Getting Under the Skin of the Menopausal Hot Flush

NCT06222073 | Recruiting

• 1 other identifier: MenoSkin
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this research is to 1) test how the skin blood vessels and sweat glands function in women who experience hot flushes by using skin microdialysis to deliver small amounts of substances to the skin that cause increased skin blood flow and sweating, and 2) examine the structure of the skin blood vessels and sweat glands in the skin of women who experience hot flushes by taking a very small skin biopsy. Any changes in the function or structure of the skin blood vessels or sweat glands in women with hot flushes would increase our understanding of what causes hot flushes and help to design effective treatments.

Conditions

Menopause

Keywords

hot flush; skin; blood flow; sweating; structure; function

Outcome Measures

Primary Outcomes (11)

• Skin function/responsiveness

  The non-dominant forearm will be inserted with 3 cutaneous microdialysis membranes. Each of the membranes will be perfused with either of the following (randomly assigned to the three sites); increasing doses of Acetylcholine, Sodium Nitroprusside (SNP) or calcitonin gene-related peptide (CGRP) to stimulate skin blood flow (and sweating) which will be assessed using laser Doppler probes housed directly over the membrane sites. The dose-response curves for skin blood flow will be mathematically modelled via non-linear regression curve fitting. The maximum responses and the effective concentration causing 50% of the maximal response (EC50) will be calculated from the nonlinear regression modelling.

  Baseline (visit 1)

• Sweat gland function/responsiveness

  The non-dominant forearm will be inserted with 3 cutaneous microdialysis membranes. Each of the membranes will be perfused with either of the following (randomly assigned to the three sites); increasing doses of Acetylcholine, Sodium Nitroprusside (SNP) or calcitonin gene-related peptide (CGRP) to stimulate sweating (and skin blood flow) which will be assessed using laser Doppler probes housed directly over the membrane sites. The dose-response curves for sweating will be mathematically modelled via non-linear regression curve fitting. The maximum responses and the effective concentration causing 50% of the maximal response (EC50) will be calculated from the nonlinear regression modelling.

  Baseline (visit 1)

• Oestradiol

  A venous blood sample will be taken and analysed to establish the oestradiol level (pg/mL).

  Baseline (visit 1)

• Interleukin-6 (IL-6)

  A venous blood sample will be taken to assess circulating inflammatory markers/cytokines. Interleukin-6 (IL-6) will be measured (pg/mL) using an ELISA.

  Baseline (visit 1)

• Interleukin-8 (IL-8)

  A venous blood sample will be taken to assess circulating inflammatory markers/cytokines. Interleukin-8 (IL-8) will be measured (pg/mL) using an ELISA.

  Baseline (visit 1)

• Tumour Necrosis Factor alpha (TNF-α)

  A venous blood sample will be taken to assess circulating inflammatory markers/cytokines. TNF-α will be measured (pg/mL) using an ELISA.

  Baseline (visit 1)

• Prostaglandin E2

  A venous blood sample will be taken to assess circulating inflammatory markers/cytokines. Prostaglandin E2 will be measured (pg/mL) using an ELISA.

  Baseline (visit 1)

• C-reactive Protein (CRP)

  A venous blood sample will be taken to assess circulating inflammatory markers/cytokines. CRP will be measured (mg/L) using an ELISA.

  Baseline (visit 1)

• Calcitonin Gene Related Peptide (CGRP)

  A venous blood sample will be taken to assess circulating inflammatory markers/cytokines. CGRP will be measured (pg/mL) using an ELISA.

  Baseline (visit 1)

• Skin structure (blood vessels)

  7 days following assessment of skin function/responsiveness (to allow the hyperaemic response to subside), a single 3mm skin punch biopsy will be taken from the non-dominant forearm. The sample will be processed and stained to highlight blood vessels and endothelia. The samples will be stained with fluorescein-labelled ulex europaeus, an endothelium-specific antibody. Confocal microscopic imaging of the samples will be analysed to quantify capillary density e.g. capillary count/length of the epidermal surface (capillaries/mm) and capillary diameter.

  Baseline (visit 2)

• Skin structure (sweat glands)

  7 days following assessment of skin function/responsiveness (to allow the hyperaemic response to subside), a single 3mm skin punch biopsy will be taken from the non-dominant forearm. The sample will be processed and stained to highlight sweat glands. The samples will be stained with protein gene product 9.5, a sweat gland/nerve fibre antibody. Confocal microscopic imaging of the samples will be analysed to quantify sweat gland density.

  Baseline (visit 2)

Study Arms (3)

Postmenopausal + Hot Flush (P+HF)

Postmenopausal women who regularly experience hot flushes.

Postmenopausal + Hot Flush (P-HF)

Postmenopausal women who do not experience hot flushes.

Premenopausal

Premenopausal women who experience regular menstruation.

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

24 postmenopausal women (12 who experience hot flushes and 12 who do not) and 12 premenopausal women will be recruited for this study. Postmenopausal participants (aged \>45 years) will be required to be amenorrhoeic for at least six months and symptomatic women should be experiencing at least four hot flushes per day. Premenopausal women will be eumenorrhoeic and will be aged 18-30 yrs. Participants will be healthy and free from cardiovascular and metabolic risk factors or diseases, and not taking any treatments to alleviate hot flushes. Participants will be required to complete a health screening questionnaire to confirm they are eligible to participate in the study.

You may qualify if:

• Aged \>45 years for the postmenopausal cohort and aged 18-30 years for the premenopausal cohort
• Female
• Amenorrhoeic for \>6 months (postmenopausal criteria)
• \>4 hot flushes per day (symptomatic postmenopausal criteria)
• Eumenorrhoeic with regular menstrual cycles (premenopausal criteria)
• Healthy
• Non-smoker
• BMI 18-30 kg/m2
• No history of cardiovascular or respiratory disease
• No history of metabolic disease e.g. type II diabetes
• Drink \<14 units of alcohol per week
• Not taking any medication or treatments to alleviate hot flushes

You may not qualify if:

• Aged \< 18 years or 31-44 years
• Male
• Smokers
• Medical history of cardiovascular/respiratory disease
• Medical history of metabolic disease e.g. type II diabetes
• Drink \>15 units of alcohol per week
• On medication or treatments to alleviate hot flushes or have taken such medication/treatment within the previous 6 months
• BMI of \<18 or \>30 kg/m2
• Vaccination (\<1 week) due to induced systemic inflammatory reaction
• Local forearm infection
• Allergy to local anaesthetic/Marcain/amide-group anaesthetics
• Pregnant

Sponsors & Collaborators

• Liverpool John Moores University: lead
• British Heart Foundation: collaborator

Study Sites (1)

Liverpool John Moores University

Liverpool, Merseyside, L3 3AF, United Kingdom

RECRUITING

Related Publications (1)

• Roberts KA, Doyle A, Jones H, Low DA. Getting under the skin of the menopausal hot flush: a protocol to examine skin function and structure in symptomatic postmenopausal women. Front Glob Womens Health. 2025 Aug 4;6:1514960. doi: 10.3389/fgwh.2025.1514960. eCollection 2025.

  PMID: 40832439 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Skin - 1 x 3mm punch biopsy sample per subject, to be processed and stored in frozen sections according to Human Tissue Act (HTA) regulations. Blood - 1 blood sample per subject, to be processed according to HTA regulations.

MeSH Terms

Conditions

Hot Flashes

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Kirsty A. Roberts, PhD

  Liverpool John Moores University

  PRINCIPAL INVESTIGATOR

• David A Low, PhD

  Liverpool John Moores University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kirsty A. Roberts, PhD

CONTACT

0151 904 6244; k.a.roberts@ljmu.ac.uk

David A Low, PhD

CONTACT

0151 904 6244; d.a.low@ljmu.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2023
• First Posted: January 24, 2024
• Study Start: January 1, 2023
• Primary Completion: October 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 18, 2025

Record last verified: 2024-10

Locations

GB (1)