Nonalcoholic Fatty Liver Disease in women with polycystic ovary syndrome
24 Oct 2022
Nonalcoholic fatty liver disease (NAFLD) is now one of the main causes of liver disease in the world, with an ever increasing prevalence, such as to consider this etiology as the most widespread in the coming years . It is now well known that NAFLD is associated with many other pathologies of metabolic origin. In fact, the presence of NAFLD is often associated with diabetes, obesity, metabolic syndrome, as well as with an increased cardiovascular risk . For this reason, although not yet in the guidelines of international associations, many data support the use of non-invasive tests for the diagnosis of liver fibrosis in diabetic patients . Despite the growing attention to this disease, however, there are other diseases that appear to be associated with the development of NAFLD but are currently less considered. This is the case, for example, of polycystic ovary syndrome (PCOS).
PCOS is one of the most common reproductive, endocrine, and metabolic disorders in women of reproductive age, with a prevalence of 4-21%  and it is caused by excessive androgens production and ovarian dysfunction. The relationship between PCOS and NAFLD has been known since 2005, and nowadays the prevalence range for NAFLD in PCOS is estimated between 14.5% and 77%. The relationship between these two conditions seems to be linked to three factors:
1) Hyperandrogenemia, one of the main characteristics of PCOS. Chronic androgen overload leads to insulin resistance and hepatic steatosis by affecting mitochondrial function and de novo lipogenesis. Moreover, it increases the pro-inflammatory state upregulating the expression of interleukins and other inflammation markers such as IL-6, TNF-α, MCP-1, and IL-1β;
2) Insulin resistance, that is increased in women with PCOS due to alterations of the insulin signaling pathway and is worsened by hyperandrogenemia;
3) Obesity, which is very common in women with PCOS with a prevalence of about 70%. Weight gain in PCOS is strictly related to the lipolytic function of androgens on adipocytes. Moreover, testosterone stimulates the release of non-esterified fatty acids from visceral adipocytes in the body leading to the accumulation of local adipose tissue, especially in the abdomen.
A recent study by Lavor et al. tried to evaluate the association between NAFLD and PCOS through non-invasive tests. They evaluated 50 women with PCOS and confronted them with 50 healthy subjects.
Patients with PCOS were more frequently obese, with greater abdominal circumference and worse levels of triglycerides and HDL cholesterol than the control group. Moreover, patients with PCOS showed more frequently insulin resistance calculated with the HOMA index than the control group (18% vs 0%, p=0.003). Despite that, there was no significant difference in liver fibrosis (with share wave elastography) or in steatosis (diagnosed with abdominal ultrasound) between the two groups . Another study by Petta et al. used hepatic steatosis index and FIB-4 score to assess the prevalence of steatosis and fibrosis in 202 women with PCOS and 101 age-matched controls. Even in this population, women with PCOS had higher body mass index, greater waist circumference and worse levels of triglycerides and HDL cholesterol than the control group. Steatosis was observed in 68.8% of patients with PCOS and 33.3% of controls (p<0.001). As far as fibrosis is concerned, no patient had a severe hepatic fibrosis, but FIB-4 was associated with higher waist circumference, lower HDL, altered insulin sensitivity and higher androgen levels .
Further studies are needed to confirm the role of non-invasive tests in this field. However, the relationship between PCOS and NAFLD is clear, therefore it is important to assess the risk of developing liver disease in this population.
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