Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis

• Published in: PloS one Vol. 9; no. 8; p. e104303
• Main Authors: Rojas-Villarraga, Adriana, Torres-Gonzalez, July-Vianneth, Ruiz-Sternberg, Ángela-María
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.08.2014; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Antibodies; Antiphospholipid antibodies; Autoimmune diseases; Biology and Life Sciences; Case-Control Studies; Chronic conditions; Comparative studies; Contraceptives; Contraceptives, Oral - administration & dosage; Estrogen; Estrogen Replacement Therapy; Estrogens; Estrogens - therapeutic use; Exposure; Female; Health risk assessment; Hormone replacement therapy; Hormone therapy; Hormones; Humans; Infertility, Female - drug therapy; Infertility, Female - pathology; Lupus; Lupus Erythematosus, Systemic - chemically induced; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - pathology; Medicine and Health Sciences; Meta-analysis; Middle Aged; Odds Ratio; Oral contraceptives; Prospective Studies; Research and Analysis Methods; Retrospective Studies; Risk; Risk analysis; Risk factors; Safety and security measures; Sex hormones; Systematic review; Systemic lupus erythematosus; Therapy; Thromboembolism; Womens health; Colombia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104303

There is conflicting data regarding exogenous sex hormones [oral contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE. MEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012), were databases from which were selected and reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case-control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model) and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51-2.56; P-value<0.001). One of eleven meta-analyses evaluating the risk for SLE associated with OC exposure had a marginally significant result. There were no associations between HRT or OC exposure and specific outcomes of SLE. It was not always possible to Meta-analyze all the available data. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration. An association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who are planning to start HRT or OC is suggested.