Two low-dose menopausal hormone regimens improved some cardiovascular parameters in healthy women but did not affect atherosclerosis progression, even when started early and continued for up to 4 years, investigators reported online July 28 in Annals of Internal Medicine.
Neither of the low-dose menopausal hormone therapy (MHT) regimens used in the study affected blood pressure, but both relieved hot flushes, added Dr. S. Mitchell Harman of the Phoenix Veterans Affairs Health Care System in Arizona and his associates.
Dr. S. Mitchell Harman
Follow-up analyses of Women’s Health Initiative data had suggested that MHT might have cardiovascular benefits if started early enough or in younger women, the researchers noted.
To further explore the association, the Kronos Early Estrogen Prevention Study (KEEPS) enrolled 727 healthy women aged 42-58 years who were considered low risk for cardiovascular disease and were within 36 months of their last menses (Ann. Intern. Med. 2014 July 28 [doi: 10.7326/M14-0353]). The women were randomized in a double-blinded fashion to oral progesterone (200 mg for 12 days per month), plus either oral estrogen (conjugated equine estrogen, 0.45 mg per day) or transdermal estrogen (17-beta-estradiol, 50 mcg per day), or to a placebo, the researchers said.
Vascular ultrasonography at baseline and after up to 4 years of treatment revealed no effect of MHT on the progression of atherosclerosis, the researchers said. Average increases in carotid artery intima-media thickness were 0.0076 mm per year and were similar across treatment groups, as were increases in coronary artery calcium scores (17.4% for the oral estrogen group, 18.9% for the transdermal estrogen group, and 21.0% for the placebo group), they reported.
Neither hormone therapy regimen led to changes in blood pressure or interleukin-6 levels, although vasomotor symptoms (hot flushes) improved with both regimens, the investigators said. Lipoprotein cholesterol levels also improved in both treatment groups, and the oral estrogen group had improvements in C-reactive protein and sex hormone–binding globulin. The transdermal estrogen group had improvements in insulin sensitivity.
The study was inadequately powered to allow comparison of clinical events, and power for the coronary artery calcium score also was limited, the researchers noted. The results also might not be generalizable to women who have substantial cardiovascular risk factors, they added.
The Aurora Foundation funded the research, and Abbott Laboratories and Bayer Healthcare donated study medications. Dr. Harman reported no relevant conflicts of interest.