HoCa - A Multidimensional Study on Menopausal Hormonal Change, Cardiometabolic Health and Embodied Experience
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 7
- 主要终点
- Change from Baseline in RAND-36 Item Health Survey (RAND-36) Total Score
研究概览
简要总结
The goal of this observational study is to understand how the loss of ovarian function after oophorectomy affects the health and well being of women aged 35-50.
The study focuses on four areas:
- Quality of life and embodied experience,
- Cardiometabolic health,
- Central nervous system function, and
- Adipose tissue health and cellular function.
Our primary goal is to understand the effects of oophorectomy on women's health in focus areas 1 to 3. To do this, we will compare women's health before surgery with follow up assessments at 1-2 months and 12 months after surgery. Some participants may start hormone replacement therapy (HRT) during follow up as part of their routine care; this is outside the study protocol. As an exploratory aim, we will examine whether 12 month outcomes-or the change from baseline to 12 months-differ between participants who begin HRT and those who do not.
Focus area 4 provides an opportunity to explore how molecular and cellular mechanisms in adipose tissue respond to the loss of ovarian hormones. These analyses are exploratory and intended to offer mechanistic insight rather than clinical endpoints.
Participants will:
- undergo bilateral (or unilateral, if only one ovary remains) oophorectomy as part of their clinical treatment,
- complete questionnaires and physiological measurements at three time points,
- a subgroup will participate in qualitative interviews about their lived experience of surgical menopause,
- and a subgroup will volunteer adipose tissue samples collected during surgery.
详细描述
Overview
This observational longitudinal study investigates how the abrupt loss of ovarian function following bilateral (or unilateral, if only one ovary remains) oophorectomy affects the health and well being of women aged 35-50 years. Surgical menopause induces rapid endocrine, metabolic, vascular, neural, and psychosocial changes. To capture these adaptations comprehensively, the study evaluates four interconnected domains: (1) quality of life and embodied experience, (2) cardiometabolic health, (3) central nervous system function, and (4) adipose tissue health and cellular function.
Participants undergo assessments at three time points: pre surgery, 1-2 months post surgery, and 12 months post surgery. These visits include validated questionnaires, physiological and neuromuscular tests, vascular and exercise assessments, and the collection of blood samples at rest and after a standardised cycle ergometer test. A subgroup participates in qualitative interviews at all visits, and another subgroup donates adipose tissue samples during surgery for exploratory cellular analyses.
Some participants may begin hormone replacement therapy (HRT) after the 1-2 month visit as part of their clinical care. Because HRT initiation is outside the study protocol, HRT related comparisons (e.g., whether 12 month outcomes or change from baseline differ between HRT starters and non starters) will be conducted exploratorily, following definitions and modelling approaches described in the Statistical Analysis Plan.
Blood samples are analysed for a broad panel of metabolic, inflammatory, hormonal, and exercise responsive biomarkers to characterise systemic adaptations to surgical menopause. These biomarker analyses are exploratory and intended to provide mechanistic insight; they are not registered as outcome measures.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 35 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 35-50 years
- •Pre- or perimenopausal status (defined as self-reported menstrual bleedings and/or follicle-stimulating hormone ≤25 IU/L)
- •One or two functional ovaries
- •Planning to undergo bilateral oophorectomy or salpingo-oophorectomy (BSO) or unilateral oophorectomy or salpingo-oophorectomy (SO) if the other ovary has been previously removed, for non-malignant reasons
排除标准
- •Oophorectomy due to ovarian cancer or other malignant conditions
- •Current systemic estrogen-containing medication
- •The following exclusion criteria apply only to participation in physiological assessments (not questionnaires or interviews):
- •Severe heart or liver disease
- •Mobility limitations that prevent participation in physical exercise tests
- •The following factors do not lead to exclusion but will be recorded and considered in analyses:
- •Use of medications such as weight reduction drugs, lipid-lowering agents, or antihypertensives
- •Concomitant hysterectomy or other surgeries performed with oophorectomy
- •Use of local vaginal oestrogen therapy
- •Initiation of systemic hormone replacement therapy (HRT) after the 1-2-month post-surgery assessments (allowed according to clinical need; not part of the study protocol)
研究组 & 干预措施
Surgical Menopause Cohort
Women aged 35-50 undergoing bilateral (or unilateral, if one ovary remains) oophorectomy for non-malignant indications.
干预措施: Surgical removal of ovaries (Procedure)
Surgical Menopause Cohort
Women aged 35-50 undergoing bilateral (or unilateral, if one ovary remains) oophorectomy for non-malignant indications.
干预措施: Hormone Replacement Therapy (HRT) (Drug)
结局指标
主要结局
Change from Baseline in RAND-36 Item Health Survey (RAND-36) Total Score
时间窗: Baseline to 1-2 months and 12 months post-surgery
The RAND-36 Item Health Survey is a 36-item health-related quality of life instrument with eight domains: Physical Functioning, Role Limitations due to Physical Health, Bodily Pain, General Health, Vitality, Social Functioning, Role Limitations due to Emotional Problems, and Emotional Well-Being. Each domain is scored on a 0-100 scale; higher scores indicate better health status. The RAND-36 total score is computed as the arithmetic mean of the eight domain scores (range 0-100; higher = better). The reported measure is the change from baseline to follow-up (follow-up minus baseline); positive values indicate improvement. Scoring follows the instrument manual and the Statistical Analysis Plan (SAP). A prespecified sensitivity analysis may use a reduced/composite RAND-36 score (e.g., a domain subset with documented performance advantages); details are specified in the SAP. This sensitivity analysis is supportive and does not replace the prespecified analysis of this primary outcome.
Change from Baseline in Resting Energy Expenditure (REE, kcal/day) Measured by Indirect Calorimetry
时间窗: Baseline to 1-2 months and 12 months post-surgery
Resting energy expenditure (REE) is measured by indirect calorimetry (ventilated hood; overnight fast 10-12 h; supine, thermoneutral room). After stabilization, VO2 and VCO2 are recorded for ≥20-30 min; a steady-state segment (e.g., ≥5 min with CV \<10% and physiologic RQ) is used to compute REE (kcal/day) via the Weir equation, higher values = higher energy expenditure. Outcome is change from baseline to follow-up (follow-up - baseline); higher positive values = higher increase in energy expenditure. Procedures/quality criteria follow the device manual and the Statistical Analysis Plan (SAP). Per SAP, supportive analyses may adjust for body composition (FFM/FM) or express REE relative to FFM; these do not replace the prespecified analysis of this primary outcome.
Change from Baseline in Menopause Rating Scale (MRS) Score
时间窗: Baseline to 1-2 months and 12 months post-surgery
The Menopause Rating Scale (MRS) is an 11-item questionnaire assessing menopausal symptom burden across three domains: Somatic (4 items), Psychological (4 items), and Urogenital (3 items). Each item is scored 0-4 (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), yielding a total score range of 0-44, where higher scores indicate worse symptom severity/health-related quality of life. The outcome is the change from baseline to the specified follow-up time point (follow-up minus baseline); positive values indicate worsening and negative values indicate improvement. Scoring follows the instrument manual and the Statistical Analysis Plan (SAP). A prespecified sensitivity analysis may use a reduced MRS score that excludes items with documented suboptimal performance; details are specified in the Statistical Analysis Plan. This sensitivity analysis is supportive and does not replace the prespecified analysis of this primary outcome.
Change from Baseline in Total Fat Mass (kg) Measured by Bioelectrical Impedance Analysis
时间窗: Baseline to 1-2 months and 12 months post-surgery
Total fat mass (FM) will be measured by bioelectrical impedance analysis (BIA; InBody) under standardized conditions, including a 10-12 h fast before assessment. FM is reported in kg; higher values indicate higher fat mass. The outcome is the change from baseline to the specified follow-up (follow-up - baseline). Measurement procedures, quality criteria, and handling of missing/outliers follow the device manual and the Statistical Analysis Plan (SAP). Per SAP, a prespecified sensitivity analysis will estimate FM using DXA (where available); this analysis is supportive and does not replace the prespecified analysis of this primary outcome.
Change from Baseline in Aortic Pulse Wave Velocity (PWV, m/s)
时间窗: Baseline to 1-2 months and 12 months post-surgery
Aortic pulse wave velocity (PWV) will be measured using an oscillometric Arteriograph device under standardized resting conditions, including a 10-12 h fast and avoidance of vigorous physical activity during the previous 24 h. Measurements are taken supine in a quiet, thermoneutral room. PWV is reported in m/s; higher values indicate greater arterial stiffness. The outcome is the change from baseline to the specified follow-up (follow-up - baseline). Procedures, calibration, and quality criteria follow the device manual and the Statistical Analysis Plan (SAP). Per SAP, supportive analyses may examine additional Arteriograph variables (e.g., AIx, aortic pressures); these do not replace the prespecified analysis of this primary outcome.
次要结局
- Change from Baseline in Athens Insomnia Scale-5 (AIS-5) Score(Baseline to 1-2 months and 12 months post-surgery)
- Change from Baseline in Women's Health Questionnaire (WHQ) Total Score (36-item)(Baseline to 1-2 months and 12 months post-surgery)
- Change from baseline in the Pelvic Floor Distress Inventory-20 (PFDI-20) total score (20-item)(Baseline to 1-2 months and 12 months post-surgery)
- Change from Baseline in Fat-Free Mass (kg) Measured by Bioelectrical Impedance Analysis(Baseline to 1-2 months and 12 months post-surgery)
- Change from Baseline in Augmentation Index (AIx, %)(Baseline to 1-2 months and 12 months post-surgery)
- Change from Baseline in Peak Fat Oxidation During Exercise (g/min)(Baseline to 1-2 months and 12 months post-surgery)
- Change from Baseline in Maximum Isometric Voluntary Contraction Force (MVC) [Newton, N](Time Frame: Baseline to 1-2 months and 12 months post-surgery)
- Change from Baseline in StartReact Effect (ms) [difference in reaction time between loud and quiet sound conditions](Baseline to 1-2 months and 12 months post-surgery)
- Change from Baseline in Motor Evoked Potential (MEP) Amplitude (mV/Mmax) Measured by Transcranial Magnetic Stimulation(Baseline to 1-2 months and 12 months post-surgery)