Among menopausal women, a doubling of serum estradiol was associated with a 10% lower risk for fracture, independent of menopausal stage and level of sex hormone-binding globulin, according to an analysis of the Study of Women’s Health Across the Nation.
Jane A. Cauley
“Our findings suggest that serum [estradiol] measures may help to identify women at high risk of fracture during the menopausal transition,” Jane A. Cauley, DrPH, professor of epidemiology and associate dean for research in the department of epidemiology at the University of Pittsburgh, and colleagues wrote.
Cauley and colleagues analyzed data from 2,960 women aged 42 to 52 years at baseline participating in the Study of Women’s Health Across the Nation (SWAN), an ongoing, longitudinal cohort study of midlife women at seven clinical sites. Women were still menstruating 3 months before baseline screenings and were not using oral contraceptives or postmenopausal hormone therapy and underwent at least two reported hormone measurements before fracture. Researchers assessed measurements of serum estradiol, follicle-stimulating hormone (FSH) and SHBG; select women also underwent DXA measurements to measure lumbar spine and femoral neck bone mineral density. Incident fractures were self-reported and menopausal status was determined based on reports of the frequency and regularity of menstrual bleeding. Researchers used chi-square and t tests to compare baseline characteristics between women who experienced a fracture vs. women without a fracture.
During an average of 8.8 years, 508 women (17.2%) experienced a fracture, including 278 traumatic fractures and 230 nontraumatic fractures (14 vertebral fractures; five incident hip fractures).
Researchers found that each doubling of serum estradiol was associated with a 10% reduced risk for fracture, independent of menopausal stage and SHBG. Neither FSH nor SHBG was associated with incident fracture. Findings persisted in sensitivity analyses restricted to 2,234 women who underwent BMD measurements, with researchers observing an 8% decreased risk for fracture with a doubling of serum estradiol (RR = 0.92; 95% CI, 0.83-1.01).
“Estradiol concentrations have been positively correlated with pro-inflammatory cytokines,” the researchers wrote. “Thus, higher [estradiol] may be associated with a lower risk of fractures by lowering the levels of pro-inflammatory cytokines.”
The researchers noted that hormone assays must be standardized across laboratories for clinical implementation and to identify specific thresholds of estradiol that define risk. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.