The possible link between these two conditions may have a number of implications for the diagnosis and treatment of various diseases among women.

A growing body of research indicates that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) may be related and, due to shared mechanisms, may increase the risk of type 2 diabetes (T2D) and other cardiometabolic complications. The findings may have a number of implications for the diagnosis and treatment of various diseases.

Although the etiology of PCOS, one of the most common endocrine disorders in women of reproductive age, is uncertain, obesity and insulin resistance are frequently present in affected individuals, and they play a role in its development. The condition affects 5% to 18% of this population depending on the diagnostic criteria used, and clinical features consist of menstrual dysfunction, infertility, hirsutism, acne, and alopecia.

Similarly, obesity and insulin resistance appear to contribute to the pathogenesis of NAFLD, which is characterized by increased accumulation of fat in the liver in the absence of significant alcohol consumption. NAFLD includes a range of diseases, from simple steatosis to non-alcoholic steatohepatitis to cirrhosis, and it has an estimated worldwide prevalence of 6.3% to 33.0%; however, if obesity or T2D is involved, the prevalence of NAFLD rises to approximately 75%.

A connection, but few reasons as to why

NAFLD and PCOS occur together more frequently than expected, in many cases simply by chance alone. Studies have consistently shown that NAFLD rates are elevated in young women with PCOS, independent of weight and metabolic syndrome features, and limited data suggest that these women have better odds of experiencing more severe forms of NAFLD.

In one recent study, by Evangeline Vassilatou, MD, PhD, an endocrinologist at the Attikon University General Hospital, in Athens, Greece, NAFLD was detected in 71 of 110 (64.5%) overweight and obese (yet otherwise apparently healthy) premenopausal women, and women with NAFLD were more often diagnosed with PCOS than women without NAFLD (43.7% versus 23.1%, respectively).

It’s currently unclear how the two conditions may influence each other: Are they a consequence of shared risk factors? Or does one condition contribute to the other independently of these factors? Accumulating evidence indicates that NAFLD may exacerbate insulin resistance and release multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that could contribute to the pathophysiology of PCOS.

On the other hand, insulin resistance and androgen excess are the main characteristics of PCOS that could increase the risk of developing NAFLD.

To examine the most relevant factors associated with NAFLD in women with PCOS, investigators recently conducted a cross-sectional study including 600 Caucasian women diagnosed with PCOS between May 2008 and May 2013 and 125 women matched for body mass index.

NAFLD, which was diagnosed by an NAFLD liver fat score, was identified in 50.6% of women with PCOS, compared with 34.0% of controls. Women with PCOS had higher readings for waist circumference, lipid accumulation product (a combination of waist circumference and fasting triglyceride levels), insulin resistance, total cholesterol, and triglycerides than controls. Upon further analysis, insulin resistance and lipid accumulation product were independently associated with NAFLD.

“This study provided further evidence that PCOS women are more prone to develop NAFLD compared with non-PCOS premenopausal women, and that features of the metabolic dysfunction that characterize PCOS are the main factors implicated in the development of NAFLD in these patients,” says Dr. Vassilatou, who wasn’t involved with the study. “Some research also suggests that androgen excess, which is a key feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor for the development of NAFLD in PCOS.”

Just scratching the surface

Dr. Vassilatou says that more research is needed to understand the role of androgens, if any, in the pathophysiology of NAFLD in women with PCOS. Also, long-term follow-up studies are necessary to reveal the range of liver-related outcomes in women with PCOS and to determine the natural history of NAFLD in these women—for example, how often it progresses from its early stages to severe liver disease. It will also be important to investigate whether obese patients with PCOS and NAFLD present more frequently with an advanced stage of liver disease, as reported in a few studies.

Although additional studies are needed to clarify the association between PCOS and NAFLD, accumulating data over the past decade indicate that clinicians should at least be aware of this connection. “Thus, these women should be screened for NAFLD, particularly obese patients with features of the metabolic syndrome. Conversely, premenopausal women with NAFLD should be screened for PCOS,” suggests Dr. Vassilatou.

Despite the need for greater screening, more work is necessary to identify the most appropriate methods, which could include ultrasound, liver function tests, and algorithms such as the NAFLD liver fat score. Furthermore, because there’s no medical therapy of proven benefit for treating NAFLD, well-designed interventional studies—with lifestyle modifications and/or the use of medical therapy targeting insulin resistance, impaired glucose tolerance, and dyslipidemia—are needed to determine the optimal management of affected patients.

To get a sense of where we are now, diet, weight loss, and exercise are currently the cornerstone of therapy and are often combined with insulin sensitizers, hypolipidemic drugs, and hepatoprotective agents, like antioxidants.

Published: March 17, 2017