Oral hormone therapy shown to significantly alter metabolome of menopausal women – health



Groundbreaking research led by a team of scientists including a University of Massachusetts Amherst biostatistician shows that oral hormone therapy (HT) significantly alters the metabolome of postmenopausal women.

This finding, which examined blood specimens from the landmark Women’s Health Initiative (WHI) study, may help provide an explanation for the disease risks and protective effects associated with different regimens of hormone therapy.

“This is the first analysis of the metabolomic effects of hormone therapy conducted inside the framework of a randomized clinical trial,” said Raji Balasubramanian, associate professor in the School of Public Health and Health Sciences, whose research connects biostatistics, molecular epidemiology, and women’s health.

Balasubramanian, in collaboration with Dr Kathryn M Rexrode at Brigham and Women’s Hospital, a teaching affiliate of Harvard Medical School, and colleagues at the Broad Institute of Harvard and MIT, Harvard’s TH Chan School of Public Health, Brown University, and several institutions in Spain, wanted to study if hormone therapy alters the universe of small molecule metabolites.

“The answer used to be a resounding yes,” said Balasubramanian, lead writer of the paper published in Circulation: Genomic and Precision Medicine.

The 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.

The combination therapy used to be found to significantly increase CHD risk by 29 per cent; estrogen alone used to be found to diminish CHD risk by 9 per cent, despite the fact that this effect used to be not statistically remarkable.

“Our focus used to be on cardiovascular disease and understanding at a molecular level why these two hormone therapy regimens had disparate effects in regard to cardiovascular disease,” Balasubramanian said.

The usage of liquid chromatography mass spectrometry (LC-MS) techniques, researchers at the Broad Institute measured 481 metabolites in blood specimens from the WHI hormone therapy trial participants: 503 from 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 measurements obtained correct before hormone therapy began and one year later, when the women were still on active remedy or placebo.

The findings revealed “profound changes in the metabolome, spanning a variety of classes including lipids, amino acids and other small molecule metabolites,” Balasubramanian said.

In truth, 62 per cent of metabolites were significantly changed with estrogen-alone therapy, and 52 per cent with estrogen plus progestin.

While lots of the changes in metabolites were consistent with every kind of hormone therapy, 22 metabolites were identified that had discordant effects. Twelve of those were associated with CHD risk in an evaluation of an independent WHI dataset.

With estrogen-alone remedy, the changes in all 12 metabolites given a protective CHD effect. With estrogen plus progestin, 11 metabolites were unchanged.

The amino acid lysine used to be significantly altered by both hormone therapies, but in the wrong way. Estrogen-alone therapy increased lysine levels, providing a protective effect, and estrogen plus progestin decreased lysine levels, elevating CHD risk.

“Getting a take care of on what subset of metabolites had differential changes between the two drugs related to cardiovascular diseases might point to the molecular underpinnings of the difference in risk between the two treatments,” Balasubramanian said.

UMass Amherst 2020 graduate Ryan Sheehan contributed to the data analytic aspects of the study and continues to work in Balasubramanian’s lab as a research associate.

Taking part in the study used to be “the most efficient experience a student could have,” he says. “Not only used to be I ready to contribute my own skills and knowledge to this important paper, but also I used to be ready to be informed such a lot approximately the processes that go on with professional research. The period of time and attention to detail that went into every step is something I will be able to try to imitate in my own work as I progress in my professional career.”

The study also lays the groundwork for identifying other hormone therapy-related metabolomic changes in a broader age group of women and how those changes are associated with differential risks for other health conditions, such as breast cancer, depending on the hormone regimen.

“We’re excited to contribute to advancing research in women’s health,” Balasubramanian said.

(This story has been published from a wire agency feed without modifications to the text.)

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