Abstract
Purpose
Early menopause (EM, age at menopause < 45 years) and premature ovarian insufficiency (POI, age at menopause < 40 years) are associated with an increased risk of osteoporosis. However, their association with increased fracture risk has not been established, with studies yielding conflicting results. The primary aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and fracture risk. The secondary aim was to evaluate this effect concerning the site of fractures.
Methods
A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 January 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for quantifying heterogeneity.
Results
Eighteen studies were included in the qualitative and quantitative analysis (462,393 postmenopausal women, 12,130 fractures). Compared with women with age at menopause > 45 years, women with EM demonstrated higher fracture risk (OR 1.36, 95% CI 1.11–1.66, p < 0.002, I² 81.5%). Women with POI did not display any difference in fracture risk compared either with women with age at menopause > 40 (OR 1.23, 95% CI 0.72–2.09, p = 0.436, I² 62.5%) or >45 years (OR 0.54, 95% CI 0.22–1.29, p = 0.17, I2 0%). No difference was evident when a separate analysis was performed for vertebral, non-vertebral and hip fractures.
Conclusions
This is the first meta-analysis showing that EM is associated with increased fracture risk compared with normal age at menopause, without any distinct effect on the site of the fracture.
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Author contributions
P.A. designed the research, extracted and analysed the data and wrote the first draft of the paper. P.S., N.K.G., N.K., A.M.A., and K.C. searched the literature, extracted and analysed the data. P.S. was responsible for the statistical analysis and reviewed the manuscript. S.A.P., M.P., E.T., E.K., I.L., and J.C.S. reviewed the manuscript and provided critical scientific input. D.G.G. resolved discrepancies regarding the quality of the studies included in the meta-analysis, provided critical scientific input and had the primary responsibility for the paper’s final content.
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J.C.S. has received grants/research support from Abbott, Mylan and Pfizer; consulting fees from Abbott, Mylan and Pfizer; and speaker’s honoraria from Abbott, Bayer, Gedeon Richter, Menarini, Mylan, and Pfizer. The remaining authors declare that they have no conflict of interest.
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Anagnostis, P., Siolos, P., Gkekas, N.K. et al. Association between age at menopause and fracture risk: a systematic review and meta-analysis. Endocrine 63, 213–224 (2019). https://doi.org/10.1007/s12020-018-1746-6
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DOI: https://doi.org/10.1007/s12020-018-1746-6