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Polycystic Ovary Syndrome

Impact of Lipotoxicity on Metabolic and Reproductive Health

Brennan, Kathleen M., MD*; Kroener, Lindsay L., MD*; Chazenbalk, Gregorio D., PhD; Dumesic, Daniel A., MD

Obstetrical & Gynecological Survey: April 2019 - Volume 74 - Issue 4 - p 223–231
doi: 10.1097/OGX.0000000000000661

Importance Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women. Women with PCOS are at increased risk of developing several metabolic and reproductive abnormalities, including metabolic syndrome. Underlying the combined metabolic and reproductive dysfunction is lipotoxicity, defined as the ectopic deposition of lipid in nonadipose tissue where it induces oxidative stress linked with insulin resistance and inflammation.

Objective To examine what metabolic components underlie insulin resistance in PCOS, how lipotoxicity through insulin resistance impairs metabolism and reproduction in these women, and why evidence-based, individualized management is essential for their care.

Evidence Acquisition PubMed search was performed using relevant terms to identify journal articles related to the subject. Relevant textbook chapters were also used.

Results Polycystic ovary syndrome by Rotterdam criteria represents a complex syndrome of heterogeneous expression with variable adverse metabolic and reproductive implications. Women with classic PCOS are often insulin resistant and at greatest risk of developing metabolic syndrome with preferential fat accumulation and weight gain. Moreover, PCOS women may also have an altered capacity to properly store fat, causing ectopic lipid accumulation in nonadipose tissue, including the ovaries, where it can perpetuate insulin resistance and inflammation and harm the oocyte.

Conclusions and Relevance A personalized approach to managing PCOS is essential to improve the health of all PCOS women through cost-effective prevention and/or treatment, to minimize the risk of pregnancy complications in those individuals wishing to conceive, and to optimize the long-term health of PCOS women and their offspring.

Target Audience Obstetricians and gynecologists, family physicians

Learning Objectives After completing this activity, the learner should be better able to explain the phenotypic variants of PCOS; describe how obesity, preferential abdominal fat accumulation, and lipotoxicity adversely affect the health of PCOS women; and propose a preconception management plan for overweight and obese PCOS women wishing to conceive.

*Assistant Clinical Professor,

Adjunct Professor, and

Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, CA

All authors, faculty, and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations relevant to this educational activity.

This study was funded in part by a grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH), under award P50HD071836 through the Oregon National Primate Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

K.M.B. and L.L.K. contributed equally to this manuscript.

Correspondence requests to: Daniel A. Dumesic, MD, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, Room 27-139 CHS, Los Angeles, CA 90095. E-mail:

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