Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age.
A young age at menopause has been associated with increased cardiovascular disease (CVD) risk.



To compare the cardiovascular risk profile between women with premature ovarian insufficiency (POI) and premenopausal controls of comparable age.



Cross-sectional case control study.



Two university medical centers.



Women above 45 years of age who were previously diagnosed with POI (n = 83) and premenopausal population controls of comparable age (n = 266).



Blood pressure, body mass index, waist circumference, electrocardiogram, bilateral carotid intima media thickness, estradiol, T, androstenedione, dehydroepiandrosterone sulfate, SHBG, insulin, glucose, lipids, TSH, free T4, N-terminal pro-B-type natriuretic peptide, C-reactive protein, uric acid, creatinine, and homocysteine were measured. Potential associations between POI status and subclinical atherosclerosis were assessed.



Women with POI exhibited an increased waist circumference (β = 5.7; 95% confidence interval [CI], 1.6, 9.9), C-reactive protein (β = 0.75; 95% CI, 0.43, 1.08), free T4 levels (β = 1.5; 95% CI, 0.6, 2.4), and lower N-terminal pro-B-type natriuretic peptide (β = -0.35; 95% CI, -0.62, -0.08), estradiol (β = -1.98; 95% CI, -2.48, -1.48), T (β = -0.21; 95% CI, -0.37, -0.06), and androstenedione (β = -0.54; 95% CI, -0.71, -0.38) concentrations compared to controls, after adjusting for confounders. After adjustment, a trend toward increased hypertension (odds ratio = 2.1; 95% CI, 0.99; 4.56) and decreased kidney function was observed in women with POI (creatinine β = 3.5; 95% CI, -0.05, 7.1; glomerular filtration rate β = -3.5; 95% CI, -7.5, 0.46). Women with POI exhibited a lower mean carotid intima media thickness (β = -0.17; 95% CI, -0.21, -0.13) and decreased odds of plaque presence compared to controls (odds ratio = 0.08; 95% CI, 0.03; 0.26).



Women with POI exhibited an unfavorable cardiovascular risk profile, including higher abdominal fat, elevated chronic inflammatory factors, and a trend toward increased hypertension and impaired kidney function compared to controls. However, we observed no signs of increased subclinical atherosclerosis in women with POI. Additional studies are required to identify specific determinants of long-term CVD risk in women with POI.
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Nadine M P
NM
Daan
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Taulant
T
Muka
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Maria P H
MP
Koster
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Jaenine E
JE
Roeters van Lennep
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Cornelis B
CB
Lambalk
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Joop S E
JS
Laven
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Clemens G K M
CG
Fauser
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Cindy
C
Meun
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Yolanda B
YB
de Rijke
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Eric
E
Boersma
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Oscar H
OH
Franco
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Maryam
M
Kavousi
Department of Reproductive Medicine and Gynecology (N.M.P.D., M.P.H.K., B.C.J.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Epidemiology (T.M., O.H.F., M.K.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Internal Medicine (J.E.R.v.L.), Division Vascular Medicine, Erasmus Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Obstetrics and Gynecology (C.B.L.), VU University Medical Center Amsterdam, 1081 HV Amsterdam, The Netherlands; Department of Obstetrics and Gynecology (J.S.E.L., C.M.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; Department of Cardiology (C.G.K.M.F.), University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; Department of Clinical Chemistry (Y.B.d.R.), Erasmus MC, University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands; and Department of Cardiology (E.B.), Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, 3015 CE Rotterdam, The Netherlands.
Bart C J M
BC
Fauser
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008594:Menopause, Premature; D024821:Metabolic Syndrome / Q000209:etiology* / Q000473:pathology; D008875:Middle Aged; D016649:Primary Ovarian Insufficiency / Q000150:complications*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers