Association of intrauterine and early-life exposures with age at menopause in the Sister Study

Am J Epidemiol. 2010 Jul 15;172(2):140-8. doi: 10.1093/aje/kwq092. Epub 2010 Jun 9.


Oocytes are formed in utero; menopause occurs when the oocyte pool is depleted. The authors hypothesized that early-life events could affect the number of a woman's oocytes and determine age at menopause. To test their hypothesis, the authors conducted a secondary analysis of baseline data from 22,165 participants in the Sister Study (2003-2007) who were aged 35-59 years at enrollment. To estimate the association between early-life events and age at natural menopause, the authors used Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals, adjusting for current age, race/ethnicity, education, childhood family income, and smoking history. Earlier menopause was associated with in-utero diethylstilbestrol exposure (hazard ratio (HR) = 1.45, 95% confidence interval (CI): 1.27, 1.65). Suggestive associations included maternal prepregnancy diabetes (HR = 1.33, 95% CI: 0.89, 1.98) and low birth weight (HR = 1.09, 95% CI: 0.99, 1.20). Having a mother aged 35 years or older at birth appeared to be associated with a later age at menopause (HR = 0.95, 95% CI: 0.89, 1.01). Birth order, in-utero smoke exposure, and having been breastfed were not related to age at menopause. In-utero and perinatal events may subsequently influence age at menopause.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Birth Order
  • Breast Feeding
  • Diethylstilbestrol / adverse effects
  • Estrogens, Non-Steroidal / adverse effects
  • Female
  • Health Status*
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Maternal Age
  • Maternal Exposure
  • Maternal-Fetal Exchange
  • Menopause*
  • Middle Aged
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Proportional Hazards Models
  • Risk Factors
  • Siblings
  • Smoking / adverse effects
  • Socioeconomic Factors


  • Estrogens, Non-Steroidal
  • Diethylstilbestrol