Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men
Abstract
Objective: To study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes. Design: Population-based prospective cohort study. Methods: For the analyses, 1454 men who participated in the fourth Tromsø study (1994–1995) were used. Cases of diabetes were retrieved and validated until 31.12.05 following a detailed protocol. The prospective association between sex hormones and diabetes was examined using Cox proportional hazard regression analysis, allowing for multivariate adjustments. Results: There was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per s.d. increase (hazard ratio (HR) 0.71, confidence interval (CI) 0.54–0.92) and in the higher quartiles of total testosterone than in the lowest quartiles (HR 0.53, CI 0.33–0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher sex hormone-binding globulin (SHBG) levels, both linearly per s.d. increase (HR 0.55, CI 0.39–0.79) and when comparing the third (HR 0.38, CI 0.18–0.81) and the fourth quartile (HR 0.37, CI 0.17–0.82) to the lowest quartile. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol (E 2) was positively associated with incident diabetes after multivariate adjustments including waist circumference when comparing the second (HR 0.49, CI 0.26–0.93) and the third (HR 0.51, CI 0.27–0.96) quartile to the highest quartile. Conclusion: Men with higher E 2 levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared to be dependent on obesity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The same inverse association between SHBG and T2D has been confirmed in multiple other studies in both men and women.
“The same inverse association between SHBG and T2D has been confirmed in multiple other studies in both men and women [120–123].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [123]
Cites
A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum
Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6079 · Cited by 3,824 · see citing works
Kapoor, D., Goodwin, E., Channer, K. S., & Jones, T. H. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02166 · Cited by 791 · see citing works
Stellato, R. K., Feldman, H. A., Hamdy, O., Horton, E. S., & McKinlay, J. B. (2000) · Diabetes Care · doi:10.2337/diacare.23.4.490 · Cited by 618 · see citing works
Oh, J.-Y., Barrett-Connor, E., Wedick, N. M., & Wingard, D. L. (2002) · Diabetes Care · doi:10.2337/diacare.25.1.55 · Cited by 594 · see citing works
Boyanov, M. A., Boneva, Z., & Christov, V. G. (2003) · The Aging Male · doi:10.1080/tam.6.1.1.7 · Cited by 381 · see citing works
Wang, C. (2000) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.8.2839 · Cited by 359 · see citing works
Endogenous sex hormones in men aged 40-80 years
Muller, M., den Tonkelaar, I., Thijssen, J., Grobbee, D., & van der Schouw, Y. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1490583 · Cited by 346 · see citing works
Haffner, S. M., Shaten, J., Stem, M. P., Smith, G. D., Kuller, L., & MRFIT Research Group (1996) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a008832 · Cited by 320 · see citing works
Leifke, E., Gorenoi, V., Wichers, C., Von Zur Mühlen, A., Von Büren, E., & Brabant, G. (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01159.x · Cited by 262 · see citing works
Svartberg, J., Midtby, M., Bonaa, K., Sundsfjord, J., Joakimsen, R., & Jorde, R. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1490145 · Cited by 257 · see citing works
Self-citationHaffner, S. M., Valdez, R. A., Mykkänen, L., Stern, M. P., & Katz, M. S. (1994) · Metabolism · doi:10.1016/0026-0495(94)90202-x · Cited by 226 · see citing works
Yialamas, M. A., Dwyer, A. A., Hanley, E., Lee, H., Pitteloud, N., & Hayes, F. J. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0454 · Cited by 220 · see citing works
Simon, D., Charles, M.-A., Lahlou, N., Nahoul, K., Oppert, J.-M., Gouault-Heilmann, M., Lemort, N., Thibult, N., Joubert, E., Balkau, B., et al. (2001) · Diabetes Care · doi:10.2337/diacare.24.12.2149 · Cited by 136 · see citing works
Yeap, B. B., Chubb, S. A. P., Hyde, Z., Jamrozik, K., Hankey, G. J., Flicker, L., & Norman, P. E. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0348 · Cited by 128 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis
Araujo, A. B., Dixon, J. M., Suarez, E. A., Murad, M. H., Guey, L. T., & Wittert, G. A. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1137 · Cited by 671 · see citing works
“Vikan, 2009 (29) 1568 men from the 4th Tromso Study (Norway) 11.”
Metformin: Taking away the candy for cancer?
Jalving, M., Gietema, J. A., Lefrandt, J. D., de Jong, S., Reyners, A. K. L., Gans, R. O. B., & de Vries, E. G. E. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.06.012 · Cited by 377 · see citing works
Camacho, E. M., Huhtaniemi, I. T., O'Neill, T. W., Finn, J. D., Pye, S. R., Lee, D. M., Tajar, A., Bartfai, G., Boonen, S., Casanueva, F. F., et al. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0890 · Cited by 392 · see citing works
Wang, C., Jackson, G., Jones, T. H., Matsumoto, A. M., Nehra, A., Perelman, M. A., Swerdloff, R. S., Traish, A., Zitzmann, M., & Cunningham, G. (2011) · Diabetes Care · doi:10.2337/dc10-2339 · Cited by 366 · see citing works
Low Testosterone in Men with Type 2 Diabetes: Significance and Treatment
Grossmann, M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0118 · Cited by 350 · see citing works
“This positive association of estradiol with diabetes has been confirmed in more recent crosssectional (79) and prospective (20) studies and remained significant after multivariate adjustment including waist circumference (20, 79).”
BackgroundBrand, J. S., van der Tweel, I., Grobbee, D. E., Emmelot-Vonk, M. H., & van der Schouw, Y. T. (2011) · International Journal of Epidemiology · doi:10.1093/ije/dyq158 · Cited by 334 · see citing works
Sex hormone binding globulin and insulin resistance
Wallace, I. R., McKinley, M. C., Bell, P. M., & Hunter, S. J. (2013) · Clinical Endocrinology · doi:10.1111/cen.12086 · Cited by 268 · see citing works
Genetic determinants of serum testosterone concentrations in men
Ohlsson, C., Wallaschofski, H., Lunetta, K. L., Stolk, L., Perry, J. R. B., Koster, A., Petersen, A.-K., Eriksson, J., Lehtimäki, T., Huhtaniemi, I. T., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002313 · Cited by 224 · see citing works
“In prospective cohort studies, low serum testosterone concentrations are associated with cardiovascular morbidity, metabolic syndrome [2,3], dyslipidemia [4], hypertension [5], type 2 diabetes mellitus [6], stroke [7], atherosclerosis [8–10], osteoporosis, sarcopenia, and increased mortality risk [11–13].”
Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Literature
Oskui, P. M., French, W. J., Herring, M. J., Mayeda, G. S., Burstein, S., & Kloner, R. A. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000272 · Cited by 225 · see citing works
“The authors also noted that their analyses for total and free testosterone lost statistical significance after adjusting for waist circumference.(66) Still, other authors have investigated the risk of developing”
Sex hormone-binding globulin and type 2 diabetes mellitus
Le, T. N., Nestler, J. E., Strauss, J. F., & Wickham, E. P. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.09.005 · Cited by 191 · see citing works
Age at Menarche and Type 2 Diabetes Risk
Elks, C. E., Ong, K. K., Scott, R. A., van der Schouw, Y. T., Brand, J. S., Wark, P. A., Amiano, P., Balkau, B., Barricarte, A., Boeing, H., et al. (2013) · Diabetes Care · doi:10.2337/dc13-0446 · Cited by 186 · see citing works
“Metabolic disease may be linked to differential exposure to sex hormones; earlymenarche is associated with higher level of sex hormones (37) and decreased levels of sex hormone–binding globulin (38), which may have a role in the pathogenesis of type 2 diabetes (39).”
BackgroundThe effects of oestrogens and their receptors on cardiometabolic health
Morselli, E., Santos, R. D. S., Criollo, A., Nelson, M. D., Palmer, B. F., & Clegg, D. J. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.12 · Cited by 192 · see citing works
Clark, J. E. (2015) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/s40200-015-0154-1 · Cited by 158 · see citing works
“Given the current opinions [36,70-72] regarding the role of such”
BackgroundMetabolic syndrome: Does it differ between women and men?
Rochlani, Y., Pothineni, N. V., & Mehta, J. L. (2015) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-015-6593-6 · Cited by 152 · see citing works
“Higher estrogen levels have been associated with an increased risk of Type 2 diabetes inmen and postmenopausal women [59, 60].”
BackgroundTestosterone replacement therapy and cardiovascular risk
Gagliano‐Jucá, T., & Basaria, S. S. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0211-4 · Cited by 197 · see citing works
Grimnes, G., Emaus, N., Joakimsen, R. M., Figenschau, Y., Jenssen, T. G., Njølstad, I., Schirmer, H., & Jorde, R. (2010) · Diabetic Medicine · doi:10.1111/j.1464-5491.2010.03092.x · Cited by 121 · see citing works
Self-citationAging and sex hormones in males
Decaroli, M. C., & Rochira, V. (2016) · Virulence · doi:10.1080/21505594.2016.1259053 · Cited by 141 · see citing works
Thaler, M. A., Seifert-Klauss, V., & Luppa, P. B. (2015) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2015.06.005 · Cited by 125 · see citing works
Endocrinology of the aging male
de Araújo, A. B., & Wittert, G. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.11.004 · Cited by 180 · see citing works
Systematic review and meta-analysis of age at menarche and risk of type 2 diabetes
Janghorbani, M., Mansourian, M., & Hosseini, E. (2014) · Acta Diabetologica · doi:10.1007/s00592-014-0579-x · Cited by 105 · see citing works
“Increasing evidence suggests that endogenous sex hormones play important roles in the pathogenesis of T2DM [38, 39].”
BackgroundNarinx, N., David, K., Walravens, J., Vermeersch, P., Claessens, F., Fiers, T., Lapauw, B., Antonio, L., & Vanderschueren, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04562-1 · Cited by 96 · see citing works
Wang, Q., Kangas, A. J., Soininen, P., Tiainen, M., Tynkkynen, T., Puukka, K. S., Ruokonen, A., Viikari, J. S. A., Kähönen, M. A. P., Lehtimäki, T. J., et al. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv093 · Cited by 100 · see citing works
Aging and the Male Reproductive System
Kaufman, J., Lapauw, B., Mahmoud, A., T'Sjoen, G. G., & Huhtaniemi, I. T. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00178 · Cited by 145 · see citing works
Associations between visceral adipose tissue, inflammation and sex steroid concentrations in men
Gautier, A., Bonnet, F., Dubois, S., Massart, C., Grosheny, C., Bachelot, A., Aubé, C., Balkau, B., & Ducluzeau, P. (2013) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2012.04401.x · Cited by 91 · see citing works
Testosterone level and risk of type 2 diabetes in men: a systematic review and meta-analysis
Yao, Q., Wang, B., An, X., Zhang, J., & Ding, L. (2017) · Endocrine Connections · doi:10.1530/ec-17-0253 · Cited by 100 · see citing works
Endogenous Sex Hormones, Metabolic Syndrome, and Diabetes in Men and Women
Kim, C., & Halter, J. B. (2014) · Current Cardiology Reports · doi:10.1007/s11886-014-0467-6 · Cited by 91 · see citing works
Haring, R., Teng, Z., Xanthakis, V., Coviello, A. D., SULLIVAN, L. M., Bhasin, S., Murabito, J. M., Wallaschofski, H., & Vasan, R. S. (2012) · Clinical Endocrinology · doi:10.1111/cen.12013 · Cited by 84 · see citing works
Androgens, diabetes and prostate cancer
Grossmann, M., & Wittert, G. (2012) · Endocrine Related Cancer · doi:10.1530/erc-12-0067 · Cited by 77 · see citing works
“In addition, circulating oestradiol is positively associated with diabetes even after adjustment for fat mass and distribution (Vikan et al. 2010).”
BackgroundSchmitz, D., Ek, W., Berggren, E., Hoglund, J., Karlsson, T., & Johansson, Å. (2021) · medRxiv · doi:10.1101/2021.07.01.21259826 · Cited by 77
Mahmoodzadeh, S., & Dworatzek, E. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00310 · Cited by 86 · see citing works
Bobjer, J., Bogefors, K., Isaksson, S., Leijonhufvud, I., Åkesson, K., Giwercman, Y., & Giwercman, A. (2016) · Clinical Endocrinology · doi:10.1111/cen.13038 · Cited by 68 · see citing works
Schipf, S., Haring, R., Friedrich, N., Nauck, M. A., Lau, K., Alte, D., Stang, A., Völzke, H., & Wallaschofski, H. (2010) · The Aging Male · doi:10.3109/13685538.2010.524955 · Cited by 52 · see citing works
“Further potential limitations may also arise from the lack of free androgen index, and estradiol; especially because additional roles of these hormones in the development of T2DM have also been suggested [7,16].”
BackgroundResultCalderón, B., Sanz-Pastor, A. G., Calañas, A., Peromingo, R., Galindo, J., García‐Moreno, F., Velasco, G. R., Martín‐Hidalgo, A., Vázquez, C., Escobar-Morreale, H. F., et al. (2014) · Obesity Surgery · doi:10.1007/s11695-014-1233-y · Cited by 70 · see citing works
“Moreover, low testosterone concentrations have been associated with insulin resistance in non-diabetic men [22], and weight loss induced by dieting has been shown to increase testosterone levels in parallel to the improvement in insulin sensitivity [23].”
BackgroundFenske, B., Kische, H., Groß, S., Wallaschofski, H., Völzke, H., Dörr, M., Nauck, M. A., Keevil, B. G., Brabant, G. E., & Haring, R. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2546 · Cited by 59 · see citing works
“Consequently, low SHBG was described as independent predictor of incident T2DM (10), reflecting a prediabetic state along with obesity, higher glucose and insulin levels (11, 14, 15).”
Adverse health effects of testosterone deficiency (TD) in men
Traish, A. M. (2014) · Steroids · doi:10.1016/j.steroids.2014.05.010 · Cited by 51 · see citing works
RAS and sex differences in diabetic nephropathy
Clotet, S., Riera, M., Pascual, J., & Soler, M. J. (2016) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00292.2015 · Cited by 49 · see citing works
Morgentaler, A., Traish, A. M., Hackett, G. I., Jones, T. H., & Ramasamy, R. (2019) · Sexual Medicine Reviews · doi:10.1016/j.sxmr.2019.06.003 · Cited by 65 · see citing works
Botella-Carretero, J. I., Balsa, J., Gómez-Martín, J. M., Peromingo, R., Huerta, L., Carrasco, M., Arrieta, F., Zamarrón, I., Martín-Hidalgo, A., & Vázquez, C. (2013) · Journal of Endocrinological Investigation · doi:10.3275/8469 · Cited by 53 · see citing works
Haring, R., Teumer, A., Völker, U., Dörr, M., Nauck, M., Biffar, R., Völzke, H., Baumeister, S., & Wallaschofski, H. (2012) · Andrology · doi:10.1111/j.2047-2927.2012.00002.x · Cited by 54 · see citing works
“…obesity (Blouin et al., 2008), dyslipidaemia (Haring et al., 2011b), hypertension (Torkler et al., 2011), subclinical inflammation (Haring et al., 2011a), metabolic syndrome (Haring et al., 2009b; Kupelian et al., 2006), type 2 diabetes (Vikan et al., 2010) and atherosclerosis (Dörr et al., 2009).”
BackgroundInfluentialLow Testosterone: A Risk Marker Rather Than a Risk Factor for Type 2 Diabetes
Holmboe, S. A., Jensen, T. K., Linneberg, A. R., Scheike, T., Thuesen, B. H., Skakkebæk, N. E., Juul, A., & Andersson, A. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1778 · Cited by 57 · see citing works
“Likewise, our observed association between low SHBG and a significantly increased risk of T2D confirms previous studies (22, 25, 26).”
ResultGyawali, P., Martin, S., Heilbronn, L. K., Vincent, A. D., Taylor, A. W., Adams, R., O’Loughlin, P. D., & Wittert, G. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1163-6 · Cited by 56 · see citing works
“In contrast, earlier prospective [11, 12, 37] and cross-sectional [24, 44] studies showed a positive association between E2 and incident T2D in men, though the DPP study population was already at risk of T2D [12] while serum E2 was not measured by LC–MS/MS in both the Tromsø study [11] and the Environment, Inflammatio…”
InfluentialTraish, A. M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-70178-3_22 · Cited by 49 · see citing works
Testosterone, SHBG and risk of type 2 diabetes in the second evaluation of the Pizarra cohort study
Soriguer, F., Rubio‐Martín, E., Fernández, D., Valdés, S., García‐Escobar, E., Martín‐Núñez, G. M., Esteva, I., Almaraz, M. C., & Rojo‐Martínez, G. (2011) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2011.02559.x · Cited by 43 · see citing works
Testosterone levels and type 2 diabetes in men: current knowledge and clinical implications
Kumar, M., Dutta, D., Anne, B., Shivaprasad, Sinha, A., Ray, S., & Chowdhury, S. (2014) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s50777 · Cited by 40 · see citing works
Do low testosterone levels contribute to ill-health during male ageing?
Yeap, B. B., de Araújo, A. B., & Wittert, G. (2012) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2012.725461 · Cited by 53 · see citing works
Effects of lifelong testosterone exposure on health and disease using Mendelian randomization
Mohammadi‐Shemirani, P., Chong, M., Pigeyre, M., Morton, R. W., Gerstein, H. C., & Paré, G. (2020) · eLife · doi:10.7554/elife.58914 · Cited by 68 · see citing works
“Given studies have identified associations between SHBG and risk of T2D independent of testosterone and a direct role of SHBG in mediating signalling on target cells, insufficient controls for SHBG may lead to residual pleiotropic effects (Lakshman et al., 2010; Rosner et al., 2010; Vikan et al., 2010).”
BackgroundHu, J.-B., Zhang, A., Yang, S.-M., Wang, Y., Goswami, R., Zhou, H., Zhang, Y., Wang, Z.-H., Li, R., Cheng, Q.-F., et al. (2016) · Journal of Diabetes · doi:10.1111/1753-0407.12322 · Cited by 42 · see citing works
“For example, a prospective investigation of Norwegian men showed that increased circulating SHBG concentrations reduced the risk of developing T2D, whereas higher estradiol concentrations were associated with an increased risk of T2D.(7) Another cross-sectional multi-ethnic study indicated that SHBG was inversely asso…”
BackgroundModulation of SHBG binding to testosterone and estradiol by sex and morbid obesity
Grasa, M., Gulfo, J., Camps, N., Alcalá, R., Monserrat, L., Moreno‐Navarrete, J. M., Ortega, F. J., Esteve, M., Remesar, X., Fernández–Löpez, J., et al. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0834 · Cited by 53 · see citing works
Joyce, K. E., Biggs, M. L., Djoussé, L., Ix, J. H., Kizer, J. R., Siscovick, D. S., Shores, M. M., Matsumoto, A. M., & Mukamal, K. J. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2623 · Cited by 40 · see citing works
“Based on previous studies, we hypothesized that higher levels of these androgens would be associated with less insulin resistance and lower risk of diabetes (13) (14) (15) (16).”
Gencer, B., Bonomi, M., Adorni, M. P., Sirtori, C. R., Mach, F., & Ruscica, M. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09628-2 · Cited by 58 · see citing works
“…[93] 794 11.8 73.6 HR 1.38 (1.02-1.85) Haring (2010) [156] 1954 7.2 58.7 RR 4.93 (1.21-20.26) Menke (2010) [157] 1114 8 40 RR 1.24 (0.85-1.78) Vikan (2010) [158] 1568 11.2 59.6 RR 1.09 (0.74-1.63) Haring (2012) [156] 2039 5.5 20-79 RR 2.05 (1.61-2.60)b Pye (2014) [159] 2599 4.3 40-79 RR 2.30…”
InfluentialGheorghe, G. S., Hodorogea, A. S., Ciobanu, A., Nanea, I. T., & Gheorghe, A. C. D. (2021) · Current Oncology · doi:10.3390/curroncol28050289 · Cited by 44 · see citing works
Canoy, D., Barber, T. M., Pouta, A., Hartikainen, A. L., McCarthy, M. I., Franks, S., Järvelin, M., Tapanainen, J. S., Ruokonen, A., Huhtaniemi, I. T., et al. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-1046 · Cited by 40 · see citing works
Role of sex hormones in diabetic nephropathy
Liu, J., Liu, Z., Sun, W., Luo, L., An, X., Yu, D., & Wang, W. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1135530 · Cited by 34 · see citing works
Type 2 Diabetes and Testosterone Therapy
Hackett, G. I. (2018) · The World Journal of Men s Health · doi:10.5534/wjmh.180027 · Cited by 39 · see citing works
“Several longitudinal studies have shown that low levels of TT and FT independently predict the later development of T2DM or metabolic syndrome [12-18].”
BackgroundSex steroids and glucose metabolism
Allan, C. A. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.122589 · Cited by 36 · see citing works
Haring, R., Travison, T. G., Bhasin, S., Vasan, R. S., Wallaschofski, H., Davda, M. N., Coviello, A. D., & Murabito, J. M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1068 · Cited by 37 · see citing works
“spective investigations have shown that low total testosterone (TT) concentrations in men were associated with a less favorable cardiovascular risk profile including obesity (6), incident metabolic syndrome (7), diabetes mellitus (8), dyslipidemia (9), hypertension (10), and mortality (11).”
BackgroundEpigenetic modification in diabetic kidney disease
Liu, Z., Liu, J., Wang, W., An, X., Luo, L., Yu, D., & Sun, W. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1133970 · Cited by 36 · see citing works
Jasuja, G. K., Travison, T. G., Davda, M. N., Rose, A. J., Zhang, A., Kushnir, M. M., Rockwood, A. L., Meikle, W. A., Coviello, A. D., D’Agostino, R. B., et al. (2013) · Diabetes Care · doi:10.2337/dc12-2477 · Cited by 32 · see citing works
“Cardiovascular disease 258 (18) 123 (12)”
ResultSouteiro, P., Belo, S., Oliveira, S. C., Neves, J. S., Magalhães, D. M. D. S., Pedro, J. M. P., Bettencourt‐Silva, R., Costa, M. M., Varela, A. T. I. F., Queirós, J., et al. (2018) · Andrologia · doi:10.1111/and.13035 · Cited by 30 · see citing works
Candeias, E., Duarte, A. I., Sebastião, I., Fernandes, M. A. S., Plácido, A. I., Carvalho, C., Correia, S. C., Santos, R. X., Seiça, R. M. F., Santos, M. S., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0155-1 · Cited by 34 · see citing works
Svartberg, J., Schirmer, H., Wilsgaard, T., Mathiesen, E. B., Njølstad, I., Løchen, M.-L., & Jorde, R. (2014) · Andrology · doi:10.1111/j.2047-2927.2013.00174.x · Cited by 32 · see citing works
“…levels tends to predict the development of metabolic syndrome and type 2 diabetes mellitus (T2DM) (Oh et al., 2002; Laaksonen et al., 2004; Vikan et al., 2010) and have been associated with both all-cause mortality and cardiovascular disease (CVD) mortality (Vikan et al., 2009a; Araujo…”
BackgroundSelf-citationSalvio, G., Ciarloni, A., Ambo, N., Bordoni, M., Perrone, M., Rossi, S., & Balercia, G. (2025) · Andrology · doi:10.1111/andr.70022 · Cited by 33 · see citing works
Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men
Basualto-Alarcón, C., Llanos, P., García‐Rivas, G., Troncoso, M. F., Lagos, D., Barrientos, G. C., & Estrada, M. (2021) · International Journal of Endocrinology · doi:10.1155/2021/5527973 · Cited by 34 · see citing works
“Although reduced levels of circulating SHBG decrease total testosterone levels, the effect of low testosterone on SHBG expression is not fully understood [105].”
BackgroundSalminen, M. J., Vahlberg, T. J., Räihä, I. J., NISKANEN, L. K., Kivelä, S., & Irjala, K. M. A. (2014) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.12312 · Cited by 29 · see citing works
Metabolic Effects of Testosterone Therapy in Men with Type 2 Diabetes and Metabolic Syndrome
Hackett, G. I. (2019) · Sexual Medicine Reviews · doi:10.1016/j.sxmr.2018.12.004 · Cited by 39 · see citing works
Thirumalai, A., Cooper, L. A., Rubinow, K. B., Amory, J. K., Lin, D. W., Wright, J. L., Marck, B. T., Matsumoto, A. M., & Page, S. T. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1483 · Cited by 27 · see citing works
Androgens for postmenopausal women’s health?
Montalcini, T., Migliaccio, V., Ferro, Y., Gazzaruso, C., & Pujia, A. (2012) · Endocrine · doi:10.1007/s12020-012-9692-1 · Cited by 31 · see citing works
“A study, however, found that the risk ofT2DM associated with testosterone, as well as, to estradiol and SHBG levels, was not independent of the body mass index or the waist circumference [65].”
The Role of Estrogens and Vitamin D in Cardiomyocyte Protection: A Female Perspective
Crescioli, C. (2021) · Biomolecules · doi:10.3390/biom11121815 · Cited by 29 · see citing works
Bonnet, F., Velayoudom Cephise, F., Gautier, A., Dubois, S., Massart, C., Camara, A., Larifla, L., Balkau, B., & Ducluzeau, P. (2013) · Clinical Endocrinology · doi:10.1111/cen.12089 · Cited by 28 · see citing works
Clinical correlates of sex hormones in women: The study of health in Pomerania
Kische, H., Groß, S., Wallaschofski, H., Völzke, H., Dörr, M., Nauck, M. A., & Haring, R. (2016) · Metabolism · doi:10.1016/j.metabol.2016.05.011 · Cited by 30 · see citing works
Möhlig, M., Arafat, A. M., Osterhoff, M. A., Isken, F., Weickert, M. O., Spranger, J., Pfeiffer, A. F. H., & Schöfl, C. (2011) · European Journal of Endocrinology · doi:10.1530/eje-10-1022 · Cited by 29 · see citing works
Manigrasso, M. B., Sawyer, R. T., Marbury, D. C., Flynn, E. R., & Maric, C. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00718.2010 · Cited by 28 · see citing works
Testosterone Levels and Quality of Life in Diverse Male Patients With Cancers Unrelated to Androgens
Fleishman, S. B., Khan, H., Homel, P., Suhail, M. F., Strebel-Amrhein, R., Mohammad, F., Mahajan, D., Rosenwald, V., Guarino, M. J., Mirzoyev, T., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.30.3818 · Cited by 33 · see citing works
Association of glyphosate exposure with multiple adverse outcomes and potential mediators.
Li, W., Lei, D., Huang, G., Tang, N., Lu, P., Jiang, L., Lv, J., Lin, Y., Xu, F., & Qin, Y.-J. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2023.140477 · Cited by 23 · see citing works
Haring, R., Xanthakis, V., Coviello, A., Sullivan, L., Bhasin, S., Wallaschofski, H., Murabito, J. M., & Vasan, R. S. (2012) · International Journal of Andrology · doi:10.1111/j.1365-2605.2012.01285.x · Cited by 22 · see citing works
“, 2009) or type 2 diabetes (Vikan et al., 2010; Schipf et al., 2011), whereas these conditions are also associated with decreased TT concentrations (Laaksonen et al.”
InfluentialMattack, N. (2015) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2015/11049.5381 · Cited by 21 · see citing works
Clark, J. E. (2012) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/2251-6581-11-19 · Cited by 19 · see citing works
“Testosterone/Adrenal Androgens [72-82] Testes Adrenal Cortex Skeletal Muscle (hypertrophy, add contractile tissue)”
BackgroundGenome-wide association studies on serum sex steroid levels
Vandenput, L., & Ohlsson, C. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.03.009 · Cited by 18 · see citing works
“…common disorders such as the metabolic syndrome (Haring et al., 2009; Kupelian et al., 2006), hypertension (Torkler et al., 2011), type 2 diabetes (Vikan et al., 2010), osteoporosis (Fink et al., 2006; Meier et al., 2008), sarcopenia (Cawthon et al., 2009), cardiovascular disease (Ohlsson et al.,…”
BackgroundRezvani, M., Saadatjou, S. A., Sorouri, S., & Fard, M. H. (2012) · Journal of research in health sciences · doi:10.34172/jrhs12730 · Cited by 19
Relation between androgens and cardiovascular risk factors in a young population
Gannagé‐Yared, M., Chédid, R., & Abs, L. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.03987.x · Cited by 19 · see citing works
Veldhuis, J., Bondar, O., Dyer, R. B., Trushin, S., Klee, E., Singh, R. J., & Klee, G. (2014) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2013-2642 · Cited by 19 · see citing works
Li, J., Lai, H. C., Chen, S., Zhu, H., & Lai, S. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.10.022 · Cited by 20 · see citing works
Huffman, J. N., Hoffmann, C., & Taylor, G. T. (2017) · World Journal of Diabetes · doi:10.4239/wjd.v8.i2.45 · Cited by 16 · see citing works
Onisiforou, A., & Zanos, P. (2024) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2024.10.011 · Cited by 15 · see citing works
“In contrast to women, increased estradiol levels in men are associated with increased risk of developing DM2 [131].”
BackgroundMarked Increase in Incident Gynecomastia: A 20-Year National Registry Study, 1998 to 2017
Koch, T., Bräuner, E. V., Busch, A. S., Hickey, M., & Juul, A. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa440 · Cited by 25 · see citing works
Gawałek, M., & Sliwowska, J. H. (2015) · Reproductive Biology · doi:10.1016/j.repbio.2015.04.001 · Cited by 15 · see citing works
Zhu, H., Wang, N., Han, B., Qin, L., Chen, Y., Zhu, C., Chen, Y., Xia, F., Cang, Z., Lu, M., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162004 · Cited by 13 · see citing works
“Previous study also showed that it was not serum TT but SHBG was the most powerful predictor of T2DM in men, which predicted T2DM independently of TT [27, 31].”
BackgroundResultManigrasso, M. B., Sawyer, R. T., Hutchens, Z. M., Flynn, E. R., & Maric‐Bilkan, C. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00569.2011 · Cited by 15 · see citing works
“Men with type 1 and type 2 diabetes, as well as experimental models of diabetes, exhibit decreased circulating testosterone (9, 12–13, 18, 39, 42, 44) and increased circulating estradiol levels (42, 44).”
BackgroundSex Hormone-Binding Globulin and the Metabolic Syndrome
Hammond, G. L. (2017) · Springer eBooks · doi:10.1007/978-3-319-53298-1_15 · Cited by 13 · see citing works
Figueiredo, M. G., Gagliano‐Jucá, T., & Basaria, S. S. (2023) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2022.12.002 · Cited by 12 · see citing works
Hypergonadotropic hypogonadism in Nigerian men with type 2 diabetes mellitus
Musa, E., El-Bashir, J. M., Bello-Sani, F., & Bakari, A. G. (2021) · Clinical Diabetology · doi:10.5603/dk.a2021.0002 · Cited by 9 · see citing works
Perspectives for metabolomics in testosterone replacement therapy
Haring, R. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0119 · Cited by 10 · see citing works
Diabetes surpasses obesity as a risk factor for low serum testosterone level
Khalil, S. H. A., Dandona, P., Osman, N. A., Assaad, R. S., Zaitoon, B. T. A., Almas, A. A., & Amin, N. G. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01373-1 · Cited by 10 · see citing works
“There was a significant decrease in patients with diabetes compared to subjects without diabetes [32, 33].”
BackgroundWan, B., Ma, N., Zhou, Z., & Lv, C. (2023) · PeerJ · doi:10.7717/peerj.15760 · Cited by 10 · see citing works
“, 2022), diabetes (Saikia, Jabbar & Das, 2021; Vikan et al., 2010), and cancer (Ruth et al.”
BackgroundZan, G., Li, L.-M., Cheng, H., Huang, L.-L., Huang, S., Luo, X., Xiao, L., Liu, C.-Q., Zhang, H.-Y., Mo, Z.-N., et al. (2021) · Environmental Pollution · doi:10.1016/j.envpol.2021.116791 · Cited by 8 · see citing works
Thirumalai, A., Rubinow, K. B., Cooper, L. A., Amory, J., Marck, B., Matsumoto, A., & Page, S. (2017) · Clinical Endocrinology · doi:10.1111/cen.13342 · Cited by 8 · see citing works
Sex Differences in Exercise Performance and Exercise Training Among Persons with Type 2 Diabetes
Quartuccio, M., Yalamanchi, S., Golden, S. H., Regensteiner, J. G., & Kalyani, R. R. (2017) · Contemporary diabetes · doi:10.1007/978-3-319-61013-9_7 · Cited by 5 · see citing works
Mores, S. M., Franch-Nadal, J., Mauricio, D., & Vlacho, B. (2026) · Frontiers in Clinical Diabetes and Healthcare · doi:10.3389/fcdhc.2026.1781581 · Cited by 7 · see citing works
The Role of Steroidomics in the Diagnosis of Alzheimer’s Disease and Type 2 Diabetes Mellitus
Vaňková, M., Velíková, M., Vejražková, D., Včelák, J., Lukášová, P., Rusina, R., Vankova, H., Jarolímová, E., Kancheva, R., Bulant, J., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108575 · Cited by 7 · see citing works
“Literature data on the relationship of estradiol and estrone levels to T2DM are discrepant [58,88,92,93] (also see the review in [43]).”
BackgroundUpdate on Testosterone Replacement Therapy in Hypogonadal Men
Leung, K. M. Y. B., Alrabeeah, K. A., & Carrier, S. (2015) · Current Urology Reports · doi:10.1007/s11934-015-0523-9 · Cited by 6 · see citing works
- Authors
- Vikan, T., Schirmer, H., Njølstad, I., & Svartberg, J.
- Affiliations
- University Hospital of North Norway (NO)
- UiT The Arctic University of Norway (NO)
- Corresponding author
- Vikan, Torkel
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04
- Volume
- 162
- Issue
- 4
- Pages
- 747-754
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2111837311
- Cited by
- 151
- References
- 43
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 11 · 2020: 8 · 2019: 6 · 2018: 4 · 2017: 13 · 2016: 14 · 2015: 11 · 2014: 11 · 2013: 9 · 2012: 18
- FWCI
- 11.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- type 2 diabetes, testosterone, sex hormone-binding globulin, estradiol, sex hormones, men, diabetes risk, waist circumference, obesity, Tromsø Study
- MeSH terms
- Blood Pressure, Cholesterol, Diabetes Mellitus, Type 2, Estradiol, Humans, Male, Norway, Prospective Studies, Surveys and Questionnaires, Regression Analysis, Retrospective Studies, Sex Hormone-Binding Globulin, Testosterone, Triglycerides, Cohort Studies, Body Mass Index, Waist Circumference
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
