National Diabetes Month
Metabolic Implications & Nutritional Management of PCOS: A Review of Research
By: Erin Kay, DO
Director’s Note: To recognize National Diabetes Month, we feature this outstanding article written by former FACTS elective student, Dr. Erin Kay, that highlights the potential impact of PCOS on multiple organs beyond the endocrine system. She summarized a systematic review by Rondanelli et al published in 2014 in Archives of Gynecology and Obstetrics titled, “Focus on metabolic and nutritional correlates of polycystic ovary syndrome and update on nutritional management of these critical phenomena.”  Their hopeful study explores nutritional management as the central treatment strategy in PCOS to improve overall health and prevent not only diabetes but also cardiovascular, reproductive, and other potential complications. Dr. Kay ends her review by adding specific ways in which fertility awareness can enhance both management and outcomes in PCOS. To learn more about PCOS and the importance of nutrition for reproductive health, we invite you to sign up for our online CME course here.
Polycystic ovary syndrome (PCOS) is a multifaceted endocrine disorder that affects nearly 1 in 10 women in the United States and 5-15% of women of reproductive age worldwide.  As the most common endocrine disorder in reproductive-aged women, it is associated with multiple metabolic, endocrine, and nutritional abnormalities, including ovarian irregularity, menstrual dysfunction, and hyperandrogenic symptoms. To be diagnosed with PCOS, a patient must exhibit two of three criteria: oligo-ovulation/anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries on ultrasound.
“As the most common endocrine disorder in reproductive-aged women, PCOS is associated with multiple metabolic, endocrine, and nutritional abnormalities, including ovarian irregularity, menstrual dysfunction, and hyperandrogenic symptoms.”
In recent years, a more comprehensive approach to managing PCOS has gained momentum, given the increased risk of comorbidities such as diabetes, high blood pressure, high cholesterol, and heart attacks. The research by Rondanelli et al  summarized herein presents a systematic review of the literature on metabolic and nutritional correlates of PCOS alongside dietary interventions.
The authors used PubMed to identify over 127 articles, filtering with the keywords “polycystic ovary syndrome,” “dietary management,” “dietary supplement,” “overweight,” “adipokines,” and “insulin resistance.” Inclusion criteria included articles written in English within the last 20 years. Senior researchers experienced in clinical nutrition also conducted a manual search to source additional articles.
Rondanelli et al classified the results of their systematic review into seven categories: obesity and insulin resistance, adipokine imbalance, weight loss, mineral deficiency and treatment, vitamin D deficiency, imbalance of omega-6/omega-3 polyunsaturated fatty acids (PUFA) ratio, and lifestyle modification.
Overweight and obesity are frequent, though not universal, characteristics of PCOS, and insulin resistance is also common, independent of body mass index (BMI). Data demonstrates insulin resistance contributes to chronic, low-grade inflammation that may lead to metabolic sequelae. Proper assessment of insulin resistance enables physicians to identify and treat patients at high risk for metabolic sequelae and infertility. However, more research is needed to clarify the correlation between severity of insulin resistance and the degree of menstrual disturbance.
Adipokines such as adiponectin, leptin, and visfatin may also serve as an endocrine link between obesity and PCOS, although the data is conflicting and may be confounded by obesity. In several studies, serum adiponectin levels were lower in PCOS patients, while leptin levels were higher. No consistent trends were observed in visfatin levels in the literature.
Nutritional correlates revealed lower levels of magnesium in women with elevated testosterone levels, with even lower levels in women with insulin resistance. Two studies demonstrated higher copper levels in women diagnosed with PCOS. Addressing mineral deficiency may improve insulin resistance and decrease oxidative stress; chromium supplementation has been shown to improve insulin resistance.
Vitamin deficiencies may have pathophysiological relevance in PCOS. Research indicates an association between vitamin D deficiency and impaired glucose clearance and insulin secretion, increased inflammatory response, abdominal obesity, and hyperandrogenism. The review reported improved glucose metabolism and menstrual frequency following vitamin D supplementation in women with PCOS. It also posited a relationship between increased dietary PUFA intake via fish oil supplements and improved endocrine and metabolic characteristics in PCOS.
“The review reported improved glucose metabolism and menstrual frequency following vitamin D supplementation in women with PCOS.”
This notable research described lifestyle modification as “the optimal treatment strategy for women with PCOS.”  A modest weight loss of 5-10% can improve insulin resistance, endocrine abnormalities, menstrual function, and fertility. Interestingly, some data suggests improvement in insulin sensitivity by increasing calories at breakfast versus dinner; redistribution of calories within an overall caloric deficit may promote weight loss and improve glucose metabolism.
“A modest weight loss of 5-10% can improve insulin resistance, endocrine abnormalities, menstrual function, and fertility.”
This systematic review outlines many of the metabolic and nutritional correlates of PCOS, equipping physicians to evaluate and treat patients with PCOS more effectively with comprehensive lifestyle and dietary management. It also highlights the importance of management of insulin resistance in women with PCOS. Left untreated, PCOS may have long-term consequences for fertility as well as metabolic health, and may lead to pre-diabetes and diabetes. Other characteristics of compromised metabolic function syndrome seen in women with PCOS include elevated triglycerides, hypertension, and low HDL cholesterol, increasing chances of cardiovascular disease and heart attacks. 
Conventional treatment of PCOS should start with lifestyle modification, as even a 5% weight reduction can improve symptoms. Medications commonly used in PCOS include metformin, anti-androgens, and combined hormonal contraception with an estrogen derivative. Oral contraceptives are used to “regulate” the menstrual cycle (i.e., cause a regular withdrawal bleed) and counteract hyperandrogenism. However, some studies suggest synthetic estrogen may actually increase insulin resistance and exacerbate the underlying pathophysiology of PCOS. 
Fertility Awareness and PCOS: A Unique Approach
Restorative reproductive medicine clinicians typically follow a more comprehensive approach to PCOS. For instance, the FACTS elective addressed the evidence-based use of myo-inositol to combat insulin resistance; myo-inositol is an inexpensive supplement available over-the-counter.  The use of bio-identical hormone supplementation may also protect the endometrium without the risks associated with using hormonal contraceptives. Charting cycles with a fertility awareness-based method (FABM) also enhances treatment of PCOS; one example is how it enables Creighton-trained medical practitioners to analyze a woman’s charts and time lab work to assess her hormonal profile and determine if she is ovulating at all. The Creighton Model Fertility Care System can be highly effective at helping women achieve pregnancy despite a PCOS diagnosis.
One of the strengths of this study is the wide breadth of articles included. Limitations include the format of the study as a systematic review rather than a meta-analysis, thus providing qualitative evidence without additional statistical analysis. More data is needed to clarify the correlation between insulin resistance and oligomenorrhea as well as the relevance of adipokines in PCOS pathophysiology. Further research should also assess dietary factors and the role of magnesium supplementation, and omega-3 PUFA (DHA and EPA) in glucose metabolism. Lastly, there is a need for research to determine the effect of synthetic estrogens in combined hormonal contraception on insulin resistance and metabolic syndrome.
 Monastra G, Unfer V, Harrath AH, Bizzarri M. Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients. Gynecol Endocrinol. 2017;33(1):1-9. doi:10.1080/09513590.2016.1247797.
 Rondanelli M, Perna S, Faliva M, Monteferrario F, Repaci E, Allieri F. Focus on metabolic and nutritional correlates of polycystic ovary syndrome and update on nutritional management of these critical phenomena. Arch Gynecol Obstet. 2014;290(6):1079-1092. doi:10.1007/s00404-014-3433-z.
 Cortés ME, Alfaro AA. The effects of hormonal contraceptives on glycemic regulation. Linacre Q. 2014;81(3):209-218. doi:10.1179/2050854914Y.0000000023.
ABOUT THE AUTHOR
Erin Kay, DO
Erin Kay, DO is a resident in family medicine at St. Vincent Ascension in Indianapolis, IN. She became interested in FABMs during her third year of medical school as a way to find root causes to gynecologic and fertility complaints while being respectful of the intricate workings of the female body. She hopes to use these methods particularly with young women and teens to help them honor their bodies. She is a FEMM practitioner and has plans to become a NaProTECHNOLOGY medical consultant.