Polycystic Ovary Syndrome and Non-Alcoholic Fatty Liver Disease - Exploring the Link

We often think of polycystic ovary syndrome (PCOS) as a hormonal disorder, but it’s also (and maybe even predominantly) a metabolic one. Women with PCOS often have symptoms from multiple types hormone dysregulation including reproductive dysfunction, often presenting as long menstrual cycles and irregular ovulation. Additionally, there is often long-term dysfunction of lipid (fat) metabolism, insulin, and glucose balance; this can ultimately result in non-alcoholic fatty liver disease (NAFLD). Other common symptoms of PCOS include adult acne (I often call this “beard acne,” for that’s the area of the face and neck where it typically shows up), abnormal facial hair growth, and difficulties in losing weight, specifically body fat. These typically occur when androgen hormone levels, such as testosterone, become too high and the ovaries stop performing as they should.

What Is NAFLD?

Diet and metabolic dysfunction can influence the development of fatty deposits in and around the liver. In small quantities, we can call this liver steatosis or “fatty liver.” When these fatty deposits become larger and consist of a greater amount of liver tissue to the point where it can start to create changes in liver tissue, it’s termed non-alcoholic fatty liver disease (NAFLD), more specifically in those who rarely consume alcohol. Therefore, we describe it as a “non–alcohol-caused” liver damage. Over the long term, this damage can result in scarring or fibrosis of the liver and can even lead to liver-tissue death and liver cancer. Other than abnormal bloodwork and imaging results, those with NAFLD don’t often present with any major signs or symptoms. Some people with a fatty liver report some discomfort around the upper right side of the abdomen or increased feelings of fatigue, but these symptoms can be quite vague.^[1]

What’s the Connection Between PCOS and NAFLD?

The risk of NAFLD is increased in the presence of obesity, insulin resistance, and diabetes. Men typically have a higher risk, but women with PCOS tend to struggle with insulin sensitivity, blood-sugar dysregulation, high androgen hormone levels, and high body-fat percentage (not in every case); therefore, women in this category are at a particular disadvantage when it comes to liver health. Even though we often associate NAFLD with obesity, this isn’t always the case in women with PCOS. Non-obese NAFLD is actually more prevalent in women with PCOS than in those without.^[2] So the risk of NAFLD is more so linked to the high levels of androgens in lean PCOS women.

How does this happen? The ovaries contain an abundant amount of insulin receptors. When insulin levels are constantly high, though, the receptors become less sensitive to the presence of insulin, and this can lead to insulin resistance: These cells are resistant to the presence of insulin. It’s like the old tale of crying wolf. The body has cried “insulin!” too many times, so the signal to bring forth those receptors isn’t going to be as strong. The insulin receptors stop responding the way they should. Two things can occur when this is the case: First, blood sugar levels are more likely to stay elevated, because insulin isn’t as effective in bringing glucose into the cells; and secondly, a signal is sent to increase the amount of androgen hormones that are released. Having too much insulin hanging around without functioning receptors for them to bind to can cause a decrease in levels of a protein called sex hormone-binding globulins (SHBG). These protein globulins hang around to bind up excess sex hormones like testosterone. So we have now created the perfect storm that leads to excess testosterone levels, which is the cause of the characteristic PCOS “beard acne” (acne around the jawline, chin, and upper neck), and abnormal facial hair growth or “whiskers” in women with PCOS. Additionally, this elevated amount of androgens can turn off the genes responsible for coding for specific cholesterol receptors which can lead to liver steatosis. These higher levels of androgens are an independent risk factor for the development of NAFLD, especially in lean women.^[2] Androgens can also increase the risk of liver cell death, further contributing to liver steatosis. Over the long term, the risks of liver diseases and cancer are increased.^[3]

Management and Treatment

First and foremost, we must address the root cause of disorder: the insulin resistance. Dietary and lifestyle changes are crucial in both PCOS and NAFLD. Incorporating physical activity is a critical part of the plan, since exercise can independently upregulate a glucose transporter called GLUT4. This alone can help improve the action of insulin and the use of glucose. This doesn’t mean that all women with PCOS or insulin resistance should start running marathons or power-lifting—all exercise plans can and should be modified based on a woman’s present exercise tolerance. The idea is to move and use muscle. Many women find benefit from increasing their strength, typically through resistance training or weight-training—but starting with lower-poundage weights to prevent injury. Dietary interventions must include a reduction or elimination of added sugars. Fruits can still be consumed, but we often recommend low-glycemic-index and low-glycemicload fruits like berries (blueberries, strawberries, raspberries). No one diet will work for every person with insulin resistance, but most often the aim is to use the Mediterranean diet as a model or starting point, with more fish, lean meats, vegetables, and olive oil; and less grain-based carbohydrates (or, at least, much smaller portions). One small study showed that following the Mediterranean diet was able to reduce liver steatosis more than a low-fat diet, regardless of the total amount of weight lost.^[3] A helpful way to pick proper carbohydrates in this form of diet is to eat those that take longer to digest. Breads, crackers, and other simple-grain products can dissociate and digest very quickly; but foods like legumes (lentils, chickpeas, beans), sweet potatoes, and other vegetable-based carbohydrates are also nice and dense in fibre, which helps to slow the breakdown process, allowing a slower delivery of carbohydrates (and therefore sugars) into the bloodstream. Other helpful dietary conventions include intermittent fasting, whereby food is consumed only in a 10–12-hour window during the day, ensuring a 12–14-hour period of fasting during the evening/night. Together, dietary and physical activity changes can significantly improve blood sugar levels, insulin sensitivity, circulating androgen levels, and even fertility.^[3]

Pharmaceuticals and Nutraceuticals

Metformin is probably the most-commonly prescribed drug for PCOS, as it can help to regulate blood sugar levels, and therefore insulin sensitivity. One study showed that metformin treatment in obese women with both PCOS and NAFLD for 8 and 12 months showed a significant reduction in liver enzymes (a marker of liver damage). Researchers also noted a reduction in insulin resistance, and a second study confirmed an increase in SHBG and HDL (the “good”) cholesterol.^[1] Although metformin seems to provide many benefits in these cases, some patients are unable to tolerate this medication or have reported side effects of digestive upset, feelings of weakness, and muscle pain.

In these cases, alternatives that should be considered include N-acetylcysteine (NAC) and omega-3 fatty acids. One study compared the effects of metformin against NAC in women with PCOS. The results are that women taking 600 mg of NAC three times daily had better cholesterol levels, fasting blood sugar levels, and fasting blood insulin levels compared to those women who were given 500 mg of metformin three times daily.^[4] Studies have also shown beneficial outcomes with omega-3 fatty acids. Taking 4 g per day of an omega-3 fish oil for eight (8) weeks led to reduced liver fat in women with PCOS.^[3] This effect has been attributed to the ability of omega-3 fatty acids to modify fat metabolism within the liver.^[1]

Conclusions

PCOS doubles the risk for steatosis, which is most influenced by women who have insulin resistance and high levels of androgens, regardless of body mass index.^[5] Even for women with PCOS who don’t have the same reproductive issues as others, there is still a high risk for fatty liver and subsequent liver damage.^[5] This truly highlights how having PCOS can influence two different but overlapping hormonal systems: metabolic and reproductive. It also opens our eyes to the increased risk of NAFLD in women who have been diagnosed with PCOS. What does this mean for women with PCOS? A medical assessment should include screening via testing for liver enzymes in the blood, as well as imaging (usually by ultrasound, CT scan, or MRI) to assess for the presence of steatosis, most importantly in women with insulin resistance.