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: 1. Quality of life and embodied experience, 2. Cardiometabolic health, 3. Central nervous system function, and 4. 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.
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. This four domain structure enables the study to integrate patient reported outcomes, whole body physiology, neural activation, vascular regulation, exercise metabolism, and adipose tissue biology, offering a multidimensional understanding of how surgical menopause impacts women's health over time. Domain 1: Quality of Life and Embodied Experience Surgical menopause can cause a variety of symptoms and affect daily functioning, health behaviours, and overall quality of life. We collect patient-reported outcomes using validated questionnaires covering quality of life, menopausal symptoms, sleep, pelvic floor symptoms, sexual function, psychosocial dimensions, and health behaviours such as physical activity and eating patterns. Participants also complete a food diary and wear a 7-day accelerometer to provide objective measures of dietary intake and physical activity. In addition, a subgroup participates in qualitative interviews, which help deepen our understanding of the lived experience of surgical menopause. Primary outcomes in this domain are the RAND-36 total score and the Menopause Rating Scale (MRS) total score, which capture changes in broad health-related quality of life and menopausal symptom burden following oophorectomy. Secondary outcomes include the Women's Health Questionnaire (WHQ), Pelvic Floor Distress Inventory-20 (PFDI-20), and the Athens Insomnia Scale-5 (AIS-5), providing a more detailed understanding of psychosocial health, pelvic floor symptoms, and sleep quality. Other prespecified outcomes contribute additional context on general well-being, emotional functioning, health behaviours, and embodied experiences. These include the 15D, Female Sexual Function Index (FSFI), Center for Epidemiological Studies Depression Scale (CES-D), Satisfaction With Life Scale (SWLS), Positive and Negative Affect Schedule (PANAS), Eating Disorder Examination Questionnaire (EDE-Q), Three-Factor Eating Questionnaire-R18 (TFEQ-R18), the International Physical Activity Questionnaire-Short Form (IPAQ-SF), and a 4-item Finnish physical activity questionnaire. These measures extend the scope of quality-of-life assessment and support interpretation of primary and secondary outcomes. Finally, qualitative interviews conducted with a subgroup of participants at each time point provide rich insights into bodily changes, identity, emotions, and the lived experience of surgical menopause. These interviews enhance the interpretation of questionnaire-based findings and allow a more integrated understanding of women's experiences during the transition to surgical menopause. Domain 2: Cardiometabolic Health Loss of ovarian function following oophorectomy may influence whole-body metabolism, body composition, vascular regulation, and exercise capacity. To characterise these possible adaptations, cardiometabolic health is assessed at each visit with standardized protocols that include indirect calorimetry, body composition measurements, vascular assessments, and exercise physiology testing using standardised cycle ergometer tests. Together, these measures help us evaluate whether endocrine changes are associated with alterations in metabolic rate, adiposity, cardiovascular function, and exercise-related responses over time. Primary outcomes in this domain are resting energy expenditure (REE), total fat mass (FM), and aortic pulse wave velocity (PWV). These endpoints capture core aspects of metabolic function, whole body adiposity, and arterial stiffness-parameters that may change after the loss of ovarian function and are relevant to longer-term cardiometabolic risk. Secondary outcomes include fat-free mass (FFM), augmentation index (AIx) as an additional marker of arterial wave reflection, and peak fat oxidation during exercise, offering insight into potential shifts in metabolic flexibility and substrate use at submaximal workloads. Other prespecified outcomes provide supporting information on anthropometry, muscular performance, vascular regulation, and exercise responses. These include body mass index (BMI), waist circumference, handgrip strength, knee extension strength, and countermovement jump (CMJ) height. Additional central hemodynamic measures-aortic systolic and diastolic blood pressure, aortic pulse pressure, and reflection time-further characterise vascular load. Microvascular and tissue-level parameters include forearm Laser Doppler readings (baseline perfusion, endothelium-dependent vasodilation, post-occlusive reactive hyperemia) and quadriceps near-infrared spectroscopy (NIRS) measures (resting StO2, minimum StO2 during exercise, StO2 recovery slope, total hemoglobin). Exercise metabolism is additionally profiled using peak oxygen uptake (VO2peak), resting fat oxidation rate, and maximal fat oxidation rate (MFO). Exploratory blood biomarkers (not registered as outcomes) At each visit, venous blood samples are collected at rest and after the standardised cycle ergometer test. These samples will be analysed for exploratory biomarkers, including a broad panel of metabolic, inflammatory, and hormonal markers, to characterise systemic adaptations to the loss of ovarian function after oophorectomy and to examine potential changes in exercise responses. These biomarker analyses are exploratory and intended to provide mechanistic insight; they are not registered as outcome measures and follow definitions and procedures described in the Statistical Analysis Plan. Domain 3: Central Nervous System Function Loss of ovarian function following oophorectomy may influence neural activation, neuromuscular performance, and corticospinal and reticulospinal responsiveness. To characterise these possible adaptations, a subsample of participants completes a set of standardised neurophysiological assessments, including isometric strength testing, reaction time tasks, and transcranial magnetic stimulation (TMS). These tests provide complementary insight into neural drive to muscle and the excitability of corticospinal and cortico reticulospinal pathways during the first postoperative year. No primary outcomes are defined for this domain. Secondary outcomes in this domain quantify neural activation and corticospinal responsiveness using complementary physiological measures. Maximum isometric voluntary contraction force (MVC) is assessed to evaluate volitional muscle activation during isometric elbow flexion. A StartReact test assesses reaction time and the StartReact effect, defined as the difference in reaction time between quiet and loud sound conditions. Cortical excitability is assessed using single pulse TMS, with the main analysis variable being motor evoked potential (MEP) amplitude normalised to the maximal compound muscle action potential (Mmax), elicited via peripheral nerve stimulation. Other prespecified outcomes further characterise neuromuscular and corticospinal function. Rate of torque development (RTD) and voluntary electromyography (EMG) amplitude (0-50 ms) are derived from force and EMG signals recorded during the StartReact test. Paired pulse TMS methods are used to quantify short interval intracortical inhibition (SICI), long interval intracortical inhibition (LICI), and intracortical facilitation (ICF) relative to single pulse comparator responses. StartleTMS, which pairs a loud acoustic stimulus with TMS, provides an additional measure of startle related facilitation of corticospinal output. Silent period duration is measured during single pulse TMS and then normalised to MEP amplitude to enable comparison across time points. Together, these measures provide a multidimensional characterisation of neural responsiveness, including voluntary activation, intracortical inhibitory and facilitatory circuits, and the excitability of corticospinal and cortico reticulospinal pathways. DOMAIN 4: Adipose Tissue Health and Cellular Function Loss of ovarian function following oophorectomy may be associated with changes in adipose tissue biology, including cellular composition, lipid handling, inflammatory signalling, and gene expression. To explore these potential mechanisms, a subsample of participants donates subcutaneous and, where available, visceral adipose tissue during surgery. From these tissues, adipose organoids ("Adipoids") are developed and exposed to controlled hormonal environments (e.g., defined hormones or conditioned media supplemented with pre and postmenopausal sera) to model post oophorectomy conditions in vitro. This domain is considered exploratory; thus, no primary or secondary outcomes are described. We describe one other prespecified outcome (exploratory mechanistic readout): Hormonal Regulation of Adipose Tissue Health and Cellular Function, which refers to a change in Adipoid cellular content/cellularity (e.g., nuclei count or cells/mL) in response to a change in hormonal environment. We will also perform additional mechanistic assays (exploratory; not registered as outcome measures), including * Lipid uptake/handling * Responses to inflammatory stimuli * Gene expression profiles * Secretome characteristics These laboratory analyses aim to reveal molecular pathways through which the loss of ovarian hormones may affect adipose biology. They are exploratory, not intended as clinical endpoints, and follow laboratory Standard Operation Protocols and the Statistical Analysis Plan. Exploratory analyses of Hormone Replacement Therapy (HRT) Some participants may begin hormone replacement therapy (HRT) after the 1-2 month visit as part of their routine clinical care. Because HRT initiation is outside the study protocol, comparisons involving HRT are conducted exploratorily. These analyses examine whether 12 month outcomes-or the change from baseline to 12 months-differ between HRT starters and non starters. HRT exposure will be defined using time varying information collected at each visit, and sensitivity analyses will explore alternative exposure windows. All analytic approaches, including covariate selection and handling of missing data, are prespecified in the Statistical Analysis Plan. These exploratory analyses do not constitute registered outcome measures for this study.
Study Type
OBSERVATIONAL
Enrollment
120
Bilateral oophorectomy, or unilateral if only one ovary remains. Other organs may also be removed during the same procedure, such as fallopian tubes (salpingectomy) and/or uterus (hysterectomy).
Post-surgery HRT as part of clinical treatment after the 1-2 month follow-up. HRT may be any commercially available systemic treatment.
Change from Baseline in RAND-36 Item Health Survey (RAND-36) Total Score
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.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Menopause Rating Scale (MRS) Score
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.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Resting Energy Expenditure (REE, kcal/day) Measured by Indirect Calorimetry
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.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Total Fat Mass (kg) Measured by Bioelectrical Impedance Analysis
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.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Aortic Pulse Wave Velocity (PWV, m/s)
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.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Women's Health Questionnaire (WHQ) Total Score (36-item)
The Women's Health Questionnaire (WHQ) is a 36-item instrument assessing midlife women's emotional and physical health across multiple domains (e.g., depressed mood, somatic symptoms, vasomotor symptoms, anxiety/fears, sleep problems, menstrual symptoms, sexual functioning, and memory/concentration). Domain scores are transformed to a 0-100 scale and averaged to a total score (range 0-100), where higher scores indicate worse health-related quality of life. The reported measure is the change from baseline to the specified follow-up time point (follow-up minus baseline); positive values indicate worsening. Scoring follows the instrument manual and the Statistical Analysis Plan (SAP). A prespecified sensitivity analysis may use a reduced WHQ total score that excludes items with documented suboptimal performance; details are specified in the SAP. This sensitivity analysis will not replace the prespecified analysis of this secondary outcome and will be interpreted as supportive.
Time frame: 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)
The Pelvic Floor Distress Inventory-20 (PFDI-20) is a 20-item questionnaire assessing pelvic floor symptom distress across three subscales: POPDI-6 (pelvic organ prolapse distress), CRADI-8 (colorectal-anal distress), and UDI-6 (urinary distress). Each subscale is scored 0-100, and the PFDI-20 total score is their sum (range 0-300), where higher scores indicate worse symptom distress and poorer health-related quality of life. The outcome is the change from baseline to the specified follow-up (follow-up minus baseline); positive values indicate worsening. Scoring follows the instrument manual and the Statistical Analysis Plan (SAP). A prespecified sensitivity analysis will examine the three PFDI-20 subscale scores (POPDI-6, CRADI-8, UDI-6), each scored 0-100 (higher = worse). These analyses are supportive only and do not replace the prespecified analysis of the PFDI-20 total score as a secondary outcome.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Athens Insomnia Scale-5 (AIS-5) Score
The Athens Insomnia Scale-5 (AIS-5) is a 5-item validated instrument assessing sleep difficulty. Each item is scored 0-3, producing a total score of 0-15, where higher scores indicate more severe insomnia symptoms. The outcome is the change from baseline to the specified follow-up time point (follow-up minus baseline); positive values indicate worsening. Scoring follows the instrument manual and the Statistical Analysis Plan (SAP). A prespecified sensitivity analysis may examine individual AIS-5 items; these analyses are supportive only and do not replace the prespecified analysis of this secondary outcome.
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Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Fat-Free Mass (kg) Measured by Bioelectrical Impedance Analysis
Fat-free mass (FFM) will be measured by bioelectrical impedance analysis (BIA; InBody) under standardized conditions, including a 10-12 h fast before assessment. FFM is reported in kg; higher values indicate higher fat-free 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 FFM using DXA (where available); this analysis is supportive and does not replace the prespecified analysis of this secondary outcome.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Augmentation Index (AIx, %)
Augmentation Index (AIx) will be measured using the Arteriograph under the same standardized resting conditions, including a 10-12 h fast and avoidance of vigorous physical activity during the preceding 24 h. AIx is expressed in %; higher values indicate greater arterial wave reflection. The outcome is the change from baseline to the specified follow-up time point (follow-up minus baseline). Measurement procedures and quality criteria follow the device manual and the Statistical Analysis Plan.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Peak Fat Oxidation During Exercise (g/min)
During steady-state cycling at 45-50% of the peak power derived from the VO2peak test, whole-body fat oxidation will be measured by indirect calorimetry. The peak value during the bout will be recorded in g/min; higher values indicate higher fat oxidation during exercise. Pre-test conditions: 10-12 h fast and no vigorous physical activity in the prior 24 h. Outcome is change from baseline. Exercise protocol, data smoothing and calculation details follow the Statistical Analysis Plan.
Time frame: Baseline to 1-2 months and 12 months post-surgery
Change from Baseline in Maximum Isometric Voluntary Contraction Force (MVC) [Newton, N]
Testing is performed under controlled pre-test conditions (10-12 h fast, no vigorous physical activity in the prior 24 h), seated in a thermoneutral room. The participant performs 3-5 isometric elbow flexion actions by maximally contracting the biceps brachii muscle while seated in an electromechanical dynamometer. Force and electromyography (EMG) activity are recorded during the contractions. The outcome is the change in force (N) from baseline to the specified follow-up (follow-up - baseline). Condition, quality criteria, and analysis are defined in the Statistical Analysis Plan.
Time frame: 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]
Reaction time, defined as the delay between the visual stimulus presentation and the increase in voluntary electromyography (EMG) signal amplitude above baseline (+7SD), is obtained through the StartReact test. Testing is performed under controlled pre-test conditions (10-12 h fast, no vigorous physical activity in the prior 24 h), seated in a thermoneutral room. The StartReact effect is reported in milliseconds (ms) as the difference in reaction time between quiet and loud sound conditions; higher values indicate a larger effect. The outcome is the change from baseline to the specified follow-up (follow-up - baseline). In addition, the StartReact test provides data on rate of torque development (0-50 ms) and voluntary EMG amplitude (0-50 ms) as force and EMG are sampled simultaneously. These variables are collected but analyzed and reported separately as Other Prespecified Outcome Measures. Condition, quality criteria, and analysis are defined in the Statistical Analysis Plan.
Time frame: 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
Cortical excitability will be evaluated using transcranial magnetic stimulation (TMS) over the motor cortex with electromyography (EMG) recordings from the biceps during a light, standardised voluntary contraction. Pre-test conditions: 10-12 h fast and no vigorous physical activity in the prior 24 h; testing in a quiet, thermoneutral room with consistent coil positioning. The main analysis variable for this outcome is normalized MEP amplitude (mV/Mmax) throughout the stimulus-response curve; higher values indicate greater corticospinal responsiveness. Maximal compound muscle action potential (Mmax) is elicited by peripheral nerve stimulation and recorded from the same muscle using the same electrode configuration. The outcome is the change from baseline to follow up (follow up - baseline). Hot spot identification, motor thresholding, trial number/rejection rules, and averaging procedures follow the Statistical Analysis Plan.
Time frame: Baseline to 1-2 months and 12 months post-surgery