Life-course origins of the ages at menarche and menopause

Figures & data

Table 1 Behavioral and health risks attributed to early or late timing of reproductive events

	Early	Late
Menarche	• Premature death^Citation4 • Breast and endometrial cancers^Citation5^–^Citation7 • Depression^Citation8,Citation12 • Cardiovascular disease^Citation6,Citation9 • Obesity and metabolic syndrome^Citation6,Citation10 • Early initiation of smoking^Citation6 • Early first sexual intercourse^Citation6,Citation11 • Teenage pregnancy^Citation15	• Depression^Citation12 • Lower bone mineral density^Citation31^–^Citation33
Menopause	• Cardiovascular and coronary diseases^Citation43 • Lower bone density^Citation41,Citation42,Citation44 • Osteoporosis^Citation41,Citation42 • Premature death^Citation4,Citation7,Citation45	• Breast and endometrial cancers^Citation7,Citation45 • Longer life expectancy^Citation7,Citation45

Table 2 Duration of reproductive years associated with health risks

Short interval	Long interval
• Premature death^Citation4 • Cardiovascular disease^Citation43 • Obesity and metabolic syndrome^Citation46,Citation47,Citation53 • Lower bone mineral density^Citation41,Citation44 • Osteoporosis^Citation44	• Breast and endometrial cancers^Citation45

Figure 1 Decline in age at menarche, by ethnicity.

Abbreviations: NHANES, National Health and Nutrition Examination Surveys; NHB, non-Hispanic black; NHES, National Health Examination Survey (1963–1970); NHW, non-Hispanic white.

Figure 2 Association between ages at menarche and menopause by numbers of studies, design, and significance.

Table 3 Association between the age at menarche and age at natural menopause

Author, study, country	Population (N)	Designa	Menarche: definition/categories (y)	Menopause: definition	Analysis	Findingsb
Benjamin (1960), South Africa^Citation108	NHW, clinical (1000)	2	Early: <13 Late: >14	12 m post menses	Frequencies (no adj)	NS
Jaszmann et al (1969), The Netherlands (Ede borough)^Citation109	42–62 y, residents, b 1905–1925 (3548)	3, mail questionnaire	Nd	LMP if 12 m post menses	Probit analysis (no adj)	NS
McKinlay et al (1972), England^Citation48	45–54 y, clinical (736)	3, mail questionnaire	Early: <13 Late: >15	LMP if post menses > 3 m before study	Frequencies (no adj)	NS
Magurský et al (1975), Czechoslovakia^Citation110	38–58 y, residents (6877)	3, interview	<10, 10–12, 12–14, 14–16, 16–18, >18	>1 y post menses Climacteric: >2 physical symptoms	Correlation coefficient between median ages (no adj)	NS
Brand and Lehert (1978),^Citation111 The Netherlands (Ede borough)	40–60 y, residents (3777)	3, mail questionnaire	Nd	LMP if 12 m post menses	AID segmentation analysis (no adj)	NS
van Keep et al (1979)^Citation100 Second report on same borough as Jaszmann et al^Citation105 and Brand and Lehert,^Citation111 The Netherlands (Ede borough)	40–60 y, residents (1196)	3, mail questionnaire	Early: <12 Late: >17	LMP if 12 m post menses	χ^2 (no adj)	Inverse
Neri et al (1982), Israel^Citation112	>40 y, Europeans, Africans, Israelis, Arabs (1197)	3, doctor-administered questionnaire	Nd	“Last bleeding”	ANOVA – adj for ethnicity	NS
Stanford et al (1987), BCDDP, USA^Citation113	NHW control group (3497)	3, interview	≤11, 12, 13, ≥14	LMP if post menses > 3 months before study	Mantel–Cox test (no adj)	NS
Okonofua et al (1990), Nigeria^Citation114	44–87 y, Yoruba residents, clinical sample (563)	3, questionnaire	Nd	Nd	Regression (no adj)	NS
Whelan et al (1990), Treloar’s study, USA^Citation115	Multiple age and generation cohorts (561)	1, with >19 y of records	<12, 12–14, ≥15	Nd	LR – adj for parity and median cycle length at age 20–35 y	NS
Parazzini et al (1992), Italy^Citation116	55–74 y, control group from hospitals (863)	3, interview	≤11, 12–14, ≥15	Nd	Univariate trend analysis (no adj)	NS
Chompootweep et al (1993), Thailand^Citation117	45–59 y, health-center clients (1327)	3, interview	Continuous variable	LMP if 12 m post menses	Correlation coefficient (no adj)	NS
Beşer et al (1994), Turkey^Citation118	40–54 y, population based	3, home interview	≤15, >15	12 m post menses	Difference in means test	NS
Boulet et al (1994), Southeast Asia^Citation107	40–60 y, clinical and resident volunteers in seven countries (2181)	3, questionnaire by interview in six to seven countries	Nd	LMP if 12 m post menses Perimenopausal if cycle irregular in last 12 m	LR	Inverse
Torgerson et al (1994), CHI, UK^Citation119	NHW, 45–49 y, population based (2074)	3, mail questionnaire	Nd	Two definitions: LMP if 6, or 12, m post menses	χ^2 (no adj)	NS
Cramer et al (1995), USA^Citation101	45–54 y, residents, 344 cases and 344 controls (688)	3, home interview	Early: ≤11, 12–13, ≥=14	LMP	OR (no adj)	Direct
van Noord et al (1997), DOM, The Netherlands^Citation91	Cohort subsample, b1911–1925(4686)	1, fifth-round questionnaire	Continuous variable	LMP if 12 m post menses “Early”/bottom vs “late”/top tertiles	t-test (no adj)	NS
Rizk et al (1998), United Arab Emirates^Citation120	>40 y, population based (742)	3, staff-administered questionnaire	Nd	6 m post menses	Correlation coefficient (no adj)	NS
Snieder et al (1998), UK^Citation69	256 MZ and 269 DZ twin pair volunteers (1050)	3, nurse-administered questionnaire	Continuous variable	Age at LMP	Pearson r-statistic (no adj)	NS
Kato et al (1998), NYU Women’s Health Study, USA^Citation121	Subsample of 34–65 y (4694)	1, baseline and follow-up data	≤11, 12, 13, ≥14	6 m post menses	Cox PHM – adj for age	NS
Hardy and Kuh (1999), 1946 MRC birth cohort, UK^Citation102	Born in 1 week in March 1946, mail questionnaires (1060)	1, five rounds (censored data)	≤ 11, 12–14, “Late”: ≥15	LMP if 12 m post menses Perimenopause is LMP if 3–12 m without period, or date when cycle irregular in last 12 m	Cox PHM – adj for parity, OC use, oophorectomy	Direct (for perimenopause)
Nagata et al (2000), Takayama Study, Japan^Citation103	Resident volunteers (1130)	1	≤ 12, 13–14, 15–16 “Late”: ≥17	LMP if 12 m post menses	Cox PHM – adj for age	Direct
Meschia et al (2000), ICARUS, Italy^Citation122	≥55 y, clinical (4300)	1, baseline data	≤11, 12, 13, 14, ≥15	≥12 m post menses	ANCOVA–adj for BMI, smoking, parity	NS
Cooper et al (2001), NHANES III, USA^Citation123	35–49 y, with natural menopause (1696)	3, interview, questionnaire	8–10, 11–13, 14–15, 16–19	LMP if 12 m post menses	LR – adj for age, smoking, oophorectomy	NS
Reynolds and Obermeyer (2001), Lebanon^Citation124	45–55 y, population based (298)	3, in-person interviews	Nd	Cessation of menses (self-report)	LR (no adj)	NS
Palmer et al (2003), Black Women’s Health Study, USA^Citation125	Cohort members (17,070)	1, mailed questionnaires at two time points	<11, 11, 12–13, 14, ≥15	Cessation of periods (self-report)	Cox PHM – adj for smoking, parity, OC, education, BMI, oophorectomy, physical activity	NS
Rödström et al (2003), Gothenburg study, Sweden^Citation93	Population based, five birth cohorts (1017)	1, examinations/questionnaires at five time points	Continuous variable	12 m post menses	MLR – adj for birth cohort, smoking, parity, BMI, social class, education	Direct
Ozdemir and Cöl (2004), Turkey^Citation104	50–65 y, residents in catchment area (204)	3, in-person interview	Early: ≤ 13 Late: ≥14	LMP if 12 m post menses Perimenopausal if cycle/flow irregular in last 12 m	χ^2 (no adj)	Direct
Nagel et al (2005), EPIC-Heidelberg, Germany^Citation126	Subsample of 35–65 y (5110)	1, questionnaires at two time points	<11, 12, 13, 14, ≥15	12 m post menses	Cox PHM – adj for age	NS
Parazzini (2007), Italy^Citation105	>55 y, clinical (31,834)	3, clinical exam, interview	≤11, 12, 13, 14, ≥15	≥12 m post menses	χ^2 – adj for age	Direct
Kaczmarek (2007), Cross-national study of health and quality of life in middle-aged women (WOMID), Poland^Citation95	35–65 y, volunteers (7183)	3, questionnaire	Early: <14 Late: ≥14	LMP if 12 m post menses Perimenopausal if bleeding stopped for 3–12 m or if cycle irregular in last 12 m	MLR – adj for education, usual cycle length, OC, parity, smoking, health status	Direct
Henderson et al (2008), Multiethnic Cohort Study, USA^Citation87	Subsample of 45–74 y, NHW, NHB, Latinas, Japanese-Americans, Hawaiians (95,704)	1, baseline (censored data)	<11, 11–12, 13–14, 15–16, ≥17	Cessation of bleeding or age started hormone therapy or surgical menopause	Cox PHM – adj for ethnicity, smoking, parity, BMI	Direct
Dorjgochoo et al (2008), Shanghai Women’s Health Study, China^Citation106	40–70 y, residents (33,054)	1, baseline data	≤11, 12–13, 14–15, ≥16	LMP if 12 m post menses	MLR – adj for age, education, occupation, income, marital status, employment, energy intake, weight gain, smoking, physical activity	Direct
Dratva et al (2009), ECRHS and SAPALDIA, Europe^Citation94	Random sample of adult populations (5288)	1, questionnaire (censored data)	Continuous variable	12 m post menses	Cox PHM – adj for countries, cohort	Direct
Sammel et al (2009), Penn Ovarian Aging Studies, USA^Citation88	35–47 y, population-based (436)	1, questionnaires at ten points	Continuous variable	Five stages of menopausal transition	Markov transition models (no adj)	NS
Otero et al (2010), Pró-Saúde Study, Brazil^Citation127	>35 y, university employees (1462)	1, questionnaire	≤11, ≥12	>12 m post menses Perimenopausal if post menses < 6 m, or 6–12 m before study	Cox PHM – adj for parity, education, smoking	NS

Notes:

a 1, cohort; 2, case-control; 3, cross-sectional.

b “Inverse” indicates early menarche associated with late menopause and/or late menarche associated with early menopause; “direct” indicates early menarche associated with early menopause and/or late menarche associated with late menopause.

Abbreviations: adj, adjusted; ANCOVA, analysis of covariance; ANOVA, analysis of variance; b, born; BCDDP, Human Breast Cancer Detection Demonstration Project; BMI, body mass index; CHI, Community Health Index; Cox PHM, Cox proportional hazard model; DOM, Doorlopend Onderz oek Morbidi teit/Mortaliteit Study; DZ, dizygotic; ECRHS, European Respiratory Health Survey; ICARUS, Italian Climacteric Research Group Study; LMP, last menstrual period; LR, logistic regression; m, month/s; MLR, multivariate linear regression; MZ, monozygotic; Nd, not described; NHB, non-Hispanic black; NHW, non-Hispanic white; no adj, no adjustment in analyses/models; NS, not significant/no association; OC, oral contraceptive; OR, odds ratio; RR, relative risk; SAPALDIA, Swiss Air Pollution and Lung Disease in Adults Cohort; y, year/s.

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