Estrogen deprivation and cardiovascular disease risk in primary ovarian insufficiency

Among women with primary ovarian insufficiency, du- ration of E deprivation and exposure predict cardiovascular disease risk.

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Volume 109, Issue 4, Pages 594–600.e1


Jacob P. Christ, B.S., Marlise N. Gunning, M.D., Giulia Palla, M.D., Marinus J.C. Eijkemans, Ph.D., Cornelis B. Lambalk, M.D., Ph.D., Joop S.E. Laven, M.D., Ph.D., Bart C.J.M. Fauser, M.D., Ph.D.



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 and 2016.


Tertiary referral centers.


A total of 385 women with POI, defined by amenorrhea and FSH levels ≥40 IU/L before 40 years of age, were recruited.



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.


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]).


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



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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.