Getting Under the Skin of the Menopausal Hot Flush

N/ARecruitingNCT06222073

Liverpool John Moores University36 enrolled

Overview

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.

In a cross-sectional design, participants will attend the laboratory on two separate occasions. At visit 1, anthropometric measurements will be recorded and a venous blood sample will be collected to determine hormone status (e.g. oestradiol level) and pro-inflammatory markers (e.g. IL-8, Prostaglandin 2E). Participants will then undergo assessment of post-ganglionic skin blood vessel and sweat gland responsiveness (transdermal/cutaneous microdialysis). At visit 2 (\~7 days later), participants will undergo a skin punch biopsy.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Menopause

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Outcomes

Primary Outcomes

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.