Table 1

Overview of outcome measures and corresponding data collection methods

Primary exposure and outcomesData collection methodsOutcome variablesJustification of methods
Primary ovarian insufficiencyBlood sampleHormone levelIf indicated for routine care: level of follicle-stimulating hormone in mIU/mLRoutine care—diagnostic value
QuestionnaireDate of last menstruation, menopausal age
Medical recordDate of last menstruation, menopausal age
Bone mineral densityMedical testDEXA scan of lumbar spine and hip by means of Hologic Delphi densitometer (VUmc) or General Electric Scanner (LUMC)BMD values in g/cm2
T-scores and Z-scores
Presence of osteopenia (defined as T-scores of −1 to −2.5)
Presence of osteoporosis (defined as T-scores of ≥−2.5)
Routine care—diagnostic value
The DEXA scan is most widely used in clinical practice to screen for osteoporosis and regarded as the ‘golden standard’
Instant vertebral assessment (IVA) by Hologic Delphi densitometer (VUmc) or General Electric Scanner (LUMC)Vertebral height reduction in %
Presence of clinical and non-clinical vertebral fractures
There is a strong additive value of IVA compared with DEXA alone78–80
Anthropomorphic measurementsHeight in cm and weight in kg
Blood sampleBone turnover markersBone formation by P1NP—mean value in ng/mL
Bone resorption by β-CTX—mean value in pg/mL
These markers have been used in previous studies and are recommended for research purposes81
Vitamin DLevel of 25-hydroxyvitamin D in serum in nmol/LVitamin D has been associated with bone turnover markers, BMD, fracture risk and risk of falling82–84
QuestionnaireFood frequency questionnaire (FFQ)Mean score of calcium intakeThe FFQ is a validated questionnaire62
Reference values are available63
General questionnairePrevious fractures, use of calcium and vitamin D supplements use of glucocorticoids, family history of osteoporosis
Medical recordEarlier DEXA scans (yes, no), if applicable treatment plan for osteoporosis such as vitamin D supplementation, recommendations for lifestyle changes
Cardiovascular statusMedical testEchocardiogram
If contraindicated: cardiac MRI
Abnormalities in heart structure
Left ventricular function by E/A ratio, deceleration time, isovolumic relaxation time, left ventricular ejection fraction, diastolic and systolic diameter and volume, E/e′ ratio
Right ventricular function: tricuspid annular plane systolic excursion
Presence of mitral, aortic or tricuspid valve defects, that is, insufficiencies or stenoses
Wall motion score index
Routine care—diagnostic value
ECGSinus rhythm, QRS complex, ST morphology (elevation or depression), PQ interval and left ventricle hypertrophyRoutine care—diagnostic value
Coronary computer tomography angiography (CCTA) by a 320-detector row volumetric scanner (Aquilion ONE) (LUMC) and 256 Scanner Philips (VUmc)Coronary artery calcium score according to Agatston
Presence of luminal narrowing and if applicable: type of narrowing and number of plaques for the left main coronary artery, left anterior descending, circumflex artery and right coronary artery
High sensitivity and specificity85
Most valid alternative method for detecting significant coronary disease (golden standard is invasive coronary angiography)86
Vascular measurementsPresence of atherosclerosis by carotid intima–media thickness (IMT) and femoral IMT in mm
Arterial stiffness (VUmc only)
Predictors of future cardiovascular events71 87 88
Blood pressureMean of three consecutive measurements in mm Hg
Anthropomorphic measurementsHeight in cm, weight in kg, Body Mass Index in kg/cm2, hip circumference in cm, waist circumference in cm, waist-hip ratio
Blood sampleBiomarkersLeft ventricular function and presence of ischaemia and infarction by NT-pro-BNP in pmol/L
Chronic inflammation (associated with atherosclerosis) by CRP in mg/L
In general population: strong predictor of coronary heart disease89 90
Lipid spectrumTotal cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceridesEstablished risk factors for CVD
GlucoseFasting blood glucoseEstablished risk factor for diabetes
Kidney functionCreatinine, estimated glomerular filtration rateRoutine care before CCTA
QuestionnaireGeneral questionnaire(Family) history of CVD and risk factors for CVD and if applicable date of diagnosis and treatment
Medical recordCardiovascular risk score based on SCORE chart and Framingham chart, adjusted for age
Cardiovascular history, contraindications for echocardiogram
Neurocognitive functionNeurocognitive test15 Words testVerbal memory in total number of wordsThese tests were selected based on their reliability, validity and availability of reference norms. The domains examined are potentially sensitive for the effect of oestrogens48 78–83
Trail Making Test A and BInformation processing speed in seconds to complete
COWA verbal fluency testVerbal fluency in total number of words
Letter–number sequencingWorking memory in total number of correct trials
WAIS III Digit spanMeasures concentration in total number of items/lists correctly repeated; can be converted to a scaled score, which is an age-based, norm-referenced score for each subject
Dutch Adult Reading Test (NART)Verbal intelligence in mean IQ estimate
Quality of lifeQuestionnaireSF-12General healthShortened version of the validated questionnaire SF-36, which has been previously used in Dutch studies91
MOS cognitive functioning scaleCognitive functioningFrequently used questionnaire92
Hospital Anxiety and Depression Scale (HADS)Anxiety and depressionValid and reliable
Dutch reference values are available93
Sexual Activity Questionnaire (SAQ)Sexual functioningThe SAQ is a valid, reliable and acceptable measure for describing the sexual functioning of women in terms of activity, pleasure and discomfort. It is quick and easy to administer and has good face validity discriminating between the sexual functioning of premenopausal and postmenopausal women94
Shortened fatigue questionnaire (VVV)FatigueReliable and validated questionnaire95
  • β-CTX, Beta-carboxy-terminal collagen crosslinks; COWA, Controlled Oral Word Association Test; CRP, C-reactive protein; CVD, cardiovascular disease;DEXA, dual-energy X-ray absorptiometry; LUMC, Leiden University Medical Center; NT-pro-BNP, N-terminal prohormone of brain natriuretic peptide; SF-12, 12-Item Short Form Health Survey; SF-36, 36-Item Short Form Health Survey; MOS, Medical Outcomes Study; VUmc, VU University Medical Center; WAIS, Wechsler Adult Intelligence Scale.