Groundbreaking research led by a team of scientists including a University of Massachusetts amherst biostatistician suggests that oral hormone therapy (HT) significantly alters the metabolism of postmenopausal women.
This finding, which examined blood samples from the Historic Women’s Health Initiative (WHI) study, may help explain the risks of disease and the protective effects associated with various diets of hormone therapy.
“This is the first analysis of the metabolic effects of hormone therapy conducted within the framework of a randomized clinical trial,” said Raji Balasubramanian, associate professor of the School of Public Health and Health Sciences, whose research links biostatistics, molecular epidemiology, and women . Health.
Balasubramanian, at Brigham and Women’s Hospital, Dr. Along with Catherine M. Rekodrode, a teaching associate at Harvard Medical School, and colleagues at Harvard and MIT’s Broad Institute, Harvard’s TH Chan School of Public Health, Brown University, and several institutions in Spain. , Wanted to study whether hormone therapy changes the universe of small molecule metabolites.
Balasubramanian, the lead author of the paper published in Circulation: Genomic and Precision Medicine, said, “The answer was yes.”
WHI’s hormone therapy trials in the 1990s examined the effects on coronary heart disease (CHD), breast cancer, and other conditions of two hormone therapies — estrogen alone and a combination of estrogen and progestin.
Combination therapy was found to increase CHD risk by up to 29 percent; Estrogen alone was found to reduce CHD risk by 9 percent, although this effect was not statistically significant.
Balasubramanian said, “Our focus was on heart disease and understanding at the molecular level why these two hormone therapy regimens had a disparate impact in relation to heart disease.”
Using liquid chromatography mass spectrometry (LC-MS) techniques, Broad Institute researchers measured 481 metabolites in blood samples from WHI hormone therapy test participants: 503 of the women in the estrogen-only group, half of whom were on placebo ; And 431 in the estrogen plus progestin group, with half on placebo.
The research team recorded the measurements just before the start of hormone therapy and one year later, when the women were still in active treatment or placebo.
Balasubramanian said, “The findings have undergone profound changes in metabolism, including a wide variety of classes including lipids, amino acids and other small molecule metabolites.”
In fact, 62 percent of the metabolites were significantly altered with estrogen-alone therapy, and 52 percent with estrogen plus progestin.
While most changes of metabolites were consistent with each type of hormone therapy, 22 metabolites were identified that had unsatisfactory effects. Twelve of them were associated with CHD risk in the evaluation of an independent WHI dataset.
With estrogen-alone treatment, changes in all 12 metabolites conferred a protective CHD effect. Along with estrogen plus progestin, 11 metabolites were up-regulated.
The amino acid lysine was significantly altered by both hormone therapies, but in the opposite direction. Estrogen-alone therapy increased lysine levels, provided a protective effect, and estrogen plus progestin reduced lysine levels, increasing CHD risk.
Balasubramanian said, “may indicate the molecular basis of the difference in risk between the two diseases, which was being a handle of the difference in difference between the two drugs related to cardiovascular diseases,” Balasubramanian said.
UMass Amherst 2020 graduate Ryan Sheehan contributed to the data analytic aspects of the study and continued to work in Balasubramanian’s laboratory as a research associate.
They say that participating in the study “may be the best experience a student can have”. “Not only was I able to contribute my own skills and knowledge to this important paper, but I was also able to learn so much about the processes that accompany professional research. The amount of time and attention to go through each stage is something that I will try to imitate in my work as I progress in my professional career. “
This study does grassroots work to identify other hormone therapy-related metabolic changes in a wider age group of women and those changes are associated with differential risk for other health conditions, such as hormone-based breast cancer.
“We are excited to contribute to advancing research in women’s health,” Balasubramanian said.
(This story is published from a wire agency feed without textual modifications.)
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