Polycystic Ovary Syndrome (PCOS) Part 1: What causes it?
Polycystic Ovary Syndrome (PCOS) is both a common and complex condition. It has been estimated to affect between 5-21% of women of reproductive age, making it the most common endocrinological disorder among this population (1,2). It is also considerably complex: not classified as a disease (due to a lack of consistent symptoms), this syndrome encompasses a large constellation of signs, symptoms and laboratory findings. In addition to the varied presentation, the exact causes of PCOS have yet to be fully elucidated and may not be the same for everyone. In fact, it has recently been recognized that there are four different phenotypes within the diagnostic criteria for PCOS (3) and many practitioners now categorize PCOS into different types. While PCOS was once thought to be a disorder strictly involving the ovaries and imbalances in female and male sex hormones, we now know that it involves many body systems(4). Some of the underlying factors which may contribute to PCOS include:
Androgen excess and hormonal imbalances
Genetic predisposition (5,6)
Insulin resistance (as well as blood sugar and lipid dysregulation)
Chronic, low-grade inflammation
Environmental factors, such as endocrine disruptors
Often, there is some interplay of several of these factors. For example, having a genetic predisposition doesn’t necessarily mean one will develop PCOS. In combination with lifestyle, nutrition, and environmental factors however, the risk may be increased. PCOS can lead to fertility challenges(7), but early detection is not only important for those wanting to conceive. PCOS may put women at risk to develop metabolic syndrome, diabetes (type II), and cardiovascular disease. It’s therefore important to recognize the syndrome, identify the root cause and treat accordingly.
Recognizing the Symptoms:
As previously mentioned, the symptoms and physical findings of PCOS are quite variable. While there are “typical” PCOS symptoms, not every woman with PCOS will have them, which can make diagnosis difficult. That being said, some of the more common symptoms include:
Menstrual cycle irregularities (a cycle lasting longer than 35 days, missed periods, or absence of menses)
Weight gain, or a tendency to gain weight around the abdomen
Hirsutism (hair growth on the face)
Thinning hair or hair loss
Skin changes (darkening around the neck or armpits)
PCOS is often a clinical diagnosis, meaning the diagnosis is made based on presentation (signs and symptoms) rather than a diagnostic test, after ruling out other possible conditions. For PCOS, we use something called the Rotterdam Criteria, which requires the presence of at least two out of the three of the following:
Oligomenorrhea/anovulation: a cycle length of > 35 days
Hyperandrogenism: this can show up as acne, hirsutism (hair growth on the face), thinning hair or male pattern baldness, or elevated androgen levels or blood work
Polycystic ovaries confirmed on ultrasound
Identifying the root cause:
Given the complexity of PCOS, it is probably not surprising that treatment is not one-size-fits-all. Due to the variability of both symptoms and etiology, it is essential to identify and understand what may be the root cause of each unique PCOS case. This allows a more integrated approach and targeted treatments that address the underlying syndrome.
Androgen excess and hormonal imbalances
It is well-known (and has been extensively researched) that PCOS involves several hormonal imbalances, more specifically hyperandrogenism (high levels of testosterone, androstenedione or dehydroepiandrosterone). There are often imbalances in other female hormones as a result of hyperandrogenism, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as well as the ratio of these two (8), which has serious implications for the ovaries and for ovulation.
Insulin resistance (IR) has emerged in more recent research as an important factor contributing to the development of PCOS, with an estimated 70% of women with PCOS also being insulin resistant(9). IR is a condition in which the cells in our body fail to respond normally to insulin. There are several factors which may put someone at risk for developing IR, including genetics, inflammation, diet, and a sedentary lifestyle. When these result in high blood glucose levels, we see increased insulin released into the blood (to move glucose into cells). Eventually, the cells in our body become resistant to these high levels of insulin, ultimately leading to IR. The ovaries are stimulated by these high levels of insulin to secrete testosterone, leading to high levels of testosterone (10,11) and contributing to the hyperandrogenism mentioned above.
Inflammation can have negative effects on ovulation and egg quality in women, and has also been identified as one of the underlying causes of insulin resistance in women with PCOS. Studies have shown that women with PCOS have higher circulating levels of several inflammatory mediators, signaling inflammation as part of the PCOS picture(12). The root of the chronic, low-grade inflammation seen in PCOS has more recently been linked to dysfunctional adipocytes (fat cells). These fat cells have been shown to secrete higher levels of inflammatory messengers, which in turn cause our cells to become insulin-resistant (13).
Thyroid abnormalities have been identified in a much higher proportion of women with PCOS than those without, making a thyroid panel an essential screening test when running blood work for PCOS(14). While the connection between hypothyroidism and PCOS isn’t fully understood, it’s not entirely surprising that our body’s main metabolism hormones have some effect on PCOS (which we’ve come to understand has a large metabolic component) and vice versa. Without getting too into the nitty-gritty of the pathophysiology, what is important to understand is that hypothyroidism can lead to polycystic ovaries(15).
A spike in blood levels of our stress hormone, cortisol, is normal when responding to acute stress. It mobilizes sugars into the blood to allow us to deal with the stressor. However, chronic stress can lead to blood sugar regulation issues. It is therefore not surprising that chronic stress has been implicated in the development of insulin resistance (16). And in a world which can feel busier by the day, this should herald the importance of stress management in our daily lives.
Environmental endocrine disruptors
We have already mentioned the dysfunction of adipocytes, and we know that fat cells act in the storage of many things – hormones, vitamins, and yes, environmental toxins too (17). It makes sense then, that environmental endocrine disruptors will have profound effects for women with PCOS. In particular, triclosan (18) and bisphenol A (BPA) (19) have been identified in higher quantities in women with PCOS. Interestingly, very new research has shown that elevated levels of BPA, a well-known endocrine disruptor, correlated with higher levels of testosterone in women with PCOS (19).
Where to start?
Given the complexity of PCOS and the variability within the condition, it can feel overwhelming to know where to begin. The good news? Because there is a considerable metabolic component to PCOS, it responds very well to nutrition and lifestyle modifications. In Part 2 of the PCOS series, I’ll be discussing what the current research tells us about diet, exercise, and lifestyle in the treatment of PCOS.
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