Clinical trial NCT06852755: Development of Biomarkers for Monitoring Menopause in Women
Official title: Development of Biomarkers for Monitoring Menopause in Women
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Perimenopausal Biomarkers
Mitochondrial Biomarkers
Keywords: Perimenopausal Transition
Mitochondria
Biomarker
Women's Health
Lead sponsor: Fu Jen Catholic University Hospital
Sponsor class: OTHER
First posted: 2025-02-28
Enrollment: 100
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study Population Description: The study population consists of adult women aged over 20 years old, categorized into three groups:

reproductive period (ages 20-45, regular menstrual cycles) perimenopausal transition period (ages 45-50, experiencing menstrual irregularities) postmenopausal period (ages over 50, no menstrual period for at least one year).

All participants must be in general good health, without major chronic diseases, infection, or pregnancy.

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.

Eligibility criteria: Inclusion Criteria:

* Biological female, age order than 20 years old.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Mitochondrial Quantitative Analysis
timeFrame: 12 months from study start
measure: Mitochondrial Qualitative Analysis
timeFrame: 12 months from study start
measure: Validation of Candidate Biomarkers
timeFrame: 12 months from study start
Secondary outcomes:
Other outcomes:
Locations:
city: New Taipei City
country: Taiwan
facility: Fu Jen Catholic University Hospital, Fu Jen Catholic University
Study officials:
References:
citation: Davis SR, Lambrinoudaki I, Lumsden M, Mishra GD, Pal L, Rees M, Santoro N, Simoncini T. Menopause. Nat Rev Dis Primers. 2015 Apr 23;1:15004. doi: 10.1038/nrdp.2015.4.
citation: Pellegrino A, Tiidus PM, Vandenboom R. Mechanisms of Estrogen Influence on Skeletal Muscle: Mass, Regeneration, and Mitochondrial Function. Sports Med. 2022 Dec;52(12):2853-2869. doi: 10.1007/s40279-022-01733-9. Epub 2022 Jul 30.
citation: Karppinen JE, Tormakangas T, Kujala UM, Sipila S, Laukkanen J, Aukee P, Kovanen V, Laakkonen EK. Menopause modulates the circulating metabolome: evidence from a prospective cohort study. Eur J Prev Cardiol. 2022 Aug 5;29(10):1448-1459. doi: 10.1093/eurjpc/zwac060.
citation: Powers MS, Schenkel L, Darley PE, Good WR, Balestra JC, Place VA. Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement. Am J Obstet Gynecol. 1985 Aug 15;152(8):1099-106. doi: 10.1016/0002-9378(85)90569-1.