Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

Abstract

Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.

Non-alcoholic fatty liver disease and risk of cardiovascular disease

“…Most of these studies support the assertion that CVD is the most common cause of mortality among patients with NAFLD. This [2,9,37].…”

“…Despite emerging evidence suggests that NAFLD is also linked to other chronic diseases [7][8][9][10], it is the adverse impact of NAFLD on CVD risk which deserves particular attention owing to the epidemics of obesity/MetS leading to a dramatic surge in the proportion of NAFLD patients in the general population.…”

MANAGEMENT OF ENDOCRINE DISEASE: Polycystic ovary syndrome and nonalcoholic fatty liver disease

“…A recent meta-analysis showed that women with PCOS have a four times higher risk of NAFLD in comparison to healthy women (116). NAFLD is usually considered as a hepatic manifestation of MetS (117); however, some studies confirmed that PCOS women without concomitant MetS and obesity have a higher prevalence of NAFLD in comparison to healthy women (57,58,118). Taking into account the fact that women with PCOS are young and that they might already have NASH, it follows that a high risk of liver-related comorbidities and complications could extend from reproductive to menopausal age.…”

NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk

“…Special emphasis is conferred to CVD risk. The relationship of polycystic ovary syndrome (PCOS) to NAFLD has recently been covered elsewhere [32] and is outside the scope of this review.…”