In the JournalsPerspective

Estradiol level influences fracture risk during menopause transition

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.

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.

    Perspective

    Author Name

    This recently published study showed that serum estradiol levels among recently menopausal women (aged 42 to 52 years) are associated with fracture risk; specifically, doubling of the estradiol level is associated with a 10% lower risk for fracture. Interestingly, FSH level, which is the more commonly ordered test to assess menopausal state, did not show an association with fracture risk. This study introduces another factor that could be helpful in prediction of fracture risk in the future, but, as the authors stated, assays need to be standardized and thresholds established before this can be a useful clinical predictor.

    Another interesting aspect of this study is that 17% of the women sustained a fracture within a decade of the baseline testing, which means these are relatively younger women with early onset osteoporosis. Workup for secondary osteoporosis was not done and was not available for analysis, but from clinical experience, the likelihood of having abnormalities in these tests is quite high. Abnormalities, such as vitamin D and calcium deficiency, primary or secondary hyperparathyroidism and idiopathic hypercalciuria, to name a few, are common in younger postmenopausal women with osteoporosis. The interaction of estradiol levels and abnormalities in these metabolic bone tests would be a very interesting topic for future studies.

    Pauline M. Camacho, MD, FACE

    Professor of Medicine, Division of Endocrinology and Metabolism,
    Loyola University Medical Center,
    Director, Loyola University Osteoporosis and Metabolic Bone Disease Center

    Disclosure: Camacho reports no relevant financial disclosures.