Abstract

To evaluate the association between estrogen (E) exposure and deficiency and cardiovascular disease (CVD) risk among women with primary ovarian insufficiency (POI). Cross-sectional study conducted between 1996 and2016. Tertiary referral centers. A total of 385 women with POI, defined by amenorrhea and FSH levels ≥40 IU/L before 40years of age, were recruited. None. Women underwent a standardized intake questionnaire including data on menstrual cyclicity. Lifetime E exposure and E-free period were assessed. Serum was analyzed for endocrine and CVD profiles. The Framingham 30-year risk of CVD was calculated. Lifetime E exposure (mean ± SD) was 19.3 ± 7.0years, E-free period was 3.1 ± 4.1years, and age at screening was 34.8±7.4years. In multivariate models E-free interval associated positively with estimated risk of hard and general CVD events (β0.18 [95% confidence interval 0.08, 0.29]; 0.20 [0.05, 0.35], respectively), and lifetime E exposure associated negatively with estimated risk of hard and general CVD events (-0.15 [-0.24, -0.05]; -0.16 [-0.29, -0.03], respectively), as well as low density lipoprotein cholesterol (-0.03 [-0.06, 0.00]) and non-high density lipoprotein cholesterol (-0.04 [-0.07, 0.00]). Prolonged E deprivation is associated with an increased estimated risk of CVD, whereas prolonged E exposure is associated with a reduced estimated risk. These results support the policy of early and continued use of E replacement therapy in women with POI. NCT0230904.

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