Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS

Abstract

Background and aimsNonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis.MethodsWe considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free androgen index (FAI) was calculated as estimate of biochemical hyperandrogenism.ResultsIn the entire population, steatosis was observed in 68.8% of patients with PCOS, compared to 33.3 of controls (p<0.001), this association being maintained after adjusting for metabolic confounders (OR 3.73, 95% CI 1.74–8.02; P = 0.001). In PCOS patients, steatosis was independently linked to WC (OR 1.04, 95% CI 1.01–1.08; P = 0.006) and ISI Matsuda (OR 0.69, 95% CI 0.53–0.88; P = 0.004), not to free androgen index (OR 1.10, 95% CI 0.96–1.26; P = 0.14). Notably, ISI Matsuda was confirmed as independently associated with steatosis in both obese (OR 0.42, 95% CI 0.23–0.77, P = 0.005) and nonobese (OR 0.69, 95% CI 0.53–0.91, P = 0.009), patients, while FAI (OR 1.45, 95% CI 1.12–1.87; P = 0.004) emerged as an independent risk factor only in nonobese PCOS. Similarly, higher FIB-4 was independently associated with higher FAI (p = 0.02) in nonobese and with lower ISI Matsuda (p = 0.04) in obese patients.ConclusionsWe found that PCOS is an independent risk factor for steatosis, and that, IR and hyperandrogenism, this last especially in nonobese patients, are the key players of liver damage in PCOS.

Lipid accumulation product independently correlate with hepatic steatosis quantified by controlled attenuation parameter in women with polycystic ovary syndrome

“…Also, Vassilatou and colleagues (29) observed that LAP is a useful indicator for detecting NAFLD diagnosed by ultrasonography in Caucasian premenopausal women with PCOS. In the present study, the prevalence rate of HS was 70.3% in women with PCOS, which is consistent with previous studies (30,31). LAP is also higher in HS group than that in control group, and further LAP could independently predict the risk for HS after controlling for the potential confounding factors.…”

Skeletal Muscle Immunometabolism in Women With Polycystic Ovary Syndrome: A Meta-Analysis

“…Fibrosis in skeletal muscle can impair muscle function and affect muscle fiber regeneration after injury (Delaney et al, 2017;Mahdy, 2019). Tissue fibrosis is often initiated and maintained through TGF-beta signaling and has been suggested to be associated with insulin resistance and steatosis in PCOS (Petta et al, 2017;Stepto et al, 2019). This association is supported by a recent paper, investigating TGF-beta ligand induced fibrosis in obese women with PCOS (Stepto et al, 2020).…”

Cutting the ovarian surface improves the responsiveness to exogenous hormonal treatment in aged mice

“…45 Additionally, Ovarian fibrosis is also observed in polycystic ovarian syndrome (PCOS). 47,48 One radical treatment is laparoscopic ovarian drilling (LOD) for PCOS patients. 49 In the original LOD method, using an insulated unipolar needle electrode, three to eight punctures (each with a diameter of 3 mm and a depth of 2-4 mm) are performed in the ovary by laparoscopy.…”