and the glucose-insulin-lipid defect in men with obesity. Metabolism 1993;42:116-20.
Morris PD, Channer KS. Testosterone and cardiovascular disease in men. Asian J Androl 2012;14:428-35.
Zhao SP, Li XP. The association of low plasma testosterone level with coronary artery disease in Chinese men. Int J Cardiol 1998;63:161-4.
Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, et al.
Hypogonadism as a risk factor for cardiovascular mortality in men: A meta-analytic study. Eur J Endocrinol 2011;165:687-701.
Sharma R, Oni OA, Gupta K, Chen G, Sharma M, Dawn B, et al.
Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J 2015;36:2706-15.
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.
Jones TH. Testosterone deficiency: A risk factor for cardiovascular disease? Trends Endocrinol Metab 2010;21:496-503.
Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: The double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf) 2010;73:602-12.
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.
Joyner J, Hutley L, Cameron D. Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes. Horm Metab Res 2002;34:223-8.
[Figure 1], [Figure 2]
[Table 1], [Table 2]