title: Early menarche, nulliparity and the risk for premature and early natural menopause.
abstract: Are parity and the timing of menarche associated with premature and early natural menopause?
  
  
  
  Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP <40 years) and early menopause (FMP 40-44 years), a risk that is amplified for nulliparous women.
  
  
  
  Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power.
  
  
  
  This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE).
  
  
  
  Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation.
  
  
  
  The median age at FMP was 50 years (interquartile range 48-53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53-2.12) and early menopause (1.31, 1.19-1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84-2.77) and early menopause (1.32, 1.09-1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04-7.87) and 2-fold increased risk of early menopause (2.16, 1.48-3.15) compared with women who had menarche at ≥12 years and two or more children.
  
  
  
  Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias.
  
  
  
  Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause.
  
  
  
  InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests.
authors.affiliation: School of Public Health, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Gita D
authors.initials: GD
authors.lastname: Mishra
authors.affiliation: School of Public Health, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Pandeya
authors.affiliation: School of Public Health, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Dobson
authors.affiliation: School of Public Health, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Chung
authors.affiliation: Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Debra
authors.initials: D
authors.lastname: Anderson
authors.affiliation: Medical Research Council Unit for Lifelong Health and Ageing at University College London, London, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Kuh
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Sandin
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Bruinsma
authors.affiliation: School of Health Sciences, Gunma University, Maebashi City, Gunma, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Health Promotion Science, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Jung Su
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Fukushima Medical Center for Children and Women, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Mizunuma
authors.affiliation: Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Cade
authors.affiliation: Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Burley
authors.affiliation: Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK.
authors.forename: Darren C
authors.initials: DC
authors.lastname: Greenwood
authors.affiliation: Centre for Longitudinal Studies, University College London Institute of Education, London, UK.
authors.forename: Alissa
authors.initials: A
authors.lastname: Goodman
authors.affiliation: UcDiakonissen and Parker Institute, Frederiksberg, Denmark.
authors.forename: Mette Kildevæld
authors.initials: MK
authors.lastname: Simonsen
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.affiliation: Department of Epidemiology and Public Health, University College London, London, UK.
authors.forename: Panayotes
authors.initials: P
authors.lastname: Demakakos
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.|Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.|Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D005260:Female; D006801:Humans; D008572:Menarche / Q000502:physiology*; D008593:Menopause / Q000502:physiology*; D008594:Menopause, Premature / Q000502:physiology*; D008875:Middle Aged; D010298:Parity / Q000502:physiology*; D011247:Pregnancy; D012307:Risk Factors
keywords: InterLACE; early menopause; final menstrual period; menarche; parity; premature menopause; reproductive health