The role of ADAMTS4 and ADAMTS9 in cardiovascular disease in premature ovarian insufficiency and idiopathic hypogonadotropic hypogonadism

Abstract

We aimed to determine the relation of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4), and a disintegrin and metalloproteinase with thrombospondin motifs-9 (ADAMTS9) with cardiovascular disease (CVD) risk, in ovarian dysfunction patients with premature ovarian insufficiency (POI), and idiopathic hypogonadotropic hypogonadism (IHH). 43 IHH and 44 POI patients were enrolled to this case-control study. Serum hormonal parameters, lipid profiles, ADAMTS4 and ADAMTS9 levels were measured. Lipid accumulation product (LAP) index, visceral adiposity index (VAI), and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The patients with at least two out of the four following criteria were accepted to have increased CVD risk; waist-to-hip ratio (WHR) ≥ 0.8, waist circumference (WC) ≥ 79cm, triglycerides (TG) ≥ 150mg/dL, high-density lipoprotein cholesterol (HDL-C) < 50mg/dL. Serum ADAMTS4 and ADAMTS9 levels were measured by enzyme-linked immunosorbent assay (ELISA). ADAMTS4 and ADAMTS9 levels were significantly higher in the IHH group than the POI group (p = 0.002, and p = 0.013, respectively). IHH group had significantly higher levels of insulin, HOMA-IR index, and LAP index (p = 0.006, p = 0.005, and p = 0.013, respectively). The mean age of patients in the IHH group (23.60 ± 5.64years) was significantly lower than the POI group (31.05 ± 6.03years), (p < 0.001). Odds ratios (OR) were 1.236 (95% CI 1.055-1.447) and 1.002 (95% CI 1.000-1.004) for LAP index and ADAMTS4, respectively, in the IHH group. These two parameters found to have high predictivity for CVD risk in the IHH group (p = 0.009 and p = 0.028, respectively). The lower levels of ADAMTS4 in the POI group, when compared with the IHH patients pointed out that even limited hormone secretion and ovulation in the POI group, may have protective effect on cardiovascular system. The higher levels of ADAMTS4 and LAP index in the IHH group demonstrated the increased risk of these patients for CVD.