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Factors that influence entry into stages of the menopausal transition

Sammel, Mary D. ScD1; Freeman, Ellen W. PhD2,3; Liu, Ziyue MS1; Lin, Hui MS4; Guo, Wensheng PhD1

doi: 10.1097/gme.0b013e3181a8f62b

Objective: The aim of this study was to estimate the probabilities and identify risk factors for entering the menopausal transition and moving into each subsequent transition stage.

Methods: Estimations of probabilities of entry into each menopausal transition stage and predictors associated with each transition stage were conducted in a population-based cohort of midlife women.

Results: The likelihood of entering the menopausal transition and moving into each subsequent stage was increased for each unit increase in follicle-stimulating hormone (FSH) (P < 0.001) and with each unit decrease in inhibin B (P < 0.001) in the adjusted multivariable model. The largest observed change in average FSH levels was the comparison of women in the late transition (stage 4), with an average of 24.78 mIU/mL, to those in the early transition (stage 3), with 10.38 mIU/mL. Women experiencing this amount of change in FSH had an odds of transitioning from stages 3 to 4 of 1.90 (95% CI, 1.86-1.95). Decreases in inhibin B resulted in odds ratios similar to the magnitude of changes in FSH. Current smoking increased the odds of transition into each stage by approximately 30% (odds ratio, 1.30; 95% CI, 1.28-1.32). Average estradiol levels did not change dramatically between stages. However, higher estradiol significantly increased the odds of entering the transition (P = 0.013). Age and race predicted transitions into some but not all stages. Body mass index, alcohol use, and age at menarche did not predict entrance into any stage of the menopausal transition after adjusting for other study variables.

Conclusions: These results show that increased FSH, decreased inhibin B, and smoking strongly predict entry into the earliest stages of the menopausal transition as defined by changes in bleeding patterns. African Americans entered the transition before white women, but race did not predict entry into late transition stages. Higher estradiol levels predict entry into the earliest transition stage but not subsequent stages.

This study estimates the probabilities and identifies the risk factors for entry into each stage of the menopausal transition. Increased follicle-stimulating hormone levels, decreased inhibin B levels, and current smoking were the strongest predictors of entry into the earliest transition stage and all subsequent stages of the transition as defined by changes in bleeding patterns.

From the 1Center for Clinical Epidemiology and Biostatistics; Departments of 2Obstetrics/Gynecology and 3Psychiatry; and 4Center for Research in Reproduction and Women's Health, University of Pennsylvania, Philadelphia, PA.

Received February 9, 2009; revised and accepted April 7, 2009.

Funding/support: This study was supported by grants from the National Institutes of Health, Bethesda, MD: RO1 AG12745 (E.W.F., M.D.S.), RR024134 (Clinical and Translational Research Center), RO1 CA84438 (W.G.), and T32 DK060455 (Z.L.).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Ellen W. Freeman, PhD, Department of Obstetrics/Gynecology, 3701 Market St., Suite 820 (Mudd), Philadelphia, PA 19104. E-mail:

©2009The North American Menopause Society