Female fragile X premutation carriers are at increased risk for metabolic syndrome from early adulthood

Women with primary ovarian insufficiency exhibit an unfavorable cardiovascular risk profile. A common cause for primary ovarian insufficiency is fragile X premutation (FXPC), and data on the cardiovascular risk factors in women with FXPC are scarce. We aimed to assess the prevalences of abnormal metabolic components among FXPC.Clinical, anthropometric and laboratory data were collected from 71 women with FXPC and compared to 78 women referred for counseling in an in-vitro fertilization clinic (control group). The mean ± SD ages of the FXPC and control groups were 33.5 ± 5.6 and 36.2 ± 5.3 years, respectively (p = 0.003). In a logistic regression analysis, the FXPC group had increased risks for hyperglycemia, hypertriglyceridemia, central obesity and low high-density lipoprotein cholesterol, of 21.8-fold (95% CI 2.7-175, p = 0.004), 6.9-fold (95% CI 2.5-18.7, p < 0.0001), 3.1-fold (95% CI 1.4-6.9, p = 0.005) and 2.4-fold (95% CI 1.1-5.2, p = 0.03), compared to the control group. The FXPC group had 2.7-fold higher prevalence of two abnormal metabolic components; 19% met the full criteria of MetS, compared to 3% of the control group. Neither CGG repeats nor ovarian reserve markers were associated with metabolic risk.Carriers of fragile X premutation are at increased metabolic risk from early adulthood; waist circumference, glucose and lipid levels are particularly elevated. We recommend metabolic screening for all women with FMR1 premutation, to enable early interventions for prevention of long-term cardiovascular comorbidities.