Longitudinal changes in sex hormone binding globulin (SHBG) and risk of incident diabetes: the study of women’s health across the nation (SWAN)
Open accessAbstract
OBJECTIVE: To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. RESEARCH DESIGN AND METHODS: We followed 2,952 participants in the Study of Women’s Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log–based discrete-time survival models anchored at baseline. RESULTS: Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87–0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] −92.3 to −1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> −1.5 to −0.2 nmol/L] HR 0.33, 95% CI 0.23–0.48; Q3 [> −0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25–0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30–0.63). CONCLUSIONS: Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.
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Stable or increasing rates of change in SHBG were independently associated with a lower risk of diabetes compared to decreasing rates of change.
“stable or increasing rates of change in SHBG were independently associated with a lower risk of diabetes compared to decreasing rates of change (110).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [110]
Increasing levels of SHBG were associated with a decreased risk of type 2 diabetes after adjusting for covariates.
“increasing levels of SHBG were associated with a decreased risk of T2D after adjusting for covariates.”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [110]
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- Authors
- 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.
- Affiliations
- Kaiser Permanente (US)
- Stanford University (US)
- University of California, Davis (US)
- 4University of Pittsburgh, Pittsburgh, PA
- Corresponding author
- Hedderson, Monique M.
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2024-02-06
- Volume
- 47
- Issue
- 4
- Pages
- 676-682
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC10973900
- OpenAlex
- W4391558569
- Cited by
- 17
- References
- 23
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 4
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (U01AG012495, U01AG012505, U01AG012531, U01AG012535, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U19AG063720)
- National Institute of Nursing Research (U01NR004061)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- sex hormone-binding globulin, testosterone, diabetes risk, perimenopause, perimenopausal women, estradiol, glucose metabolism, androgenic activity
- MeSH terms
- Diabetes Mellitus, Estradiol, Female, Humans, Menopause, Sex Hormone-Binding Globulin, Testosterone, Women's Health
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