The Association of Endogenous Sex Hormones, Adiposity, and Insulin Resistance with Incident Diabetes in Postmenopausal Women
Open accessAbstract
CONTEXT: In postmenopausal women, endogenous bioavailable testosterone (T) and estradiol (E2) have been positively associated, and SHBG has been negatively associated, with incident type 2 diabetes (T2DM). Previous studies have not explored possible factors explaining these relationships. OBJECTIVE: Our objective was to examine the association of endogenous sex hormones with incident T2DM in postmenopausal women and possible explanatory factors. DESIGN, SETTING, AND PARTICIPANTS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective study that included 1612 postmenopausal women aged 45-84 yr, followed between the years 2000-2006, who were not taking hormone replacement therapy, had no prevalent cardiovascular disease or diabetes, and had complete ascertainment of sex hormones. MAIN OUTCOME MEASURES: T2DM was defined based on fasting glucose and/or treatment for diabetes. RESULTS: There were 116 incident cases of diabetes during follow-up. Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG, we found significantly greater hazards of developing incident T2DM (all P for trend <or=0.001). After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance, bioavailable T was no longer associated with incident T2DM. The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models (both P for trend <0.02). Dehydroepiandrosterone had no relationship with incident T2DM. CONCLUSIONS: Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women.
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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 [121]
The Multivariable analyses section (page not available) reports an inverse association between SHBG and incident T2D in postmenopausal women. The SHBG section says this corroborates a previous finding, but the paper does not establish the claim that multiple other studies confirmed the association in both men and women. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe association between SHBG and T2D holds after adjusting for BMI and other common risk factors, implying lower SHBG as a predictor for T2D is at least partially independent of BMI.
“Importantly, the association between SHBG and T2D also holds after adjusting for BMI and other common risk factors, implying lower SHBG as a predictor for T2D is at least partially independent of BMI [118, 121, 124].”
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 [121]
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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
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
Testosterone concentrations in women and men with NIDDM
Andersson, B., Märin, P., Lissner, L., Vermeulen, A., & Björntorp, P. (1994) · Diabetes Care · doi:10.2337/diacare.17.5.405 · Cited by 268 · see citing works
Villareal, D. T., & Holloszy, J. O. (2004) · JAMA · doi:10.1001/jama.292.18.2243 · Cited by 241 · see citing works
Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study
Ding, E. L., Song, Y., Manson, J. E., Rifai, N., Buring, J. E., & Liu, S. (2007) · Diabetologia · doi:10.1007/s00125-007-0785-y · Cited by 208 · see citing works
Alexanderson, C., Eriksson, E., Stener-Victorin, E., Lystig, T., Gabrielsson, B., Lönn, M., & Holmäng, A. (2007) · Endocrinology · doi:10.1210/en.2007-0305 · Cited by 69 · see citing works
Basu, R., Dalla Man, C., Campioni, M., Basu, A., Nair, K. S., Jensen, M. D., Khosla, S., Klee, G., Toffolo, G., Cobelli, C., et al. (2007) · Diabetes · doi:10.2337/db06-1504 · Cited by 63 · see citing works
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Research works printed but not linked: 1
- Ding EL, Song Y, Malik VS, Liu S 2006 Sex differences of endog- enous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 295:1288 -1299
Cited by
Sorted by citations
The role of estrogens in control of energy balance and glucose homeostasis
Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1055 · Cited by 1,329 · see citing works
Mauvais-Jarvis, F., Manson, J. E., Stevenson, J. C., & Fonseca, V. A. (2017) · Endocrine Reviews · doi:10.1210/er.2016-1146 · Cited by 341 · see citing works
Mauvais-Jarvis, F. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.10.002 · Cited by 335 · see citing works
Ribas, V., Nguyen, M. T. A., Henstridge, D. C., Nguyen, A.-K., Beaven, S. W., Watt, M. J., & Hevener, A. L. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00504.2009 · Cited by 309 · see citing works
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
Obesity in menopause - our negligence or an unfortunate inevitability
Kozakowski, J., Gietka-Czernel, M., Leszczyńska, D., & Majos, A. (2017) · Menopausal Review · doi:10.5114/pm.2017.68594 · Cited by 189 · see citing works
Metabolic 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
Narinx, 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
Hevener, A. L., Zhou, Z., Moore, T. M., Drew, B. G., & Ribas, V. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.06.013 · Cited by 72 · see citing works
The Impact of Skeletal Muscle ERα on Mitochondrial Function and Metabolic Health
Hevener, A. L., Ribas, V., Moore, T. M., & Zhou, Z. (2020) · Endocrinology · doi:10.1210/endocr/bqz017 · Cited by 54 · see citing works
Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study
Coviello, A. D., Zhuang, W. V., Lunetta, K. L., Bhasin, S., Ulloor, J., Zhang, A., Karasik, D., Kiel, D. P., Vasan, R. S., & Murabito, J. M. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0050 · Cited by 33 · see citing works
The Role of Skeletal Muscle Estrogen Receptors in Metabolic Homeostasis and Insulin Sensitivity
Hevener, A. L., Zhou, Z., Drew, B. G., & Ribas, V. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-70178-3_13 · Cited by 23 · see citing works
Venkatesh, V. S., Grossmann, M., Zajac, J. D., & Davey, R. A. (2022) · Obesity Reviews · doi:10.1111/obr.13429 · Cited by 22 · see citing works
Hedderson, M. M., Capra, A., Lee, C., Habel, L. A., Lee, J., Gold, E. B., Badon, S. E., Mitro, S. D., & El Khoudary, S. R. (2024) · Diabetes Care · doi:10.2337/dc23-1630 · Cited by 17 · see citing works
Sofer, Y., Nevo, N., Vechoropoulos, M., Shefer, G., Osher, E., Landis, N., Tordjman, K., Hammond, G. L., & Stern, N. (2018) · Endocrine Connections · doi:10.1530/ec-17-0240 · Cited by 6 · see citing works
- Authors
- Kalyani, R. R., Franco, M., Dobs, A. S., Ouyang, P., Vaidya, D., Bertoni, A., Gapstur, S. M., & Golden, S. H.
- Affiliations
- Johns Hopkins University (US)
- Spanish National Centre for Cardiovascular Research (ES)
- Wake Forest University (US)
- American Cancer Society (US)
- Corresponding author
- Golden, Sherita Hill
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-11-01
- Volume
- 94
- Issue
- 11
- Pages
- 4127-4135
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2775652
- OpenAlex
- W2165285485
- Cited by
- 179
- References
- 7
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 19 · 2016: 20 · 2015: 19 · 2014: 8 · 2013: 11 · 2012: 19
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- National Institutes of Health (n01hc095169-003, N01-HC- 95159, 5k23dk071565-05, n01hc95159-40-0-1, N01‐HC‐95169)
- National Heart, Lung, and Blood Institute (N01 HC-95159, N01-HC095169, N01-HC-095159, N01 HC95169)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23-DK071565, 5 K23 DK071565, P30DK079637)
- National Center for Research Resources (N01 HC 95169, N01-HC-95159, KL2RR025006)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, postmenopausal women, endogenous sex hormones, bioavailable testosterone, estradiol, sex hormone-binding globulin, dehydroepiandrosterone, adiposity, body mass index, insulin resistance, HOMA-IR, incident diabetes risk
- MeSH terms
- Adipose Tissue, Aged, Aged, 80 and over, Blood Glucose, Dehydroepiandrosterone, Diabetes Mellitus, Diabetes Mellitus, Type 2, Estradiol, Ethnicity, Fasting, Female, Humans, Longitudinal Studies, Middle Aged, Sex Hormone-Binding Globulin, Testosterone, Cohort Studies, Proportional Hazards Models, Postmenopause, Glucose Intolerance, Adiposity
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