What Are the Side Effects of Hormone Therapy? - Chromatography Explores

New research by a team of scientists in the US and Spain has shown that oral hormone therapy can alter the metabolome of postmenopausal women. This finding could help to explain why women who have undergone hormone therapy have different disease risks depending on the hormone therapy they have had.

The study was published in the journal Circulation: Genomic and Precision Medicine compared the metabolomes from women who had oestrogen only and those who had oestrogen plus progestin. In the paper - Metabolomic Effects of Hormone Therapy and Associations With Coronary Heart Disease Among Postmenopausal Women – the researchers used liquid chromatography to analyse almost 500 metabolites. They found significant differences in twelve metabolites associated with coronary heart disease.

Landmark study keeps delivering

The work carried out by the researchers in the US and Spain follows on the work carried out under the Women’s Health Initiative (WHI) hormone therapy trials that in the 1990s examined the effects of hormone therapies on coronary heart disease, breast cancer and other illnesses. The WHI is a long-term study that began in 1992 and concluded in 2005, although extension studies are still ongoing, and participants still report health data.

The WHI study examined the effects of oestrogen and a combined therapy using oestrogen and progestin. The combination therapy was found to increase the risk of heart disease compared to a placebo and oestrogen. The researchers behind the paper referenced above were interested in studying how hormone therapy altered the metabolome of participants in the WHI.

Analysing the metabolome with LC-MS

The metabolome refers to the complete set of small molecules within an organism. It requires powerful analytical techniques allied with powerful data analysis techniques. Using liquid chromatography-mass spectrometry techniques, the researchers analysed almost 500 metabolites from blood samples taken from WHI participants. The use of chromatography to analyse biomolecules is discussed in the article, New Monodense Large Pore Silica-Based Materials for the Analysis of Biomacromolecular Compounds by Reversed-Phase Liquid Chromatography.

In a press release, the reports main author Raji Balasubramanian stated that the findings revealed “profound changes in the metabolome, spanning a wide range of classes including lipids, amino acids and other small molecule metabolites.”  The team identified 12 metabolites that had been associated with a changed heart disease risk. The oestrogen alone treatment provided a beneficial change in risk, the combination treatment didn’t significantly alter the metabolites.

Balasubramanian explained that “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.”  It is hoped that the study will allow researchers to identify other hormone therapy-related metabolomic changes.