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The relation of age at menarche with age at natural menopause: a population study of 336 788 women in Norway.

ABSTRACT: STUDY QUESTION:Is age at menarche associated with age at menopause or with duration of the reproductive period (interval between menarche and menopause)? SUMMARY ANSWER:The association of age at menarche with age at menopause was weak and non-linear, and the duration of the reproductive period decreased by increasing age at menarche. WHAT IS KNOWN ALREADY:It remains uncertain whether age at menarche is associated with age at menopause. Some studies report that women with early menarche also have early menopause. Other studies report that women with early menarche have late menopause, or they report no association. The duration of the reproductive period may be an indicator of the cumulative endogenous exposure to estrogens and progestogens during life course and is associated with risk of breast cancer and endometrial cancer. STUDY DESIGN, SIZE, DURATION:A retrospective cohort study of 336 788 women, aged 48-71 years, in the BreastScreen Norway during the years 2006-2014 was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS:Information about age at menarche and menopausal status was obtained by self-administered questionnaires. We used time to event approaches to estimate the associations. MAIN RESULTS AND THE ROLE OF CHANCE:Median age at menopause was 51 years in most menarche groups. Women with menarche at age 16 years or age ? 17 years had menopause 1 year later [median: 52 years, interquartile range (IQR): 49-54 years] than women with menarche at age 13 years (median: 51 years, IQR: 49-54 years, reference) (crude hazard ratio (HR) = 0.95; 95% CI: 0.93-0.97 and 0.95; 95% CI: 0.92-0.99, Pnon-linearity < 0.001). The reproductive period decreased with increasing age at menarche (Pnon-linearity < 0.001), and women with menarche at age ? 9 years had 9 years longer median reproductive period than women with menarche at age ? 17 years (median: 43 versus 34 years). Adjustment for year of birth did not change the HR estimates notably. LARGE SCALE DATA:Not applicable. LIMITATIONS, REASONS FOR CAUTION:Information about age at menarche and age at menopause was based on self-reports. Particularly for age at menarche, the long time interval between the event and data collection may have caused imprecise reporting. WIDER IMPLICATIONS OF THE FINDINGS:Our study suggests that age at menarche is a strong indicator for the duration of women's reproductive period. Our findings should encourage studies of the independent role of duration of the reproductive period on the risk of breast cancer and endometrial cancer, since these cancers have been associated with exposure to estrogens and progestogens. STUDY FUNDING/COMPETING INTEREST(S):The present study was funded by the Norwegian Cancer Society [Grant number 6863294-2015]. The authors declare no conflicts of interest.

SUBMITTER: Bjelland EK

PROVIDER: S-EPMC5972645 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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The relation of age at menarche with age at natural menopause: a population study of 336 788 women in Norway.

Bjelland E K EK Hofvind S S Byberg L L Eskild A A

Human reproduction (Oxford, England) 20180601 6

<h4>Study question</h4>Is age at menarche associated with age at menopause or with duration of the reproductive period (interval between menarche and menopause)?<h4>Summary answer</h4>The association of age at menarche with age at menopause was weak and non-linear, and the duration of the reproductive period decreased by increasing age at menarche.<h4>What is known already</h4>It remains uncertain whether age at menarche is associated with age at menopause. Some studies report that women with ea ...[more]

PMID: 29635353

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Project description:Study questionHave mean age at menarche or mean age at natural menopause changed from the 1939 birth cohort to the 1964 birth cohort?Summary answerWe estimated a minor decrease in mean age at menarche and an increase by nearly 3 years in mean age at natural menopause.What is known alreadyIn the Western world, age at menarche decreased across birth cohorts from the early 1800s until the 1950s. Whether mean age at menarche has continued to decrease in birth cohorts after the 1950s remains uncertain. It is also uncertain whether mean age at natural menopause has changed across birth cohorts.Study design, size, durationWe performed a retrospective population study of 312 656 women who were born in Norway during the years 1936-1964.Participants/materials, setting, methodsThe data were obtained by two self-administered questionnaires from women who participated in the Norwegian breast cancer screening program (BreastScreen Norway) during the years 2006-2014. We used flexible parametric survival models with restricted cubic splines to estimate mean age at menarche, mean age at menopause and mean number of years between menarche and menopause according to the women's year of birth. The women who were still having menstrual periods contributed with follow-up time until the time of data collection, and the women who had reported surgical removal of the uterus and/or both ovaries prior to natural menopause contributed with follow-up time until the time of surgery.Main results and the role of chanceThe mean age at menarche was 13.42 years (95% CI: 13.40-13.44 years) among women born during 1936-1939, and it was 13.24 years (95% CI: 13.22-13.25 years) among women born during 1960-1964. The mean age at natural menopause increased from 50.31 years (95% CI: 50.25-50.37 years) among women born during 1936-1939 to 52.73 years (95% CI: 52.64-52.82 years) among women born during 1960-1964. The mean number of years between menarche and menopause increased from 36.83 years (95% CI: 36.77-36.89 years) to 40.22 years (95% CI: 40.11-40.34 years).Limitations, reasons for cautionInformation about age at menarche and age at menopause was based on self-reports.Wider implications of the findingsLate menopause is associated with increased risk of breast cancer but also with increased life expectancy. Thus, higher mean age at menopause may partly explain the increase in breast cancer incidence after menopause and the increase in life expectancy in recent time. Also, a longer interval between menarche and menopause could suggest that the number of years of female fecundity has increased.Study funding/competing interest(s)This work was funded by the South-Eastern Norway Regional Health Authority [grant number 2016112 to M.S.G.] and by the Norwegian Cancer Society [grant number 6863294-2015 to E.K.B.]. The authors declare no conflicts of interest.

Project description:Study questionDoes age at natural menopause increase with increasing of number of childbirths?Summary answerAge at menopause increased with increasing number of childbirths up to three childbirths; however, we found no further increase in age at menopause beyond three childbirths.What is known alreadyPregnancies interrupt ovulation, and a high number of pregnancies have therefore been assumed to delay menopause. Previous studies have had insufficient statistical power to study women with a high number of childbirths. Thus, the shape of the association of number of childbirths with age at menopause remains unknown.Study design, size, durationA retrospective population study of 310 147 women in Norway who were 50-69 years old at data collection.Participants/materials, setting, methodsThe data were obtained by two self-administered questionnaires completed by women attending BreastScreen Norway, a population-based screening program for breast cancer. The associations of number of childbirths with age at menopause were estimated as hazard ratios by applying Cox proportional hazard models, adjusting for the woman's year of birth, cigarette smoking, educational level, country of birth, oral contraceptive use and body mass index.Main results and the role of chanceWomen with three childbirths had the highest mean age at menopause (51.36 years; 95% CI: 51.33-51.40 years), and women with no childbirths had the lowest (50.55 years; 95% CI: 50.48-50.62 years). Thus, women with no childbirths had higher hazard ratio of reaching menopause compared to women with three childbirths (reference group) (adjusted hazard ratio, 1.24; 95% CI: 1.22-1.27). Beyond three childbirths, we estimated no further increase in age at menopause. These findings were confirmed in sub-analyses among (i) women who had never used hormonal intrauterine device and/or systemic menopausal hormonal therapy; (ii) women who were born before 1950 and (iii) women who were born in 1950 or after.Limitations, reasons for cautionInformation about age at menopause was based on self-reports.Wider implications of the findingsIf pregnancies truly delay menopause, one would expect that women with the highest number of childbirths had the highest age at menopause. Our results question the assumption that interrupted ovulation during pregnancy delays menopause.Study funding/competing interest(s)This work was supported by the South-Eastern Norway Regional Health Authority [2016112 to M.S.G.] and by the Norwegian Cancer Society [6863294-2015 to E.K.B.]. The authors declare no conflicts of interest.Trial registration numberN/A.

Project description:BackgroundHormonal reproductive factors have been suggested to play an important role in the etiology of rheumatoid arthritis (RA), an autoimmune inflammatory disorder affecting primarily women. We conducted a two-sample Mendelian randomization (MR) study examining three relevant exposures, age at menarche (AAM), age at natural menopause (ANM), and age at first birth (AFB) with the risk of RA.MethodsWe collected summary statistics from the hitherto largest GWAS conducted in AAM (N = 329,345), ANM (N = 69,360), AFB (N = 251,151), and RA (Ncase = 14,361, Ncontrol = 43,923), all of European ancestry. We constructed strong instruments using hundreds of exposure-associated genetic variants and estimated causal relationship through different MR approaches including an inverse-variance weighted method, an MR-Egger regression and a weighted median method. We conducted a multivariable MR to control for pleiotropic effect acting in particular through obesity and socioeconomic status. We also performed important sensitivity analyses to verify model assumptions.ResultsWe did not find any evidence in support for a causal association between genetically predicted reproductive factors and risk of RA (ORper-SD increment in AAM = 1.06 [0.98-1.15]; ORper-SD increment in ANM = 1.05 [0.98-1.11], OR per-SD increment in AFB = 0.85 [0.65-1.10]). Results remained consistent after removing palindromic SNPs (ORper-SD increment in AAM = 1.06 [0.97-1.15], ORper-SD increment in ANM = 1.05 [0.98-1.13], ORper-SD increment in AFB = 0.81 [0.61-1.07]) or excluding SNPs associated with potential confounding traits (ORper-SD increment in AAM = 1.03 [0.94-1.12], ORper-SD increment in ANM = 1.04 [0.95-1.14]). No outlying instrument was identified through the leave-one-out analysis.ConclusionsOur MR study does not convincingly support a casual effect of reproductive factors, as reflected by age at menarche, age at menopause, and age at first birth, on the development of RA. Despite the largely augmented set of instruments we used, these instruments only explained a modest proportion of phenotypic variance of exposures. Our knowledge regarding this topic is still insufficient and future studies with larger sample size should be designed to replicate or dispute our findings.

Dataset Information

The relation of age at menarche with age at natural menopause: a population study of 336 788 women in Norway.

Publications

The relation of age at menarche with age at natural menopause: a population study of 336 788 women in Norway.

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