Sex Steroid Hormones and Fracture in a Multiethnic Cohort of Women: The Women's Health Initiative Study (WHI).
We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity.



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 white women 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.



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 = 0.03.



Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture.
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Jane A
JA
Cauley
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Michelle E
ME
Danielson
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Guru Rajesh
GR
Jammy
University of California at San Francisco, San Francisco, California 94143.
Doug C
DC
Bauer
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Ohio State University, Columbus, Ohio 43210.
Rebecca
R
Jackson
Department of Epidemiology and Environmental Health, University at Buffalo, State University of New York, Buffalo, New York 14260.
Jean
J
Wactawski-Wende
Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California 90502.
Rowan T
RT
Chlebowski
Department of Medicine and Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota 55455.|Department of Medicine, Minneapolis Veteran's Administration Health System, Minneapolis, Minnesota 55417.|Center for Chronic Disease Outcomes Research, Veteran's Administration Health Care System, Minneapolis, Minnesota 55417.
Kristine E
KE
Ensrud
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Robert
R
Boudreau
D000284:Administration, Oral; D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D001213:Asian / Q000706:statistics & numerical data; D001682:Biological Availability; D002136:Calcium, Dietary / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology; D004958:Estradiol / Q000378:metabolism*; D005006:Ethnicity / Q000706:statistics & numerical data*; D015444:Exercise; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use; D006304:Health Status; D006620:Hip Fractures / Q000453:epidemiology / Q000378:metabolism; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D007198:Indians, North American / Q000706:statistics & numerical data; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D011863:Radioimmunoassay; D057566:Self Report; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D016103:Spinal Fractures / Q000453:epidemiology / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*; D014481:United States / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D044465:White People / Q000706:statistics & numerical data
D002136:Calcium, Dietary; D005938:Glucocorticoids; D012738:Sex Hormone-Binding Globulin; D014807:Vitamin D; D013739:Testosterone; D004958:Estradiol; C104450:25-hydroxyvitamin D