Cardiovascular risk in women with premature ovarian insufficiency compared to premenopausal women at middle age

PMID:27300572

DOI:10.1210/jc.2016-1141

Author
Daan NM¹, Muka T², Koster MP¹, Roeters van Lennep JE³, Lambalk CB⁴, Laven JS⁵, Fauser CG⁶, Meun C⁵, de Rijke YB⁷, Boersma E⁸, Franco OH²,Kavousi M², Fauser BC¹.

Author information
 

• ¹Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands;
• ²Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
• ³Department of Internal Medicine, division Vascular Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands;
• ⁴Department of Obstetrics and Gynecology, VU University Medical Center Amsterdam, Amsterdam, the Netherlands.;
• ⁵Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
• ⁶Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands;
• ⁷Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
• ⁸Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands.

Abstract

CONTEXT:

A young age at menopause has been associated with increased cardiovascular disease (CVD) risk.

OBJECTIVE:

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

DESIGN:

Cross-sectional case control study.

SETTING:

Two University Medical Centers.

PARTICIPANTS:

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

MAIN OUTCOME MEASURES:

blood pressure, body mass index, waist circumference, electrocardiogram (ECG), bilateral carotid intima media thickness (C-IMT), estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), insulin, glucose, lipids, thyroid stimulating hormone (TSH), freeT4, NTpro-BNP, C-reactive protein (CRP), uric acid, creatinine, homocysteine. Potential associations between POI status and subclinical atherosclerosis were assessed.

RESULTS:

Women with POI exhibited an increased waist circumference (β=5.7; 95%CI: 1.6, 9.9), CRP (β=0.75; 95%CI: 0.43, 1.08), free-T4 levels (β=1.5; 95% CI: 0.6, 2.4), and lower NTpro-BNP (β= -0.35; 95%CI: -0.62, -0.08), estradiol (β= -1.98; 95% CI: -2.48, -1.48), testosterone (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 towards increased hypertension (OR=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, eGFR β=-3.5; 95%CI: -7.5, 0.46). Women with POI exhibited a lower mean C-IMT (β=-0.17; 95% CI: -0.21, -0.13), and decreased odds of plaque presence compared to controls (OR = 0.08, 95%CI: 0.03; 0.26).

CONCLUSIONS:

Women with POI exhibited an unfavorable cardiovascular risk profile, including higher abdominal fat, elevated chronic inflammatory factors, and a trend towards 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.