Changes in carotid artery intima-media thickness 3 years after cessation of menopausal hormone therapy: follow-up from the Kronos Early Estrogen Prevention Study

Objective: Little is known regarding the progression of preclinical atherosclerosis upon cessation of menopausal hormone therapy (MHT). This study evaluated changes in carotid artery intima-media thickness (CIMT) in a subgroup of participants during 4 years and 3 years after the Kronos Early Estrogen Prevention Study (KEEPS). Methods: Of the women enrolled in KEEPS at Mayo Clinic (n = 118), a subset (n = 76) agreed to participate in this follow-up study. KEEPS MHT assignments were placebo (PBO), n = 33; transdermal 17 beta-estradiol (tE(2)), n = 23; and oral conjugated equine estrogens group (oCEE), n = 20. CIMT was measured by B-mode ultrasonography. Longitudinal analysis of CIMT was performed using all available data from pre-, on-, and post-treatment periods. Results: At 7 years, median age of participants was 60.2 years; median time since menopause was 8.5 years. The mean difference in rates of increase was significantly greater over the post-than on-treatment period within the oCEE group (0.010 [0.002-0.017] mm/y), but not within the PBO (0.006 [-0.001 to 0.012] mm/y; P = 0.072) or tE(2) (0.002 [-0.005 to 0.010] mm/y; P = 0.312) groups. There were, however, no significant treatment differences in the linear trends over those intervals (P = 0.524). Conclusions: Cessation of MHT at the lower doses and formulations used in KEEPS did not appear to alter the trajectory of CIMT over a 3-year follow-up period. CIMT, however, increased in all groups over the entire 7-year timeframe as expected with age and timing of menopause possibly key contributors.