Deep metabolic phenotyping reveals tissue-specific actions of transdermal oestradiol and oral micronised progesterone in postmenopausal women

Jiawen Dong; Nikola Srnic; Kaitlyn Dennis; Kieran Smith; Harsha Dissanayake; Tawa Hassan-Sule; Michelle Haylock; Sarah White; Amy Barrett; Hamish Miller; Riccardo Pofi; Thomas Marjot; Anupa Shah; Sharon Dixon; Katie Barber; Radha Venkatakrishnan; Leanne Hodson; Tomlinson Jeremy W

doi:10.1530/endoabs.117.P147

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Endocrine Abstracts (2026) 117 P147 | DOI: 10.1530/endoabs.117.P147

SFEBES2026 Poster Presentations Metabolism, Obesity and Diabetes (68 abstracts)

Deep metabolic phenotyping reveals tissue-specific actions of transdermal oestradiol and oral micronised progesterone in postmenopausal women

Jiawen Dong ¹ , Nikola Srnic ¹ , Kaitlyn Dennis ¹ , Kieran Smith ¹ , Harsha Dissanayake ¹ , Tawa Hassan-Sule ¹ , Michelle Haylock ¹ , Sarah White ¹ , Amy Barrett ¹ , Hamish Miller ¹ , Riccardo Pofi ¹ , Thomas Marjot ^1,2 , Anupa Shah ^3,4 , Sharon Dixon ⁵ , Katie Barber ^3,4 , Radha Venkatakrishnan ⁶ , Leanne Hodson ¹ & Jeremy W Tomlinson ¹

Author affiliations

¹Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, United Kingdom; ²Translational Gastroenterology and Liver Unit (TGLU), Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom; ³Community Gynaecology, Principal Medical Limited, Bicester, United Kingdom; ⁴Oxford Menopause Ltd, Ardington, United Kingdom; ⁵Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom; ⁶Department of Gynaecology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom

Background: Cardiometabolic risk increases after the menopause, with evidence suggesting an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Hormone replacement therapy (HRT) may modify cardiometabolic disease risk in menopausal women and previous studies have focussed on oral combined preparations. Although transdermal oestradiol (E2) with oral micronised progesterone is the current preferred regimen, its metabolic impacts are not well characterised.

Methods: Postmenopausal women (n = 8) underwent paired deep metabolic phenotyping before and after 12-weeks of low-dose transdermal E2 and nightly 100 mg oral micronised progesterone. Investigations included liver magnetic resonance imaging to assess hepatic fat content, mixed meal testing (after an overnight fast) incorporating stable isotope tracers ([U¹³C]palmitate, ²H₂O), adipose microdialysis, abdominal/gluteal adipose biopsies and dual energy x-ray absorptiometry scanning.

Results: All 8 participants successfully completed the study, but only 3 demonstrated a detectable increase in plasma E2 levels. After treatment, body weight increased ((mean ± standard deviation) +0.91 ± 1.2 kg, P < 0.05), android fat mass increased (375.5 ± 376.2 g, P < 0.05) but gynoid fat mass remained unchanged compared to baseline. Circulating liver enzymes were unchanged and although hepatic fat content increased, this did not reach statistical significance (+0.74 ± 1.0 %, P = 0.11). Fasting triglyceride concentrations reduced after treatment (-0.22 ± 0.28 mmol/l, P < 0.05). Subgroup analysis of participants who exhibited increased E2 levels showed decreased non-esterified fatty acid (NEFA) spillover from adipose tissue after treatment, measured through ¹³C incorporation from a labelled fatty acid into the plasma NEFA pool.

Conclusions: This is the first study to assess how transdermal E2 and oral micronised progesterone impacts metabolic disease risk using deep metabolic phenotyping. Preliminary analysis suggests that there may be divergent responses in E2-absorbers and non-absorbers, and begins to highlight potential differential impacts of oestrogen and progesterone on adipose tissue function.