Endocrine Abstracts

Introduction: Early menopause (defined as age of menopause <45 years) and premature ovarian failure (defined as age of menopause <40 years) are associated with accelerated bone loss and increased risk of osteoporosis in later life. However, their association with increased fracture risk has not been established, with studies yielding conflicting results. The aim of this study was to systematically review and meta-analyze studies evaluating the effect of age at onset of menopause on fracture risk.

Methods: Search was conducted in three databases (PubMed, Central, Embase). Eligible for the review were studies that have reported fractures (total, vertebral, non-vertebral, hip) in women with premature ovarian failure or early menopause versus women with natural menopause. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI) and combined by the Dersimonian/Laird method. The I² index was employed to indicate heterogeneity; publication bias was inspected by Funnel plots and tested by the Egger’s test. Meta-analysis was performed using RStudio (Version 1.0.414, RStudio, Inc.) and the programming language R (version 3.4.3, 2017, The R Foundation for Statistical Computing).

Result: Twelve (four case-control and eight cohort) studies, including a total of 39,510 postmenopausal women (9,668 of which with fractures), were eligible for qualitative and quantitative analysis. Women with premature ovarian failure (age < 40 years) had similar probability of experience a fracture (OR: 1.24, 95% CI: 0.77–1.99, I²: 58%, 5 studies) compared to women with age of menopause > 40 years. Women with early menopause (age < 45 years) had similar probability of experience a fracture (OR: 1.43, 95% CI: 0.87–2.36, I²: 94%, 9 studies) compared to women with age of menopause > 45 years.

Conclusions: There is no evidence that women with premature ovarian failure or early menopause experience higher bone fracture risk in later life compared to women with natural menopause. More prospective cohort studies with adequate sample sizes and superior methodological characteristics are needed in order to estimate the effect of early age of menopause on bone fractures.