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Does accelerated reproductive aging underlie premenopausal risk for cardiovascular disease?

Bleil, Maria E. PhD; Gregorich, Steven E. PhD; McConnell, Daniel PhD; Rosen, Mitchell P. MD; Cedars, Marcelle I. MD

doi: 10.1097/GME.0b013e31828950fa
Original Study

Objective The menopausal transition is associated with an increase in risk for cardiovascular disease; however, whether variability in reproductive aging relates to cardiovascular risk factors in the premenopausal period has not been studied.

Methods In a multiethnic sample of 951 healthy, regularly cycling women aged 25 to 45 years (mean [SD] age, 35.2 [5.5] y), we examined antimüllerian hormone (AMH), a validated marker of ovarian reserve, in relation to the overall number of cardiometabolic risk factors, calculated as the sum of the five components of metabolic syndrome (triglycerides ≥150 mg/dL; high-density lipoprotein <50 mg/dL; homeostasis model assessment of insulin resistance ≥2.6; waist circumference equal to or higher than race-specific cutoff; and hypertensive [vs normotensive] status), and in relation to each of these risk factors individually.

Results In age-adjusted models, results showed that the number of cardiometabolic risk factors was 52.1% higher among women with low versus high AMH levels and 46.0% higher among women with mid versus high AMH levels. In addition, results showed that low and mid levels of AMH (vs high) were associated with an increase in risk with respect to high-density lipoprotein (odds ratio [OR], 1.814; 95% CI, 1.211-2.718 and OR, 1.568; 95% CI, 1.083-2.269, respectively), waist circumference (OR, 2.012; 95% CI, 1.380-2.934 and OR, 1.881; 95% CI, 1.333-2.654, respectively), and hypertensive status (OR, 2.373; 95% CI, 1.095-5.143 and OR, 2.052; 95% CI, 0.976-4.314, respectively) outcomes. Associations, however, attenuated when body mass index was covaried (Ps > 0.05).

Conclusions Cross-sectional evidence suggests that having a greater ovarian reserve is associated with having a healthier cardiometabolic risk factor profile. Future longitudinal studies are needed to determine whether this association may be mediated by body mass index.

From the Departments of 1Psychiatry and 2Medicine, University of California San Francisco, San Francisco, CA; 3Department of Epidemiology, University of Michigan, Ann Arbor, MI; and 4Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA.

Received September 22, 2012; revised and accepted January 22, 2013.

Funding/support: Preparation of this manuscript and the research described here were supported by the National Institutes of Health (NIH)/National Institute of Child Health and Human Development and NIH/National Institute on Aging (R01 HD044876), NIH/National Institute on Aging (K08 AG03575), NIH/University of California San Francisco Clinical and Translational Science Institute (UL1 RR024131), and the Hellman Family Foundation.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Maria E. Bleil, PhD, University of California San Francisco, Suite 465, 3333 California Street, San Francisco, CA 94143-0848. E-mail:

© 2013 by The North American Menopause Society.