COmmencing Menopausal HOrmone Replacement Therapy and the Effect on Metabolic-dysfunction Associated Steatotic Liver Disease: a Pilot Mechanistic Study
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide, currently affecting approximately 1-in-4 people globally. The prevalence is expected to rise further, driven at least partly by the epidemic of obesity and diabetes. MASLD is a condition of fat build-up in the liver that can progress to liver scarring which is associated with higher chances of death. Women are more than twice as likely to develop MASLD after menopause compared to before menopause, and previous research has shown that this may be caused by a lack of oestrogen. A lack of oestrogen is also believed to lead to harmful changes in adipose (body fat), which has an important role in the development of MASLD. Oestrogen contained in hormone replacement therapy (HRT) is an effective treatment for hot flushes and other problems in menopause. The popularity of HRT has increased dramatically in the United Kingdom in recent years, however the exact way in which it affects adipose and MASLD is unclear. The investigators will study how HRT affects the processes that drive MASLD in 10 women before and after using the treatment. This is a small-scale pilot study to understand feasibility of recruitment and test the procedures for a future, larger-scale studies. The investigators will recruit women who are about to begin HRT for the first time and perform the same tests for each participant before starting HRT, and after using HRT for 12-weeks. The participants will undergo meal testing including non-radioactive, stable isotopes, and blood and breath samples will be collected to measure fat processing. The total fat content of the liver will be measured using magnetic resonance imaging (MRI) scans. Adipose samples will be collected, fat metabolites will be measured and the distribution of fat around the body will be assessed using a dual energy x-ray absorptiometry (DEXA) scan. To find out how HRT affects these processes, the results from before and after using HRT will be compared. Understanding how HRT affects adipose and the liver may help reduce the development of MASLD in women after the menopause and improve their health and survival.
• Potential participant is willing and able to give informed consent for participation in the trial
• In the Investigator's opinion, is able and willing to comply with all trial requirements
• Female, aged 18 years and above
• Body mass index 18 to 45 kg/m2
• Postmenopausal status:
‣ For women ≥ 40 defined clinically (amenorrhoea for ≥ 1 year) or biochemically (FSH \>30IU/L on 2 occasions 4-6 weeks apart).
⁃ For women \< 40 defined as a combination of oligomenorrhoea/amenorrhoea for ≥ 4 months and FSH \>30IU/L on 2 occasions 4-6 weeks apart
⁃ Women who have undergone bilateral oophorectomy (no additional testing is required)
• Low oestradiol levels
• No exposure to systemic oestrogen-based HRT within the previous 3 months
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.