Polycystic Ovary Syndrome

Polycystic ovarian syndrome (PCOS) is a disorder involving excessive androgen production. PCOS affects an estimated 6%-8% of women in the United States,[1] but diagnosis can be difficult due to the variability of presentation and actual prevalence may be considerably higher. The etiology is unknown, but the condition appears to be a complex outcome of genetic, metabolic, and environmental factors. Alterations in gonadotropin secretion and action, insulin secretion and action, weight and energy balance, and androgen biosynthesis all appear to play roles in the development of clinical PCOS.

The presumed cause in most cases is insulin resistance, which leads to increased insulin production. In turn, insulin stimulation of ovarian cells leads to androgen production.

The onset of PCOS is typically in peripubertal years, and clinical presentation is quite varied. There are at least 3 different sets of diagnostic criteria for PCOS in adults, with the Rotterdam criteria being most commonly used in the US. All 3 include the key features of androgen excess (hirsutism and acne) and ovulatory dysfunction. However, other features can include polycystic ovaries on ultrasound, obesity, insulin resistance, and infertility due to oligo-ovulation with accompanied menstrual irregularities. PCOS is also associated with dyslipidemia, type 2 diabetes, and obstructive sleep apnea. The diagnosis of PCOS requires a history of biochemical and/or clinical evidence of hyperandrogenism and persistent oligomenorrhea.[2]

Patients with the diagnosis are at increased risk for depression and eating disorders and may have an impaired quality of life compared to women with similar BMIs who do not exhibit PCOS symptoms.

Lifestyle changes, especially those that lead to weight loss, are the first line of therapy and can ameliorate multiple symptoms.

Risk Factors

Genetics. Twin studies suggest that more than 70% of cases can be attributed to polygenic heritable traits.[3] However, it appears that other congenital or environmental factors must also be present for the condition to manifest.[4]

Obesity. Obesity, particularly abdominal obesity, increases risk of PCOS.

Diagnosis

Diagnosis of PCOS can be difficult, as presentations can be atypical. Many patients are not hirsute or obese. A thorough history and physical examination are essential.

For diagnosis in adults, according to the Rotterdam Consensus Group criteria, 2 of the following 3 points should be met, and other diseases with similar clinical presentation should be ruled out: [2],[5]

1. Menstrual irregularity. Anovulation, oligo-ovulation, amenorrhea, oligomenorrhea, or irregular bleeding.

2. Signs of hyperandrogenism. Hirsutism, acne, male-pattern baldness, or elevated serum total or free testosterone concentration. If serum testosterone is normal in the absence of drugs that cause or mask hyperandrogenism, PCOS is much less likely. Anabolic steroids and antiepileptic drugs cause symptoms similar to PCOS. Oral contraceptives and systemic acne medications may mask hyperandrogenism.

3. Polycystic ovaries, visible on transvaginal ultrasound. As an isolated finding, polycystic ovaries are not diagnostic. Rotterdam criteria require 12 or more follicles of sufficient size and/or increased ovarian volume for this criterion to be fulfilled. Transvaginal ultrasound should be employed in atypical presentations, to evaluate for ovarian or adrenal neoplasms.

In adolescents, PCOS can be diagnosed if clinical or biochemical evidence of hyperandrogenism is present along with persistent oligomenorrhea, after other pathologies have been excluded. Polycystic ovaries and anovulation may be present in normal stages of reproductive maturation and are not sufficient for diagnosis in this age group. As in older patients, ultrasound is recommended in atypical cases.

Postmenopausal women can be diagnosed with PCOS if they have a long-term history of oligomenorrhea and hyperandrogenism. Ultrasound abnormalities are less common in this population.

PCOS is a diagnosis of exclusion. Other possibly pathologies should always be considered. The laboratory studies that may be performed based on the individual’s history and physical exam include:

  • DHEA-S (dehydroepiandrosterone sulfate) or 17-hydroxyprogesterone to screen for congenital adrenal hyperplasia or adrenal tumor.
  • Prolactin to screen to screen for hyperprolactinemia.
  • Cortisol to screen for Cushing’s syndrome.
  • TSH to screen for thyroid dysfunction.
  • IGF-1 to screen for acromegaly.
  • FSH to rule out ovarian insufficiency.
  • Urine human chorionic gonadotropin (hCG) to rule out pregnancy.
  • A glucose tolerance test is indicated in most cases, especially if signs of insulin resistance are present, such as acanthosis nigricans and/or skin tags.

Patients with atypical features such as virilization, unexplained congenital hyperandrogenism, or unresponsiveness to standard PCOS treatment should be referred for specialized work-up.

Because PCOS confers increased cardiometabolic risk, cardiovascular risk factors, including BMI, blood pressure, and lipids, should be evaluated. Smoking should be strongly discouraged, as in all patients.

PCOS is associated with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Screening for these conditions is not recommended at this time.

Testing for sleep apnea (sleep questionnaire, overnight polysomnography) may be indicated, because women with PCOS are at increased risk.

If proper treatment options or referral sources are in place, patients with PCOS should be screening for depression and anxiety.[2]

Treatment

In obese women, aggressive but sustainable weight-loss strategies can be considered first, as many PCOS sequelae improve with weight loss. Obese adolescents should also be helped to lose weight.

Oral contraceptives are recommended as first-line therapy in adolescents and adults to manage menstrual irregularities, hirsutism, and acne. Combined estrogen-progestin oral contraceptives also protect against endometrial hyperplasia.

Weight loss, physical activity, and metformin are usually necessary to reduce insulin resistance. Metformin is not recommended as a first-line therapy for cutaneous symptoms, for prevention of pregnancy complications, or for treatment of obesity. It can, however, be used to help with menstrual irregularities in patients who cannot take oral contraceptives or who desire pregnancy. The use of thiazolidinediones is not recommended in PCOS patients due to safety concerns.[2]

Physical means of hair removal (e.g., electrolysis, laser treatment) may be required to treat hirsutism.

Acne is treated with topical or oral agents if oral contraceptives are contraindicated or do not improve symptoms.

Treatment of infertility is often necessary if the patient desires pregnancy.

  • Weight loss and exercise may be beneficial; even small weight reductions may improve fertility.
  • Assisted reproductive technologies (e.g., in vitro fertilization) may be necessary.
  • Clomiphene may be used to induce ovulation. Metformin is used as an adjuvant treatment in those undergoing in vitro fertilization in order to prevent ovarian hyperstimulation. While evidence suggests it can restore ovulation, possibly by promoting weight loss, metformin’s role in treating infertility is limited.

Nutritional Considerations

PCOS appears to be related to diet and lifestyle factors, particularly as they influence body weight, insulin resistance inflammation, oxidative stress and, in turn, androgen activity. Between 30%-75% of women with PCOS are obese, and women with PCOS often have excess body fat, particularly central adiposity, even in the absence of obesity.[6] A meta-analysis of diet studies found that weight loss improved PCOS symptoms in overweight women regardless of diet composition.[7] Other studies have shown that losing as little as 5%-10% of weight results in resumption of menses and decrease in blood androgen levels.[8]

Dietary goals should target excess weight and insulin resistance. A low-fat, plant-based diet causes weight loss and reduces insulin resistance, which affects 50%-70% of women with PCOS.[9] This is particularly important because of insulin’s tendency to reduce sex hormone-binding globulin (SHBG) and increase free testosterone concentrations.[10] Low-fat, high-fiber diets reduce circulating androgens, increase SHBG,[11] and effectively address dyslipidemia (elevated triglycerides, low HDL) and elevations of C-reactive protein and homocysteine.

Diets high in fruits, vegetables, whole grains, and legumes also reduce oxidative stress and inflammation.[12] These may be involved in PCOS for several reasons. First, a genetic basis exists for the inflammation found in PCOS, with polymorphisms for proinflammatory cytokines (e.g., tumor necrosis factor, interleukin-6) being found independent of obesity and in association with insulin resistance.[13] Second, a systematic review and meta-analysis found that several markers of oxidative stress were altered in women with PCOS independent of obesity.[6] Oxidative stress impairs glucose uptake in muscle and adipose tissue in humans. In contrast, animal products and processed foods should be minimized or avoided. These foods contain cholesterol oxidation products and lipid peroxides that increase both oxidative stress and inflammation.[14]

One of the key ingredients in a diet that emphasizes whole grain intake, legumes and nuts in place of refined carbohydrates is inositol hexaphosphate (Ip6, phytic acid). In clinical trials, inositol has been shown to improve insulin action, decrease androgen levels, and improve ovulatory function in both lean and obese women with PCOS.[15],[16] ,[17] The benefits of metformin in PCOS appear at least partly due to increasing inositol availability.[18]

A dietary supplement with at least the minimum intake of the trace mineral chromium (i.e., the Recommended Daily Allowance of 25 μg/day) may be helpful, for several reasons. Insulin resistant women with PCOS were found to have significantly lower serum chromium levels compared with controls.[19] Double-blind, randomized controlled trials have shown that women with PCOS who were given supplemental chromium (between 200 and 1,000 μg/day) experienced significant improvements in insulin resistance.[20] ,[21] In addition, a recent NHANES cohort study of more than 28,000 individuals found that individuals taking a dietary supplement containing chromium had a 27% lower risk for developing type 2 diabetes, compared with those who took supplements without chromium.[22] Chromium supplementation has also been shown in women with PCOS to significantly improve the chances of ovulation and reduce hirsutism.[23]

Orders

See Basic Diet Orders Chapter

Exercise prescription.

Smoking cessation counseling, if appropriate.

Mood disorder screening, if appropriate.

What to Tell the Family

PCOS can often be effectively treated through weight loss, dietary changes, and medical therapies. Diets that are low in fat and high in fiber are likely to achieve the best results, particularly when coupled with exercise. Families of affected patients would do well to adopt a similar diet and increased exercise to facilitate the patient’s adherence and for their own health benefits.

References

  1. Azziz R et al: The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89:2745, 2004  [PMID:15181052]
  2. Legro RS et al: Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 98:4565, 2013  [PMID:24151290]
  3. Vink JM et al: Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 91:2100, 2006  [PMID:16219714]
  4. Franks S, McCarthy MI, Hardy K: Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl 29:278, 2006  [PMID:16390494]
  5. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41, 2004  [PMID:14688154]
  6. Murri M et al: Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 19:268, 2013 May-Jun  [PMID:23303572]
  7. Moran LJ et al: Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet 113:520, 2013  [PMID:23420000]
  8. Stamets K et al: A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Fertil Steril 81:630, 2004  [PMID:15037413]
  9. Hahn S et al: Clinical and biochemical characterization of women with polycystic ovary syndrome in North Rhine-Westphalia. Horm Metab Res 37:438, 2005  [PMID:16034717]
  10. Holte J: Polycystic ovary syndrome and insulin resistance: thrifty genes struggling with over-feeding and sedentary life style? J Endocrinol Invest 21:589, 1998  [PMID:9856413]
  11. Berrino F et al: Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev 10:25, 2001  [PMID:11205485]
  12. Johnston C: Functional Foods as Modifiers of Cardiovascular Disease. Am J Lifestyle Med 3:39S, 2009  [PMID:20368755]
  13. Escobar-Morreale HF, Luque-Ramírez M, González F: Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril 95:1048, 2011  [PMID:21168133]
  14. Surai KP, Surai PF, Speake BK, Sparks NHC. Antioxidant-prooxidant balance in the intestine: food for thought. 1. prooxidants. Nutr Genomics Functional Foods . 2003;1:51-70.
  15. Nestler JE et al: Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 340:1314, 1999  [PMID:10219066]
  16. Gerli S, Mignosa M, Di Renzo GC: Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 7:151, 2003 Nov-Dec  [PMID:15206484]
  17. Bizzarri M, Carlomagno G: Inositol: history of an effective therapy for Polycystic Ovary Syndrome. Eur Rev Med Pharmacol Sci 18:1896, 2014  [PMID:25010620]
  18. Baillargeon JP et al: Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril 82:893, 2004  [PMID:15482765]
  19. Chakraborty P et al: Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biol Trace Elem Res 152:9, 2013  [PMID:23322284]
  20. Jamilian M, Asemi Z: Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Nutr Metab 67:42, 2015  [PMID:26279073]
  21. Ashoush S et al: Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial. J Obstet Gynaecol Res 42:279, 2016  [PMID:26663540]
  22. McIver DJ et al: Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements. J Nutr 145:2675, 2015  [PMID:26446484]
  23. Jamilian M et al: The Effects of Chromium Supplementation on Endocrine Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial. Biol Trace Elem Res 172:72, 2016  [PMID:26613790]

Last updated: January 12, 2018

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TY - ELEC T1 - Polycystic Ovary Syndrome ID - 1342095 Y1 - 2018/01/12/ PB - Nutrition Guide for Clinicians UR - https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342095/all/Polycystic_Ovary_Syndrome ER -