The association between in utero cigarette smoke exposure and age at menopause.

Menopause onset, on average, occurs earlier among women who smoke cigarettes than among women who do not smoke. Prenatal smoke exposure may also influence age at menopause through possible effects on follicle production in utero. Smoking information was obtained from the mothers of 4,025 participants in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project, a US study begun in 1975 to examine the health effects of prenatal diethylstilbestrol exposure. Between 1994 and 2001, participants provided information on menopausal status. Cox proportional hazards modeling compared the probability of menopause among participants who were and were not prenatally exposed to maternal cigarette smoke. Participants prenatally exposed to maternal cigarette smoke were more likely than those unexposed to be postmenopause (hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). The association was present among only those participants who themselves had never smoked cigarettes (hazard ratio = 1.38, 95% confidence interval: 1.10, 1.74) and was absent among active smokers (hazard ratio = 1.03, 95% confidence interval: 0.81, 1.31). In this cohort of participants predominantly exposed to diethylstilbestrol, results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause. The possibility that active cigarette smoking modifies this effect is also suggested.