Effect of short-term medroxyprogesterone acetate on left ventricular mass: role of insulin-like growth factor-1

Previous studies using 17beta-estradiol and medroxyprogesterone acetate (MPA) have shown that hormone replacement therapy (HRT) increases left ventricular mass (LVM). To determine if insulin-like growth factor-1 (IGF-1) is associated with the increase in LVM, we measured IGF-1 and IGF-binding protein-3 (IGFBP-3) levels in 19 postmenopausal women before and after 8 weeks of oral treatment with MPA 5 mg/d. LVM was measured by two-dimensional echocardiography. Changes in IGF-1, IGFBP-3, and LVM from baseline were analyzed by paired ttest. Regression analysis was used to determine if changes in the IGF-1 axis with MPA treatment affect the increase in LVM. LVM increased 4.4% during the study (P = .006 vbaseline). IGF-1 increased 17% with MPA (P = .008), whereas IGFBP-3 did not change. The IGF-1/IGFBP-3 ratio increased 16.8% (P = .0003). Regression analysis of LVM with IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio suggested that IGF-1 during MPA therapy explains 2.4% and the IGF-1/IGFBP-3 ratio explains 3.2% of the variation in LVM. There was no effect of IGFBP-3 on LVM. Most of the variation in LVM with MPA (90.5%) was explained by baseline LVM. The IGF-1/IGFBP-3 ratio on MPA treatment was inversely related to the change in LVM: women with a lower LVM at baseline had the greatest increase in LVM with MPA. These findings suggest that MPA increases IGF-1 and LVM. Because the increase in IGF-1 with MPA treatment explains a fraction of the increase in LVM, other mechanisms must also be operative.