Development of Biomarkers for Monitoring Menopause in Women
- Conditions
- Perimenopausal BiomarkersMitochondrial Biomarkers
- Registration Number
- NCT06852755
- Lead Sponsor
- Fu Jen Catholic University Hospital
- Brief Summary
This cross-sectional study aims to develop and validate mitochondrial biomarkers for monitoring menopause in women. The study will involve 100 participants divided into three groups: reproductive period, perimenopausal transition period, and postmenopausal period. Peripheral blood samples will be collected, and mitochondrial quality and quantity will be assessed using both qualitative and quantitative analyses. The study will identify potential biomarkers through metabolomics and validate them for monitoring the perimenopausal transition, providing a novel approach for women's health management during menopause.
- Detailed Description
Background： Gender equality and equitable health have emerged as international trends in recent years. Despite existing solutions for women's health issues, many needs remain unmet. According to projections, the global menopausal population is expected to reach 1.2 billion by 2030, surpassing the prevalence of the most common chronic diseases. Presently, solutions exist for common menopausal symptoms such as hot flashes, night sweats, fatigue, irritability, and urinary incontinence. However, unresolved challenges encompass psychological changes and monitoring systems. Therefore, this project aims to develop biomarkers for menopause in women as a future monitoring system.
Most women enter menopause between the ages of 48 and 52. During this period, ovarian follicles cease activity, leading to the one-year period following the appearance of significant menstrual irregularities, known as the menopausal transition or perimenopause (1). As ovarian function gradually declines and estrogen secretion diminishes, various systemic changes occur, resulting in several menopause-related conditions such as osteoporosis, cardiovascular diseases, and urinary system issues. The decline in estrogen triggers a negative feedback loop, causing an increase in follicle-stimulating hormone (FSH) secretion and a reduction in E2 (17β-estradiol) production (2). Currently, menopausal hormone therapy (MHT) using estrogen can alleviate menopausal symptoms and restore overall E2 levels but doesn't lower FSH to premenopausal levels (3-4). However, a precise biomarker for monitoring menopause has not yet been established. Under estrogen deficiency, mitochondrial morphology and function may be compromised, while estrogen presence relates to reduced oxidative reactions, enhanced respiratory function, and stable membrane properties (5). This project aims to provide a comprehensive view through metabolomics to identify biomarkers within mitochondria that can be used for menopause monitoring.
Study Design： This study is a cross-sectional study. A total of 100 women will be included and grouped into three categories: 25 cases of reproductive period, 50 cases of perimenopausal transition period, and 25 cases of postmenopausal period. The peripheral blood will be collected. Following mitochondrial extraction, both qualitative and quantitative analyses are conducted. High-confidence protein markers are identified as candidate molecules using combined data from RNA-seq and LC/MS/MS. These candidate markers will undergo further validation testing.
Methods： After Ficoll separation, peripheral blood will be divided into mononuclear cells, plasma, and red blood cells. Further extraction of mitochondria will be carried out from both mononuclear cells and plasma. Quantitative experiments involve hippocampal measurements of metabolic energy and JC-1 assessment of mitochondrial health, while mitochondrial DNA copy number will be evaluated using digital PCR. Qualitative experimental analysis employs Western blotting to assess markers such as cytochrome c and HSP60 for mitochondria and PCNA for nuclear proteins. Candidate biomarker validation experiments use combined data from RNA-seq and LC/MS/MS to identify high-confidence protein markers as candidates, which are further validated for feasibility using the ELISA method.
Effect：
1. Understand the changes in mitochondrial quality and quantity during the perimenopausal transition in women.
2. Develop monitoring indicators for the perimenopausal transition in women.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 100
- Biological female, age order than 20 years old.
- Person with cancer.
- Person with any known acute or chronic infection.
- Person with known chronic illness under follow up or treatment.
- Pregnancy, one year withing delivery, under breast feeding, or three months within breast feeding.
- Under any female horemone therapy.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Mitochondrial Quantitative Analysis 12 months from study start This outcome measure involves evaluating mitochondrial energy metabolism, including ATP content, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) using a hippocampal metabolic analyzer. Additionally, mitochondrial membrane potential will be assessed using flow cytometry to analyze the distribution of JC-1, indicating mitochondrial health. Digital PCR will be employed to measure mitochondrial DNA copy numbers, determining mitochondrial mass and comparing differences between groups.
Mitochondrial Qualitative Analysis 12 months from study start This measure assesses mitochondrial protein markers using Western blot analysis. PCNA will be used as a nuclear protein marker, while cytochrome c and HSP60 will be used as mitochondrial protein markers to evaluate mitochondrial quality
Validation of Candidate Biomarkers 12 months from study start This outcome measure focuses on the validation of high-confidence protein markers identified through RNA-Seq and LC-MS/MS data. The validation will be conducted using customized protein databases and further experiments to confirm the feasibility of these candidate biomarkers for monitoring perimenopausal transition.
- Secondary Outcome Measures
Name Time Method
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (1)
Fu Jen Catholic University Hospital, Fu Jen Catholic University
🇨🇳New Taipei City, Taiwan