Abstract
The effect of oral hormone therapy on the metabolome of postmenopausal women is profound. Different hormone therapy regimens result in discordant metabolomic effects that impact the risk for coronary heart disease, reports a study led by Raji Balasubramanian, Sc.D., associate professor in the School of Public Health and Health Sciences, University of Massachusetts, Amherst.
The study is based on the assessment of 481 metabolites in 934 women who participated in the Women's Health Initiative hormone therapy (WHI-HT) trials and reported in the journal Circulation: Genomic and Precision Medicine. Balasubramanian's investigations build on earlier WHI-HT studies that report a 29% increase in the risk of coronary heart disease upon combined oral treatment with conjugated equine estrogens and medroxyprogesterone acetate (CEE+MPA) but not upon treatment with CEE alone.
To explain this difference in outcomes of the WHI-HT regimens, Balasubramanian and colleagues asked whether hormone therapy alters small-molecule metabolites. “The answer is a resounding yes,” says Balasubramanian.
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In addition to coronary heart disease, the CEE+MPA regimen also increased risk of invasive breast cancer, stroke, pulmonary embolism, dementia, gallbladder disease, and urinary incontinence, while it reduced hip fractures, colorectal cancer, and diabetes. Earlier studies on the trial also show an association of CEE alone with a higher risk of stroke, and a lower risk of hip fracture
“Our focus was on cardiovascular disease and understanding at a molecular level why these two hormone therapy regimens had disparate effects in regard to cardiovascular disease,” Balasubramanian says.
The study sets the stage for identifying other hormone therapy-related metabolomic changes in women of a broader age range and investigations into associations with other diseases, such as breast cancer.