Findings from subanalysis of Kronos Early Estrogen Prevention Study Cessation of low-dose menopausal hormone therapy did not seem to affect progression of preclinical atherosclerosis, researchers reported. In a follow-up analysis from the Kronos Early Estrogen Prevention Study (KEEPS), low doses of hormone therapy -- both oral and transdermal -- did not change the trajectory of carotid artery intima-media thickness (CIMT) during the 4 years of treatment, according to Virginia Miller, PhD, of the Mayo Clinic in Rochester, Minnesota, and colleagues, in Menopause. Although women on transdermal hormones and placebo saw a significant increase in CIMT during the 4 years of treatment, which wasn't seen in the oral estrogen group, there weren't any significant differences in the linear trend across these three treatment groups (P=0.067 across all groups): Oral: 0.008 mm absolute change (95% CI -0.011 to 0.027) Transdermal: 0.035 mm (95% CI 0.017 to 0.052) Placebo: 0.035 mm (95% CI 0.020 to 0.050) Similarly, 3 years after hormone therapy was stopped, all treatments groups -- oral, transdermal, and placebo -- showed a similar progression of absolute CIMT change (P=0.524 across all groups): Oral: 0.034 mm (95% CI 0.017 to 0.050) Transdermal: 0.033 mm (95% CI 0.018 to 0.048) Placebo: 0.043 mm (95% CI 0.030 to 0.057) "Unlike KEEPS which showed no benefit on reduction of atherosclerosis, there are some studies that suggest beneficial effects of hormone therapy started close to menopause on reduction of heart disease," commented JoAnn Pinkerton, MD, executive director of the North American Menopause Society (NAMS), who wasn't involved with the study. Pinkerton, who's also affiliated with the University of Virginia Health System in Charlottesville, highlighted how these findings are actually in direct contrast to the ELITE (Early versus Late Intervention Trial with Estradiol) trial, which saw a benefit on CIMT with early initiation of hormone therapy in menopause, supporting the much-debated "timing hypothesis." But this benefit in ELITE was not seen when estradiol was initiated more than a decade after the start of menopause. "However, looking at the evidence overall, NAMS and other major medical societies do not recommend that hormone therapy be used for prevention of heart disease. The primary indication for the use of hormone therapy is for women close to menopause under age 60 and within 10 years of menopause with bothersome menopausal symptoms or at elevated risk of bone loss," she explained to MedPage Today. This extended, randomized subgroup analysis of KEEPS included 76 women, which included 20 individuals on oral conjugated equine estrogen (Premarin 0.45 mg/d), 23 of whom were on transdermal 17ß-estradiol (Climara 50 µg/d skin patch), and 33 women on placebo pills and patches. For both active treatment groups, progesterone was administrated orally for 12 days each both (Prometrium, micronized progesterone 200 mg/d). Women initiated menopausal hormone therapy close to the start of menopause, as is recommended by NAMS, with the median time since menopause of 8.5 years at the conclusion of the 7-year study. CIMT was measured by B-mode ultrasonography at baseline, annually for the 4 years during treatment, as well as 3 years after stopping treatment. Body morphometrics, fasting blood clinical chemistries, and plasma hormone levels were also assessed. However, the small sample size was a notable limitation, Pinkerton noted, who also highlighted that all these participants were also non-smoking white women, potentially limiting the generalizability. "The participants in the follow-up study were different from the overall KEEPS population with lower systolic blood pressure and higher HDL cholesterol measurements during KEEPS, which may have affected the results." "Evaluation of progression of cardiovascular disease with other formulations of estrogen (oral E2) or similar formulations of higher dosage as used in KEEPS for longer treatment periods or longer follow-up are warranted," the authors recommended, noting how these could possibly yield different findings. The study was supported by the Aurora Foundation to the Kronos Longevity Research Institute, the American Heart Association, and the Mayo Foundation. Miller and co-authors disclosed no relevant relationships with industry.
Cessation of low-dose menopausal hormone therapy did not seem to affect progression of preclinical atherosclerosis, researchers reported.