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

Abstract

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.

Figure 1.

Prevalence of women who were still menstruating as a function of age, by A) level of exposure to diethylstilbestrol (DES) in utero (solid line, unexposed; dashed line, exposed) and B) exposure to maternal diabetes (solid line, unexposed; dashed line, participant's mother had diabetes prior to pregnancy; dotted line, participant's mother had diabetes during pregnancy only), Sister Study, 2003–2007.

Figure 2.

Prevalence of women who were still menstruating, by birth weight (solid line, normal birth weight (≥2,500 g); dashed line, low birth weight (<2,500 g)), Sister Study, 2003–2007.