Polycystic ovaries contain about twice as many small cysts as normal. These cysts are egg-containing follicles that have not developed properly. PCOS is the leading cause of infertility in women, and it comes in 4 types.

Underlying causes:

• high insulin
• high testosterone
• low serotonin and dopamine
• a disturbance in the gut bacteria

Polycystic ovary syndrome (PCOS) is a relatively common and frequently misunderstood condition with variable clinical presentation. Its key features are irregular or absent menses often followed by episodic heavy and prolonged menses; infertility; central obesity; androgenisation (acne, male pattern hair loss, and hirsutism); and multiple ovarian cysts. It is estimated to affect 5-10% of women and is thought to have both genetic and environmental roots.

Most women with PCOS will present with only two or three of the clinical features of PCOS:

• Approximately 70% will have missed periods (oligomenorrhea) or lack of periods (amenorrhea).
• Obesity is present in 70%.
• Hirsutism to a varying degree is present in roughly 75%
• Ovarian cysts – unilateral or bilateral- are present in 90%.

Ethnicity plays a role in the presentation of PCOS. For example, women of Asian descent are less likely to have hirsutism. The variability in presentation of PCOS reflects heterogeneous causative factors. Thus, the approach for each woman needs to be individualised based on her particular presenting symptoms and laboratory findings.

PCOS types

The ovarian “cysts” of PCOS are unique in that they appear as multiple (10-20) small cysts, often forming a bubbly ring around the ovary on ultrasound. These cysts are easily distinguishable on ultrasound from benign solitary ovarian cysts that occur in up to 20% of women and from complex cysts and ovarian cancer that are also usually solitary. The numerous PCOS cysts are actually ovarian follicles that have been halted in their monthly march toward ovulation. These cysts develop a “thick skin” (thecation) under the stimulation of luteinising hormone (LH).
When a woman presents with any two features of PCOS, further evaluation for PCOS is warranted.

There are a variety of definitions of PCOS but the two most accepted ones are:

• NIH consensus: A woman should have all of the following: oligoovulation, signs of androgen excess (clinical or biochemical), other entities are excluded that would cause polycystic ovaries.
• Rotterdam consensus: Any 2 of the following: oligoovulation and/or anovulation, excess androgen activity, polycystic ovaries (12 or more S-7mm follicles) by ultrasound (Hart et al, 2004).

By the Rotterdam criteria, a woman can have one of four PCOS syndromes:

• PO: polycystic ovaries with anovulation
• PH: polycystic ovaries with hyperandrogenism and normal ovulation
• PHO: polycystic ovaries with hyperandrogenism and anovulation
• HO: hyperandrogenism and anovulation with normal ovaries on ultrasound

Research has shown that women with the PO syndrome do not show a tendency toward insulin resistance and metabolic syndrome in contrast to women who have all three features of PCOS.

Underlying causes of PCOS

Insulin resistance

The most common underlying cause of PCOS is insulin resistance, which is observed in both normal weight and overweight women with PCOS. Insulin resistance occurs at some level in 50-80% of women with PCOS.
Insulin resistance can occur through multiple mechanisms including genetic predisposition and lifestyle impact. Obesity has a well-known correlation with insulin resistance and plays an increasing role in PCOS given the current obesity epidemic in the Western world and much of the developed world. Overweight and obese women with PCOS are more likely to have glucose intolerance than normal weight women with the syndrome.

However, even normal weight women with PCOS tend to have altered body fat distribution with more central (visceral) obesity that is associated with elevated insulin levels and insulin resistance.

Insulin resistance in at least 50% of PQQ women appears to be related to inflammatory pathways that block insulin receptors, resulting in less glucose uptake by muscle cells, increased glucose in the blood and increased insulin levels. High circulating insulin then appears to increase ovarian and adrenal hormone production and pituitary LH release directly through the insulin receptor.

Inflammatory pathways also appear to modulate the activity of the key regulatory enzyme of androgen biosynthesis, shedding light on the co-occurrence of insulin resistance and androgenisation commonly seen in the syndrome.

Deficiency of Glucose Transporters

Another mechanism for insulin resistance in PCOS is decreased glucose transporter- GLUT-4activity. GLUT-4 is instrumental in fat cell responsiveness to insulin. Thus, the GLUT-4 deficiency results in elevated glucose levels leading to a compensatory increase in circulating insulin levels.

Ovarian Sensitivity to Insulin

Why the ovaries are so sensitive to insulin when the rest of the body’s cells are resistant to it? Research shows that insulin action in the ovaries is mediated by different mechanism to the rest of the body, involving inositol. Thus, the high circulating insulin levels have more influence on the ovaries than on other tissues in the body.

Disordered Function of the Pituitary Gland

Insulin also has a direct impact on the pituitary gland. The elevated insulin increases the pulse frequency of the gonadotropins which results in LH dominance over FSH, increased ovarian androgen production, decreased follicular maturation, and decreased sex-hormone-binding. This means that ovarian follicles are stimulated to be released, but not not mature. In a positive feedback loop, increased androgens increase insulin resistance.

Oestrogen Dominance

Oestrogen dominance and unopposed oestrogen are issues that pose additional health risks in PCOS. Higher levels of oestrone and oestradiol are derived from increased aromatase activity in the excess visceral fat tissue. Increased oestrogen feeds back to the pituitary to reduce follicle stimulating hormone (FSH), resulting in arrest of ovarian follicle development (the “cysts” seen in the ovaries are actually arrested follicles). Arrested follicles prevent ovulation, with the subsequent failure of ovarian progesterone production that follows normal ovulation.

Early on, prolonged unopposed oestrogen produces episodes of irregular, heavy, prolonged bleeding (dysfunctional uterine bleeding). Over time there is an elevated risk for uterine hyperplasia and cancer due to persistently unopposed oestrogen.

Increased Testosterone Production

Another route to PCOS is thought to be through a primary disturbance in testosterone production. Increased testosterone alone can contribute to the cascade of PCOS through increasing visceral fat, leading to insulin resistance, elevated circulating insulin levels, and ovarian dysfunction. In normal ovarian physiology androgens produced by LH-stimulated theca cells undergo aromatisation to oestrogens by FSH-stimulated granulosa aromatase.

As aromatase activity increases and oestrogen levels increase, ovulation usually follows. In some PCOS patients, the ratio of follicular androstenedione (theca cell androgen) to estradiol is elevated and a mutation in the P450 aromatase gene has been found to be a cause of this shift.

Increased Prolactin Production

Elevated prolactin levels have been shown to correlate with PCOS. While very high prolactin levels are usually caused by a prolactin-secreting pituitary tumour, mildly elevated prolactin levels can be triggered by stress.

Increased prolactin levels can also be caused by the persistently elevated oestradiol levels seen in PCOS. An overly sensitive pituitary has been implicated as women with PCOS have been shown to have a more vigorous and/or prolonged prolactin response to infusions of TRH (thyroid releasing hormone). PCOS is also associated with a more vigorous prolactin response to dopamine blockers.

Prolactin promotes insulin resistance, so again the final common pathway is in part through the insulin receptors on the ovaries. In addition, elevated prolactin levels are known to promote excess hair growth.

Lab Tests for PCOS

Serum LH and LH/FSH ratio are significantly higher in women with PCOS, but these tests are abnormal in only about 40% of patients with PCOS. Mean serum total testosterone concentration is significantly higher in about 70% of women with PCOS.

Androstenedione is significantly higher in about 50% of women with PCOS. When testing for all of the above, an abnormality will be detected in about 80% of women with PCOS.

If serum testosterone levels exceed 150ng/dL a virilizing tumor of the ovaries should be ruled out with pelvic ultrasound.

Other laboratory tests that may be indicative of other diagnoses or of co-morbid conditions include:

• serum prolactin
• HCG
• fasting glucose and insulin
• lipid profile
• DHEA-S- levels greater than 700 suggest adrenal dysfunction warranting adrenal imaging
• 17-hyd roxyprogesterone
• elevated LH, estrone, and testosterone in the presence of normal estradiol (in idiopathic hyperprolactinemia, estradiol levels are suppressed)
• 24 hour urinary oestrogen levels are increased in PCOS

Ultrasound can identify polycystic ovaries, typically bilaterally enlarged ovaries with more than eight follicles per ovary, with follicles less than 10mm in diameter. More than 90% of women with PCOS have this finding, although this also occurs in 25% of normal women.

My Approach to PCOS

Women who seek support for PCOS are primarily concerned with correcting abnormal periods (particularly when it evolves into dysfunctional uterine bleeding), infertility, weight gain, hair growth, and acne.

Additional preventive interests include associated increased risks for endometrial cancer and cardiovascular disease from hyperinsulinism. The risk of endometrial cancer is three times higher in women with PCOS. There is also conflicting evidence for a three-fold increased risk for breast cancer in the postmenopausal years with chronic anovulation.

The functional medicine approach to a woman with PCOS takes into consideration the unique pathophysiology of each woman, addressing as required:

• Dietary measures focused on weight loss and reduction in circulating insulin levels through carbohydrate restriction, particularly refined carbohydrates, unless the lean type of PCOS is presenting
• Insulin resistance
• Elevated ovarian and adrenal androgens
• Elevated oestrogen
• Elevated LH
• Insufficient progesterone
• Elevated prolactin
• Lack of ovulation
• Inflammation
• Oxidation
• Underlying stress
• Obesity and metabolic syndrome

In addition, frequently associated co-morbidities such as fatty liver, hypertension, depression with anxiety, cardiovascular disease, and dyslipidemia are also addressed.