Androgens, Irregular Menses, and Risk of Diabetes and Coronary Artery Calcification in the Diabetes Prevention Program

Abstract

Context: It is unclear whether relative elevations in androgens or irregular menses (IM) are associated with greater cardiometabolic risk among women who are already overweight and glucose intolerant.

Research design and methods: We conducted a secondary analysis of the Diabetes Prevention Program (DPP) and the Diabetes Prevention Program Outcomes Study (DPPOS). Participants included women with sex hormone measurements who did not use exogenous estrogen (n = 1422). We examined whether free androgen index (FAI) or IM was associated with diabetes risk during the DPP/DPPOS or with coronary artery calcification (CAC) at DPPOS year 10. Models were adjusted for menopausal status, age, race or ethnicity, randomization arm, body mass index (BMI), and hemoglobin A1c.

Results: Women had an average age of 48.2 ± 9.9 years. Elevations in FAI and IM were associated with greater BMI, waist circumference, and blood pressure and lower adiponectin. FAI was not associated with diabetes risk during the DPP/DPPOS [hazard ratio (HR) 0.97; 95% confidence interval (CI), 0.93 to 1.02] or increased odds of CAC [odds ratio (OR) 1.06; 95% CI, 0.92 to 1.23]. IM was also not associated with diabetes risk during the DPP/DPPOS (HR 1.07; 95% CI, 0.87 to 1.31) or increased odds of CAC (OR 0.89; 95% CI, 0.53 to 1.49). Women who had both relative elevations in FAI and IM had similar diabetes risk and odds of CAC as women without these conditions. Differences by treatment arm and menopausal status were not observed.

Conclusions: Among midlife women who were already glucose intolerant and overweight, androgen concentrations and IM did not additionally contribute to increased risk for diabetes or CAC.

Trial registration: ClinicalTrials.gov NCT00038727.

Copyright © 2017 Endocrine Society

Figures

Figure 1.

Risk of incident diabetes associated with relative elevations in FAI and IM during the DPP (top panel) and the DPPOS (bottom panel) [hazard ratio (HR) and 95% confidence interval (CI)]. Reference group is women without either abnormality. Women without either abnormality are the reference group, so that an HR >1 indicates greater diabetes risk if women have elevations in both FAI and IM. Model 1 is adjusted for menopausal status. Model 2 is adjusted for menopausal status, age, and race or ethnicity. Model 3 is adjusted for menopausal status, age, race or ethnicity, and randomization arm. Model 4 is adjusted for menopausal status, age, race or ethnicity, randomization arm, and BMI. Model 5 is adjusted for menopausal status, age, race or ethnicity, randomization arm, BMI, and baseline hemoglobin A1c.

Figure 2.

Associations between relative elevations in FAI and IM with odds of any CAC at year 10 DPPOS [odds ratio (OR) and 95% confidence interval (CI)]. The reference group is women without either abnormality, so that an OR >1 indicates greater odds of CAC if women have elevations in both FAI and IM. Model 1 is adjusted for menopausal status. Model 2 is adjusted for menopausal status, age, and race or ethnicity. Model 3 is adjusted for menopausal status, age, race or ethnicity, and randomization arm. Model 4 is adjusted for menopausal status, age, race or ethnicity, randomization arm, and BMI. Model 5 is adjusted for menopausal status, age, race or ethnicity, randomization arm, BMI, and baseline hemoglobin A1c.