Events in Early Life are Associated with Female Reproductive Ageing: A UK Biobank Study.
The available oocyte pool is determined before birth, with the majority of oocytes lost before puberty. We hypothesised that events occurring before birth, in childhood or in adolescence ('early-life risk factors') could influence the size of the oocyte pool and thus the timing of menopause. We included cross-sectional data from 273,474 women from the UK Biobank, recruited in 2006-2010 from across the UK. We analysed the association of early menopause with events occurring before adulthood in 11,781 cases (menopause aged under 45) and 173,641 controls (menopause/pre-menopausal at ≥ 45 years), in models controlling for potential confounding variables. Being part of a multiple birth was strongly associated with early menopause (odds ratio = 1.42, confidence interval: 1.11, 1.82, P = 8.0 × 10(-9), fully-adjusted model). Earlier age at menarche (odds ratio = 1.03, confidence interval: 1.01, 1.06, P = 2.5 × 10(-6)) and earlier year of birth were also associated with EM (odds ratio = 1.02, confidence interval: 1.00, 1.04, P = 8.0 × 10(-6)). We also confirmed previously reported associations with smoking, drinking alcohol, educational level and number of births. We identified an association between multiple births and early menopause, which connects events pre-birth, when the oocyte pool is formed, with reproductive ageing in later life.
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon &Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
Katherine S
KS
Ruth
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
John R B
JR
Perry
Health Statistics Group, University of Exeter Medical School, St Luke's Campus, Exeter EX1 2LU, UK.
William E
WE
Henley
Epidemiology and Public Health, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, UK.
David
D
Melzer
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon &Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
Michael N
MN
Weedon
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon &Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
Anna
A
Murray
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D018070:Biological Specimen Banks; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D019655:Quantitative Trait, Heritable; D012098:Reproduction; D012307:Risk Factors; D012741:Sexual Maturation; D006113:United Kingdom; D055815:Young Adult