Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age

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, 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.

Results: 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).

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT02616510.