Functional Nutrition for PCOS

Contents

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What is PCOS?

Polycystic ovary syndrome (PCOS) is a complex hormonal and metabolic disorder characterized by elevated androgen hormone levels, menstrual irregularities, and/or ovarian follicular cysts (1).

A follicular ovarian cyst is a follicle (fluid-filled sac that contains an immature egg) that fails to release its egg for ovulation and instead continues to grow (2).


How common is PCOS?

It is estimated that 8% to 13% of women have PCOS (3).


What are the underlying causes of PCOS?

Because the pathogenesis is not fully understood, it can be difficult to determine what is a cause and what is an effect in the development of PCOS, but scientists believe the following factors are involved (4):

1. Genetic susceptibility

A wide variety of gene variants have been linked with PCOS, many of which are also related to insulin resistance, type 2 diabetes, and obesity (56).

These are a few of the most common SNPs associated with PCOS:

  • rs13405728 (LHCGR gene) (7)
  • rs2414096 (CYP19 gene) (8)
  • rs346795081 (THADA gene) (9)
  • rs346803513 (DENND1A gene) (9)
  • rs346999236 (TOX3 gene) (9)

Evidence from twin studies suggests that genetic influences are responsible for more than 70% of PCOS pathogenesis (10).

2. Exposure to excess androgens in utero 

Evidence from animal studies suggests that exposure to excess androgens (mainly testosterone) in utero results in the development of many of the features of PCOS in adolescence (1112131415).

It’s not feasible to directly measure human fetal exposure to testosterone, but a few human studies have used indirect measurements, and their results seem to confirm this theory (1617181920).

3. Disordered gonadotropin secretion

Under normal conditions, the hypothalamus secretes gonadotropin-releasing hormone (GnRH), which in turn stimulates the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the pituitary gland (21).

In the ovaries, LH works together with FSH to regulate follicle development, ovulation, and the production of steroid hormones (including androgens) (2122).

Most women with PCOS have high LH levels and an elevated LH:FSH ratio due to increased GnRH secretion, which can lead to increased androgen production and the development of follicular ovarian cysts (232425).

4. Inflammation

PCOS is associated with chronic low-grade inflammation, indicated by elevated C-reactive protein (CRP), inflammatory cytokines (IL-6 and IL-18), and increased leukocyte count (26272829).

There is some evidence that inflammation stimulates the ovaries to produce androgens, which may contribute to hyperandrogenism (30).

5. Insulin resistance

It has been estimated that 70% of women with PCOS have insulin resistance, which may play a role in pathogenesis (313233).

High levels of insulin contribute to hyperandrogenism by increasing GnRH and LH, as well as decreasing sex hormone-binding globulin (SHBG) levels (31343536).

In turn, high levels of androgens can also increase insulin resistance, creating a vicious cycle (3137).

6. Endocrine-disrupting chemicals 

Any chemical (not produced by the body) that interferes with the synthesis, secretion, transport, metabolism, binding action, or elimination of hormones is considered to be an “endocrine disruptor” (38).

Evidence from animal studies suggests that exposure to BPA (an endocrine disruptor found in plastics) during fetal development increases the risk of developing hormonal imbalances and PCOS (394041).

In addition, women with PCOS tend to have higher levels of BPA in their blood (42).

7. Autoimmunity

PCOS has been linked with autoimmune disease and increased levels of several certain autoantibodies (434445464748).

More research is needed, but one theory is that low levels of progesterone may overstimulate the immune system, leading to the production of autoantibodies (43).

8. Obesity?

Between 50% and 80% of women with PCOS also have obesity, but it’s unclear whether obesity increases the risk of PCOS or vice versa (49505152).

One study found that the prevalence of PCOS was 9.8% in normal-weight individuals and 9.9% in overweight individuals, suggesting that excess weight only slightly increases risk (53).

However, there is evidence that obesity can exacerbate some aspects of PCOS, including glucose intolerance and dyslipidemia (52).


Is it possible for males to develop PCOS?

Although they don’t have ovaries, it is possible for males to experience certain features of PCOS, suggesting that there might be a male equivalent of the syndrome (54).

Male relatives of women with PCOS are more likely to be diagnosed with the following conditions:

  • Dyslipidemia (5556)
  • Early-onset androgenetic alopecia (male pattern baldness) (5758)
  • Hormonal imbalances (59606162)
  • Hypertension (63)
  • Insulin resistance (6364)

However, this is just a theory at this point, and more research is needed.


What are the symptoms of PCOS?

  • Absent or irregular periods (65)
  • Acanthosis nigricans (patches of velvety, darkened skin) (6667)
  • Acne (6668)
  • Alopecia (hair loss) (69)
  • Hirsutism (abnormal growth of coarse, dark hair in areas of the body where men typically have hair) (6670)
  • Infertility (71)
  • Oily skin (72)
  • Pelvic pain (x)
  • Polycystic ovaries (73)
  • Skin tags (73)
  • Sleep disturbances (7475)
  • Weight gain (76)

How is PCOS diagnosed?

Using the Rotterdam criteria (most common), a diagnosis of PCOS is made when 2 of the 3 following criteria are met (73):

1. Androgen excess

May be determined by clinical signs (hirsutism, acne, or androgenic alopecia) AND/OR by elevated serum androgen level.

2. Ovulatory dysfunction

Determined by menstrual history that includes oligo- (irregular) or anovulation (no ovulation), which may manifest as: 

  • Frequent bleeding at intervals <21 days OR
  • Infrequent bleeding at intervals >35 days OR
  • Normal bleeding intervals (25-35 days) with a mid-luteal progesterone level (</=5 ng/mL) suggesting anovulation (77).

3. Polycystic ovaries 

Determined by an ultrasound that shows the presence of 12 or more follicles 2-9 mm in diameter and/or an increased ovarian volume >10 mL (without a cyst or dominant follicle) in either ovary.

Before making a diagnosis, disorders that mimic the features of PCOS must be ruled out (73):

  • Thyroid disease
  • Hyperprolactinemia
  • Nonclassical congenital adrenal hyperplasia

In some women, other conditions with overlapping symptoms must also be ruled out, depending on their clinical presentation (73):

  • Pregnancy 
  • Hypothalamic amenorrhea
  • Primary ovarian insufficiency
  • Androgen-secreting tumor
  • Cushing’s syndrome
  • Acromegaly

In adolescents, diagnosis is based on (73):

  • The presence of clinical and/or biochemical evidence of hyperandrogenism AND
  • The presence of persistent oligomenorrhea.

In perimenopause and menopause, there are no diagnostic criteria for PCOS, but it is suggested by (73):

  • A well-documented history of oligomenorrhea and hyperandrogenism during the reproductive years. 

What are the different PCOS types?

There are 4 types of PCOS (497879):

1. Classic polycystic ovary PCOS (66% of cases) 

  • Characterized by polycystic ovaries, hyperandrogenism, and chronic anovulation.
  • Typically presents with abdominal obesity, increased levels of LH and LH/FSH ratio, increased androgens, and elevated insulin and insulin resistance (80).
  • Most common and severe type of PCOS (80).

2. Non-classic ovulatory PCOS (13% of cases)

  • Characterized by polycystic ovaries and hyperandrogenism, but menstrual cycles are regular.
  • BMI, waist circumference, testosterone, and insulin are typically only mildly elevated (80).
  • Considered to be a milder form of classic PCOS (80).

3. Non-classic mild or normoandrogenic PCOS (11% of cases)

  • Characterized by polycystic ovaries and chronic anovulation, but androgens are normal (but may have very mildly elevated testosterone, although still within the normal range) (80).
  • Typically have a normal BMI, waist circumference, and insulin level, but an increased LH and LH/FSH ratio (80).
  • It has been suggested that this type of PCOS may actually be a different disorder or have a different pathogenetic pathway (80).

4. Classic non-polycystic ovary PCOS (9% of cases)

  • Characterized by hyperandrogenism and chronic anovulation, but ovaries are normal.
  • Main difference from the classic type is a lower LH and LH/FSH ratio (but still above the normal range) and normal ovaries (80).

What conditions commonly co-occur with PCOS?

1. Cardiovascular disease

PCOS is associated with an increased risk of CVD and stroke, although higher BMI may be a mediator (8182838485).

One study found that women with PCOS who also have type 2 diabetes or metabolic syndrome are at the highest risk of heart disease (86). 

However, not all studies confirm this relationship. 

Other research studies have found that women with PCOS do not actually experience more heart attacks or strokes compared to women without PCOS (8487).

More information is needed to clarify this relationship.

2. Type 2 diabetes

Strong evidence shows that women with PCOS are at a significantly increased risk of developing type 2 diabetes compared to women without PCOS, regardless of age and weight (888990).

One study found that women with PCOS and a normal BMI had a 3x diabetes risk compared to normal-weight women without PCOS (91).

The insulin resistance typically seen in patients with PCOS seems to be at least partially responsible for this increase in diabetes risk (92).

3. Endometrial Cancer

Women with PCOS are 3x more likely to develop endometrial cancer (9% lifetime risk) (939495).

Long-term exposure to unopposed estrogen (due to anovulation) is thought to be a major contributing factor to the development of endometrial cancer in PCOS (96).

4. Thyroid disorders

Evidence suggests that patients with PCOS are at least three times more likely to be diagnosed with autoimmune thyroiditis (Hashimoto’s) than healthy participants (979899).

Scientists aren’t sure why this occurs, but some have hypothesized that hypothyroidism contributes to PCOS because higher levels of thyrotropin releasing hormone (TRH) cause altered LH:FSH ratio and raise DHEA-S levels (100).

5. Liver disease

Between 30% and 60% of women with PCOS also have non-alcoholic fatty liver disease (NAFLD) (101102103104105).

Insulin resistance and hyperandrogenism are the main factors that contribute to fatty liver and liver damage in PCOS (102103106).

6. Obstructive sleep apnea

Women with PCOS are approximately 10 times more likely to be diagnosed with obstructive sleep apnea (OSAS) (107108109).

It’s unclear exactly why this occurs, but there is evidence that insulin resistance, rather than obesity, plays a role (75).

7. Psychiatric disorders

Patients with PCOS are at an increased risk of depressionanxiety, bipolar disorder, and obsessive compulsive disorder, and their symptoms tend to be more severe than patients without PCOS (110111112113114).

Eating disorders are also more common. Symptoms of bulimia nervosa are present in 5-10% of women with PCOS, while as many as 18% display symptoms of binge eating disorder (115116117118119).

PCOS symptoms (especially hirsutism, infertility, and weight gain) may contribute to the increased risk for depression and anxiety (110112).

8. Leptin resistance

Leptin is a hormone secreted by fat cells that helps regulate body weight by reducing appetite (120).

Patients with PCOS tend to have higher levels of leptin (indicating leptin resistance), which may be related to higher BMI and insulin resistance (121122123).


How is PCOS typically treated by conventional medicine?

1. Oral contraceptives

Combined oral contraceptives (containing both estrogen and progestin) are considered first-line treatment for menstrual irregularity and hyperandrogenism in PCOS (3124).

They improve PCOS symptoms by decreasing LH secretion, reducing androgen production, and increasing SHBG, which binds androgens (125126).

However, this is just an artificial way of balancing hormones, rather than addressing the underlying causes.

2. Weight loss 

For patients with PCOS who have BMIs in the overweight or obese categories, weight loss is generally recommended as a first-line treatment (73).

Some evidence shows that menstrual function can be improved with as little as 5-10% reduction in body weight or visceral fat (127128).

3. Metformin 

Metformin is a diabetes drug used to improve blood sugar control.

It is recommended for women with PCOS who have type 2 diabetes or impaired glucose tolerance who have not been successful with lifestyle modification, or for women with menstrual irregularity who cannot take or do not tolerate hormonal contraceptives (373).

Strong evidence shows that metformin (combined with lifestyle changes) is associated with lower BMI, lower body fat, and improved menstruation for women with PCOS (129).

4. Other treatments

Depending on an individual’s symptoms and goals, other treatments may be prescribed, such as the following (323):

  • Anti-androgen drugs
  • Anti-obesity drugs
  • Bariatric surgery
  • Hair removal (creams, electrolysis, laser therapy)
  • In vitro fertilization
  • Laparoscopic ovarian surgery 
  • Ovulation induction drugs (letrozole, clomiphene citrate, gonadotropins)

Which diets are recommended for PCOS?

1. Low-glycemic diet

Strong evidence shows that a low-glycemic diet improves insulin sensitivity and menstrual function in women with PCOS who have higher BMIs (130131132133).

This effect might be explained by the fact that large spikes in blood glucose typically trigger an inflammatory response (134).

2. Low-carbohydrate diet

There is some evidence that a moderately low-carbohydrate diet (40% CHO, 15% PRO, 45% FAT) with limited saturated fat (7-12%) improves insulin sensitivity in women with PCOS (135136137).

3. Ketogenic diet

One very small study (11 participants) found that a 24-week ketogenic diet (</=20 g CHO/day) lead to weight loss, improvements in hormone levels, and reduced serum insulin levels in women with PCOS and BMI>27 (138).

However, only 5 women actually completed the study, while the other 6 women found the diet too difficult to follow or simply failed to attend follow-up appointments (138). 

4. DASH diet

Research suggests that a calorie-restricted DASH diet (50-55% CHO, 15-20% PRO, 30% FAT) reduces insulin levels, improves hormone levels, and leads to weight loss in women with PCOS who have BMIs in the overweight or obese range (139140141).

5. Low Starch, Low Dairy Diet

Evidence from 2 small studies suggests that a low dairy, low starch diet (no dairy products except maximum 1 oz cheese, no grains/legumes/added sugar) increases fat oxidation, improves insulin sensitivity, and reduces testosterone levels in women with PCOS (142143).

6. Other

Although many women with PCOS report positive results from following a gluten-free diet, there is not enough research to support it at this time.


Which nutrients are important to consider?

1. Chromium

Research has shown that chromium plays a role in insulin signaling and is responsible for enhancing the metabolic action of insulin (144145).

Very weak evidence suggests that chromium picolinate supplementation (200-1000 mcg/day) for 4 months might improve glucose tolerance in women with PCOS (146147).

2. Magnesium

Magnesium is required for proper glucose utilization and insulin signaling, and higher intake is linked with decreased insulin resistance in women with PCOS (148149).

Two trials have examined the effect of magnesium oxide supplementation (250 mg/day) with other nutrients (vitamin E and zinc) in women with PCOS, and results showed improvements in insulin metabolism, lipid profiles, and antioxidant capacity (150151).

3. Omega-3

There is some evidence that omega-3 supplementation (1200-3600 mg/day) results in improved lipid profile, and decreased insulin resistance in women with PCOS (152153154155 156).

However, some studies are conflicting, so more research is needed (157).

4. Selenium 

One study found that selenium supplementation (200 mcg/day) for 8 weeks significantly improved insulin sensitivity and reduced triglyceride and VLDL-C levels (158).

More research is needed to confirm these results.

5. Vitamin B12

Patients with PCOS who are taking metformin should supplement with vitamin B12 (annual 1 mg injections), because this drug is known to decrease B12 levels, potentially leading to deficiency (159160161162).

6. Vitamin D

Low vitamin D levels (<20 ng/mL) have been found in 67-85% of women with PCOS (163).

There is some evidence that vitamin D supplementation (20,000/week for 6 months or one mega-dose of 300,000 IU) might improve insulin sensitivity and menstruation, but other studies show no effect (164165166).

7. Zinc

One small clinical trial found that supplementation with 220 mg zinc sulfate (containing 50 mg zinc) for 8 weeks significantly increased zinc levels while also improving insulin sensitivity (167).

However, more studies with larger sample sizes are needed to confirm these effects.


What are some supplements that may help?

1. Berberine

Berberine is an alkaloid compound that can be extracted from many different medicinal herbs, including barberry, goldenseal, and Oregon grape (168).

Limited evidence suggests that supplementation with berberine (900-1500 mg/day) is just as effective as metformin for improving insulin resistance and hormone balance (169).

More research is needed to confirm these effects and to determine the underlying mechanism.

2. Cinnamon

Cinnamon has been suggested as a treatment for insulin resistance, because of its ability to improve insulin signaling (170).

Some evidence shows that cinnamon supplementation (1-1.5 g/day) may improve insulin resistance in women with PCOS, although other studies are conflicting (171172173).

3. Curcumin

Evidence from rodent studies suggests that curcumin supplementation might reduce insulin resistance in PCOS, due to its ability to reduce the expression and levels of inflammatory markers (TNF-alpha, IL-6, and CRP) (174175).

However, research in humans is needed to confirm these effects and establish dosage recommendations.

4. Green tea

Evidence suggests that supplementation with green tea capsules (1000-2000 mg/day for 6-12 weeks) resulted in decreased body weight, fasting insulin, free testosterone, and inflammatory markers in women with PCOS and elevated BMI (176177).

These effects may be due to the ability of green tea to reduce oxidative stress (178).

5. Inositol

Inositol is a sugar found naturally in food (especially grains and legumes), but it can also be produced by the body (179180).

Two forms of inositol (D-chiro-inositol and myo-inositol) are involved in insulin-mediated androgen synthesis, glucose uptake, and FSH signaling (181182183).

Research shows that supplementation with D-chiro-inositol and/or myo-inositol (two forms of inositol) in doses of 1-4 g/day lead to improved insulin resistance and reproductive functioning in women with PCOS (181184185186187188).

Ovasitol is a popular brand that comes in a powder form and contains 2000 mg myo-inositol and 50 mg D-chiro-inositol.

6. Licorice root

One study in rodents found that licorice root extract inhibited symptoms of PCOS by regulating imbalanced hormone levels and irregular ovarian follicles (189).

More research is needed in humans, but licorice does appear to reduce serum testosterone levels in healthy women, so it could potentially be useful in PCOS (190191).

7. N-acetylcysteine

N-acetylcysteine (NAC) is an antioxidant found naturally in onions and a precursor to glutathione (192).

Some evidence suggests that supplementation with NAC (1200-1800 mg/day) in women with PCOS results in higher odds of having a live birth, getting pregnant, and ovulating (193194195).

8. Probiotics

Evidence regarding probiotic supplementation for patients with PCOS is conflicting, although some studies suggest improvements in hormonal and inflammatory markers (196197198199200201).

One study found that Bifidobacterium lactis improved levels of sex hormones, but only in patients who were effectively colonized (197).

More research is needed to clarify results, determine effective dosing, and differentiate between the effects of specific bacterial strains.

9. Spearmint

Preliminary research suggests that spearmint tea (consumed twice/day) might decrease testosterone levels in women with symptoms of PCOS (202203).

10. Other

Other supplements that are sometimes recommended for hormone balancing (on a case-by-case basis, after measuring hormone levels & understanding what needs to be balanced) include: ashwagandha, black cohosh, DIM, holy basil, maca root, and vitex agnus-castus (chasteberry).


What other lifestyle changes are recommended?

1. Exercise

Research shows that a variety of exercise types lead to improvements in insulin sensitivity, body fat percentage, lipid profiles, inflammatory markers, and ovulation in women with PCOS (204205206207208).

A minimum of 150 minutes/week of moderate-intensity physical activity or 75 minutes/week of vigorous-intensity physical activity (including muscle-strengthening activities 2 days/week) is generally recommended (3).

2. Sleep

Hormone imbalances and other symptoms caused by PCOS have been linked with sleep disturbances (74209210).

Sleep disorders should be ruled out, and sleep hygiene should be addressed in all women with PCOS (211).

3. Stress reduction

Stress is thought to play a role in PCOS by increasing inflammation and insulin resistance  (212213).

Research shows that using mindfulness-based stress reduction (MBSR) techniques leads to decreased stress levels, reductions in fasting glucose, and improved mental health (214215).

MBSR involves relaxation and breathing techniques, meditation, yoga, and journaling (216).


Other treatments

1. Acupuncture

For women seeking alternative treatments, acupuncture has been shown to reduce the number of ovarian cysts, improve insulin sensitivity, and reduce cortisol levels in some women with PCOS, although more research is needed (217218219).

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