Serum Estradiol Levels Predictive of Fractures During Menopausal Transition

foot fracture
foot fracture
Measuring serum estradiol during the menopausal transition might help identify women at higher risk for fractures.

Measuring serum estradiol (E2) during the menopausal transition might help identify women at higher risk for fractures, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

To determine whether physicians can better predict fracture incidence by measuring annual hormone levels during the menopausal transition, researchers followed 2960 women (average age, 46.4 years) during their menopausal transitions (average follow-up, 8.8 years).

Participants were measured annually for levels of E2, follicle-stimulating hormone, and sex hormone-binding globulin, and were classified by menopause stage on each visit. Women included in the final results were required to have been premenopausal 3 months before baseline screening, and to have had at least 2 repeat hormone measurements.

In total, 17.2% of the population (n = 508) experienced an incident fracture during follow-up. Of these fractures, 278 were traumatic and 230 were nontraumatic; these included 95 ankle, 110 foot, 69 wrist, 50 leg, 54 arm, 5 hip, and 14 vertebral fractures.

The researchers discovered that neither follicle-stimulating hormone nor sex hormone-binding globulin were significantly associated with fracture risk, but women with doubled log E2 levels had a 10% lower risk for fracture independent of covariates, including menopause stage (relative risk, 0.90; 95% CI, 0.82-0.98). Furthermore, there was no significant interaction between E2 and hormone therapy.

Women who experienced an incident fracture during follow-up were more likely to be white and to report high alcohol consumption, diabetes, and worse physical function scores. They were also less likely to report premenopausal status at baseline.

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Limitations to this study included an inability to examine traumatic and nontraumatic fractures separately.

In summarizing their findings, the researchers said “that serum E2 measures may help to identify women at high risk [for] fracture during the menopausal transition. However, hormone assays must be standardized across laboratories for clinical implementation and to identify specific thresholds of E2 that define risk.”

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Cauley JA, Ruppert K, Lian Y, et al. Serum sex hormones and the risk of fracture across the menopausal transition: study of women’s health across the nation [published online January 23, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-02047