Hormone therapy with conjugated equine estrogens, either alone or combined with medroxyprogesterone acetate, may be associated with long-term changes in cardiovascular biomarkers in postmenopausal women, according to a study from the Women’s Health Initiative.
Investigators included 2,696 participants who were randomly assigned to receive conjugated equine estrogens (CEE) alone, CEE with medroxyprogesterone acetate (MPA), or placebo. Blood samples were collected at baseline and after 1, 3, and 6 years.
Women who received CEE alone showed an 11% reduction in low-density lipoprotein (LDL) cholesterol compared with placebo. A similar 12% reduction was observed with CEE plus MPA. High-density lipoprotein (HDL) cholesterol increased by 13% in the CEE group and by 7% in the combination group. However, triglycerides rose by 14% and 8%, respectively.
Lipoprotein(a) levels were 15% lower in the CEE group and 20% lower in the CEE plus MPA group. The most pronounced reductions—about 35% to 40%—were seen in women who identified as American Indian or Alaska Native and Asian or Pacific Islander.
“Lipoprotein(a), LDL [cholesterol], and homeostatic model assessment for insulin resistance were lower and HDL [cholesterol] levels were higher for [hormone therapy] compared with placebo,” said lead study author Matthew Nudy, MD, of the Penn State College of Medicine.
Insulin resistance decreased by 14% in the CEE group and 8% with combination therapy. Fibrinogen levels fell by about 4% in both groups, while factor VII antigen increased modestly.
The investigators noted that although hormone therapy improved several cardiovascular biomarkers, it didn't reduce the risk of coronary heart disease in prior Women’s Health Initiative trials and was associated with increased stroke risk.
The analysis accounted for blood pressure, body mass index, and race and ethnicity, and adjusted for increased statin use in the placebo group over time. Sensitivity analyses confirmed the primary findings despite changes in medication use and treatment adherence.
The investigators concluded that oral hormone therapy produced favorable changes in several cardiovascular biomarkers but also increased triglycerides and clotting-related factors. They suggested further research into other hormone formulations and delivery methods, including transdermal options.
The findings may help inform clinical counseling among younger menopausal women considering hormone therapy for symptom management. However, the benefits and risks should be weighed in the context of overall cardiovascular outcomes.
Full disclosures and methodology details are available in the published study.
Source: Obstetrics and Gynecology