Hyperandrogenemia in Early Adulthood Is an Independent Risk Factor for Abnormal Glucose Metabolism in Middle Age

CONTEXT: The role of androgen excess as a contributing factor to abnormal glucose metabolism (AGM) and insulin resistance in women remains controversial. OBJECTIVE: To investigate whether hyperandrogenemia (HA) estimated by serum testosterone (T) level and free androgen index (FAI) at ages 31 and 46 years is associated with insulin resistance, insulin secretion and AGM by age 46. DESIGN: Prospective study including 5889 females followed at ages 31 and 46 years. SETTING: General community. PARTICIPANTS: Women with HA were compared with normoandrogenic women at ages 31 and 46 years. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: AGM, including prediabetes and type 2 diabetes mellitus, homeostatic model assessments of insulin resistance (HOMA-IR) and of pancreatic β-cell function (HOMA-B). RESULTS: At age 31 years, HA women displayed increased HOMA-IR (P = 0.002), HOMA-B (P = 0.007), and higher fasting insulin (P = 0.03) than normoandrogenic women after adjusting for body mass index (BMI). At age 46 years, there was a nonsignificant trend toward higher fasting glucose (P = 0.07) and glycated hemoglobin A1 (P = 0.07) levels in HA women. Women in the highest T quartile (odds ratio [OR] = 1.80; 95%CI, 1.15-2.82) at age 31 years and in the 2 highest FAI quartiles at ages 31 (Q4: OR = 3.76; 95% CI, 2.24-6.32) and 46 (Q4: OR = 2.79; 95% CI, 1.74-4.46) years had increased risk for AGM, independently of BMI, when compared with women in Q1. SHBG was inversely associated with AGM (at age 31 years: Q4: OR = 0.37; 95% CI, 0.23-0.60, at age 46 years: Q4: OR = 0.28; 95% CI, 0.17-0.44). CONCLUSION: Hyperandrogenemia and low SHBG in early and middle age associates with AGM independently of BMI.