title: Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with turner syndrome: a systematic review and meta-analysis.
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 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. Twenty-five 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.
authors.affiliation: Mayo Graduate School, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Dahima
authors.initials: D
authors.lastname: Cintron
authors.affiliation: Knowledge and Evaluation Research Unit in Endocrinology, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.|Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.|Division of Endocrinology, Department of Internal Medicine, University Hospital "Dr. Jose E. Gonzalez", Autonomous University of Nuevo Leon, Monterrey, 64460, Mexico.
authors.forename: Rene
authors.initials: R
authors.lastname: Rodriguez-Gutierrez
authors.affiliation: Knowledge and Evaluation Research Unit in Endocrinology, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.|Department of Nutrition, Diabetes and Metabolism, Pontifical Catholic University of Chile, Santiago, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Serrano
authors.affiliation: University of Puerto Rico- Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Paula
authors.initials: P
authors.lastname: Latortue-Albino
authors.affiliation: Mayo Clinic Libraries, Rochester, MN, 55905, USA.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.affiliation: Division of Preventive, Occupational, and Aerospace Medicine, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. murad.mohammad@mayo.edu.
authors.forename: Mohammad Hassan
authors.identifier: http://orcid.org/0000-0003-4607-0234
authors.initials: MH
authors.lastname: Murad
mesh_terms: D015519:Bone Density / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D011788:Quality of Life; D014424:Turner Syndrome / Q000150:complications / Q000188:drug therapy*
chemical_list: D004967:Estrogens
keywords: Adverse events; Estrogen; Fractures; Lipids; Quality of life; Vasomotor symptoms