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Updated: Feb 12, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estrogen deprivation and cardiovascular disease risk in primary ovarian insufficiency
Jacob P Christ1, Marlise N Gunning2, Giulia Palla3
1Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands; Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio.
Objective:
To evaluate the association between estrogen (E) exposure and deficiency and cardiovascular disease (CVD) risk among women with primary ovarian insufficiency (POI).
Design:
Cross-sectional study conducted between 1996 and 2016.
Setting:
Tertiary referral centers.
Patient(S):
A total of 385 women with POI, defined by amenorrhea and FSH levels ≥40 IU/L before 40 years of age, were recruited.
Intervention(S):
None.
Main Outcome Measure(S):
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.
Result(S):
Lifetime E exposure (mean ± SD) was 19.3 ± 7.0 years, E-free period was 3.1 ± 4.1 years, and age at screening was 34.8 ± 7.4 years. In multivariate models E-free interval associated positively with estimated risk of hard and general CVD events (β 0.18 [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]).
Conclusion(S):
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.
Clinical Trial Registration Number:
NCT0230904.
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