{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:35:54Z","timestamp":1792805754908,"version":"4.5.0"},"reference-count":84,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Secihti (Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n)","id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Estrogen plays a crucial role in adipose tissue homeostasis, influencing fat distribution, lipid metabolism, and insulin sensitivity. Through estrogen receptor (ER) activation, particularly ER\u03b1, estradiol (E2) regulates adipogenesis, inhibits adipocyte hypertrophy, and promotes insulin signaling. It enhances lipid oxidation, reduces lipogenesis, and suppresses pro-inflammatory cytokine production, thereby maintaining metabolic health. Primary ovarian insufficiency (POI), characterized by estrogen deficiency before the age of 40, disrupts this regulatory network, leading to adverse metabolic effects. Objetives: This review examines the effects of estrogen on adipose tissue, lipid metabolism, and carbohydrate metabolism, with a particular focus on clinical evidence in women with POI. Methods: A narrative review of the metabolic alterations associated with POI, emphasizing the molecular, biochemical, and metabolic mechanisms underlying estrogen deficiency, with a special focus on adipose tissue. Results: Women with POI exhibit increased visceral fat accumulation, reduced lean mass, and alterations in adipokine secretion, resembling the metabolic phenotype of postmenopausal women. The decline in estrogen levels contributes to central adiposity, impaired lipid metabolism, and insulin resistance, exacerbating the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). The loss of estrogenic regulation leads to enhanced lipolysis in visceral fat, raising free fatty acid flux to the liver, promoting hepatic steatosis, and worsening insulin resistance. Studies indicate that POI patients have significantly higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides compared to age-matched controls, reinforcing their heightened CVD risk. Reduced sex hormone-binding globulin (SHBG) levels increase free androgen availability, aggravating central fat deposition. These metabolic disturbances can potentially accelerate atherosclerosis and vascular aging, increasing morbidity and mortality in POI patients. Conclusions: Understanding the role of estrogen in adipose tissue and its disruption in POI highlights the importance of early intervention. Although the available evidence is limited and largely extrapolated from menopause studies, strategies such as hormone replacement therapy, lifestyle modifications, and lipid profile optimization are essential to mitigate metabolic consequences and improve long-term health outcomes in women with POI.<\/jats:p>","DOI":"10.3390\/metabo15040242","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T07:47:44Z","timestamp":1743580064000},"page":"242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Metabolic Changes in Patients with Premature Ovarian Insufficiency: Adipose Tissue Focus\u2014A Narrative Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9562-8874","authenticated-orcid":false,"given":"Miriam","family":"S\u00e1nchez-Garc\u00eda","sequence":"first","affiliation":[{"name":"Hospital Angeles Culiac\u00e1n, Policlinics, Culiac\u00e1n Sinaloa 80100, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5433-2032","authenticated-orcid":false,"given":"Kapy","family":"Le\u00f3n-Wu","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Hospital de Especialidades del Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2502-305X","authenticated-orcid":false,"given":"Regina","family":"de Miguel-Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Hospital Angeles del Pedregal, Ciudad de M\u00e9xico 10700, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-4325","authenticated-orcid":false,"given":"Nitzia","family":"L\u00f3pez-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Hospital de Cardiolog\u00eda del Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3025-8339","authenticated-orcid":false,"given":"Claudia","family":"Ram\u00edrez-Renter\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Enfermedades Endocrinas, Hospital de Especialidades del Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7590-7262","authenticated-orcid":false,"given":"Etual","family":"Espinosa-C\u00e1rdenas","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Hospital de Especialidades del Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3459-923X","authenticated-orcid":false,"given":"Ernesto","family":"Sosa-Eroza","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Hospital de Especialidades del Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-0383","authenticated-orcid":false,"given":"Manuel R.","family":"Garc\u00eda-S\u00e1enz","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Hospital de Especialidades del Centro M\u00e9dico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-3127-9_1","article-title":"The Estrogen Receptors: An Overview from Different Perspectives","volume":"1366","author":"Eyster","year":"2016","journal-title":"Methods Mol. 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