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.

Additional Metadata
Keywords Cardiovascular disease, estrogen, hormone replacement therapy, primary ovarian insufficiency
Persistent URL dx.doi.org/10.1016/j.fertnstert.2017.11.035, hdl.handle.net/1765/105520
Journal Fertility and Sterility
Christ, J.P. (Jacob P.), Gunning, M.N. (Marlise N.), Palla, G. (Giulia), Eijkemans, M.J.C, Lambalk, C.B, Laven, J.S.E, & Fauser, B.C.J.M. (2018). Estrogen deprivation and cardiovascular disease risk in primary ovarian insufficiency. Fertility and Sterility. doi:10.1016/j.fertnstert.2017.11.035