Sex hormones control fat levels in the body and shed light on cardiovascular disease risk by gender

UCL researchers have for the first time found evidence that cross-sex hormone treatment – given to people who are transitioning genders – induces changes in fat metabolism that require further exploration.

The findings support a role for sex hormones in the control of fat metabolism and will help enable sex-specific management of cardiovascular disease (CVD) and other conditions, said the research team from the UCL Centre for Adolescent Rheumatology Versus Arthritis and Centre for Cardiometabolic and Vascular Science.

CVD is the leading cause of mortality worldwide. Women of child-bearing age have around half the CVD risk and almost a 10-year delay to first heart attack event compared to age matched men. Various risk factors have been shown to confer differential CVD susceptibilities for men compared to women.

These sex differences in CVD risk could be due to reduced levels in women compared to men of the particles responsible for transporting fats to arteries – very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) – which cause a blockage (atherosclerosis) to blood flow, or due to increased levels in women of the particles responsible for transporting fats away from arteries (high-density lipoproteins – HDL).

In addition, CVD risk is increased in patients with autoimmunity. Diseases which are frequently triggered during puberty have a strong bias towards young women and are associated with altered fat metabolism (increased VLDL/LDL and reduced HDL). Investigating the relationship between sex hormones and fat metabolism is important for understanding the development of atherosclerosis and CVD in different biological and disease settings.

This new study, published in iScience, used in-depth analysis of fat metabolites to identify fats that differ post-puberty between young men and women and to validate the role of sex hormones in driving these differences in young trans-gender individuals undergoing cross-sex-hormone treatment.

The study found:

  • There was a direct association between the female sex hormone oestradiol and increased blood levels of anti-CVD HDL fats (in young post-pubertal cis-women and trans-women), as well as between testosterone and increased blood levels of pro-CVD VLDL fats (in young post-pubertal cis-men and trans-men).
  • Differences in HDL were induced by oestradiol in a dose dependent and chromosome independent manner.

Knowledge of sex differences in fat metabolism post-puberty could help inform sex-tailored strategies for CVD risk management from a younger age, and may have implications for altering their cardiovascular risk factors later in life, potentially leading to a decrease in CVD related morbidity and mortality worldwide.

The multidisciplinary research team are optimistic about these findings. Dr George Robinson, lead author and postdoctoral researcher, said: “We have highlighted fundamental sex differences in fat metabolism driven by sex hormones which will help us understand differences in disease susceptibilities such as cardiovascular disease and autoimmunity.”

Dr Coziana Ciurtin, Principal Investigator, Consultant Rheumatologist and Principal Investigator of the Centre for Adolescent Rheumatology, said: “This study will provide a wealth of information towards the development of personalised and sex-specific management of autoimmune disease from a young age, especially in the context of CVD and other comorbidities, potentially leading to a decrease in morbidity and mortality in younger people.”

Professor Liz Jury, Principal Investigator and Professor in Experimental Rheumatology, said: “It is very important to consider sex differences in medical research, evident from the sexual dimorphisms observed across disease, now supported by our new and significant study.”

Read the full research article.

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