Polycystic Ovary Syndrome - A Review of the Condition and Current Nutritional Therapies

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PCOS—The Condition

Polycystic ovary syndrome (PCOS) is a condition represented by both reproductive and endocrine symptoms. It currently impacts at least 5–10% of reproductive-age women.^[1] The diagnostic criteria for PCOS is largely reflected by the Rotterdam Criteria, whereby a patient must have two of the following three criteria to be diagnosed with the condition:

• Inconsistent or absent ovulation, causing inconsistent menstrual periods;
• Hyperandrogenism which is either clinical (abnormal male-pattern hair growth, male-pattern hair loss, acne) or biochemical (elevated testosterone levels on bloodwork); and
• Polycystic appearance of the ovaries on transvaginal ultrasound.^[2]

Additionally, any other condition which might explain the appearance of these symptoms must be ruled out such as other pituitary-, adrenal-, or thyroid-based pathologies. Other common signs and symptoms of the condition include obesity, infertility or subfertility, diabetes and blood-sugar dysregulation, elevated cholesterol, and mood disorders such as anxiety and depression.^[2]

Why Does PCOS Occur?

At this point, we know that PCOS is largely due to changes in the levels of two main hormones: insulin and androgens. Firstly, we know that patients with PCOS experience an androgen excess. As discussed prior, this excess can be biochemical (visible on lab work) or clinical (seen in symptom picture of the patient). Elevated levels of androgens in comparison with other female hormones (estrogen, progesterone) impact physical symptoms and cause changes in ovarian function. Because the menstrual cycle is governed by the relative levels of all the patient’s sex hormones, this can mean that ovulation does not occur at proper intervals. This has impacts for the menstrual cycle overall, and often patients will express having cycles which are inconsistent, infrequent, or absent completely. However, these changes in cycle are not required to be diagnosed with PCOS, as some patients have regular cycles despite having the condition.^[1] Secondly, we know that patients with PCOS tend to experience poor blood-sugar regulation and tend to experience excess insulin levels and insulin resistance. Insulin in a healthy individual regulates the proper absorption of sugars (glucose) into cells to be used for energy production. In the case of PCOS, insulin resistance is more common, whereby the body’s cells no longer respond to insulin appropriately, and higher and higher levels of insulin must be released in order for the patient’s cells to respond to signalling.^[2] The primary root of PCOS likely actually lies in this poor insulin regulation and sensitivity, which then induces the increase in androgen levels seen in the condition by altering the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary.

Long-Term Consequences of PCOS

Due to the changes in blood-sugar regulation in PCOS, one of the largest long-term consequences of the condition is that patients may be more likely to experience type 2 diabetes in their lifetime. This increased risk is not necessarily only seen in patients who are overweight/obese, but it also impacts those who have non–obesity-related PCOS. Patients with PCOS who become pregnant are also more likely to have gestational diabetes.^[3] Also, potentially due to higher circulating levels of blood glucose, patients are more at risk for cardiovascular disease in the long term.^[3] The other major risk for patients with PCOS in the long term include increased risk of endometrial cancer. This may occur because patients with PCOS may have irregular cycles, which means that they are less likely to regularly have a menstrual period and shed their uterine lining. This is a risk factor for endometrial hyperplasia (a precursor to endometrial cancers). Additionally, risk factors for endometrial cancer include obesity and diabetes, which are more common in patients with PCOS. While there may be some increased risk for breast cancer and ovarian cancer because of obesity and hormonal changes, PCOS has not been deemed a correlated risk factor for either of these conditions.^[3] Lastly, due to lack of ovulation and changes to hormone levels, subfertility and infertility are also potential risks of this condition in reproductive years. The prevalence of infertility in patients with PCOS may be as high as 70–80%.^[4]

Testing for PCOS

Several tests can be used to help in identifying PCOS in patients. Serum testing may include testing for androgen and other sex-hormone levels, pituitary hormones such as LH and FSH, insulin and blood-sugar levels through either fasting blood glucose or hemoglobin A1c (HbA1c). Imaging techniques may be used to identify the presence of polycystic ovaries through transvaginal ultrasound (TVUS). The presence of positive testing in any of these tests is not required for a diagnosis of PCOS to be applied.

Conventional Therapies for PCOS

To help in regulating cycles, and encouraging regular withdrawal bleeds, often the oral contraceptive pill is utilized patients with PCOS to help in shedding the uterine lining more regularly.^[5] The oral contraceptive pill and other forms of hormonal birth control such as progestin-based intrauterine devices (IUDs) may also help in correcting hormonal balance issues and may help in reducing high-androgen symptoms such as acne and hirsutism in patients as well.^[5] Metformin is also commonly prescribed to patients with PCOS to help in improving insulin sensitivity and thereby helping to reduce androgen levels.^[6] To help with fertility and ovulation, medications such as clomiphene citrate may be added to the patient’s regimen either with or without the application of in vitro fertilization (IVF).^[5]

Nutritional Interventions in PCOS

Natural nutritional and supplemental interventions in the care of PCOS are still primarily in the early stages of evidence; however, some evidence may be promising in management. The following interventions are not exhaustive but include treatments that may improve ovulation rate, improve fertility outcomes, contribute to improved blood-sugar regulation, and reduce high-androgen symptoms.

Weight Loss and Exercise

Even a small weight loss of 5–10% of total body weight has been shown to improve clinical outcomes.^[2] By reducing weight, patients generally experience lower insulin levels and improved androgen levels, so this can help in restoring ovulation and fertility and improve the patient’s metabolic profile.^[6] Some diets which might be used clinically to induce weight loss and improve insulin regulation include those which are lower in refined sugars and carbohydrates such as the paleo diet or ketogenic diet, diets shown to help in regulation of blood sugar in diabetes including the Mediterranean diet, intermittent fasting-based diets, and calorie-restricted diets. Increasing exercise levels can also aid in weight loss and improving insulin function in the body.

N Acetylcysteine (NAC)

NAC is an acetylated amino acid which has been shown to increase cellular antioxidant levels and is a precursor in the reduction of glutathione (a powerful antioxidant in the body). As women with PCOS may have higher-than-normal levels of oxidative damage, it may be supportive in reducing this oxidative stress. It may also be helpful for improving insulin sensitivity. While a review of eight papers did not find that NAC was consistently helpful in improving menstrual regularity, hyperandrogenism symptoms, or insulin regulation, it did find that it was helpful for encouraging improvements in ovulation, as well as increased likelihood of live pregnancy rates overall.^[7] This particular treatment is also considered safe and has been researched alongside commonly used conventional therapies such as clomiphene citrate and metformin.

Inositol

Inositols are a family of B vitamin–like compounds which are found naturally in the body as well as in several foods. 1D chiro-Inositol (DCI) and myo inositol (MI) are two of the nine forms of inositol which have been studied and have been found to be helpful in the management of PCOS. This is potentially due to several reasons. Both compounds have been shown to be incorporated as a part of insulin-signalling molecules, which might be how they impact insulin regulation in PCOS.^[8] MI may also be involved in ovarian function and improving the quality of oocytes which are ovulated.^[8] Studies have shown an improvement in overall hormonal signalling with administration of inositol, both with and without folic acid, demonstrating improvement in insulin levels and increasing the likelihood of spontaneous ovulation. Inositol can induce some gastrointestinal upset in patients, which can be mitigated in most cases by dividing doses or reducing doses until tolerance can be reached. There is also some evidence that the two molecules (both MI and DCI) may be best utilized in combination versus alone.^[8]

Chromium

Chromium picolinate is a trace mineral which is commonly present in the diet and has previously been shown to help in improving insulin resistance in patients. It has been shown to help in improving body mass index (BMI) in patients with PCOS, as well as testosterone concentration and fasting insulin levels.^[9] A study comparing the use of chromium picolinate to metformin in patients who were typically resistant to ovulation induction with clomiphene citrate found that metformin was preferable in terms of improving hyperandrogen symptoms, but both chromium and metformin comparably improved responsiveness to the medication.^[10] Therefore, chromium can be used to help in blood-sugar regulation and weight loss, as well as to potentially help patients not responding to medication appropriately.

Vitamin D3

Patients with PCOS are more likely to experience vitamin D3 deficiency on blood testing. Lower levels may correlate to worsening in insulin regulation, and may be correlated with poorer ovarian function.^[11] However, there is still very limited evidence in terms of the effect of vitamin D3 supplementation on improvement in symptoms. Some preliminary evidence suggests supplementation of vitamin D3 alongside metformin may be helpful in improving treatment outcomes in menstrual regularity and ovulation.^[11] Testing and appropriate supplementation based on serum levels is generally indicated in care.

Conclusion

There is still much we don’t know regarding PCOS and nutritional therapies. There are some promising possibilities in treatment for improving outcomes with or without conventional therapies, such as metformin and clomiphene citrate in terms of long-term fertility, weight loss, insulin regulation, and ovulation.