May 2017 Issue

Women's Health: New Data on Polycystic Ovary Syndrome
By Angela Grassi, MS, RDN, LDN
Today's Dietitian
Vol. 19, No. 5, P. 12

Research shows diet and nutritional supplement interventions can help improve metabolic and reproductive health.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 9% to 18% of reproductive age women.1 Despite the high prevalence, PCOS is commonly overlooked and undertreated. A recent international study showed nearly 50% of women saw three or more health professionals and one-third waited for more than two years before receiving a PCOS diagnosis. Few women were satisfied with the information they received about PCOS at diagnosis, with more than one-half reporting not receiving any information about long-term complications or emotional support.2

Lack of education in medical schools and underfunding for increasing awareness and clinical trials (currently PCOS receives less than 0.01% of funding from the National Institutes of Health), are two main reasons PCOS doesn't receive more attention.3 Some professionals suggest that the name of the condition itself is misleading and adds confusion. After all, women with PCOS don't actually have cysts on their ovaries, but rather many small immature follicles that are commonly mistaken as cysts.

What's clear is that women with PCOS face lifelong health risks that extend beyond their reproductive years. Lifestyle management is the primary treatment approach to preventing or ameliorating these risks.

PCOS Changes With Age
Once viewed solely as a reproductive disorder because it's one of the main causes of ovulatory infertility, PCOS is now considered an endocrine disorder causing an increased risk of type 2 diabetes, metabolic syndrome, cardiovascular disease, and cancer later in life for those who have it. According to one estimate, by age 40, nearly 50% of women with PCOS will develop prediabetes or type 2 diabetes.4

Today, more research is being conducted on women with PCOS as they age and transition through menopause. The reproductive life span in women with PCOS has been found to extend beyond that of women without PCOS due to higher adrenal and ovarian androgen levels. Androgen levels decline in women with PCOS with age, resulting in a higher likelihood of pregnancy later in life for some women who have struggled with infertility during their childbearing years.5

Despite the decline in androgen levels, the metabolic consequences associated with PCOS worsen with age. A study published in Diabetes showed that the prevalence of type 2 diabetes in middle-aged women with PCOS was 6.8 times higher than that of the general female population of similar age.4

Connection With Mood and Eating Disorders
In addition to having an increased risk of metabolic disorders, women with PCOS have been shown to have higher rates of anxiety and depression.6 Women with PCOS may suffer from more mood disorders due to an imbalance in hormones or perhaps from the daily struggles of living with a frustrating condition. Regardless of the cause, it's recommended that practitioners screen their PCOS patients for anxiety and depression and refer them to appropriate mental health professionals for treatment.6

Routine screening for eating disorders also is recommended for women with PCOS.7 A study published in Fertility and Sterility found that the risk of disordered eating behaviors was more than four times greater among women with PCOS compared with controls. High insulin levels have been associated with increased cravings and binge-eating behaviors. A study published in Appetite found 60% of obese women with PCOS were categorized with binge-eating behavior.8

Nutrition Strategies
Diet and lifestyle modifications are the primary treatment approaches for women with PCOS, yet the optimal diet hasn't yet been determined. A systematic review and meta-analysis published in the Journal of the Academy of Nutrition and Dietetics found that the type of diet didn't matter as much as weight loss. Losing weight improved both metabolic and reproductive parameters associated with PCOS. This review, however, only included six articles from five studies.9

Eating plans that include foods with a lower glycemic index and glycemic load, or modifying carbohydrate, fat, or protein amounts have been shown to reduce metabolic markers associated with PCOS, even without weight loss.9

Anti-Inflammatory Diets
Compared with women without PCOS, women with the condition have higher levels of insulin and inflammatory markers.10 In a 2015 study, researchers investigated the use of an anti-inflammatory diet in women with PCOS. In this study, 100 overweight women with PCOS ate a reduced-calorie diet for 12 weeks. The diet consisted of five small meals with 25% proteins, 25% fat, and 50% carbohydrates. The diet was designed to include moderate to high amounts of fiber with an emphasis on anti-inflammatory foods such as fish, legumes, green tea, and low-fat dairy. Chicken, red meat, and added sugars were limited.11

The results were encouraging. The mean weight loss was 7.2% with significant reductions in cholesterol, blood pressure, and fasting blood glucose. Levels of C-reactive protein (CRP) were reduced by 35%, and 63% of the women regained menstrual cyclicity.

The DASH (Dietary Approaches to Stop Hypertension) diet, which also is designed to be rich in antioxidants, has been investigated in women with PCOS as well. Women who followed the DASH diet for eight weeks saw significant reductions in insulin and CRP levels, along with improvements in waist circumference measurements.12

Nutritional Supplements
Research is expanding to determine what benefits nutritional supplements can offer women with PCOS. The following are some of the many promising supplements that have been well studied.

N-Acetylcysteine
N-acetylcysteine (NAC) is a powerful antioxidant and amino acid. NAC is a derivative of L-cysteine, a precursor to glutathione, and is involved in fighting oxidative stress and inflammation. NAC also has been shown to protect insulin receptors and influence insulin receptor activity and insulin secretion from pancreatic cells. Therapeutic doses of NAC in studies are 1.6 to 3 g daily. NAC is well tolerated with minimal side effects.

A systematic review and meta-analysis showed that NAC improved BMI, total testosterone, insulin, and lipid levels equally as well as metformin did in women with PCOS.13

The review also showed NAC produced significant improvements in pregnancy and ovulation rates compared with placebo among women with PCOS. However, NAC wasn't associated with greater benefits than metformin for improving pregnancy rates, spontaneous ovulations, and menstrual regularity.13

Inositol
Both myo-inositol (MYO) and D-chiro-inositol (DCI) have been well studied in women with PCOS and are showing promising results as first-line treatment. MYO in particular has been shown to improve insulin sensitivity as well as egg quality and ovulation. Newer research is showing that a combination of MYO and DCI in the ideal 40:1 ratio that mimics the body's own tissue levels works better than inositol alone for improving metabolic aspects and restoring hormone balance.14

Inositols are pseudovitamins found in foods such as fruits, beans, cereals, and buckwheat. MYO and DCI work as inositol-phosphoglycan mediators, or "secondary messengers" that regulate activities of hormones, including follicle-stimulating hormone, thyroid-stimulating hormone, and insulin. It's believed women with PCOS have a defect in their ability to use inositol properly, which could perhaps be a reason why they have higher insulin levels. The therapeutic dosage is 2 to 4 g MYO daily with 50 to 100 mg DCI daily. Inositol is well tolerated with minimal side effects. It may have the potential to lower blood sugar, especially in those taking insulin sensitizers or other supplements that also may lower blood sugar.

Vitamin D
Studies on PCOS show an inverse relationship between vitamin D and metabolic and hormonal disorders. A systematic review published in Nutrients, however, found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in women with PCOS.15

Vitamin D receptors have been located on oocytes, immature ova or egg cells involved in reproduction. Vitamin D supplementation (100,000 IU/month) has been shown to improve fertility in women with PCOS by increasing the number of mature follicles and improving menstrual regularity, but the results weren't statistically significant.16

Fish Oil
Fish oil offers many benefits to women with PCOS, including helping to reduce elevated triglyceride levels, improving fatty liver, and decreasing inflammation. Omega-3 oil also has been found to lower testosterone and regulate menstrual cycles in both overweight and lean women with PCOS.17

Vitamin B12
Results from the Diabetes Prevention Program Outcomes Study show that metformin affects the absorption of vitamin B12 by causing alterations of the vitamin B12-intrinsic factor complex in the ileum. Vitamin B12 deficiency is progressive over time in metformin users. Consequences of decreased vitamin B12 concentrations—such as macrocytic anemia, neuropathy, and mental changes—can be profound.18

Since the average dose of metformin in the PCOS population is high (1,500 mg to 2,000 mg per day), it's recommended that patients who take metformin have their vitamin B12 levels checked annually and supplement with vitamin B12. The sublingual methylcobalamin form is best absorbed.

Dietitians' Important Role
PCOS is a complex and overlooked condition with significant long-term metabolic risk factors throughout a woman's lifespan. Since diet and lifestyle are the primary treatments, dietitians play an important role in helping women with PCOS optimize their health and prevent disease.

— Angela Grassi, MS, RDN, LDN, is founder of the PCOS Nutrition Center, where she provides evidence-based nutrition information and counseling to women with polycystic ovary syndrome. Chosen as one of the top 10 influential RDs making a difference by Today's Dietitian in 2014, Grassi is the author of PCOS: The Dietitian's Guide and coauthor of The PCOS Workbook: Your Guide to Complete Physical and Emotional Health and The PCOS Nutrition Center Cookbook: 100 Easy and Delicious Whole Food Recipes to Beat PCOS. She wishes to disclose that she has affiliations with Nordic Naturals and Theralogix. For more information, visit her website, www.PCOSnutrition.com.


References

1. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544-551.

2. Gibson-Helm M, Teede H, Dunaif A, Dokras A. Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2017;102(2):604-612.

3. FY 2016 president's budget request. National Institutes of Health, Office of Budget website. https://officeofbudget.od.nih.gov/br2016.html. Accessed January 9, 2017.

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5. Puurunen J, Piltonen T, Morin-Papunen L, et al. Unfavorable hormonal, metabolic, and inflammatory alterations persist after menopause in women with PCOS. J Clin Endocrinol Metab. 2011;96(6):1827-1834.

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9. Moran LJ, Ko H, Misso M, et al. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet. 2013;113(4):520-545.

10. González F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012;77(4):300-305.

11. Salama AA, Amine EK, Salem HA, Abd El Fattah NK. Anti-inflammatory dietary combo in overweight and obese women with polycystic ovary syndrome. N Am J Med Sci. 2015;7(7):310-316.

12. Asemi Z, Esmaillzadeh A. DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: a randomized controlled clinical trial. Horm Metab Res. 2015;47(3):232-238.

13. Thakker D, Raval A, Patel I, Walia R. N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Obstet Gynecol Int. 2015;2015:817849.

14. 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.

15. He C, Lin Z, Robb SW, Ezeamama AE. Serum vitamin D levels and polycystic ovary syndrome: a systematic review and meta-analysis. Nutrients. 2015;7(6):4555-4577.

16. Fibrouzabadi Rd, Aflatoonian A, Modarresi S, Sekhavat L, Mohammad Taheri S. Therapeutic effects of calcium & vitamin D supplementation in women with PCOS. Complement Ther Clin Pract. 2012;18(2):85-88.

17. Nadjarzadeh A, Dehghani Firouzabadi R, Vaziri N, Daneshbodi H, Lotfi MH, Mozaffari-Khosravi H. The effect of omega-3 supplementation on androgen profile and menstrual status in women with polycystic ovary syndrome: a randomized clinical trial. Iran J Reprod Med. 2013;11(8):665-672.

18. Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761.

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