Sex steroid hormones and fracture in a multiethnic cohort of Women: The Women's Health Initiative Study (WHI)

Jane A. Cauley, Michelle E. Danielson, Guru Rajesh Jammy, Doug C. Bauer, Rebecca Jackson, Jean Wactawski-Wende, Rowan T. Chlebowski, Kristine E. Ensrud, Robert Boudreau

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Context: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity. Design and Setting: We performed a nested case-control study within the prospective Women's Health Initiative Observational Study. Incident nonspine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 whitewomen who experienced an incident fracture was chosen. One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone-binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone. Results: In multivariable and race/ethnicity-adjusted models, higher BioE2 (>8.25 pg/mL) and higher BioT (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; 95% CI, 0.50 to 0.85; P trend = 0.001 and OR, 0.76; 95% CI, 0.60 to 0.96; P trend = 0.02, respectively). The interaction term between race/ethnicity and either BioE2 or BioT was not significant. There was no association between SHBG and fracture risk. In models stratifying by race/ethnicity, higher BioE2 was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36 to 0.87) and black women (OR, 0.61; 95% CI, 0.39 to 0.96). Higher BioT was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), P trend 5 0.03. Conclusions: Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture. (J Clin Endocrinol Metab 102: 1538-1547, 2017).

Original languageEnglish (US)
Pages (from-to)1538-1547
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
StatePublished - May 1 2017

Bibliographical note

Funding Information:
The Women's Health Initiative Study is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through Contracts HHSN268201100046C HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.

Publisher Copyright:
© 2017 Endocrine Society.


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