Chromium And Pcos

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In 1935, gynecologists Irving F. Stein and Michael L. Leventhal described a condition of ovarian cysts and ovulatory disturbances.[1] It soon became clear that these were symptoms of excessive androgen production.[2],[3]

Introduction: polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Some vitamins and mineral can play role in improvement of PCOS. Chromium (Cr) is an essential element. Insulin resistance is present in two serious health problems in women; polycystic ovarian syndrome (PCOS) and gestational diabetes. Several studies have now demonstrated that chromium supplements enhance the metabolic action of insulin and lower some of the risk factors for cardiovascular disease, particularly in overweight individuals.

Polycystic ovary syndrome (PCOS) affects an estimated 6-8% of women in the United States.[4] Diagnosis can be difficult due to the variability of presentation, so actual prevalence may be considerably higher.

Doses of 600 mg per day of D-chiro-inositol have been shown to improve insulin and androgen levels in lean women with PCOS (Luorno et al. 2002 31), while doses of 1000 mg per day have been effective at improving a range of metabolic and cardiovascular health indicators on a more representative PCOS population (Lagana et al. Chromium picolinate decreased FBS and insulin levels and, thus, increased insulin sensitivity in clomiphene citrate-resistance PCOS women. These effects were comparable with metformin; however, metformin treatment was associated with decreased hyperandrogenism.

The etiology is complex, thought to arise from interactions between genes and the environment. While previously thought to be predominantly related to dysregulation of androgen production, it is now believed to be result of a ‘two-hit’ scenario, the first hit being a congenital predisposition such as sub-optimal fetal nutrition or heritable genetic variants related to insulin resistance, steroidogenesis, and ovarian function. The second, postnatal hit is insulin-resistant hyperinsulinism, such as seen in those with metabolic syndrome and obesity.[5]

The onset of PCOS is typically in peripubertal years, and clinical presentation is varied. The key features are 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.[6]

Patients with the diagnosis are at increased risk for depression and eating disorders and may have an impaired quality of life, compared with 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.

Genetics. Twin studies suggest that more than 70% of cases can be attributed to polygenic heritable traits.[7] However, it appears that other congenital or environmental factors must also be present for the condition to manifest.[8]

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

Diagnosis

Chromium

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.

There are at least 3 different sets of diagnostic criteria for PCOS in adults, with the Rotterdam criteria being most used in the US. 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:[6],[9]

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.

Natural Treatment For Pcos

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, blood sugar and lipids, should be evaluated. Smoking should be strongly discouraged, as in all patients.

A picture of alexa. 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 screened for depression and anxiety.[6]

In obese women, aggressive but sustainable weight-loss strategies should be considered first, as many PCOS sequelae improve with weight loss. Details are described in the Nutrition Considerations section, below. Obese adolescents should also be helped to lose weight.

Apart from nutritional interventions, oral contraceptives are recommended as first-line pharmacologic 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, ovulation induction, prevention of pregnancy complications, or treatment of obesity. It can, however, be used to help with many PCOS symptoms in women who have an insufficient response to dietary interventions and have contraindications to oral contraceptives. The use of thiazolidinediones is not recommended in PCOS patients due to safety concerns.[6]

Physical means of hair removal (e.g., electrolysis, laser treatment) may be necessary 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 or letrozole are now preferred 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.[10] A meta-analysis of diet studies found that weight loss improved PCOS symptoms in overweight women regardless of diet composition.[11] Other studies have shown that losing as little as 5-10% of weight results in resumption of menses and decrease in blood androgen levels.[12]

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.[13] This is particularly important because of insulin’s tendency to reduce sex hormone-binding globulin (SHBG) and increase free testosterone concentrations.[14] Low-fat, high-fiber diets reduce circulating androgens, increase SHBG, and effectively address dyslipidemia (elevated triglycerides, low HDL) and elevations of C-reactive protein and homocysteine.[15]

Diets high in fruits, vegetables, whole grains, and legumes also reduce oxidative stress and inflammation.[16] 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.[17] Second, a systematic review and meta-analysis found that several markers of oxidative stress were altered in women with PCOS, independent of obesity.[10] 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.[18]

One of the key nutrients 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.[19],[20],[21] The benefits of metformin in PCOS appear at least partly due to increasing inositol availability.[22]

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.[23] 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.[24],[25] 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.[26] Chromium supplementation has also been shown in women with PCOS to significantly improve the chances of ovulation and reduce hirsutism.[27]

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 dietary changes, weight loss, 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.

  1. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol. 1935;29:181-191.
  2. Alpañés M, Fernández-Durán E, Escobar-Morreale HF. Androgens and polycystic ovary syndrome. Expert Rev Endocrinol Metab. 2012;7(1):91-102. [PMID:30736114]
  3. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 194: Polycystic Ovary Syndrome. Obstet Gynecol. 2018;131(6):e157-e171. [PMID:29794677]
  4. Azziz R, Woods KS, Reyna R, et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-9. [PMID:15181052]
  5. Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016;37(5):467-520. [PMID:27459230]
  6. Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565-92. [PMID:24151290]
  7. Vink JM, Sadrzadeh S, Lambalk CB, et al. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab. 2006;91(6):2100-4. [PMID:16219714]
  8. Franks S, McCarthy MI, Hardy K. Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl. 2006;29(1):278-85; discussion 286-90. [PMID:16390494]
  9. 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. 2004;19(1):41-7. [PMID:14688154]
  10. Murri M, Luque-Ramírez M, Insenser M, et al. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update. 2013;19(3):268-88. [PMID:23303572]
  11. 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):520-45. [PMID:23420000]
  12. Stamets K, Taylor DS, Kunselman A, 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. 2004;81(3):630-7. [PMID:15037413]
  13. Hahn S, Tan S, Elsenbruch S, et al. Clinical and biochemical characterization of women with polycystic ovary syndrome in North Rhine-Westphalia. Horm Metab Res. 2005;37(7):438-44. [PMID:16034717]
  14. Holte J. Polycystic ovary syndrome and insulin resistance: thrifty genes struggling with over-feeding and sedentary life style? J Endocrinol Invest. 1998;21(9):589-601. [PMID:9856413]
  15. Berrino F, Bellati C, Secreto G, et al. Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev. 2001;10(1):25-33. [PMID:11205485]
  16. Johnston C. Functional Foods as Modifiers of Cardiovascular Disease. Am J Lifestyle Med. 2009;3(1 Suppl):39S-43S. [PMID:20368755]
  17. Escobar-Morreale HF, Luque-Ramírez M, González F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril. 2011;95(3):1048-58.e1-2. [PMID:21168133]
  18. 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.
  19. Nestler JE, Jakubowicz DJ, Reamer P, et al. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340(17):1314-20. [PMID:10219066]
  20. 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. 2003;7(6):151-9. [PMID:15206484]
  21. Bizzarri M, Carlomagno G. Inositol: history of an effective therapy for Polycystic Ovary Syndrome. Eur Rev Med Pharmacol Sci. 2014;18(13):1896-903. [PMID:25010620]
  22. Baillargeon JP, Jakubowicz DJ, Iuorno MJ, 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. 2004;82(4):893-902. [PMID:15482765]
  23. Chakraborty P, Ghosh S, Goswami SK, et al. Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biol Trace Elem Res. 2013;152(1):9-15. [PMID:23322284]
  24. 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. 2015;67(1):42-8. [PMID:26279073]
  25. Ashoush S, Abou-Gamrah A, Bayoumy H, et al. Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial. J Obstet Gynaecol Res. 2016;42(3):279-85. [PMID:26663540]
  26. McIver DJ, Grizales AM, Brownstein JS, et al. Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements. J Nutr. 2015;145(12):2675-82. [PMID:26446484]
  27. Jamilian M, Bahmani F, Siavashani MA, 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. 2016;172(1):72-8. [PMID:26613790]

Citation

Barnard, Neal D., editor. 'Polycystic Ovary Syndrome.' Nutrition Guide for Clinicians, 3rd ed., Physicians Committee for Responsible Medicine, 2021. nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342095/all/Polycystic_Ovary_Syndrome.
Polycystic Ovary Syndrome. In: Barnard NDN, ed. Nutrition Guide for Clinicians. Physicians Committee for Responsible Medicine; 2021. https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342095/all/Polycystic_Ovary_Syndrome. Accessed May 10, 2021.
Polycystic Ovary Syndrome. (2021). In Barnard, N. D. (Ed.), Nutrition Guide for Clinicians (3rd edition). Physicians Committee for Responsible Medicine. https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342095/all/Polycystic_Ovary_Syndrome
Polycystic Ovary Syndrome [Internet]. In: Barnard NDN, editors. Nutrition Guide for Clinicians. Physicians Committee for Responsible Medicine; 2021. [cited 2021 May 10]. Available from: https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342095/all/Polycystic_Ovary_Syndrome.

Chromium And Pcos

* Article titles in AMA citation format should be in sentence-case
TY - ELECT1 - Polycystic Ovary SyndromeID - 1342095ED - Barnard,Neal D,BT - Nutrition Guide for CliniciansUR - https://nutritionguide.pcrm.org/nutritionguide/view/Nutrition_Guide_for_Clinicians/1342095/all/Polycystic_Ovary_SyndromePB - Physicians Committee for Responsible MedicineET - 3DB - Nutrition Guide for CliniciansDP - Unbound MedicineER -

Written by Joyce Smith, Staff Writer. Women with Polycystic Ovarian Syndrome who supplemented with chromium picolinate for 8 weeks experienced significantly less alopecia, hirsutism, acne and had reduced levels of inflammation and oxidative stress compared to those PCOS women who did not take chromium.

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder that affects 6-8% of women of reproductive age worldwide 1. People with PCOS may have infrequent or prolonged menstrual periods, alopecia (baldness), hirsutism (excess hair growth on the face and body), acne, insulin resistance, obesity and polycystic ovaries.2 Some studies have suggested that people with PCOS may have hyperglycemia, impaired insulin metabolism, and an abundance of adipose tissue, all of which contribute to free radical formation and reactive oxygen species (ROS) and increase the biomarkers for inflammation and oxidative stress 3.

Other studies have suggested that people with increased levels of inflammation, particularly due to elevated C-reactive protein (CPR) and interleukin 18 (IL-18) 4, may have an increased risk of developing atherosclerosis because of accelerated endothelium dysfunction 5.

Because of limited available research, researchers chose to investigate the effects of chromium supplementation on endocrine profiles, inflammatory cytokines, and biomarkers of oxidative stress among women with PCOS.

This randomized, double- blind, placebo-controlled clinical trial consisted of two groups of 60 PCOS women (18-48 years of age) who received either 200 mcg of chromium picolinate supplements daily (n=30) or placebo (n=30) for 8 weeks. Three dietary and three physical activity records were completed at weeks3, 5, and 7 of treatment. Participants kept three-day food diaries which were used to compute their nutrient intakes.

Endocrine profiles were quantified on all patients from fasting blood samples taken before and after 8 weeks of chromium supplementation. These included serum prolactin, follicular-stimulating hormone (FSH), and luteinizing hormone (LH) concentrations, serum free testosterone, dehydroepiandrosterone (DHEA), and 17-OH progesterone concentrations.

Also recorded were high sensitivity C-reactive protein (hs-CRP), a measure of inflammation and the following biomarkers of oxidative stress: nitric oxide (NO) 6, Total Oxygen Capacity (TAC) 7, glutathione (GSH), and malondialdehyde (MDA) 89.

Anthropometric measures were documented, including height and weight, to assess body shape, size and composition. The presence and degree of hirsutism 10, alopecia 11, and acne 12 were also documented. A P value of < 0.05 was considered statistically significant.

After 8 weeks of intervention, the chromium group had a greater pregnancy rate (P=0.08) and decreased alopecia (baldness) (P=0.22); however, neither reached significance.

The chromium group had a significant reduction in acne (P=0.04), hirsutism (P=0.002), serum hs-CRP (P=0.02), plasma MDA (P<0.001), and a significant rise in TAC concentrations (P<0.001) compared to the placebo group.

Summary of Effects of Chromium Supplementation
Chromium GroupPlacebo p-value
Pregnancy Rate16.7 % (5/30) 3.3 % (1/30),P=0.08*
Serum hs-CPR(−717.0 ± 1496.1ng/mL) (+227.1 ± 1669.6 ng/mL)P=0.02
Plasma MDA(−0.1 ± 0.7 μmol/L) (+1.1 ± 1.5 μmol/L)P<0.001
TAC (+250.7 ± 265.2mmol/L)(+13.0 ± 201.6 mmol/L)P<0.001
Alopecia16.7%6.7%P=0.22*
Hirsutism(−1.8 ± 2.5)(-0.2 ± 0.8)P=0.002
Acne20.0 % 3.3 %P=0.04
NO, GSH, Endocrine profile*No significant changes

There were no significant changes in endocrine profiles and NO and GSH levels following chromium supplementation.

Unfortunately the effects of chromium supplementation on serum chromium concentrations were not included in the panel of tests because of limited funds. Also, patients who had impaired glucose tolerance and insulin resistance might have added value to the study had they not been excluded from it. Overall, chromium supplementation had “beneficial effects on acne, hirsutism, hs-CRP, TAC, and MDA levels” but had no effect on endocrine profiles, NO, and GSH.

Source: Mehri Jamilian M., Bahmani F., Siavashani M.A., 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. Clinical Endocrinology (2015), 82, 885–891; doi: 10.1111/cen.12699

© 2014 John Wiley & Sons Ltd

Posted October 24, 2016.

References:

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  2. Jamilian M, Razavi M, Fakhrie Kashan Z, Ghandi Y, Bagherian T, Asemi Z. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology. 2015;82(6):885-891.
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