{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:38:53Z","timestamp":1791463133600,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Therapeutic carbohydrate restriction diets have been becoming increasingly popular over the years, resulting in dramatic weight loss and an improvement in metabolic disorders. Obesity, insulin resistance, and diabetes are the risk factors for many gynecologic morbidities such as uterine leiomyoma, endometrial polyps, and polycystic ovarian syndrome. There is evidence suggesting that the pathogenesis of cardiovascular disease is similar to that seen in many causes of abnormal uterine bleeding. We aim to explain how cardiovascular disease risk factor reduction with the use of therapeutic carbohydrate restriction may prevent and potentially treat these gynecologic disorders.<\/jats:p>","DOI":"10.3390\/nu15173760","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T06:10:22Z","timestamp":1693203022000},"page":"3760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic Carbohydrate Restriction as a Metabolic Modality for the Prevention and Treatment of Abnormal Uterine Bleeding"],"prefix":"10.3390","volume":"15","author":[{"given":"Andrea C.","family":"Salcedo","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Pathology and Human Anatomy, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211.e1","DOI":"10.1016\/j.ajog.2011.12.002","article-title":"The estimated annual cost of uterine leiomyomata in the United States","volume":"206","author":"Cardozo","year":"2012","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.ajog.2006.02.020","article-title":"Health care resource use for uterine fibroid tumors in the United States","volume":"195","author":"Flynn","year":"2006","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"34.e1","DOI":"10.1016\/j.ajog.2007.05.039","article-title":"Inpatient hysterectomy surveillance in the United States, 2000\u20132004","volume":"198","author":"Whiteman","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/AOG.0000000000002103","article-title":"Outpatient Hysterectomy Volume in the United States","volume":"130","author":"Cohen","year":"2017","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1089\/jwh.2013.4288","article-title":"Abnormal uterine bleeding, health status, and usual source of medical care: Analyses using the Medical Expenditures Panel Survey","volume":"22","author":"Matteson","year":"2013","journal-title":"J. Womens Health"},{"key":"ref_6","first-page":"175","article-title":"Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics","volume":"78","author":"Moss","year":"1975","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/REP-21-0087","article-title":"Vascular biology of uterine fibroids: Connecting fibroids and vascular disorders","volume":"162","author":"Kirschen","year":"2021","journal-title":"Reprod. Camb. Engl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1093\/humupd\/dmt042","article-title":"The role of angiogenic factors in fibroid pathogenesis: Potential implications for future therapy","volume":"20","author":"Tal","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.fertnstert.2006.11.190","article-title":"Wall discontinuities and increased expression of vascular endothelial growth factor-A and vascular endothelial growth factor receptors 1 and 2 in endometrial blood vessels of women with menorrhagia","volume":"88","author":"Mints","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.12688\/f1000research.15994.1","article-title":"An update on clonality: What smooth muscle cell type makes up the atherosclerotic plaque?","volume":"7","author":"Schwartz","year":"2018","journal-title":"F1000Research"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.5812\/ijem.4020","article-title":"Cardiovascular Risk in Women with PCOS","volume":"10","author":"Scicchitano","year":"2012","journal-title":"Int. J. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/j.1524-6175.2005.04384.x","article-title":"Systemic hypertension among women with uterine leiomyomata: Potential final common pathways of target end-organ remodeling","volume":"7","author":"Silver","year":"2005","journal-title":"J. Clin. Hypertens. Greenwich Conn."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"He, Y., Zeng, Q., Li, X., Liu, B., and Wang, P. (2013). The Association between Subclinical Atherosclerosis and Uterine Fibroids. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057089"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1093\/humrep\/dew249","article-title":"Uterine fibroids and cardiovascular risk","volume":"31","author":"Uimari","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1089\/jwh.2018.7122","article-title":"Uterine Fibroids and the Risk of Cardiovascular Disease in the Coronary Artery Risk Development in Young Adult Women\u2019s Study","volume":"28","author":"Fuchs","year":"2019","journal-title":"J. Womens Health"},{"key":"ref_16","unstructured":"Dolan, M.S., Hill, C., and Valea, F.A. (2022). Comprehensive Gynecology, Elsevier. [8th ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/aje\/153.1.11","article-title":"Risk factors for uterine leiomyoma: A practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation","volume":"153","author":"Faerstein","year":"2001","journal-title":"Am. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"205031211984824","DOI":"10.1177\/2050312119848247","article-title":"Endometrial polyps: Pathogenesis, sequelae and treatment","volume":"7","author":"Nijkang","year":"2019","journal-title":"SAGE Open Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.fertnstert.2008.01.002","article-title":"Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization","volume":"91","author":"Onalan","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_20","first-page":"922","article-title":"Markers of insulin resistance in perimenopausal women with endometrial pathology","volume":"84","author":"Wyroba","year":"2013","journal-title":"Ginekol. Pol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists\u2019 Committee on Practice Bulletins\u2014Gynecology (2018). Polycystic Ovary Syndrome: ACOG Practice Bulletin, Number 194. Obstet. Gynecol., 131, e157\u2013e171.","DOI":"10.1097\/AOG.0000000000002656"},{"key":"ref_22","first-page":"5","article-title":"The pathogenesis of endometrial polyps: A systematic semi-quantitative review","volume":"34","author":"Indraccolo","year":"2013","journal-title":"Eur. J. Gynaecol. Oncol."},{"key":"ref_23","first-page":"269","article-title":"The role of oxidative stress markers in development of endometrial polyp","volume":"11","author":"Kansu","year":"2016","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1042\/CS20080069","article-title":"End-organ dysfunction and cardiovascular outcomes: The role of the microcirculation","volume":"116","author":"Lockhart","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.jacc.2018.11.050","article-title":"Nonalcoholic Fatty Liver Disease and the Heart","volume":"73","author":"Stahl","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ijgo.2010.11.011","article-title":"FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age","volume":"113","author":"Munro","year":"2011","journal-title":"Int. J. Gynaecol. Obstet. Off. Organ. Int. Fed. Gynaecol. Obstet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists\u2019 Committee on Practice Bulletins\u2013Gynecology (2021). Management of Symptomatic Uterine Leiomyomas: ACOG Practice Bulletin, Number 228. Obstet. Gynecol., 137, e100\u2013e115.","DOI":"10.1097\/AOG.0000000000004401"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Aboeldalyl, S., James, C., Seyam, E., Ibrahim, E.M., Shawki, H.E.D., and Amer, S. (2021). The Role of Chronic Inflammation in Polycystic Ovarian Syndrome\u2014A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052734"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4102\/jir.v5i1.67","article-title":"Insulin resistance and other risk factors of cardiovascular disease amongst women with abnormal uterine bleeding","volume":"5","author":"Salcedo","year":"2022","journal-title":"J. Insul. Resist."},{"key":"ref_30","first-page":"387","article-title":"Immunology of Normal and Abnormal Menstruation","volume":"9","author":"Berbic","year":"2013","journal-title":"Womens Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/humupd\/dmr031","article-title":"Growth factors and myometrium: Biological effects in uterine fibroid and possible clinical implications","volume":"17","author":"Ciarmela","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12933-018-0762-4","article-title":"Association between insulin resistance and the development of cardiovascular disease","volume":"17","author":"Ormazabal","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1177\/1933719111408111","article-title":"Adipocytes Enhance the Proliferation of Human Leiomyoma Cells Via TNF-\u03b1 Proinflammatory Cytokine","volume":"18","author":"Nair","year":"2011","journal-title":"Reprod. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00441-015-2324-3","article-title":"Possible involvement of inflammatory\/reparative processes in the development of uterine fibroids","volume":"364","author":"Protic","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.fertnstert.2009.02.016","article-title":"Novel finding of high density of activated mast cells in endometrial polyps","volume":"92","author":"Black","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.fertnstert.2013.06.050","article-title":"Cellular immune environment in endometrial polyps","volume":"100","author":"Berbic","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.mce.2011.12.017","article-title":"Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-\u03b1 and GPER signalling","volume":"351","author":"Williams","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e12423","DOI":"10.1111\/cob.12423","article-title":"Impact of sex hormones dysregulation and adiposity on the outcome of postmenopausal breast cancer patients","volume":"11","author":"Coradini","year":"2021","journal-title":"Clin. Obes."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1111\/j.1582-4934.2009.00810.x","article-title":"Immune cells and angiogenesis","volume":"13","author":"Ribatti","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1152\/physrev.1997.77.4.1033","article-title":"Mast cells","volume":"77","author":"Metcalfe","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1053\/j.gastro.2011.12.050","article-title":"Body mass index increases risk for colorectal adenomas based on meta-analysis","volume":"142","author":"Ben","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/sj.bjc.6606045","article-title":"Physical activity and risk of colon adenoma: A meta-analysis","volume":"104","author":"Wolin","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cgh.2010.02.001","article-title":"Abdominal Visceral Adipose Tissue Predicts Risk of Colorectal Adenoma in Both Sexes","volume":"8","author":"Nam","year":"2010","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_44","unstructured":"Lobo, R.A. (2022). Comprehensive Gynecology, Elsevier. [8th ed.]."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rudnicka, E., Suchta, K., Grymowicz, M., Calik-Ksepka, A., Smolarczyk, K., Duszewska, A.M., Smolarczyk, R., and Meczekalski, B. (2021). Chronic Low Grade Inflammation in Pathogenesis of PCOS. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073789"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/jog.14650","article-title":"Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial","volume":"47","author":"Li","year":"2021","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1159\/000479371","article-title":"An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence","volume":"88","author":"Oberfield","year":"2017","journal-title":"Horm. Res. Paediatr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mce.2013.01.001","article-title":"The Polycystic Ovary Syndrome and recent human evolution","volume":"373","author":"Corbett","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_49","unstructured":"Douglas, N., and Lobo, R.A. (2022). Comprehensive Gynecology, Elsevier. [8th ed.]."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/ajcn\/86.2.276","article-title":"Low-carbohydrate nutrition and metabolism","volume":"86","author":"Westman","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hallberg, S.J., Gershuni, V.M., Hazbun, T.L., and Athinarayanan, S.J. (2019). Reversing Type 2 Diabetes: A Narrative Review of the Evidence. Nutrients, 11.","DOI":"10.3390\/nu11040766"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S0140-6736(75)91633-5","article-title":"The role of lipid in the pathogenesis of atherosclerosis","volume":"305","author":"Stehbens","year":"1975","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0033-0620(86)90021-6","article-title":"An appraisal of cholesterol feeding in experimental atherogenesis","volume":"29","author":"Stehbens","year":"1986","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1001\/archsurg.1978.01370130030005","article-title":"The Lipid Hypothesis: Pathophysiological Basis","volume":"113","author":"Davignon","year":"1978","journal-title":"Arch. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s11745-008-3274-2","article-title":"Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet","volume":"44","author":"Volek","year":"2009","journal-title":"Lipids"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/ajcn\/nqy096","article-title":"Effects of low-carbohydrate-compared with low-fat-diet interventions on metabolic control in people with type 2 diabetes: A systematic review including GRADE assessments","volume":"108","author":"Fedorowicz","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chawla, S., Tessarolo Silva, F., Amaral Medeiros, S., Mekary, R., and Radenkovic, D. (2020). The Effect of Low-Fat and Low-Carbohydrate Diets on Weight Loss and Lipid Levels: A Systematic Review and Meta-Analysis. Nutrients, 12.","DOI":"10.3390\/nu12123774"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fechner, E., Smeets, E., Schrauwen, P., and Mensink, R. (2020). The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans\u2014A Systematic Review and Meta-Analysis. Nutrients, 12.","DOI":"10.3390\/nu12040991"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/ejcn.2013.116","article-title":"Beyond weight loss: A review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets","volume":"67","author":"Paoli","year":"2013","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/cphy.c130024","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_61","first-page":"45","article-title":"Metabolic effects of glucagon in humans","volume":"15","year":"2019","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e177","DOI":"10.1016\/j.jacc.2019.03.010","article-title":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease","volume":"74","author":"Arnett","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"The Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), Aas, A.-M., Axelsen, M., Churuangsuk, C., Hermansen, K., Kendall, C.W.C., Kahleova, H., Khan, T., Lean, M.E.J., and Mann, J.I. (2023). Evidence-based European recommendations for the dietary management of diabetes. Diabetologia, 66, 965\u2013985.","DOI":"10.1007\/s00125-023-05894-8"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.fertnstert.2006.11.012","article-title":"Polycystic ovary syndrome and risk of uterine leiomyomata","volume":"87","author":"Wise","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13679-023-00516-1","article-title":"Ketogenic Diet as a Possible Non-pharmacological Therapy in Main Endocrine Diseases of the Female Reproductive System: A Practical Guide for Nutritionists","volume":"12","author":"Camajani","year":"2023","journal-title":"Curr. Obes. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e1071","DOI":"10.1210\/clinem\/dgaa839","article-title":"Update on PCOS: Consequences, Challenges, and Guiding Treatment","volume":"106","author":"Hoeger","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/17\/3760\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:40:55Z","timestamp":1760128855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/17\/3760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,28]]},"references-count":66,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["nu15173760"],"URL":"https:\/\/doi.org\/10.3390\/nu15173760","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,28]]}}}