Oral Hormone Therapy Women Linked To Heart Disease

In post menopausal women, oral hormone therapy with estrogen-only or estrogen plus progestin pills can alter metabolism and linked to increased heart disease risk.

Oral hormone therapy can significantly alter the products of metabolism in post menopausal women. For this research, blood samples from the landmark Women’s Health Initiative (WHI) study were examined. This can help explain the disease risks and the protective effects which are linked to different hormone therapy regimen.

The study led by a team of scientists including a University of Massachusetts Amherst biostatistician was published in the Circulation: Genomic and Precision Medicine.

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‘Oral hormone therapy with estrogen-only or estrogen plus progestin pills can alter metabolism in post menopausal women. By changing level of amino acid lysine, estrogen-only pill shows protective effect while estrogen plus progestin showed increased risk of Coronary artery disease (CHD).’
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Raji Balasubramanian, associate professor in the School of Public Health and Health Sciences, whose research connects biostatistics, molecular epidemiology and women's health said, “ This is the first analysis of the metabolomic effects of hormone therapy conducted within the framework of a randomized clinical trial.

The study proved that hormone therapy alters the small molecules was conducted by Raji 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 T.H. Chan School of Public Health, Brown University and several institutions in Spain.

The 1990s WHI’s hormone therapy examined the effects of estrogen alone and a combination of estrogen and progestin on coronary heart disease (CHD), breast cancer, and other conditions that require hormone therapies.

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According to this study, the combination therapy increased the risk of CHD by 29 percent; estrogen alone decreased the risk of CHD by 9 percent although this effect was not statistically significant.

Balasubramanian said, “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.

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The researchers Broad Institute measured 481 metabolites in blood samples from the WHI hormone therapy trial participant using liquid chromatography mass spectrometry (LC-MS).

The trial included 503 women from estrogen-only group out of which half were given placebo. 431 women were given estrogen plus progestin and half of them were given placebo.

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The research team recorded measurements before the hormone therapy began and when the women were still active treatment a year later.

Changes In The Metabolome

The findings showed changes in the metabolome of classes like lipids, amino acids and other small molecule metabolites. 62 percent metabolites were changed with estrogen-alone therapy and 52 percent with estrogen plus progestin.

22 metabolites were identified which had differing effects out of which 12 were associated with CHD risk. The changes in all 12 metabolites showed protective CHD effect with estrogen-alone treatment. 11 metabolites were unchanged with estrogen plus progestin treatment. The amino acid lysine showed significant changes with both hormone therapies but the changes were opposite to each other.

Estrogen-alone therapy showed a protective effect by increasing lysine levels whereas estrogen plus progestin increased CHD risk by decreasing lysine levels.

Balasubramanian said, “Getting a handle 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.

The study can also identify other hormone therapy-related metabolomic changes in women and how these changes are associated with differential risks for other health conditions like breast cancer, depending on the hormone regimen.

Source-Medindia