Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic r
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META-ANALYSIS
Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and metaanalysis Dahima Cintron1 Rene Rodriguez-Gutierrez2,3,4 Valentina Serrano2,5 Paula Latortue-Albino6 Patricia J Erwin7 Mohammad Hassan Murad ●
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Received: 8 May 2016 / Accepted: 29 June 2016 © Springer Science+Business Media New York 2016
1
Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA
2
Knowledge and Evaluation Research Unit in Endocrinology, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
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Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twentyfive studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04–0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82–13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.
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Division of Endocrinology, Department of Internal Medicine, University Hospital “Dr. Jose E. Gonzalez”, Autonomous University of Nuevo Leon, Monterrey 64460, Mexico
Keywords Estrogen Lipids Fractures Vasomotor symptoms Quality of life Adverse events
Abstract Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from
Electronic supplementary material The online version of this article (doi:10.1007/s12020-016-1046-y) contains supplementary material, which is available to
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