Prevalence of Hypogonadotropic Hypogonadism in Type 2 Diabetes Male Patients

Mozhgan Afkhamizadeh¹, Seyed Bahman Ghaderian^2*, Reza Rajabian¹, Armaghan Moravej Aleali¹

¹Endocrine Research Center, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
²Health Research Institute, Diabetes Research Center, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran.

DOI: 10.4236/ojemd.2015.53004                

Abstract

Background: Erectile dysfunction is common in patients with diabetes mellitus. In addition, reduced testosterone itself is considered as a risk factor for diabetes; therefore hypogonadism was studied in diabetes. Objective: This study was done to determine the prevalence of hypo- and hypergonadotropic hypogonadism in the type 2 diabetes male patients in Mashhad in north-east of Iran. Methods: This study was done on type 2 diabetic men aged 40 - 60 years in the endocrine clinic, Endocrinology Research Center, Mashhad University of Medical Sciences, Iran. Fasting blood samples were collected at 8 am for measurement of fasting blood sugar (FBS), HbA1C, total serum testosterone, FSH, Sex Hormone Binding Globulin (SHBG), LH, prolactin, thyroxin-stimulating hormone (TSH), and immediately was sent to laboratory. Results: Out of total 96 type 2 diabetic males (mean age of 51.4 ± 11.26 years, range of 40 - 60 years), 11 (12.94%) patients were excluded because of inadequate samples, insufficient information and fulfillment of the exclusion criteria of the study. Hypogonadism based on Testosterone, Calculated free testosterone (CFT), and boiavailable testosterone (BT) were observed in 10 (11.8%), 31 (36.6%), and 30 (35.3%) of the patients, respectively. Libido was decreased in 55 (64.7%) of the patients. Based on the obtained SHBG values there were 7 (8.2%), 52 (61.2%), and 26 (30.6%) cases of low, normal and high values, respectively. According to TSH observed values there were 6 (7.1%) patients and 1 case of sub-clinical hypothyroidism and hyperthyroidism, respectively, and the rest 78 (91.8%) cases were euthyroid. Prolactin level was normal in all cases. Conclusion: Hypogonadotropic hypogonadism is common in type 2 diabetic men, and whether its treatment is useful for erectile dysfunction or not, needed additional investigation.

Keywords

Type 2 Diabetes, Testosterone, Hypogonadism, Hypogonadotropic

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Martin, J.B., Kasper, D.L., et al. (2011) Harrisonns Principles of Internal Medicine. 18th Edition, McGrow Hill, New York.
[2]	Barrett-Conner, E. (1992) Lower Endogenous Androgen Levels and Dyslipidemia in Men with Non-Insulin Dependent Diabetes Mellitus. Annals of Internal Medicine, 117, 807-811. http://dx.doi.org/10.7326/0003-4819-117-10-807
[3]	Barrett-Conner, E., Khow, Kt and Yen, S.S. (1990) Endogenous Sex Hormone Levels in Older Adult Men with Diabetes Mellitus. American Journal of Epidemiology, 132, 895-901.
[4]	Goodman-Gruen, D. and Barrett-Conner, E. (2000) Sex Differences in the Association of Endogenous Sex Hormone Levels and Glucose Tolerance Status in Older Men and Women. Diabetes Care, 23, 912-918. http://dx.doi.org/10.2337/diacare.23.7.912
[5]	Chang, T.C., Tung, C.C. and Hsiao, Y.L. (1994) Hormonal Changes in Elderly Men with Non-Insulin Dependent Diabetes Mellitus and the Hormonal Relationships to Abdominal Obesity. Gerontology, 40, 260-267. http://dx.doi.org/10.1159/000213594
[6]	Ando, S., Rubens, R. and Rottiers, R. (1984) Androgen Plasma Levels in Male Diabetics. Journal of Endocrinological Investigation, 7, 21-24. http://dx.doi.org/10.1007/BF03348370
[7]	Defay, R., Papoz, L., Barney, S., Bonnot-Lours, S., Caces, E. and Simon, D. (1998) Hormonal Status and NIDDM in the European and Melanesian Populations of New Caledonia: A Case-Control Study. The Caledonia Diabetes Mellitus (CALDIA) Study Group. International Journal of Obesity and Related Metabolic Disorders, 22, 927-934. http://dx.doi.org/10.1038/sj.ijo.0800697
[8]	Anderson, B., Marin, P., Lissner, L., Vermeulen, A. and Bjorntorp, P. (1994) Tesosterone Concentration in Women and Men with NIDDM. Diabetes Care, 17, 405-411. http://dx.doi.org/10.2337/diacare.17.5.405
[9]	Betancourt-Albrecht, M. and Cunningham, Gr. (2003) Hypogonadism and Diabetes. International Journal of Impotence Research, 15, 514-520.
[10]	Malkin, C.J., Pugh, P.G., Jones, R.D., Jones, T.H. and Channer, K.S. (2003) Testosterone as a Protective Factor against Atherosclerosis: Immunomodulation and Influence upon Plaque Development and Stability. Journal of Endocrinology, 178, 373-380. http://dx.doi.org/10.1677/joe.0.1780373
[11]	Rauscher, M. (2007) Low Testosterone a Possible Risk Factor for Diabetes in Men. Diabetes Care, 30, 234-238.
[12]	Dhindsa, S., Prabhkar, S., Sethi, M., Bandyopdhyay, A., Chaudhuri, A. and Dahdona, P. (2004) Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes. Journal of Clinical Endocrinology & Metabolism, 89, 5462-5468. http://dx.doi.org/10.1210/jc.2004-0804
[13]	Vermeulen, A. and Koufman, J.M. (2002) Diagnosis of Hypogonadism in the Aging Male. Aging Male, 5, 170-176. http://dx.doi.org/10.1080/tam.5.3.170.176
[14]	Harman, S.M., Metter, E.J., Tobin, J.D., Pearson, J. and Blackman, M.R. (2001) Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men: Baltimore Longitudinal Study of Aging. Journal of Clinical Endocrinology & Metabolism, 86, 724-731. http://dx.doi.org/10.1210/jcem.86.2.7219
[15]	Gray, A., Feldman, H.A., McKinlay, J.B. and Longcope, C. (1991) Age, Disease, and Changing Sex Hormone Levels in Middle-Aged Men: Results of the Massachusetts Male Aging Study. Journal of Clinical Endocrinology & Metabolism, 73, 1016-1025. http://dx.doi.org/10.1210/jcem-73-5-1016
[16]	Tsai, E.C., Matsmoto, A.M., Fujimoto, W.Y. and Boyko, E.J. (2004) Association of Bioavailable, Free and Total Testosterone with Insulin Resistance: Influence of Sex Hormone-Binding Globulin and Body Fat. Diabetes Care, 27, 861-868. http://dx.doi.org/10.2337/diacare.27.4.861
[17]	Muller, M., Den tonkelaar, I., Thijssen, J., Grobbeee, D.E. and Van der Schouw, Y.T. (2003) Endogenous Sex Hormones in Men Aged 40 - 80 Years. European Journal of Endocrinology, 149, 583-589. http://dx.doi.org/10.1530/eje.0.1490583
[18]	Bhasin, S. and Bremner, W.J. (1997) Emerging Issues in Androgen Replacement Therapy. Journal of Clinical Endocrinology & Metabolism, 82, 3-8.
[19]	Feldman, H.A., Longcope, C., Derby, C.A., Johannes, C.B., Araujo, A.B., Coviello, A.D., et al. (2002) Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results of Massachusetts Male Aging Study. Journal of Clinical Endocrinology & Metabolism, 87, 589-598. http://dx.doi.org/10.1210/jcem.87.2.8201
[20]	Morley, J.E., Kaiser, F.E., Perry, H.M., Patrick, P., Morley, P.M., Stauber, P.M., et al. (1997) Longitudinal Changes in Testosterone, Lueinizing Hormone, and Follicle Stimulating Hormone in Healthy Older Men. Metabolism, 46, 410-413. http://dx.doi.org/10.1016/S0026-0495(97)90057-3
[21]	Mulligan, T., Iranmanesh, A., Kerzner, R., Demers, L.W. and Veldhuis, J.D. (1999) Two Week Pulsatile Gonadotropin Releasing Hormone Infusion Unmasks Dual (Hypothalamic and Leydig Cell) Defects in the Healthy Aging Male Gonadotropic Axis. European Journal of Endocrinology, 141, 257-266. http://dx.doi.org/10.1530/eje.0.1410257
[22]	Bruning, J.C., Gautman, D., Burks, D.J., Gillette, J., Schubert, M., Orban, P.C., et al. (2000) Role of Brain Insulin Receptor in Control of Body Weight and Reproduction. Science, 289, 2122-2125. http://dx.doi.org/10.1126/science.289.5487.2122
[23]	Haffner, S.M., Karhapaa, P., Mykkanen, L. and Laak, M. (1994) Insulin Resistance, Body Fat Distribution, and Sex Hormone in Men. Diabetes, 43, 212-219. http://dx.doi.org/10.2337/diab.43.2.212
[24]	Zumoff, B., Strain, G.W., Miller, L.K., Rosner, W., Senie, R., Seres, D.S., et al. (1990) Plasma Free and Non-Sex-Hormone-Binding-Globulin Bound Testosterone Are Decreased in Obese Men in Proportion to Their Degree of Obesity. Journal of Clinical Endocrinology & Metabolism, 71, 929-931. http://dx.doi.org/10.1210/jcem-71-4-929
[25]	Dandona, P., Weinstock, R., Thusu, K., Abel-Rahman, E., Aljada, A. and Wadden, T. (1998) Tumor Necrosis Factor-Alfa in Sera of Obese Patients: Fall with Weight Loss. Journal of Clinical Endocrinology & Metabolism, 83, 2907-2910.
[26]	Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L. and Ferrante Jr., A.W. (2003) Obesity Is Associated with Macrophage Accumulation in Adipose Tissue. Journal of Clinical Investigation, 112, 1796-1808. http://dx.doi.org/10.1172/JCI200319246
[27]	Watanobe, H. and Hayakawa, Y. (2003) Hypothalamic Inerlukin-1β and Tumor Necrosis Factor-α, but Not Interlukin-6 Mediate the Endotoxin-Induced Suppression of the Reproductive Axis in Rats. Endocrinology, 144, 4868-4875. http://dx.doi.org/10.1210/en.2003-0644
[28]	Russell, S.H., Small, C.J., Stanley, S.A., Franks, S., Ghateri, M.A. and Bloom, S.R. (2001) The in Vitro Role of Tumor Necrosis Factor-α and Interlukin-6 in the Hypothalamic-Pituitary-Gonadal Axis. Journal of Neuroendocrinology, 13, 296-301. http://dx.doi.org/10.1046/j.1365-2826.2001.00632.x
[29]	Bhasin, S. (2000) The Dose-Dependent Effects of Testosterone on Sexual Function and on Muscle Mass Function. Mayo Clinic Proceedings, 75, S70-S75, Discussion S75-S76.
[30]	Bhasin, S., Woodhouse, L., Casaburi, R., Singh, A.B., Bhasin, D., Berman, N., et al. (2001) Testosterone Dose-Response Relationship in Healthy Young Men. American Journal of Physiology. Endocrinology and Metabolism, 281, E1172-E1181.
[31]	Snyder, P.J., Peachey, H., Berlin, J.A., Hannoush, P., Haddad, G., Dlewati, A., et al. (2000) Effect of Testosterone Replacement in Hypogonadal Men. Journal of Clinical Endocrinology & Metabolism, 85, 2670-2677.