{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:20:15Z","timestamp":1777724415899,"version":"3.51.4"},"reference-count":78,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:p>\n                    We assessed the available evidence regarding adverse effects on surrogate and patient-important health outcomes of third- and fourth-generation combined oral contraceptives among premenopausal women. We performed a systematic review and meta-analysis including randomized controlled trials and observational studies comparing third- and fourth-generation combined oral contraceptives with other generation contraceptives or placebo. Studies that enrolled women aged 15 to 50\u2009years, with at least three cycles of intervention and 6\u2009months of follow-up were included. A total of 33 studies comprising 629,783 women were included. Low-density lipoprotein cholesterol levels were significantly lower in fourth-generation oral contraceptives (mean differences (MD): \u22120.24\u2009mmol\/L; [95% CI \u22120.39 to \u22120.08]), while total cholesterol was significantly increased in levonorgestrel users when compared to third-generation oral contraceptives (MD: 0.27\u2009mmol\/L; [95% CI 0.04 to 0.50]). A decreased arterial thrombosis incidence was shown in fourth-generation oral contraceptive users, as compared to levonorgestrel (incidence rate ratio (IRR): 0.41; [95% CI 0.19 to 0.86]). No difference was found in the occurrence of deep venous thrombosis between fourth-generation oral contraceptives and levonorgestrel users (IRR: 0.91; [95% CI 0.66 to 1.27]; p\u2009=\u20090.60; I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090%). Regarding the remaining outcomes, data were heterogeneous and showed no clear difference. In premenopausal women, the use of third- and fourth-generation oral contraceptives is associated with an improved lipid profile and lower risk of arterial thrombosis. Data were inconclusive regarding the rest of outcomes assessed. This review was registered in PROSPERO with CRD42020211133.\n                  <\/jats:p>","DOI":"10.1177\/10815589231184227","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T02:50:28Z","timestamp":1688698228000},"page":"871-888","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Harms of third- and fourth-generation combined oral contraceptives in premenopausal women: A systematic review and meta-analysis"],"prefix":"10.1177","volume":"71","author":[{"given":"Andrea","family":"Flores-Rodriguez","sequence":"first","affiliation":[{"name":"Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Diaz Gonzalez-Colmenero","sequence":"additional","affiliation":[{"name":"Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"},{"name":"Research Unit, University Hospital \u201cDr. Jos\u00e9 E. Gonz\u00e1lez,\u201d Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Garcia-Leal","sequence":"additional","affiliation":[{"name":"Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Saenz-Flores","sequence":"additional","affiliation":[{"name":"Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick","family":"Burciaga-Jimenez","sequence":"additional","affiliation":[{"name":"Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge A","family":"Zu\u00f1iga-Hernandez","sequence":"additional","affiliation":[{"name":"Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neri A","family":"Alvarez-Villalobos","sequence":"additional","affiliation":[{"name":"Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"},{"name":"Research Unit, University Hospital \u201cDr. Jos\u00e9 E. Gonz\u00e1lez,\u201d Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"},{"name":"Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene","family":"Rodr\u00edguez-Guajardo","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics Department, University Hospital \u201cDr. JosJos\u00e9 E. Gonz\u00e1lez,\u201d Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Monterrey, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe A","family":"Morales-Martinez","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics Department, University Hospital \u201cDr. JosJos\u00e9 E. 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