Menarche and Time to Cycle Regularity Among Individuals Born Between 1950 and 2005 in the US

Zifan Wang; Gowtham Asokan; Jukka-Pekka Onnela; Donna D Baird; Anne Marie Z Jukic; Allen J Wilcox; Christine L Curry; Tyler Fischer-Colbrie; Michelle A Williams; Russ Hauser; Brent A Coull; Shruthi Mahalingaiah

doi:10.1001/jamanetworkopen.2024.12854

. 2024 May 29;7(5):e2412854. doi: 10.1001/jamanetworkopen.2024.12854

Menarche and Time to Cycle Regularity Among Individuals Born Between 1950 and 2005 in the US

Zifan Wang ^1,^✉, Gowtham Asokan ², Jukka-Pekka Onnela ², Donna D Baird ³, Anne Marie Z Jukic ³, Allen J Wilcox ³, Christine L Curry ⁴, Tyler Fischer-Colbrie ⁴, Michelle A Williams ⁵, Russ Hauser ^1,⁵, Brent A Coull ^1,², Shruthi Mahalingaiah ¹

¹Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

²Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

³Epidemiology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, North Carolina

⁴Health, Apple Inc, Cupertino, California

⁵Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

Accepted for Publication: March 1, 2024.

Published: May 29, 2024. doi:10.1001/jamanetworkopen.2024.12854

^✉

Corresponding Author: Zifan Wang, PhD, MS, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Bldg 1, Room 1404, Boston, MA 02115 (zwang@hsph.harvard.edu).

Author Contributions: Dr Wang and Mr Asokan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Wang and Mr Asokan contributed equally to this work.

Concept and design: Wang, Jukic, Williams, Hauser, Coull, Mahalingaiah.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Wang, Asokan, Mahalingaiah.

Critical review of the manuscript for important intellectual content: Asokan, Onnela, Baird, Jukic, Wilcox, Curry, Fischer-Colbrie, Williams, Hauser, Coull, Mahalingaiah.

Statistical analysis: Wang, Asokan, Onnela, Coull, Mahalingaiah.

Obtained funding: Curry, Williams, Hauser, Coull, Mahalingaiah.

Administrative, technical, or material support: Asokan, Jukic, Wilcox, Curry, Fischer-Colbrie, Coull, Mahalingaiah.

Supervision: Hauser, Mahalingaiah.

Conflict of Interest Disclosures: Dr Curry and Mr Fischer-Colbrie are employed by Apple Inc and report owning Apple stocks. No other disclosures were reported.

Funding/Support: This research was supported in part by award Z01ES103333 from the Intramural Research Program of the National Institutes of Health (Drs Baird, Jukic, and Wilcox). Support for Drs Baird, Jukic, and Wilcox was provided by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. Apple Inc is the sponsor of this study.

Role of the Funder/Sponsor: Apple Inc provided platforms and software for the collection and management of the data and participated in the review and approval of the manuscript. It played no role in the design and conduct of the study, analysis and interpretation of the data, preparation of the manuscript, or in the decision to submit the manuscript for publication.

Meeting Presentation: Preliminary findings of this work were presented at the American Society for Reproductive Medicine Scientific Congress & Expo; October 16, 2023; New Orleans, Louisiana.

Data Sharing Statement: See Supplement 2.

Additional Contributions: Malaika Gabra, BA, Mackenzie Collyer, BS, Elizabeth Peebles, BA, Carrie Sarcione, MEd, and Ariel Scalise, MPH, Harvard T.H. Chan School of Public Health, assisted with this study and are paid staff members of the Apple Women's Health Study (AWHS), who provided support on the administrative parts of this study. The AWHS team would like to thank the study participants for consenting and contributing to the advancement of women’s health research.

^✉

Corresponding author.

PMCID: PMC11137638 PMID: 38809557

Key Points

Question

In the US, what are the temporal trends in age at menarche and time from menarche to cycle regularity?

Findings

This cohort study of 71 341 US female individuals born between 1950 and 2005 found significant trends toward earlier menarche and longer time to regularity over time, and these trends were more pronounced among those who were non-Hispanic Black, Asian, or of other or multiple races (compared with non-Hispanic White individuals) and among low socioeconomic status groups. Body mass index at menarche partially mediated the trend for menarche.

Meaning

These findings suggest that early-life menstrual characteristics have been trending in directions that indicate higher risk of later adverse health outcomes, which may contribute to health disparities.

This cohort study of racially and ethnically diverse US individuals born between 1950 and 2005 examines temporal trends in menarche and time to regularity.

Abstract

Importance

Early menarche is associated with adverse health outcomes. Trends toward earlier menarche have been observed in the US, but data remain limited on differences by sociodemographic factors and body mass index (BMI). Time from menarche to cycle regularity is another understudied early-life characteristic with health implications.

Objectives

To evaluate the temporal trends and disparities in menarche and time to regularity and explore early-life BMI as a mediator.

Design, Setting, and Participants

This ongoing cohort study enrolled participants from an ongoing mobile application–based US cohort from November 14, 2019, to March 20, 2023.

Exposures

Birth year (categorized as 1950-1969, 1970-1979, 1980-1989, 1990-1999, and 2000-2005).

Main Outcomes and Measures

Main outcomes were age at menarche and time to regularity, which were self-recalled at enrollment. In addition, early (aged <11 years), very early (aged <9 years), and late (aged ≥16 years) age at menarche was assessed.

Results

Among the 71 341 female individuals who were analyzed (mean [SD] age at menarche, 12.2 [1.6] years; 2228 [3.1%] Asian, 3665 [5.1%] non-Hispanic Black, 4918 [6.9%] Hispanic, 49 518 [69.4%] non-Hispanic White, and 8461 [11.9%] other or multiple races or ethnicities), 5223 were born in 1950 to 1969, 12 226 in 1970 to 1979, 22 086 in 1980 to 1989, 23 894 in 1990 to 1999, and 7912 in 2000 to 2005. The mean (SD) age at menarche decreased from 12.5 (1.6) years in 1950 to 1969 to 11.9 (1.5) years in 2000 to 2005. The number of individuals experiencing early menarche increased from 449 (8.6%) to 1223 (15.5%), the number of individuals experiencing very early menarche increased from 31 (0.6%) to 110 (1.4%), and the number of individuals experiencing late menarche decreased from 286 (5.5%) to 137 (1.7%). For 61 932 participants with reported time to regularity, the number reaching regularity within 2 years decreased from 3463 (76.3%) to 4075 (56.0%), and the number not yet in regular cycles increased from 153 (3.4%) to 1375 (18.9%). The magnitude of the trend toward earlier menarche was greater among participants who self-identified as Asian, non-Hispanic Black, or other or multiple races (vs non-Hispanic White) (P = .003 for interaction) and among participants self-rated with low (vs high) socioeconomic status (P < .001 for interaction). Within a subset of 9865 participants with data on BMI at menarche, exploratory mediation analysis estimated that 46% (95% CI, 35%-61%) of the temporal trend in age at menarche was explained by BMI.

Conclusions and Relevance

In this cohort study of 71 341 individuals in the US, as birth year increased, mean age at menarche decreased and time to regularity increased. The trends were stronger among racial and ethnic minority groups and individuals of low self-rated socioeconomic status. These trends may contribute to the increase in adverse health outcomes and disparities in the US.

Introduction

Menarche is the culmination of a complex sequence of events involving the maturation of the reproductive axis.^1,2 Early menarche is associated with increased risk of adverse health outcomes, such as cardiovascular diseases, cancers, spontaneous abortion, and premature death,^{3,4,5,6,7,8,9} whereas late menarche is associated with increased risk of fractures.^10,11 Studies have found trends toward earlier menarche during the past 5 to 10 decades in the US as well as globally.^{12,13,14,15,16,17,18,19} In the US, studies have additionally evaluated whether this trend varied by sociodemographic factors.^{13,20,21,22,23,24,25,26} Some of them^{13,21,22,23,25} showed significant racial and ethnic differences, whereas others^20,24,26 did not, and most^13,20,22,24 were limited to non-Hispanic Black vs White comparisons. Furthermore, most studies^{20,21,23,24,26} focused on mean age at menarche, with the frequency of early or late menarche rarely evaluated. Notably, obesity is a risk factor for early-onset puberty,^{27,28,29,30,31} and the prevalence of childhood obesity has increased in the US,^32,33 leading to hypotheses on the potential role of obesity in the trends toward earlier menarche. However, whether obesity is the primary factor underlying the trends in menarche remains debatable.³⁴ Whether and to what extent the trend in menarche is attributable to changes in early-life body mass index (BMI) remains to be determined.²⁸

The menstrual cycle is a vital sign.³⁵ The maturation of the reproductive axis, measured as the time from menarche to established cycle regularity, is another important but understudied hallmark of early-life menstrual health. Within 1 to 2 years after menarche, irregular cycles are considered a normal process of pubertal transition.^36,37 Full maturation of the reproductive axis leads to more regular menstrual function.³⁸ Longer time to regularity has been associated with lower fecundability, longer menstrual cycles, and increased risk of metabolic conditions and all-cause mortality.^39,40,41,42 Whereas the trends in time to regularity (influenced by environmental pollutants)^43,44 were evaluated in Japanese¹⁴ and French⁴⁵ cohorts, it is not known whether it has also changed during the past several decades in the US.

In this study, we used data from a large, mobile application–based cohort of adults in the US to evaluate temporal trends in menarche and time to regularity among members of a racially and ethnically diverse study population born between 1950 and 2005. We analyzed overall temporal trends and whether observed trends differ by sociodemographic factors. Additionally, we explored whether BMI at menarche might mediate the observed temporal trends.

Methods

Study Population

The Apple Women’s Health Study is a prospective digital cohort study in the US. Users of the Apple Research app on their iPhone were eligible if they had ever menstruated at least once in life, live in the US, were at least 18 years old (19 years in Alabama and Nebraska and 21 years in Puerto Rico), and were able to communicate in English. Eligibility also required sole use of an iCloud account and an iPhone. Enrollment began on November 14, 2019, and is ongoing. Participants provided written informed consent at enrollment. This study was approved by the institutional review board at Advarra. Details were described previously.⁴⁶ On enrollment, participants were asked to complete surveys of demographics as well as reproductive and medical history. For this analysis, we included participants who reported female sex assigned at birth, who were enrolled until March 20, 2023, and who provided age at menarche information. We excluded those born in 1931 to 1949 due to potential survival bias and too few individuals representing this group. A conceptual model is shown in eFigure 1 in Supplement 1. The final study population included 71 341 participants; data analysis was limited to subsets who answered the relevant questions (eFigure 2 in Supplement 1). This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Birth Year and Age at Menarche

We grouped self-reported year of birth as 1950 to 1969 (n = 5223), 1970 to 1979 (n = 12 226), 1980 to 1989 (n = 22 086), 1990 to 1999 (n = 23 894), and 2000 to 2005 (n = 7912). Participants were asked the question, “At what age did you have your first menstrual period? It’s okay to estimate,” with the following response options: “7 years old or younger,” integer options between 8 and 15 years old, “16 years old or older,” “I don’t know,” or “I prefer not to answer.” Those who indicated they did not know or preferred not to answer or did not respond were excluded. We derived the following measures: (1) age at menarche (in years) (we assigned the value of 7 to those aged ≤7 years [196 (0.3%)] and the value of 16 to those aged ≥16 years [2447 (3.4%)]); (2) early menarche (yes/no) (age at menarche <11 years⁴⁷); (3) very early menarche (yes/no) (age at menarche <9 years⁴⁸); and (4) late menarche (yes/no) (age at menarche ≥16 years).⁴⁹

Time to Cycle Regularity

Participants were asked, “After your first menstrual cycle, how long did it take for your cycle to become regular?” with the following response options: “less than 1 year,” “1-2 years,” “3-4 years,” “more than 5 years,” “after using hormones (eg, birth control pills),” “They’re not yet regular,” “I don’t know,” or “I prefer not to answer.” Those who indicated don’t know or prefer not to answer or who did not respond were considered missing. We further excluded 224 individuals with potentially inaccurate time-to-regularity information (eMethods in Supplement 1). For the remaining 61 932 participants, we categorized time to regularity as 2 years or less, 3 to 4 years, more than 5 years, not yet regular, or regular after using hormones.

Covariates

We considered the following self-reported variables to evaluate whether the temporal trends in age at menarche or time to regularity differ by sociodemographic factors: (1) self-identified race and ethnicity (Asian, Hispanic, non-Hispanic Black, non-Hispanic White, and other and multiple races (including American Indian or Alaska Native, Middle Eastern or North African, Native Hawaiian or other Pacific Islander, “None of these fully describe me,” and self-identified with >1 option)⁵⁰; (2) subjective socioeconomic status (SES) at enrollment based on the MacArthur Scale of Subjective Social Status⁵¹ (categorized as 0-3 [low], 4-5 [medium], and 6-9 [high]), which was used as a surrogate for premenarche SES; and (3) geographic location (based on state of residence and categorized as Northeast, Midwest, South, and West).

In addition, among a subset of 9865 participants (13.8%) who retrospectively reported weight and height at menarche, we derived BMI (calculated as weight in kilograms divided by height in meters squared) for age z scores, percentiles, and categories at menarche using the Centers for Disease Control and Prevention Growth Chart.^52,53,54 We considered BMI at menarche as a potential mediator of temporal trends in age at menarche or time to regularity.

Statistical Analysis

We calculated means (SDs) for continuous variables and reported numbers (percentages) for binary or categorical variables, overall and stratified by birth year categories (χ² tests were performed to identify differences in time to regularity by birth year categories). We summarized the percentages of time to regularity by age at menarche. We used generalized linear regression (gaussian or binomial distributions for continuous or binary categorical variables), with birth year as the exposure variable to generate P values for temporal trends.

To understand how temporal trends differ by sociodemographic factors, we performed analyses stratified by each covariate. A test of trend was performed within each level of the covariate by including birth year as the exposure variable in regression models. We also tested whether the slope of trends differed by covariates by including an interaction term between each covariate and birth year in the regression models and performing a type 3 test for significance.

We evaluated trends over time in the subset of 9865 participants with data on BMI at menarche. We performed an exploratory causal mediation analysis^55,56 with nonparametric bootstrap (500 simulations) to quantify the proportions (95% CIs) of temporal trends in menarche or time to regularity mediated by BMI z score at menarche. We evaluated these temporal trends as a secondary analysis after stratifying by BMI categories at menarche or adjusting for BMI at menarche z scores.

To evaluate the robustness of our results, we performed sensitivity analyses, including evaluating the temporal trends in time to regularity when further adjusted for age at menarche, using models that mutually adjusted for race and ethnicity and SES and using multinomial logistic models for the categorical time-to-regularity variable, with 2 years or less as the referent group. Analyses were conducted in Python, version 3.6 (Python Software Foundation) and R, version 4.1.2 (R Project for Statistical Computing). All statistical tests were 2-sided with 95% CIs. P < .05 was considered statistically significant.

Results

The Table shows the characteristics of the 71 341 participants. Among them, 2228 (3.1%) self-identified as Asian, 4918 (6.9%) as Hispanic, 3665 (5.1%) as non-Hispanic Black, 49 518 (69.4%) as non-Hispanic White, and 8461 (11.9%) as other or multiple races. A total of 21 561 (30.2%) had a high subjective SES level. The mean (SD) age at menarche was 12.2 (1.6) years, and 9174 (12.9%) had early menarche (aged <11 years). A total of 38 524 (62.2%) reached regularity within 2 years after menarche, whereas 6950 (11.2%) did not establish regularity. Characteristics of the 9865 participants with weight and height information at menarche are given in eTable 1 in Supplement 1. Compared with the full study population, these participants tend to have earlier birth years, be non-Hispanic White, and have high subjective SES.

Table. Characteristics of the 71 341 Apple Women’s Health Study Participants, Overall and by Birth Year Category^a.

Characteristic	Total (N = 71 341)	Birth year
Characteristic	Total (N = 71 341)	1950-1969 (n = 5223)	1970-1979 (n = 12 226)	1980-1989 (n = 22 086)	1990-1999 (n = 23 894)	2000-2005 (n = 7912)
Race and ethnicity
Asian	2228 (3.1)	86 (1.6)	311 (2.5)	668 (3.0)	908 (3.8)	255 (3.2)
Hispanic	4918 (6.9)	176 (3.4)	750 (6.1)	1511 (6.8)	1861 (7.8)	620 (7.8)
Non-Hispanic Black	3665 (5.1)	283 (5.4)	720 (5.9)	1194 (5.4)	1088 (4.6)	380 (4.8)
Non-Hispanic White	49 518 (69.4)	4131 (79.1)	8862 (72.5)	15 505 (70.2)	16 088 (67.3)	4932 (62.3)
Other or multiple races^b	8461 (11.9)	392 (7.5)	1245 (10.2)	2481 (11.2)	3057 (12.8)	1286 (16.3)
Geographic region
Northeast	11 300 (15.8)	898 (17.2)	1830 (15.0)	3408 (15.4)	3898 (16.3)	1266 (16.0)
Midwest	15 787 (22.1)	996 (19.1)	2444 (20.0)	4627 (20.9)	5680 (23.8)	2040 (25.8)
South	26 343 (36.9)	1851 (35.4)	4650 (38.0)	8239 (37.3)	8675 (36.3)	2928 (37.0)
West	17 527 (24.6)	1418 (27.1)	3208 (26.2)	5686 (25.7)	5549 (23.2)	1666 (21.0)
SES scale
Low (0-3)	18 131 (25.4)	658 (12.6)	2237 (18.3)	5242 (23.7)	7280 (30.5)	2714 (34.3)
Medium (4-5)	29 031 (40.7)	1768 (33.9)	4924 (40.3)	9231 (41.8)	10 017 (41.9)	3091 (39.1)
High (6-9)	21 561 (30.2)	2635 (50.4)	4726 (38.7)	6874 (31.1)	5667 (23.7)	1659 (21.0)
Age at menarche, mean (SD), y	12.2 (1.6)	12.5 (1.6)	12.4 (1.6)	12.2 (1.6)	12.1 (1.6)	11.9 (1.5)
Menarche
Early (age <11 y)	9174 (12.9)	449 (8.6)	1234 (10.1)	2826 (12.8)	3442 (14.4)	1223 (15.5)
Very early (age <9 y)	795 (1.1)	31 (0.6)	92 (0.8)	236 (1.1)	326 (1.4)	110 (1.4)
Late (age ≥16 y)	2447 (3.4)	286 (5.5)	498 (4.1)	850 (3.8)	676 (2.8)	137 (1.7)
Time to cycle regularity^c	61 932	4538 (7.3)	10 327 (16.7)	18 611 (30.0)	21 183 (34.2)	7273 (11.7)
≤2 y	38 524 (62.2)	3463 (76.3)	7254 (70.2)	11 818 (63.5)	11 914 (56.2)	4075 (56.0)
3-4 y	3980 (6.4)	262 (5.8)	609 (5.9)	1100 (5.9)	1427 (6.7)	582 (8.0)
>5 y	3613 (5.8)	266 (5.9)	766 (7.4)	1249 (6.7)	1149 (5.4)	183 (2.5)
Not yet regular	6950 (11.2)	153 (3.4)	559 (5.4)	1857 (10.0)	3006 (14.2)	1375 (18.9)
Regular after hormones	8865 (14.3)	394 (8.7)	1139 (11.0)	2587 (13.9)	3687 (17.4)	1058 (14.5)
Time to cycle regularity (among those who established cycle regularity at enrollment not due to hormone use), mean (SD), y^d (N = 46 117)	1.43 (1.5)	1.27 (1.4)	1.40 (1.5)	1.45 (1.5)	1.48 (1.5)	1.40 (1.3)

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Abbreviation: SES, socioeconomic status.

^{^a}

Data are presented as number (percentage) of participants unless otherwise indicated. Numbers may not add up to the total number or 100% due to missingness.

^{^b}

Other includes American Indian or Alaska Native, Middle Eastern or North African, Native Hawaiian or Pacific Islander, or none of these categories can fully describe the participant. Multiple races correspond to those who selected more than 1 race and ethnicity category.

^{^c}

Details of inclusion and exclusion of the 61 932 individuals who provided information on time to regularity are described in the eMethods in Supplement 1.

^{^d}

Among the 46 117 participants who reported reaching cycle regularity at enrollment (not due to hormone use), we assigned the following values to each category of response: 0.5 years for those who reached cycle regularity at less than 1 year, 1.5 years for those who reached cycle regularity at 1 to 2 years, 3.5 years for those who reached cycle regularity at 3 to 4 years, and 5.5 years for those who reached cycle regularity at more than 5 years.

Figure 1 shows the temporal trends of age at menarche and time to regularity. The mean (SD) age at menarche decreased from 12.5 (1.6) to 11.9 (1.5) years comparing those born in 1950 to 1969 vs 2000 to 2005 (P < .001 for trend) (Figure 1A and Table). The number of individuals experiencing early menarche increased from 449 (8.6%) to 1223 (15.5%), the number of individuals experiencing very early menarche increased from 31 (0.6%) to 110 (1.4%) for very early menarche, and the number of individuals experiencing late menarche decreased from 286 (5.5%) to 137 (1.7%) (P < .001 for trend) (Figure 1B and Table). From the 1950 to 1969 birth years to the 2000 to 2005 birth years, the number reaching regularity within 2 years decreased from 3463 (76.3%) to 4075 (56.0%), and the number not yet in regular cycles increased from 153 (3.4%) to 1375 (18.9%) (P < .001 for trend) (Figure 1C and Table). The mean (SD) time to regularity among those who spontaneously established regularity increased from 1.27 to 1.40 years (P < .001 for trend) (Table). eFigure 3 in Supplement 1 shows lower percentages of time to regularity less than 2 years among those with either early or late menarche (inverse U-shaped association). Further adjusting for age at menarche resulted in similar distributions of time to regularity (eFigure 4 in Supplement 1).

The temporal trends stratified by race and ethnicity are presented in Figure 2 (estimates in eTable 2 in Supplement 1). Participants who were Asian, Hispanic, non-Hispanic Black, or of other or multiple races or ethnicities had consistently earlier mean age at menarche than non-Hispanic White participants. All racial and ethnic groups had temporal trends toward earlier menarche (P < .001 for trend), but when compared with non-Hispanic White participants, the magnitude of decrease in mean age at menarche across birth year categories was larger among those self-identified as non-Hispanic Black, Asian, and other or multiple races or ethnicities (P = .003 for interaction). All racial and ethnic groups showed a decreasing proportion of time to regularity within 2 years and an increased proportion of not establishing regularity (P < .001 for trend) (eFigure 5 and eTable 2 in Supplement 1), although there was no interaction between race and ethnicity and birth year. The temporal trends stratified by SES are presented in Figure 3 (estimates in eTable 3 in Supplement 1). Compared with those with high SES, those with low SES had earlier menarche, lower proportion of time to regularity within 2 years (eFigure 6 in Supplement 2), and larger magnitude of decrease in age at menarche. The heterogeneity by race and ethnicity for the trend toward earlier menarche remained when further adjusted for SES and vice versa (eTable 4 in Supplement 1). There was no interaction between geographic region and birth year when adjusting for race and ethnicity (eTable 5 in Supplement 1).

Figure 3. — All trends were statistically significant at P < .05. Error bars indicate 95% CIs.

Overall, using multinomial logistic regressions yielded P-for-trend values of <.001 for each category of time to regularity compared with ≤2 years. Among the 9865 participants who provided weight and height at menarche, the BMI z score, percentile, and prevalence of obesity increased across birth year categories (eFigure 7 and eTable 1 in Supplement 1). An exploratory mediation analysis showed that the proportion of the temporal trends toward earlier menarche mediated by BMI z score at menarche was 46% (95% CI, 35%-61%) (Figure 4). When stratified by BMI categories at menarche, the healthy and underweight group still showed a trend toward earlier menarche (eTable 6 in Supplement 1). When adjusted for BMI z scores, a trend toward earlier menarche remained (eTable 6 in Supplement 1), as did heterogeneity by race and ethnicity (eFigure 8 in Supplement 1). There was no evidence of significant mediation by BMI at menarche for the temporal trends in time to regularity (eTable 7 in Supplement 1).

Figure 4. — The exploratory mediation analysis estimated that 46% (95% CI, 35%-61%) of the temporal trend in age at menarche was explained by BMI at menarche. Total effect represents the overall change in age at menarche per 10-year lapse in birth year, direct effect represents the proportion of this change that is independent of BMI z score at menarche, and indirect effect represents the proportion of this change mediated through BMI z score at menarche. Error bars indicate 95% CIs.

Discussion

This cohort study of 71 341 participants born between 1950 and 2005 in the US found temporal trends toward earlier menarche (earlier mean age, higher percentage of early menarche, and lower percentage of late menarche) and longer time from menarche to cycle regularity (lower percentage of time to regularity within 2 years, higher percentage of time to regularity within 3-4 years, and higher percentage of not establishing regularity). These trends remained across all sociodemographic groups but were stronger among certain non-White (specifically, Asian, non-Hispanic Black, and other or multiple races or ethnicities) and low SES groups. In an exploratory analysis, BMI at menarche may explain a significantly large proportion of the temporal trends toward earlier menarche.

Our findings of a temporal trend toward earlier menarche are consistent with some US-based studies, with similar magnitude of changes.^12,13,16 Other studies indicated that age at menarche stabilized during the past 50 years, whereas evidence that the median decreased by 2.5 to 4 months in the past 25 years remains,^20,57 consistent with a change from 12.2 to 11.9 years of age for those born in 1980 to 1989 vs 2000 to 2005 in our study. Despite a relatively small magnitude of change in mean age, our study is among the first to show that the percentages of early and very early menarche have also increased by almost 2-fold across birth years from 1950 to 2005, raising concerns that more individuals may be vulnerable to adverse health outcomes related to early menarche.^3,4,5,6 Late menarche has decreased, which may have other health implications, such as the decreasing rates of fractures.^58,59

We found that non-Hispanic Black participants had consistently earlier mean age at menarche than White participants, also similar to prior US-based studies.^{13,20,21,22,23,24,25,26} We also found that non-Hispanic Black participants had a larger magnitude of change toward earlier menarche across birth year categories compared with non-Hispanic White participants. Similarly, we found other groups (Asian and other or multiple races), rarely evaluated in previous studies of menarche, also had consistently earlier mean ages and larger magnitudes of change toward earlier menarche than non-Hispanic White participants. We found similar patterns for self-rated low SES (compared with high SES). The factors driving this widening gap of disparities remain to be explored; transethnic genome-wide association studies indicated that these disparities are unlikely to be attributed to genetic variations, suggesting they may be driven by other environmental or contextual factors that may, through racism, impact different pathways, leading to earlier menarche.⁶⁰

Onset of menarche is closely related to attainment of adequate body fat via pathways such as increased insulin-like growth factor 1 and leptin that stimulate gonadotropin-releasing hormone.⁶¹ In our exploratory analysis, we found that BMI at menarche may explain 46% of the temporal trends in menarche. This finding suggests that childhood obesity, a risk factor for earlier puberty,^{27,28,29,30,62} which has increased in the US,^32,33 could be a contributing factor to the trend toward earlier menarche. However, the remaining 54% remain unclear. Our exploratory analysis also showed that BMI may have contributed to earlier menarche among non-Hispanic White, Black, and other or multiple races, whereas the trend among Asian and Hispanic individuals remains to be further explored. Previous studies also showed that the biggest decrease in age at menarche occurred before the obesity epidemic in the US,³⁴ suggesting that other factors need to be explored to explain these trends and disparities, including environmental factors (eg, endocrine-disrupting chemicals, metals, or air pollutants could impact pubertal timing,^63,64,65 with disproportionally higher exposure among certain racial and ethnic minority groups),^66,67,68 dietary patterns (eg, sugar intake via insulin-mediated pathways),^69,70,71 psychosocial stress,⁷² and adverse childhood experiences.⁷³

Our findings of temporal trends toward longer time to regularity and higher proportion of never establishing regularity in the US have not been previously reported. Because longer time to regularity has been associated with adverse outcomes,^39,40,41,42 it may serve as an early-life vital sign. These temporal trends may be driven by longer time to maturation of the reproductive axis (eg, impacted by endocrine disruptors)⁷⁴ or increasing ovulation disorders⁷⁵ that impact cycle regularity. Although earlier studies suggest that regular menstruation should be established within 1 to 2 years after menarche,^37,38,76,77 evidence remains limited on whether delays beyond 2 years warrant clinical or lifestyle intervention.⁷⁸ In our study, the mean time to regularity among those who spontaneously established regularity was 1.2 to 1.5 years within the 2-year window. However, the proportions taking 3 to 4 years or never establishing regularity were increasing. A French cohort born between 1935 and 1950 showed a decrease from 64% to 53% for time to regularity within 1 year, but data are limited for the US.⁴⁵ We also found differences by race and ethnicity (eg, Hispanic individuals reported a higher rate of not establishing regularity compared with their non-Hispanic White peers, consistent with a study⁷⁹ showing that Hispanic individuals having the highest risk of cycle irregularity in adulthood). Our findings suggest the necessity of further studies on the postmenarche years and the need for early intervention during relevant time windows. Continued research on the association of BMI and other factors on reproductive development is needed, and findings should be conveyed to health professionals.

Strengths and Limitations

This study has several unique strengths. First, a large study size of 71 341 participants in a heterogeneous population allowed for sufficient statistical power to detect racial and ethnic differences, even for groups that were previously understudied. Second, we evaluated temporal trends in the percentages of early or late menarche in addition to mean age. Third, our study is the first, to our knowledge, to evaluate and report a temporal trend toward longer time to regularity, suggesting future research directions on this understudied early-life marker of menstrual health. Fourth, our study is the first, to our knowledge, to use digital observational cohort data evaluating BMI at menarche as a potential contributor to the observed temporal trends.

Our study also has limitations. First, the retrospective self-report may induce recall bias and misclassification, likely differential across birth year categories. However, previous validation studies^80,81,82 showed moderate to high correlations between recalled and original age and body size at menarche. Second, BMI at menarche was only available among a subset of participants with demographic distributions different from the full study population. Third, data are limited for additional early-life factors that may contribute to these trends. Fourth, our results may not be generalizable to all US individuals who menstruate or to other populations. Potential selection bias may arise due to self-selection into the study that may be impacted by sociodemographic characteristics.

Conclusions

In this US cohort study of 71 341 individuals born between 1950 and 2005, we observed temporal trends toward earlier menarche and longer time to regularity. These trends appeared across all sociodemographic groups but were stronger among certain racial and ethnic groups (Asian, non-Hispanic Black, or other and multiple races or ethnicities) and low subjective SES groups. Body mass index at menarche mediated a significantly large proportion of the trends toward earlier menarche. Further awareness among health care practitioners and researchers is needed to understand the reasons for these trends and their health implications.

Supplement 1.

eMethods. Detailed Exclusion of Individuals With Potentially Inaccurate Time to Regularity Information

eFigure 1. Conceptual Model of the Research Question and Potential Mechanisms

eFigure 2. Flowchart of Participants in This Study

eFigure 3. Percentage of Participants in Each Time to Cycle Regularity by Age at Menarche

eFigure 4. Percentage of Participants With Predicted Time to Cycle Regularity Across Birth Year Categories, With Age at Menarche Fixed at the Mean (12.2 Years of Age)

eFigure 5. Temporal Trends of Time to Cycle Regularity by Birth Year Category, Stratified by Race/Ethnicity

eFigure 6. Temporal Trends of Time to Cycle Regularity by Birth Year Category, Stratified by Socioeconomic Status (SES)

eFigure 7. Temporal Trends of BMI Across Age Categories, Based on BMI z Scores and Percentiles Using the CDC Growth Chart (N = 9865)

eFigure 8. Predicted Mean Age at Menarche Across Birth Years by Race/Ethnicity, When Adjusted for BMI at Menarche

eTable 1. Characteristics of the Subset of 9865 AWHS Participants Who Provided Self-Recalled Weight and Height at Menarche, Overall and by Birth Year Category

eTable 2. Age at Menarche and Time to Cycle Regularity Measures by Birth Year Groups, Stratified by Race/Ethnicity

eTable 3. Age at Menarche and Time to Cycle Regularity Measures by Birth Year Groups, Stratified by Socioeconomic Status

eTable 4. Effect Estimates for the Temporal Trend in Age at Menarche, Mutually Adjusted for Race/Ethnicity and Socioeconomic Status

eTable 5. Age at Menarche and Time to Cycle Regularity Measures by Birth Year Groups, Stratified by Geographical Region

eTable 6. Effect Estimates for the Temporal Trend in Age at Menarche and Time to Regularity, Accounting for BMI at Menarche

eTable 7. Causal Mediation Analysis for the Temporal Trends in Time to Regularity Measures Among 8752 Participants With BMI z-Score at Menarche (Mediator)

jamanetwopen-e2412854-s001.pdf^{(1.3MB, pdf)}

Supplement 2.

Data Sharing Statement

jamanetwopen-e2412854-s002.pdf^{(15.2KB, pdf)}

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