The current diagnostic criteria from the 2003 Rotterdam PCOS consensus workshop is that at least two of the following three features must exist (and exclusion of other etiologies of their hyperandrogenism and/or amenorrhea/oligomenorrhea):

• Oligo- or anovulation
• Clinical and/or biochemical signs of hyperandrogenism
• Polycystic ovaries (> 12 follicles 2-9 mm or volume > 10 ml)

So many variables exist with this syndrome, that it’s no wonder it can be hard to come up with a definitive diagnosis. There can be other manifestations of hyper-androgenism (hair loss, acne) in And, not all PCOS women are infertile because of random unpredictable ovulation. Yet PCOS is likely the single most common cause of a lack of ovulation, leading to abnormal menstrual cycles and infertility

An important feature of PCOS is that there are some hormonal changes including hyperinsulinism and/or insulin resistance and elevated total testosterone. Total testosterone is not a very accurate laboratory test in women, and the range of normal has not been established, so testing testosterone levels has limited value.

The underlying cause of PCOS is varied and still evolving. What we currently know is the following:

1. elevated secretions of androgens from the ovaries and/or adrenal glands that overwhelm the body’s ability to convert these androgens to estrogen
2. abnormal ratios of the pituitary hormones, leutinizing hormone (LH) to follicle stimulating hormone (FSH)
3. failure of the monthly maturing of a follicle in the ovaries
4. a resistance to insulin
5. likely a genetically driven defect in the action of insulin

Metabolic dysfunctions including abnormalities in lipid levels, insulin and blood sugar levels, and high blood pressure are significant medical problems, that can be related to the underlying syndrome of PCOS.

Besides the potential changes including increased body weight, acne, facial hair, hair thinning, the irregular menstrual cycles and potential of infertility, there are significant diseases that can result from the underlying syndrome, including an increased risk of cardiovascular disease, type II diabetes and uterine cancer.

The metabolic goals of a holistic natural medicine approach are to:

1. lower androgens
2. inhibit the conversion of testosterone to the more potent dihydrotestosterone
3. to induce regular ovulation, and
4. to modify insulin resistance and lower the hyper-secretion of insulin

Diet and exercise are common to both conventional and alternative treatments of PCOS-to promote weight loss, increase insulin sensitivity, decrease male hormone levels, and thus restoring ovulation. Dietary changes that may improve insulin resistance are the primary emphasis with a reduction of refined carbohydrates and total calories, while increasing the high fiber foods of vegetables, legumes and whole grains. Many individuals with PCOS will respond to a diet that is not more than 80 gm/day of carbohydrates, and 60-90 gm per day of protein.

There are several natural substances that bind to and stimulate sex hormone binding globulin (SHBG), which then binds some of the testosterone in our blood stream, which in turn reduces the hyperandrogenism of PCOS. The root of the nettles plant contains many lignans and these compounds have an affinity to SHBG in humans. Nettles root can also affect aromatase inhibition which could inhibit the conversion of the weaker testosterone to dihydrotestosterone.
Caffeine containing beverages (coffee, green tea, black teak, oolong tea and even colas), were seen to have a relationship between intake and increases in SHBG. This then, had a favorable effect on hormone levels,. As caffeine intake and SHBG increases, estrogen level decreases. This is just one of the mechanisms by which green tea may have breast health implications and favorably influencing the risk of breast cancer.

Flax seeds and soy, are two important foods groups relevant in a PCOS diet. The flax seeds again, containing lignans, which increases SHBG, lowering blood testosterone levels and perhaps reducing the hyperandrogenic effects.1 I recommend 1-2 tbsp per day of flax seeds or ground flax meal.

One of the potential significant aspects of PCOS is a buildup of the lining of the uterus. This occurs because the ovaries still produce adequate estrogen, but not enough progesterone, due to a lack of ovulation. The uterus then receives what is called unopposed estrogen stimulation. This thickening is called hyperplasia, and the cells over time can become atypical or even malignant. The potential role of soy foods in the diets of women with PCOS may have some contradictions but basically, it is thought that soy can reduce blood estrogen levels and increase SHBG and that women with higher soy diets excrete more than twice the amount of estrogen in their stool in one study, and increased the excretion of estrogens in the urine in another. There are indeed, other soy studies that do not show the same results. I recommend one to two servings of a soy food per day, or something equivalent to 50mg-100 mg of soy isoflavones daily.

Saw palmetto inhibits the activity of an enzyme, 5-alpha reductase, thereby reducing the conversion of testosterone to dihydrotestosterone, the more potent form. This may have implications in reducing acne, excess facial and body hair, as well as hair loss from the scalp. Saw palmetto was recently studied as part of a formula and was able to initiate a reduction in hair loss and an improvement in hair density in patients with testosterone related hair loss.

3.5 gms of a licorice root extract standardized to contain 7.6% W.W. glycyrrhizic acid (0.25 grams total glycyrrhizic acid per day), q.d. for 2 months was given to nine “healthy” women, ages 22-26 years. Outcome measures included blood pressure, plasma renin activity (PRA), plasma cortisol, plasma aldosterone, total serum testosterone, androstenedione, 17-OH-progesterone (17OHP) and gonadotropins, which were tested at baseline, after 1 and 2 months taking licorice, and one month post-treatment. Mean total serum testosterone significantly decreased after one and two months of treatment (27.8 ± 8.2 vs. 19. ± 9.4 and 17.5 ± 6.4 ng/dL, respectively).

It’s interesting to note that this is the first trial to follow-up on earlier trials that found that licorice may reduce testosterone secretion in women with polycystic ovary syndrome (Acta Obst Gynecol Jpn 1988;40:789-92) and another showing a similar result in hyperandrogenic and oligomenorrheic women.

Calcium and vitamin D are two of the most reaching nutrients our body needs affecting muscles, bones, thyroid, brain, heart, hormones, colon, breast and more. Calcium and vitamin D regulation may also contribute to the development of faulty ovarian follicle development in women with PCOS, resulting in reproductive and menstrual dysfunction. Vitamin D also plays a role in glucose metabolism and is commonly deficient in individuals with type 2 diabetes. Supplementing with vitamin D has been shown to improve glucose tolerance, insulin secretion and insulin sensitivity in those with DM., A deficiency of vitamin D may be more frequent in women with PCOS and in a small study, five of thirteen women had an overt vitamin D deficiency. Seven of the nine women with no menses or infrequent menses, had a return to a normal menstrual cycle within two months of being given 50,000 IU once or twice per week of vitamin D and 1,500 mg per day of calcium.10

Chromium is a trace mineral that enhances the action of insulin. Supplementing with chromium has been shown in some studies to improve the blood sugar control in those with type 2 DM. Giving PCOS women 1,000 mcg per day of chromium for as little as two months was able to improve insulin sensitivity by 30% and by 38% in obese women with PCOS.

A little known supplement, D-chiro-inositol is not commercially available, but pinitol, a compound similar to D-chiro-inositol, is available. Pinitol appears to mediate insulin activity. In an important study about this nutrient, 600 mg of pinitol twice per day for three months lowered blood glucose levels by 19%, lowered average glucose levels by 12% and significantly improved insulin resistance.

Conventional treatment of PCOS includes diet and exercise, and a drug, Metformin, used to improve insulin resistance. This can lead to normal ovulation. Other medications are used to induce ovulation such as clomiphene citrate, spironolactone to decrease testosterone on the hair follicle, and oral contraceptives to address irregular menstrual cycles and excess body hair. A topical medication, Vaniqa, is used topically, to reduce facial hair.

PCOS is a complicated condition, requiring long term attention and regular medical attention, keeping in mind the potential for increased risks of diabetes, hypertension, hyperlipidemia, uterine cancer.

As a practitioner with more awareness and experience with PCOS, we have an important role in detecting the long undiagnosed patient, the inadequately managed patient, and the discouraged patient.

In summary, a comprehensive plan for PCOS would include:

Weight loss in those who are overweight
Daily aerobic exercise one hour per day
Low simple carbohydrates (Up to 80 gm/day of carbohydrates and 60-90 gm per day of protein)
Flax seeds 1-2 tbsp per day
Soy food 1 to 2 servings per day
Vitamin D 2,000 i.u. per day or without testing, up to 5,000 i.u. per day
Calcium 1,000mg-1,500 mg per day (including dietary sources)
Chromium 1,000 mcg per day
Green tea (90% polyphenols, 80% catechins, 45% EGCG) 300mg-500 mg per day or 3 cups of tea per day
Nettles root 600 mg per day
Saw Palmetto extract 400 mg per day
Pinitol 600 mg twice per day

Consider Licorice root extract

Important resources:

Women’s Encyclopedia of Natural Medicine. Tori Hudson, N.D., McGraw/Hill publishing

PCOS, A Woman’s Guide to Dealing with Polycystic Ovary Syndrome. Colette Harris with Dr. Adam Carey. Thorson’s publishing

PCOS, The Hidden Epidemic. Samuel Thatcher, M.D., PhD. Perspectives Press

The Natural Diet Solution for PCOS and Infertility. Nan Dunne, N.D. (paperback and e-book

PCOS Health Review – free newsletter; Nan Dunne, N.D. and Bill Slater

References

• Schottner M, Gansser D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin. Planta Med 1997; 63(6): 529-532
• Gansser D, Spiteller G. Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts. Z Naturforsch 1995;50(1-2):98-104.
• Schottner M, GanBer D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG). Planta Med 1997; 63:529-532
• Gansser D, Spiteller G. Aromatase inhibitors from Urtica dioica roots. Planta Med. 1995;61(2): 138-140.
• Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese Women. Nutrition and Cancer 1998; 30(1): 21-24.
• Kumar N, Cantor A, Allen K, et al. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer 2002;94:1166-1174.
• Goldin B, Adlercreutz H, Gorbach S, et al. The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women. Am J Clin Nutr 1986;44:945-953
• Xu X, Duncan A, Wangen K, Kurzer M. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiology, Biomarkers and Prevention 2000;9:781-786.
• Martini M, Dancisak B, Haggans C, Thomas W, Slavin J. Nutrition and Cancer 1999;34(2): 133-139.
• Prager N, Bicket K, French N, Marovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. JAH and Comple Med 2002;8(2): 143-152.
• Armanini D, et al. Steroids 2005;69:763-6.
• Acta Obst Gynecol Jpn 1982;34:939-44
• Thys-Jacobs S, Donovan D, Papadopoulos A, et al. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 1999;64:430-435.
• Raghuramulu N, Raghunath M, Chandra S, et al. Vitamin D improves oral glucose tolerance and insulin secretion in human diabetes. J Clin Biochem Butr 1992;13:45-51.
• Borissova A, Tankova T, Kirilov G, et al. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients, Int J Clin Pract 2003;57:258-261.
• Gaby A. Chromium. Integrative Med 2006;5(4):22-26.
• Lydic L, McNurlan M, Komaroff E, et al. Effects of chromium supplementation on insulin sensitivity and reproductive function in polycystic ovarian syndrome: a pilot study. Fertil Steril 2003;80 (Suppl 3): S45-S46.
• Lydic M, McNurlan M, Bembo S, Mitchell L, Komaroff E, Gelato M. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril 2006;86:243-246.
• Davis A, Christiansen M, Horowitz J, et al. Effect of pinitol treatment on insulin action in subjects with insulin resistance. Diabetes Care 2000;23:1000-1005.
• Kim J, Kim J, Kang M, et al. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus: a randomized contolled study. Eur J Clin Nutr 2005;59:456-458.

Armanini D, Castello R. Scaroni C, et al. Treatment of polycystic ovary syndrome with spironolactone plus licorice. Eur J Obstet Gynecol 2007;131:61-67.

Commentary: It’s very useful to find a second study on licorice and it’s role in PCOS. Glycyrrhetinic acid has been shown to reduce serum testosterone and induce regular ovulation. (Yaginuma T, Izumi R, Yasui H, et al. Effect of traditional herbal medicine on serum testosterone levels and its inductions of regular ovulation in hyperandrogenic and oligomenorrheic women. Nippon Sanka Fujinka Gakkai Zasshi 1982;34:939-944) ( Takahashi K, Yoshino K, Shirai T, et al. Effect of a traditional herbal medicine on testosterone secretion in patients with polycystic ovary syndrome detected by ultrasound. Nippon Sanka Fujinka Gakkai Zasshi 1988;789-92.)

Spironolactone is often used as part of a treatment plan in PCOS women with bothersome hirsutism. While Spironolactone can be helpful, fatigue and polyuria are a frequent side effect. It may be that licorice and glycyrrhetinic acid have a potential synergistic effect on the androgen receptors, reduce the side effects associated with Spironolactone, as well as reducing serum testosterone and inducing regular ovulation. Licorice extract along with a lower carbohydrate/higher protein diet, therapies that increase SHBG such as nettles root, green tea, flax seeds and soy and insulin sensitizing strategies such as daily aerobic exercise, fenugreek powder, cinnamon extract, d-pinitol, chromium (and possibly glucophage) offer a comprehensive approach for women with PCOS.

PCOS is not really classified as a disease, because it is not a specific and constant set of symptoms and physical characteristics. Rather, it is better described as a syndrome, with a collection of symptoms, physical and laboratory findings. There are two consistent aspects of PCOS: hyper-androgenism (or an increase in male hormones) and a lack of or infrequent ovulation. The most common characteristics of PCOS are obesity, excess body hair (hirsutism), and irregular/infrequent/lack of ovulation and thus irregular menses and poor fertility. Over 95% of women who have all three of the classic signs of obesity, hirsutism and infertility and/or irregular menses, have PCOS. One of the problems with PCOS, is that many women have this syndrome, but don’t have all three of the classic signs. So, not all women with PCOS are obese, in fact not even 50%. Many PCOS women are of normal weight or even underweight, have no excess hair growth on the face of chest or legs, and may even have pretty regular menses.

So many variables exist with this syndrome, that it’s no wonder it can be hard to come up with a definitive diagnosis. There can be other manifestations of hyper-androgenism in women including hair thinning or acne. And, not all PCOS women are infertile, yet PCOS is likely the single most common cause of a lack of ovulation, leading to abnormal menstrual cycles and infertility

An important feature of PCOS is that there are some kind of changes in hormones- for sure, elevated levels of the male hormones, although this is often not detected by the poor sensitivity of laboratory testing. The underlying cause of PCOS is varied and still evolving. What we currently know is the following:

1. elevated secretions of male hormones from the ovaries and/or adrenal glands that overwhelm the body’s ability to convert these male hormones to estrogen
2. abnormal ratios of the pituitary hormones, leutinizing hormone (LH) to follicle stimulating hormone (FSH)
3. failure of the monthly maturing of a follicle in the ovaries
4. a resistance to insulin
5. and likely a genetically driven defect in the action of insulin

Metabolic dysfunctions including abnormalities in blood fat(lipid) levels, insulin and blood sugar levels, and high blood pressure are significant medical problems, that can be related to the underlying syndrome of PCOS.

Besides the potential changes in one’s appearance of weight gain, acne, facial hair, or hair thinning, the irregular menstrual cycles and potential of infertility, there are significant diseases that can result from the underlying syndrome, including and increased risk of cardiovascular disease, type II diabetes and uterine cancer.

With all this going on, you might wonder how could it possibly be underdiagnosed? The answers lie in more than one area. Women with PCOS often have a similar story to tell: they went to their dermatologist for acne- then were given topical treatments or antibiotics. Or, they went to their gynecologist for irregular menses and were put on birth control pills. These two common stories are the result of compartmentalization in medicine, and not enough health care providers understanding this syndrome and all the body systems it can affect. Things are changing though, and this multiple system syndrome, is now better understood, with more common accurate diagnoses being made, and better treatments both natural and conventional.

The metabolic goals of a holistic natural medicine approach are to…

1. lower androgens
2. inhibit the conversion of testosterone to the more potent dihydrotestosterone
3. to induce regular ovulation
4. to modify insulin resistance and lower the hyper-secretion of insulin.

Diet and exercise are common to both conventional and alternative treatments of PCOS – to promote weight loss, increase insulin sensitivity, decrease male hormone levels, and thus restoring ovulation. Dietary changes that may improve insulin resistance are the primary emphasis with a reduction of refined carbohydrates and total calories, while increasing the high fiber foods of vegetables, legumes and whole grains. Many individuals with PCOS will respond to a diet that is not more than 80 gm/day of carbohydrates, and 60-80 gm per day of protein

There are several natural substances that bind to and stimulate sex hormone binding glogulin (SHBG), which then binds some of the testosterone in our blood stream, which in turn reduces the hyperandrogenism of PCOS. The root of the nettles plant contains many lignans and these compounds have an affinity to SHBG in humans. , Nettles root can also affect aromatase inhibition which could inhibit the conversion of the weaker testosterone to dihydrotestosterone.

Caffeine containing beverages (coffee, green tea, black teak, oolong tea and even colas), were seen to have a relationship between intake and increases in SHBG. This then, had a favorable effect on hormone levels,. As caffeine intake and SHBG increases, estrogen level decreases. This is just one of the mechanisms by which green tea may have breast health implications and favorably influencing the risk of breast cancer.

Flax seeds and soy, are two important foods groups relevant in a PCOS diet. The flax seeds again, containing lignans, which increases SHBG, lowering blood testosterone levels and perhaps reducing the hyperandrogenic effects1 I recommend 1-2 tbsp per day of flax seeds or ground flax meal.

One of the potential significant aspects of PCOS is a buildup of the lining of the uterus. This occurs because the ovaries still produce adequate estrogen, but not enough progesterone, due to a lack of ovulation. The uterus then receives what is called unopposed estrogen stimulation. This thickening is called hyperplasia, and the cells over time can become atypical or even malignant. The potential role of soy foods in the diets of women with PCOS may have some contradictions but basically, it is thought that soy can reduce blood estrogen levels and increase SHBG and that women with higher soy diets excrete more than twice the amount of estrogen in their stool in one study, and increased the excretion of estrogens in the urine in another. There are indeed, other soy studies that do not show the same results. I recommend one serving of a soy food per day, or something equivalent to 50mg-100 mg of soy isoflavones daily.

Saw palmetto inhibits the activity of an enzyme, 5-alpha reductase, thereby reducing the conversion of testosterone to dihydrotestosterone, the more potent form. This may have implications in reducing acne, excess facial and body hair, as well as hair loss from the scalp. Saw palmettos was recently studied as part of a formula and was able to initiate a reduction in hair loss and an improvement in hair density in patients with testosterone related hair loss.

Calcium and vitamin D are two of the most reaching nutrients our body needs affecting muscles, bones, thyroid, brain, heart, hormones, colon, breast and more. Calcium and vitamin D regulation may also contribute to the development of faulty ovarian follicle development in women with PCOS, resulting in reproductive and menstrual dysfunction. Vitamin D also plays a role in glucose metabolism and is commonly deficient in individuals with type 2 diabetes. Supplementing with vitamin D has been shown to improve glucose tolerance, insulin secretion and insulin sensitivity in those with DM., A deficiency of vitamin D may be more frequent in women with PCOS and in a small study, five of thirteen women had an overt vitamin D deficiency. Seven of the nine women with no menses or infrequent menses, had a return to a normal menstrual cycle within two months of being given 50,000 IU once or twice per week of vitamin D and 1,500 mg per day of calcium.10

Chromium is a trace mineral that enhances the action of insulin. Supplementing with chromium has been shown in some studies to improve the blood sugar control in those with type 2 DM. Giving PCOS women 1,000 mcg per day of chromium for as little as two months was able to improve insulin sensitivity by 30% and by 38% in obese women with PCOS.

A little known supplement, D-chiro-inositol is not commercially available, but pinitol, a compound similar to D-chiro-inositol, is available. Pinitol appears to mediate insulin activity. In an important study about this nutrient, 600 mg of pinitol twice per day for three months lowered blood glucose levels by 19%, lowered average glucose levels by 12% and significantly improved insulin resistance.

Conventional treatment of PCOS includes diet and exercise, and a drug, Metformin, used to improve insulin resistance. This can lead to normal ovulation. Other medications are used to induce ovulation such as clomiphene citrate, spironolactone to decrease testosterone on the hair follicle, and oral contraceptives to address irregular menstrual cycles and excess body hair. A newer drug, Vaniqa, is used topically, to reduce facial hair.

Working with a licensed alternative medicine provider with knowledge of this condition, the ability to run laboratory tests and to assess for complications of the syndrome and an understanding of the mechanism of the natural ingredients, would be optimal. It’s a complicated condition, requiring long term attention and regular medical care. But, don’t despair if you have this syndrome. We finally have lots of options to address the symptoms and the metabolic dysregulation, and natural medicines play a big part.

In summary, a comprehensive plan for PCOS would include:

Weight loss in those who are overweight
Daily aerobic exercise one hour per day
Low simple carbohydrates
Up to 80 gm/day of carbohydrates
60-80 gm per day of protein
Flax seeds 1-2 tbsp per day
Soy food 1 serving per day
Vitamin D 2,000 i.u. per day (or more under doctor’s supervision)
Calcium 1,000mg-1,500 mg per day
Chromium 1,000 mcg per day
Green tea (90% polyphenols, 80% catechins, 45% EGCG) 300mg-500 mg per day or 3 cups of tea per day
Nettles root 600 mg per day
Saw Palmetto extract 400 mg per day
Pinitol 600 mg twice per day

Important resources:

Women’s Encyclopedia of Natural Medicine. Tori Hudson, N.D., McGraw/Hill publishing

PCOS, A Woman’s Guide to Dealing with Polycystic Ovary Syndrome. Colette Harris with Dr. Adam Carey. Thorson’s publishing

PCOS, The Hidden Epidemic. Samuel Thatcher, M.D., PhD. Perspectives Press

The Natural Diet Solution for PCOS and Infertility. Nan Dunne, N.D. (paperback and e-book) 
PCOS Health Review- free newsletter; Nan Dunne, N.D. and Bill Slater

Schottner M, Gansser D, Spiteller G. Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin. Planta Med 1997; 63(6): 529-532

Gansser D, Spiteller G. Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts. Z Naturforsch 1995;50(1-2):98-104.

Gansser D, Spiteller G. Aromatase inhibitors from Urtica dioica roots. Planta Med. 1995;61(2): 138-140.

Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese Women. Nutrition and Cncer 1998; 30(1): 21-24.

Kumar N, Cantor A, Allen K, et al. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer 2002;94:1166-1174.

Goldin B, Adlercreutz H, Gorbach S, et al. The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women. Am J Clin Nutr 1986;44:945-953

Xu X, Duncan A, Wangen K, Kurzer M. Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiology, Biomarkers and Prevention 2000;9:781-786.

Martini M, Dancisak B, Haggans C, Thomas W, Slavin J. Nutrition and Cancer 1999;34(2): 133-139.

Prager N, Bicket K, French N, Marovici G. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. JAH and Comple Med 2002;8(2): 143-152.

Thys-Jacobs S, Donovan D, Papadopoulos A, et al. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 1999;64:430-435.

Raghuramulu N, Raghunath M, Chandra S, et al. Vitamin D improves oral glucose tolerance and insulin secretion in human diabetes. J Clin Biochem Butr 1992;13:45-51.

Borissova A, Tankova T, Kirilov G, et al. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients, Int J Clin Pract 2003;57:258-261.

Gaby A. Chromium. Integrative Med 2006;5(4):22-26.

Lydic L, McNurlan M, Komaroff E, et al. Effects of chromium supplementation on insulin sensitivity and reproductive function in polycystic ovarian syndrome: a pilot study. Fertil Steril 2003;80 (Suppl 3): S45-S46.

Lydic M, McNurlan M, Bembo S, Mitchell L, Komaroff E, Gelato M. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril 2006;86:243-246.

Davis A, Christiansen M, Horowitz J, et al. Effect of pinitol treatment on insulin action in subjects with insulin resistance. Diabetes Care 2000;23:1000-1005.

Kim J, Kim J, Kang M, et al. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus: a randomized contolled study. Eur J Clin Nutr 2005;59:456-458.