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Cited by 1,354Hormonal and reproductive studiesOvarian function and disordersDiabetes, Cardiovascular Risks, and Lipoproteins

The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.

Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis

Ding, Eric L., Song, Yiqing, Malik, Vasanti S., Liu, Simin·2006·JAMA
DOI 10.1001/jama.295.11.1288
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Abstract

CONTEXT: Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of type 2 diabetes, such that hyperandrogenism may increase risk in women while decreasing risk in men. OBJECTIVE: To systematically assess studies evaluating the association of plasma levels of testosterone, sex hormone-binding globulin (SHBG), and estradiol with risk of type 2 diabetes. DATA SOURCES: Systematic search of EMBASE and MEDLINE (1966-June 2005) for English-language articles using the keywords diabetes, testosterone, sex-hormone-binding-globulin, and estradiol; references of retrieved articles; and direct author contact. STUDY SELECTION: From 80 retrieved articles, 43 prospective and cross-sectional studies were identified, comprising 6974 women and 6427 men and presenting relative risks (RRs) or hormone levels for cases and controls. DATA EXTRACTION: Information on study design, participant characteristics, hormone levels, and risk estimates were independently extracted by 2 investigators using a standardized protocol. DATA SYNTHESIS: Results were pooled using random effects and meta-regressions. Cross-sectional studies indicated that testosterone level was significantly lower in men with type 2 diabetes (mean difference, -76.6 ng/dL; 95% confidence interval [CI], -99.4 to -53.6) and higher in women with type 2 diabetes compared with controls (mean difference, 6.1 ng/dL; 95% CI, 2.3 to 10.1) (P<.001 for sex difference). Similarly, prospective studies showed that men with higher testosterone levels (range, 449.6-605.2 ng/dL) had a 42% lower risk of type 2 diabetes (RR, 0.58; 95% CI, 0.39 to 0.87), while there was suggestion that testosterone increased risk in women (P = .06 for sex difference). Cross-sectional and prospective studies both found that SHBG was more protective in women than in men (P< or =.01 for sex difference for both), with prospective studies indicating that women with higher SHBG levels (>60 vs < or =60 nmol/L) had an 80% lower risk of type 2 diabetes (RR, 0.20; 95% CI, 0.12 to 0.30), while men with higher SHBG levels (>28.3 vs < or =28.3 nmol/L) had a 52% lower risk (RR, 0.48; 95% CI, 0.33 to 0.69). Estradiol levels were elevated among men and postmenopausal women with diabetes compared with controls (P = .007). CONCLUSIONS: This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of type 2 diabetes in men and women. High testosterone levels are associated with higher risk of type 2 diabetes in women but with lower risk in men; the inverse association of SHBG with risk was stronger in women than in men.

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Crossref · 10.1001/jama.295.11.1288

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Metadata

Authors
Ding, E. L., Song, Y., Malik, V. S., & Liu, S.
Affiliations
  • Brigham and Women's Hospital (US)
  • American Medical Association (US)
  • University of California, Los Angeles (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2006-03-15
Volume
295
Issue
11
Pages
1288
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.295.11.1288
OpenAlex
W2028647952
Cited by
1,354
References
26
Citations by year
2026: 36 · 2025: 51 · 2024: 64 · 2023: 58 · 2022: 71 · 2021: 62 · 2020: 65 · 2019: 66 · 2018: 61 · 2017: 91 · 2016: 82 · 2015: 76 · 2014: 68 · 2013: 83 · 2012: 90
FWCI
38.20
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (CA009001-29)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK066401-02, R01DK066401)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, sex differences, testosterone, sex hormone-binding globulin, estradiol, endogenous sex hormones, hyperandrogenism, diabetes risk, women's health
MeSH terms
Diabetes Mellitus, Type 2, Estradiol, Female, Humans, Male, Risk Factors, Sex Characteristics, Sex Hormone-Binding Globulin, Gonadal Steroid Hormones, Testosterone

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