Sex Hormones as Regulators of the Age- and Sex-dependent Benefits of Caloric Restriction

Not Applicable

Recruiting

• Conditions: Overweight and Obese Adults; Healthy

• Registration Number: NCT07065643
• Lead Sponsor: University of Aberdeen

Brief Summary

Obesity increases the risk of type 2 diabetes, cardiovascular disease, and certain cancers, primarily due to elevated abdominal fat storage. With nearly two-thirds of the UK population living with overweight or obesity, there is an urgent necessity for evidence-based public health guidance to promote healthy weight. Calorie deficit can facilitate weight loss and body fat reduction, leading to health benefits, such as improved blood glucose control. Current weight management advice centres on lifestyle modification, incorporating changes to diet and physical activity to support a calorie deficit. However, existing dieting recommendations fail to consider gender or age. This is a surprising oversight, as it is well established that health outcomes vary significantly between men and women across the lifespan. Further, the menopause may have an impact on fat storage linked to changes in sex hormones. Our recent research, involving both mice and humans, has indicated that females are less responsive to weight loss and fat reduction during dieting. This study aims to understand endocrine and metabolic sex-based differences in obesity and calorie restriction, with a particular focus on women's health. We plan to conduct a diet study with 75 participants, encompassing both younger and older men and women, to monitor changes in energy expenditure and body composition using gold-standard techniques, such as doubly-labelled water. Blood and abdominal fat tissue samples will be collected to investigate how sex hormones might elucidate these differences. The aim of the study is to enhance our understanding of diet and women's health to combat obesity and promote healthy ageing.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-03
• Study First Submitted QC: 2025-07-03
• Study Start: 2025-07-09
• Study First Posted: 2025-07-15
• Last Update Submitted: 2025-07-17
• Last Update Posted: 2025-07-18
• Primary Completion: 2027-12
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Primary Outcome Measures

Name	Time	Method
Change in body mass expressed as weight in kilograms (kg)	From baseline (day 1) to end of intervention (day 53); additional measurements taken three times a week throughout the intervention duration	Measured using digital scale
Change in energy expenditure expressed in kilocalories per day (kcal/day)	From day 11 (start of the calorie-restricted diet) to the end of the intervention (day 52); with additional doses consumed on day 25 and 39	Measured using stable isotope method - doubly labelled water (DLW) - with urine sample collection

Secondary Outcome Measures

Name	Time	Method
Change in resting metabolic rate (RMR) expressed in kcal/day	From day 8 (start of the maintenance diet) to end of the intervention (day 53)	Measured using ventilated hood indirect calorimetry
Change in bone mineral content in grams (g)	From day 8 (start of the maintenance diet) to end of the intervention (day 53)	Measured using Dual Energy X-Ray Absorptiometry (DXA) scan
Change in total body water (TBW) in litres (l)	From day 11 (start of the calorie-restricted diet) to end of the intervention (day 53)	Measured using deuterium dilution, with urine sample collection
Change in total body density expressed in litres (l)	From day 8 (start of the maintenance diet) to end of the intervention (day 53)	Measured using BodPod air displacement plethysmography
Change in body fat-mass percentage (%)	From day 8 (start of the maintenance diet) to end of the intervention (day 53)	Derived from Lohman's 4-compartment model (body mass; body density; total body water; and bone mineral content)
Change in non-esterified fatty acids (NEFA) concentration in fasted blood sample	From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie-restricted diet (day 32)	Analysed by KONE
Change in Body Mass Index (BMI) expressed as kg/m^2	From baseline (day 1) to end of intervention (day 53); additional measurements taken three times a week throughout the intervention duration	BMI will be calculated using weight and height measures
Change in concentration of caloric-restriction (CR) related hormones in fasted blood sample	From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie restricted diet (day 32)	Includes: leptin, adiponectin, cortisol; analysed by ELISA
Body height measured in meters (m)	Only at baseline	Measured using stadiometer
Change in sex hormones concentration in fasted blood sample	From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie restricted diet (day 32)	Includes: oestrogens, progesterone, androgens; analysed by high -sensitivity liquid chromatography-mass spectrometry (LC-MS)
Change in adipose tissue metabolism assessed by phosphorylation of hormone-sensitive lipase (HSL)	From day 8 (start of the maintenance diet) to end of the intervention (day 53)	Measured via abdominal subcutaneous fat biopsy using fine needle aspiration and immunoblotting method.
Change in adipose tissue metabolism assessed by adipocite size	From day 8 (start of the maintenance diet) to end of the intervention (day 53)	Measured via abdominal subcutaneous fat biopsy using fine needle aspiration and histomorphometry method

Trial Locations

Locations (1)

Rowett Institute, University of Aberdeen; 🇬🇧 Aberdeen, United Kingdom