Association of the age at menarche with site-specific cancer risks in pooled data from nine cohorts

Barbara J. Fuhrman*, Steven C. Moore, Celia Byrne, Issam Makhoul, Cari M. Kitahara, Amy Berrington De González, Martha S. Linet, Elisabete Weiderpass, Hans Olov Adami, Neal D. Freedman, Linda M. Liao, Charles E. Matthews, Rachael Z. Stolzenberg-Solomon, Mia M. Gaudet, Alpa V. Patel, I. Min Lee, Julie E. Buring, Alicja Wolk, Susanna C. Larsson, Anna E. PrizmentKim Robien, Michael Spriggs, David P. Check, Neil Murphy, Marc J. Gunter, Harold L. Van Dusen, Regina G. Ziegler, Robert N. Hoover

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis.

Original languageEnglish
Pages (from-to)2246-2255
Number of pages10
JournalCancer Research
Issue number8
StatePublished - Apr 2021
Externally publishedYes


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