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Design and methods of the Apple Women’s Health Study: a digital longitudinal cohort study

Open AccessPublished:October 02, 2021DOI:https://doi.org/10.1016/j.ajog.2021.09.041

      Background

      Prospective longitudinal cohorts assessing women’s health and gynecologic conditions have historically been limited.

      Objective

      The Apple Women’s Health Study was designed to gain a deeper understanding of the relationship among menstrual cycles, health, and behavior. This paper describes the design and methods of the ongoing Apple Women’s Health Study and provides the demographic characteristics of the first 10,000 participants.

      Study Design

      This was a mobile-application-based longitudinal cohort study involving survey and sensor-based data. We collected the data from 10,000 participants who responded to the demographics survey on enrollment between November 14, 2019 and May 20, 2020. The participants were asked to complete a monthly follow-up through November 2020. The eligibility included installed Apple Research app on their iPhone with iOS version 13.2 or later, were living in the United States, being of age greater than 18 years (19 in Alabama and Nebraska, 21 years old in Puerto Rico), were comfortable in communicating in written and spoken English, were the sole user of an iCloud account or iPhone, and were willing to provide consent to participate in the study.

      Results

      The mean age at enrollment was 33.6 years old (±standard deviation, 10.3). The race and ethnicity was representative of the US population (69% White and Non-Hispanic [6910/10,000]), whereas 51% (5089/10,000) had a college education or above. The participant geographic distribution included all the US states and Puerto Rico. Seventy-two percent (7223/10,000) reported the use of an Apple Watch, and 24.4% (2438/10,000) consented to sensor-based data collection. For this cohort, 38% (3490/9238) did not respond to the Monthly Survey: Menstrual Update after enrollment. At the 6-month follow-up, there was a 35% (3099/8972) response rate to the Monthly Survey: Menstrual Update. 82.7% (8266/10,000) of the initial cohort and 95.1% (2948/3099) of the participants who responded to month 6 of the Monthly Survey: Menstrual Update tracked at least 1 menstrual cycle via HealthKit. The participants tracked their menstrual bleeding days for an average of 4.44 (25%–75%; range, 3–6) calendar months during the study period. Non-White participants were slightly more likely to drop out than White participants; those remaining at 6 months were otherwise similar in demographic characteristics to the original enrollment group.

      Conclusion

      The first 10,000 participants of the Apple Women’s Health Study were recruited via the Research app and were diverse in race and ethnicity, educational attainment, and economic status, despite all using an Apple iPhone. Future studies within this cohort incorporating this high-dimensional data may facilitate discovery in women’s health in exposure outcome relationships and population-level trends among iPhone users. Retention efforts centered around education, communication, and engagement will be utilized to improve the survey response rates, such as the study update feature.

      Key words

      Introduction

      Multiple factors influence the menstrual cycle length, duration of flow, and cyclicity. Common factors include stress, nutrition and body weight, physical activity, and combination lifestyle factors. Furthermore, menstrual cycle function is an indicator of health and longevity.
      • Wang Y.X.
      • Arvizu M.
      • Rich-Edwards J.W.
      • et al.
      Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study.
      For example, bone density is built and maintained in the presence of cyclic ovarian function.
      • Seifert-Klauss V.
      • Prior J.C.
      Progesterone and bone: actions promoting bone health in women.
      Fertility, terminal breast differentiation, and aspects of cognition and memory are also influenced by menstrual status and function.
      • Wesselink A.K.
      • Wise L.A.
      • Hatch E.E.
      • et al.
      Menstrual cycle characteristics and fecundability in a North American preconception cohort.
      • Arendt L.M.
      • Kuperwasser C.
      Form and function: how estrogen and progesterone regulate the mammary epithelial hierarchy.
      • Sundström Poromaa I.
      • Gingnell M.
      Menstrual cycle influence on cognitive function and emotion processing-from a reproductive perspective.
      The endocrine pathways involved in menstrual cycle physiology include the hypothalamic-pituitary-ovarian axis and a healthy functioning of the thyroid and adrenal glands; the anatomic structures necessary include the uterus, endometrium, and ovaries.

      Why was this study conducted?

      The Apple Women’s Health Study aims to advance the understanding of menstrual cycles and their relationship to health conditions such as infertility, menopause, and health across the lifespan. This paper describes the study design and methods, the demographics of the first 10,000 enrollees, and the study retention rates measured by the response to the Monthly Survey: Menstrual Update and menstrual tracking in HealthKit.

      Key findings

      The racial and ethnic distribution of the enrolled cohort was similar to that of the US population. Non-White participants were slightly more likely to drop out of the study than White participants over 6 months of follow-up. Notably, 38% (3490/9238 eligible participants) of the cohort did not respond to the Monthly Survey: Menstrual Update after enrollment. Thirty-five percent (3099/8972) of women who were eligible responded to the 6-month Monthly Survey: Menstrual Update. The participants tracked their menstrual bleeding days for an average of 4.44 (25%–75%; range, 3–6) calendar months during the 6 month follow-up period. In addition, 82.7% (8266/10,000) of the cohort tracked at least one menstrual cycle via HealthKit.

      What does this add to what is known?

      This is the first longitudinal research study of this scale and scope to use a mobile application to collect survey and sensor-based data on menstrual cycles and women’s health.
      Furthermore, irregular patterns or the absence of menstrual cycles can serve as indicators of underlying health problems. The presence of irregular menstrual cycles may indicate hormonal disturbances, including thyroid disorders, prolactinomas, systemic illness (including cancers), anatomic pathology such as uterine fibroids, polyps, or adenomyosis; it has also has been linked to an increase in all-cause mortality.
      • Wang Y.X.
      • Arvizu M.
      • Rich-Edwards J.W.
      • et al.
      Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study.
      Abnormalities in the bleeding length and amount affect up to 30% of those who menstruate.
      • Liu Z.
      • Doan Q.V.
      • Blumenthal P.
      • Dubois R.W.
      A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding.
      The existing data on the menstrual cycle characteristics, including the normal distributions of the cycle length and bleeding days are based on prior and well-designed but demographically-limited cohorts.
      • Treloar A.E.
      • Boynton R.E.
      • Behn B.G.
      • Brown B.W.
      Variation of the human menstrual cycle through reproductive life.
      ,
      • Bull J.R.
      • Rowland S.P.
      • Scherwitzl E.B.
      • Scherwitzl R.
      • Danielsson K.G.
      • Harper J.
      Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles.
      Little is known about how these conditions vary across subpopulations or how they relate to future health conditions. An understanding of population-based variation in menstrual cycle characteristics is lacking.
      The objectives of this study are to (1) advance the understanding of the menstrual cycle, including how it relates to exercise, sleep, environmental, behavioral, and other physiological processes, and (2) inform screening and risk assessment for gynecologic health conditions using menstrual cycle, reproductive, health, and sensor data. We present here the design of the Apple Women’s Health Study (AWHS) and the characteristics of the first 10,000 participants enrolled in the study, including their follow-up after 6 months of participation.

      Materials and Methods

      Survey design

      The survey questions for the AWHS were derived from previous, similarly large longitudinal studies on women’s health. These surveys included the National Health and Nutrition Examination Survey developed by the Centers for Disease Control and Prevention, the Perceived Stress Scale, All of Us study—a large research program sponsored by the National Institutes of Health, Nurses’ Health Study 2, and the Ovulation and Menstruation Health Study.
      Harvard University
      The ovulation and menstruation health (OM) pilot study survey instrument.
      • Denny J.C.
      • Rutter J.L.
      • et al.
      All of Us Research Program Investigators
      The “All of Us” Research Program.
      • Cohen S.
      • Kamarck T.
      • Mermelstein R.
      A global measure of perceived stress.
      • Bao Y.
      • Bertoia M.L.
      • Lenart E.B.
      • et al.
      Origin, methods, and evolution of the three nurses’ health studies.
      The questions were modified for a mobile user experience and were standardized across 2 other research studies also housed in the Apple Research app. For menstrual-cycle-specific questions, the exposures hypothesized to affect the hypothalamic-pituitary-ovarian axis in a cycle-specific way were included. Once the research teams had completed the initial drafting of the baseline survey, it was reviewed by Apple, Inc. to conform to their design standards across the 3 studies.
      The interface for the Research app was designed to be intuitive and simple. The research profile completed at enrollment is common to all 3 studies and includes the initial demographic survey. To implement the intuitive and simple survey concept, the baseline women’s health study survey was split across the initial year of the study to distribute the participant burden over time as noted in Supplemental Table 1. The health history survey was given at month 4, and the reproductive history was given at month 10. The Monthly Survey: Menstrual Update (MSMU) was initiated after the first completed month of enrollment and then monthly thereafter. The time to survey completion was estimated in 5-minute increments on the basis of usability testing by Apple, Inc. The response time for the enrollment processes (screening, eligibility, demographics) was estimated to be 25 minutes. The expected response times as listed in the Research app for monthly surveys such as the MSMU, Pregnancy Update, and Lactation Update were 5 minutes each.

      Apple research app platform

      The study is hosted within the Apple Research app (available on the Apple App Store), which allows a participant to find, enroll, and participate in Apple-supported, health-related research studies.
      The Research app was designed with 3 studies for a simultaneous launch, where the demographics and certain questions were standardized across the studies. The other 2 studies were the Apple Heart and Movement Study and the Apple Hearing Study.
      Brigham and Women’s Hospital
      Apple heart and movement study.
      ,
      University of Michigan
      Michigan public health apple hearing study.
      All the shared data are stored securely in a system within Apple that is designed to meet the technical safeguard requirements of the Health Insurance Portability and Accountability Act. Access to any contact information or other identifying data that the participants provide through the Research app is restricted to the Principal Investigator staff.

      Study population description

      The AWHS is a longitudinal cohort study of persons who have menstruated at least once in their life. The study began enrolling on November 14, 2019. The planned duration of this study is 10 years, that is, until November 2029, with a potential for extension or additional long-term follow-up. The goal is to recruit 500,000 participants over 10 years. The study was approved by the Advarra Central Institutional Review Board (number PRO00037562) and registered to ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT04196595).

      Eligibility, screening, and consent

      Individuals were eligible for enrollment if they had installed the Apple Research app on their iPhone 6s or later with iOS version 13.2 or later, were living in the United States, had menstruated at least once, were at least 18 years old (at least 19 years old in Alabama and Nebraska, at least 21 years old in Puerto Rico), were comfortable communicating in written and spoken English, were the sole users of their iCloud account or iPhone, and were willing to provide informed consent to participate in the study (Supplemental Table 2).
      After self-report and self-verification of eligibility, the participants followed the steps for enrollment as delivered by the Research app. They were instructed to read the informed consent form (ICF), which is included in Appendix A, and provide an electronic signature if they consented to participate; a part of this process is shown in Supplemental Figure 1. The ICF covers key aspects, including the study objectives, study procedures (surveys and demographic data), the types of study data that require additional consent (Health app Data, Research Sensor and Usage Data, Medical Conditions and History, and other related information such as clinically sourced data from Health app). The ICF included the participation risks (theoretical potential for breach of confidentiality) and benefits (no incentives or compensation) and the option for study withdrawal at any time for any reason. The current informed consent document is available in the supplemental documents. The participants who were enrolling were informed that they will be reconsented every 2 years.
      The individuals who downloaded the Research app, enrolled in AWHS, and met the inclusion criteria proceeded to study participation. They were then provided the survey tasks for completion, starting with the demographics section.
      Incentive: There was no compensation for study participation.

      Recruitment and marketing

      On September 10, 2019, the Apple Research app was announced publicly. The Research app houses the following 3 research studies: the AWHS, the Apple Heart and Movement Study, and the Apple Hearing Study. The AWHS was launched on November 14, 2019. Institutional review board-approved recruitment efforts included a Harvard T.H. Chan School of Public Health study website,
      • Harvard T.H.
      Chan School of Public Health. Apple women’s health study. 2019.
      which was made public and includes frequently asked questions and background information regarding the study. Social media accounts were created on Twitter and Instagram (March 10, 2020), YouTube (March 12, 2020), Facebook (April 13, 2020) and LinkedIn (August 7, 2020) to post recruitment materials inviting potential participants to join the study, with new posts added approximately 1 to 3 times per week. In addition, media events included a podcast,
      • Mahalingaiah S.
      • Onnela J.
      • Levin D.
      media articles, and press interviews after study launch.

      Data Collection and Methods

      Survey data

      On enrollment, the participants who onboarded with the AWHS responded to the Research Profile Survey within the Research app and to the Demographic Survey; the data included the year of birth, state of residence, race and ethnicity, marital status, employment status, gender identity, and sex assigned at birth (Supplemental Figure 1 and Supplemental Table 3). The participants were asked to respond to a baseline Menstrual Status Survey at enrollment (Supplemental Table 3). The response categories for the baseline Menstrual Status Survey included currently menstruating, lactating, menopausal, and pregnant. For the remaining months within the first year of follow-up, the participants were given monthly surveys to provide a menstrual status update, pregnancy update, and/or a lactation update. Health surveys were given quarterly to assess the changes in sleep, physical activity, nutrition, stress, alcohol use, tobacco use, electronic nicotine use, and marijuana use within the previous calendar month. Reproductive history was assessed at the tenth month (Supplemental Table 1). As detailed in Supplemental Table 3, a more extensive health overview (including questions on nutrition, sleep, stress, alcohol use, tobacco use, electronic nicotine use, marijuana use, second-hand smoke, and overall self-rated health) and medical history (gynecologic, endocrine, heart, blood, digestive, kidney, lung, musculoskeletal, cancer, brain and nervous system, mental health and infectious disease conditions, surgeries, and family medical history) are given annually, initially at month 4 and month 7, respectively (Figure 1). A summary of the surveys, topics, sources, number questions is shown in Table 4.
      Figure thumbnail gr1
      Figure 1Timeline of data collection
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Table 4Summary of surveys, topics, number and source of questions
      SurveysTopicsNumber of questionsSource of questions
      ProfileName, date of birth, email, phone number, country, and state.7Study-specific
      DemographicsRace and ethnicity, social economic status, zip code, body measurements, sex, gender identity11Study-specific, All of Us study (NIH), Behavioral Risk Factor Surveillance System, Centers for Disease Control and Prevention, US Census Current Population Survey, MacArthur Scale of Subjective Social Status
      Menstrual status surveyMenstrual status, tracking cycles, tracking pregnancy, tracking health4Study-specific
      Monthly surveyMenstrual updateMenstrual status, monthly tracking check-in, hormone use, health factors, pregnancy planning6Study-specific
      Pregnancy updatePregnancy update, due date, pregnancy details, lactation.10Study-specific
      Lactation updateLactation update1Study-specific
      Annual health surveyPhysical activity, nutrition, sleep habits, stress level, alcohol use, tobacco use, electronic nicotine use, marijuana use, second-hand smoke, overall health30Study-specific, National Health and Nutrition Examination Survey, Centers for Disease Control and Prevention, Perceived Stress Scale, All of Us study (NIH)
      Quarterly health surveyHealth update (sleep, nutrition, physical activity, stress, alcohol use, nicotine use)6Study-specific
      Annual medical historyMenstrual status; gynecologic, endocrine, heart, blood, digestive, kidney, lung, musculoskeletal, mental health and brain and nervous system conditions; cancer, infectious diseases, surgeries, gynecologic surgeries, gender and sexual orientation, family medical history, medical forms24Study-specific, Derived from OM Study, and Brief Health Literacy Screening Tool
      Reproductive historyParticipant’s birth details, early menstrual cycles, hormone use, hormone use details, pregnancy history18Study-specific and Derived from OM Study
      Adapted from Harvard University,
      Harvard University
      The ovulation and menstruation health (OM) pilot study survey instrument.
      Denny et al,
      • Denny J.C.
      • Rutter J.L.
      • et al.
      All of Us Research Program Investigators
      The “All of Us” Research Program.
      Cohen et al,
      • Cohen S.
      • Kamarck T.
      • Mermelstein R.
      A global measure of perceived stress.
      Adler et al,
      Stanford University
      MacArthur Scale of Subjective Social Status – Adult Version.
      Centers for Disease Control and Prevention,
      Centers for Disease Control and Prevention (CDC)
      Behavioral Risk Factor Surveillance System.
      Chew et al,
      • Chew L.D.
      • Bradley K.A.
      • Boyko E.J.
      Brief questions to identify patients with inadequate health literacy.
      Centers for Disease Control and Prevention.
      Centers for Disease Control and Prevention
      NHANES 2017-2018 Questionnaire Instruments.
      NIH, National Institutes of Health.
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.

      Monthly surveys and timing

      The participants receive monthly surveys on the basis of the status reported in the baseline Menstrual Status Survey. The monthly surveys include the MSMU, the Lactation Update, and the Pregnancy Update.
      The MSMU included a total of 6 questions to ascertain the status in the last calendar month regarding the accuracy of tracked period days, status update for pregnancy, lactation, and menopause, current hormone use, reason for hormone use, and monthly update of health factors (change in exercise or weight, significant sleep disruption, stress, illness, and hospitalization or surgery). The purpose of the MSMU is to give additional context for the logged menstrual bleeding days and associated symptom logging in HealthKit. The MSMU is given to those who have previously indicated the capacity to currently menstruate on the baseline survey; it is not given to those who have indicated current pregnancy, menopause, or to those who are no longer menstruating. The MSMU is delivered within the Research app on the first Sunday of every month, starting in month 2 of participation, at least 4 weeks after enrollment. The survey is available for 1 week after delivery and then expires and is no longer available to the participant. Programming logic was applied in the analysis phase as follows: the monthly surveys were counted when the participants responded at least 4 weeks after enrollment. Any monthly survey with participant responses before 4 weeks of enrollment was excluded from this count. For this analysis, the respondents were censored at pregnancy and menopause.

      Research sensor and usage data

      The participants consented to the collection of data and derived metrics that were retrieved from certain iPhone sensors and from a paired optional Apple Watch. These include frequently visited locations with an anonymized identifier, watch-on-wrist state, and Optical Sensor (including accelerometer and heart rate) as summarized in Supplemental Table 4.

      HealthKit data

      HealthKit provides a central repository for health and fitness data on iPhones and Apple Watches. With the user’s permission, specific apps communicate with HealthKit to access and share these data while maintaining the user’s privacy and control. HealthKit stores the data merged from multiple sources and contains data types such as menstrual bleeding days, symptoms and associated user recorded features (cervical mucous changes, temperature changes, sexual activity), heart rate, sleep analysis, and clinical records (lab tests, diagnoses) from clinical interfaces. A bleeding event can be tracked either via Cycle Tracking or by any third-party menstrual tracking application that has been permitted to write to HealthKit by the participant. This allows for ongoing collection of menstrual characteristics and symptoms and reduces missing data owing to lack of direct participant input. For this descriptive analysis, we evaluate the months of contributed cycle tracking data where a logged bleeding event in the HealthKit was attributed to the calendar month of that bleeding event.

      Participation

      This study was designed to allow participation through the following ways: (1) response to survey questions; (2) contribution of HealthKit data, which include logged menstrual cycles; and (3) contribution of SensorKit data, which include sensor-based data streams from SensorKit.
      In general, a participant is considered to be actively participating by contributing data from any of these sources.
      Given that one of the main goals of this study is to understand menstrual health and its risk factors, we report on (1) the response rates to the MSMU, and (2) tracked bleeding events in HealthKit as measures of ongoing participation for this descriptive analysis.
      Nonparticipation in the MSMU is defined as no response to the monthly survey. Invalid responses are defined as those responses that seem biologically unlikely, such as a concurrent state of menopause and pregnancy. We defined completion rate (% completed) as the proportion of individuals who have completed the survey among those eligible for the baseline Menstrual Status Survey or MSMU.

      Defining demographic variables

      Race and ethnicity

      We utilized the same question that was used to determine the race and ethnicity from the NIH-sponsored All of Us study, which asks, “Which categories describe you? Select all that apply: American Indian or Alaska Native [subchoices: American Indian, Alaska Native, Center or South American Indian, none of these fully describe me, I prefer not to answer]; Asian [subchoices: Asian Indian, Cambodian, Chinese, Filipino, Hmong, Japanese, Korean, Pakistani, Vietnamese, none of these fully describe me, I prefer not to answer]; Black, African American, or African [subchoices: African American, Barbadian, Caribbean, Ethiopian, Ghanaian, Haitian, Jamaican, Liberian, Nigerian, Somali, South African, none of these fully describe me, I prefer not to answer]; Hispanic, Latino, or Spanish [subchoices: Colombian, Cuban, Dominican, Ecuadorian, Honduran, Mexican or Mexican American, Puerto Rican, Salvadoran, Spanish, none of these fully describe me, I prefer not to answer]; Middle Eastern or North African [subchoices: Afghan, Algerian, Egyptian, Iranian, Iraqi, Israeli, Lebanese, Moroccan, Syrian, Tunisian, none of these fully describe me, I prefer not to answer]; Native Hawaiian or other Pacific Islander [subchoices: Chamorro, Chuukese, Fijian, Marshallese, Native Hawaiian, Palauan, Samoan, Tahitian, Tongan, none of these fully describe me, I prefer not to answer]; White [subchoices: Dutch, English, European (not listed), French, German, Irish, Italian, Norwegian, Polish, Scottish, Spanish, none of these fully describe me, I prefer not to answer]; none of these fully describe me; I prefer not to answer.” In field testing of the 2 questions typically used to separately determine the race and ethnicity, the All of Us study found that the focus group participants found it burdensome to have 2 questions. The All of Us study, where our race and ethnicity question is sourced from, uses a single question, with the response of “select all that apply” to determine the race and ethnicity. We have classified the responses into traditional reporting of race and ethnicity of the following categories: White, non-hispanic; Hispanic, Latina, Spanish and/or other Hispanic; Black or African American or African; Asian; Other; >1 race or ethnicity, in nonrestrictive categories.
      • Coughlin S.S.
      • Chen J.
      • Cortes J.E.
      Health care access and utilization among adult cancer survivors: results from the National Institutes of Health “All of Us” Research Program.

      MacArthur social status scale and socioeconomic status

      We utilized the MacArthur Scale of Subjective Social Status, which asks, “Think of this ladder as representing where people stand in the country you live in. At the top of the ladder are the people who are the best off – those who have the most money, the most education, and the most respected jobs. At the bottom are the people who are the worst off – those who have the least money, least education, the least respected jobs, or no job. The higher up you are on this ladder, the closer you are to the people at the very top; the lower you are, the closer you are to the people at the very bottom. Where would you place yourself on this ladder? Please select where you think you stand at this time in your life relative to other people around you. Ladder 0 (worst off) to 10 (best off).” The scale has been noted to correlate with health status across the lifespan.
      • Adler N.
      • Singh-Manoux A.
      • Schwartz J.
      • Stewart J.
      • Matthews K.
      • Marmot M.G.
      Social status and health: a comparison of British civil servants in Whitehall-II with European- and African-Americans in CARDIA.
      ,
      Stanford University
      MacArthur Scale of Subjective Social Status – Adult Version.
      Notably, the MacArthur Scale is correlated with but is not the same as objective socioeconomic status (SES).
      • Tan J.J.X.
      • Kraus M.W.
      • Carpenter N.C.
      • Adler N.E.
      The association between objective and subjective socioeconomic status and subjective well-being: a meta-analytic review.
      One main benefit of the MacArthur Scale is that it may be more applicable as a marker of subjective social status than using measures of objective SES in non-White populations.
      • Adler N.
      • Singh-Manoux A.
      • Schwartz J.
      • Stewart J.
      • Matthews K.
      • Marmot M.G.
      Social status and health: a comparison of British civil servants in Whitehall-II with European- and African-Americans in CARDIA.
      We categorized the responses into: 0 to 3 corresponding to low, 4 to 5 corresponding to middle, and 6 to 9 corresponding to high. There are no established categorizations for this variable. We refer to this metric as the SES.
      The study population described in this paper was enrolled from November 14, 2019 until May 20, 2020, and we allowed at least 6 months of follow-up for all the women enrolled during this time.

      Planned statistical analyses

      Statistical analyses are planned for the following 3 categories: (1) longitudinal analysis of survey data, (2) longitudinal analysis of passively collected smartphone and watch data, and (3) longitudinal analysis of associations between the survey data and passively collected data. In each category, we will perform exploratory descriptive analyses and formulate more specific hypothesis-driven models.
      For all 3 types of longitudinal analyses, we will use longitudinal extensions of regression methods, such as linear and generalized linear mixed models,
      • Fitzmaurice G.M.
      • Laird N.M.
      • Ware J.H.
      Applied longitudinal analysis.
      statistical learning techniques for high-dimensional data,
      • Hastie T.
      • Silverman B.
      The elements of statistical learning.
      and functional data analysis methods.
      • Ramsay J.
      • Silverman B.
      Functional data analysis.
      For the longitudinal analysis of the survey data, we will quantify the associations among both participant characteristics and risk factors and the menstrual cycle length, and how these associations vary across the age range of the study population. For the longitudinal analysis of passive data, we will perform individual-level analyses to identify the possible change points in behaviors over time and how they relate to subsequent health outcomes. For the longitudinal analysis of passive and survey data, the predictors will initially be the daily summary statistics derived from passively collected data and the outcomes of interest will consist of all the items on which survey data are available.

      Study statistical power

      We estimated the power to detect meaningful differences in (1) the mean menstrual cycle length and (2) the prevalence of health conditions of interest. We estimated loss to follow-up (20%) and incomplete survey response (90%–95%) over the course of 12 menstrual cycles. To calculate a conservative power estimate, we estimated a high incomplete survey response rate. This rate assumes an incomplete response if there is any skip of any question across the year. The survey is designed to not require a response to any question; a participant may choose not to answer by selecting a prefer not to answer response option or advancing through the survey questions. We present the conservative power calculations on the basis of a 2-sided alpha=0.01 test rather than the more common alpha=0.05 level (Supplemental Table 5).

      Menstrual cycle

      We estimated our power to detect the differences in the mean menstrual cycle length among a general dichotomy of the study sample. Such a comparison will be of interest when comparing the outcome across subpopulations defined by demographics (eg, race and ethnicity), lifestyle factors (eg, low or high physical activity), or potential exposures (eg, marijuana products or alcohol consumption) (Supplemental Table 6). Although the longitudinal methods will use all cycles from all participants, we evaluated scenarios where 5% to 10% of 400,000 participants provide menstrual cycle data on 12 cycles and conservatively calculated minimally detectable differences in cycle length using data from those 5% to 10%. We assumed a two-sided alpha=0.01 test, and a within-participant longitudinal correlation in the cycle length of 0.6.
      • Lisabeth L.
      • Harlow S.D.
      • Lin X.
      • Gillespie B.
      • Sowers M.
      Sampling strategies for prospective studies of menstrual function.
      We estimate that we will have the power to detect the menstrual cycle length differences of <1 day for all the scenarios considered, as shown in Supplemental Table 6.

      Gynecologic health conditions

      We estimated the power of the study to detect differences in the prevalence of health conditions for high-risk vs low-risk groups for various initial sample sizes and health condition prevalence estimates in the baseline group (Supplemental Table 6). We estimate that we will have the power to detect relatively small differences in prevalence for all scenarios, even when the health condition is rare (0.5% prevalence), and the high-risk group is small (10% of the sample).

      Results

      Baseline characteristics of the first 10,000 participants

      We present the demographic characteristics of the first 10,000 enrolled and eligible participants who provided demographic information and show their retention across the first 6 months of participation. From the launch of the study to May 20, 2020, there were: 11,113 people who downloaded the Research app and clicked through to the AWHS; 10,459 who consented; and 10,030 who responded to the demographics survey. Eleven participants formally withdrew from the study within their first month of participation. The participant flow for the first 10,000 participants is shown in Figure 2. On average, 370 participants enrolled per week.
      Figure thumbnail gr2
      Figure 2Participant flow in the Apple Women's Health Study, first 10,000 participants. Study onboarding as of May 20, 2020; categories of ineligibility are not mutually exclusive
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      The mean (standard deviation) age at enrollment was 33.6 years (10.3). Although most of the participants were White and non-hispanic (69%), there were 12% Latina, 6% Black, 4% Asian, and 5% identifying as >1 race and ethnicity. Other races and ethnicities represented include American Indian or Alaskan Native (3%). Most participants had graduated college or beyond (51%), were employed for pay (either part-time, full-time, or self-employed) (70%), and reported the use of an Apple Watch (72%). Most participants also gender-identified as a ‘woman’ (96%) and were assigned ‘female’ at birth (99%). Forty percent of the participants were married and 33% were never married. The distribution of SES for the 10,000 participants on the MacArthur Scale are as follows: low (0–3): 31%, middle
      • Arendt L.M.
      • Kuperwasser C.
      Form and function: how estrogen and progesterone regulate the mammary epithelial hierarchy.
      ,
      • Sundström Poromaa I.
      • Gingnell M.
      Menstrual cycle influence on cognitive function and emotion processing-from a reproductive perspective.
      : 42%, and high
      • Liu Z.
      • Doan Q.V.
      • Blumenthal P.
      • Dubois R.W.
      A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding.
      • Treloar A.E.
      • Boynton R.E.
      • Behn B.G.
      • Brown B.W.
      Variation of the human menstrual cycle through reproductive life.
      • Bull J.R.
      • Rowland S.P.
      • Scherwitzl E.B.
      • Scherwitzl R.
      • Danielsson K.G.
      • Harper J.
      Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles.
      • Bao Y.
      • Bertoia M.L.
      • Lenart E.B.
      • et al.
      Origin, methods, and evolution of the three nurses’ health studies.
      : 25%. At the time of enrollment, more participants were living in the Southern region (35%) of the United States than any other but with many women also living in the Northeast (15%), Midwest (20%), and West (25%). A small proportion of women were living in the US territories (0.3%) or had no data available on their location (4%) (Table 1). The states with the most participants enrolled, adjusted for the total population by state from the 2010 census were Massachusetts, Alabama, and Oregon (Supplemental Figure 2). Menstrual tracking data in HealthKit (either retroactive data or data collected during study period) were available for 82.7% of the women, and SensorKit data on heart rate were available for 24% of the women (Table 1).
      Table 1Demographics of Apple Women’s Health Study participants
      DemographicsParticipants at baseline, first 10,000 participants
      Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020). First demographics entry captured for each participant


      Mean±SD or mean (25%–75% range) or % (n)
      Participants responding to month 6 of the “Monthly Survey: Menstrual Update” (n=3099)
      Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020). First demographics entry captured for each participant


      Mean±SD or mean (25%–75% range) or % (n)
      Age (y),
      Age based on birth year
      mean±SD
      33.6±10.333.0±8.5
      Race, % (n)
       White, non-Hispanic69.1 (6910)73.7 (2284)
       Hispanic, Latina, Spanish and/or other Hispanic
      Includes all individuals identifying as Hispanic (exclusively or in addition to another race group). Detailed breakdown available in Supplemental Table 8
      12.0 (1202)10.2 (317)
       Black or African

      American or African
      6.1 (609)4.7 (147)
       Asian4.3 (428)4.4 (135)
       Other2.7 (274)2.2 (67)
       >1 race5.1 (513)4.7 (145)
       Prefer not to answer, or missing0.6 (64)0.1 (4)
      Gender identity, % (n)
       Woman96.1 (9612)97.2 (3013)
       Man0.3 (31)<0.1 (3)
       Transwoman<0.1 (1)0 (0)
       Transman0.17 (17)<0.1 (3)
       Genderqueer or nonbinary1.04 (104)1.3 (39)
       Another gender identity or multiple selected0.9 (92)0.8 (25)
       I prefer not to answer0 (0)0 (0)
       Skip or missing1.4 (143)0.5 (16)
      Sex assigned at birth, % (n)
       Female98.5 (9845)99.5 (3085)
       Intersex0.2 (19)0 (0)
       Skip or missing1.3 (136)0.5 (14)
      Education, n (%)
       Never attended school or only attended kindergarten0.2 (18)<0.1 (1)
       Grades 1 through 11 (primary, middle, or some high school)2.5 (250)1.3 (39)
       Grade 12 or GED (high school graduate)12.4 (1237)9.1 (280)
       1 to 3 y after high school (technical school or some college or associate’s degree)32.6 (3261)29.1 (904)
       College 4 y or more (college graduate)30.5 (3053)35.5 (1099)
       Master’s degree15.6 (1563)18.9 (586)
       Doctorate degree4.7 (473)5.5 (171)
       I prefer not to answer0 (0)0 (0)
       Skip or missing1.5 (145)0.6 (19)
      Employment status, % (n)
       Employed for pay (part-time, full-time, self-employed)70.3 (7031)77.1 (2388)
       Unemployed5.6 (559)3.5 (109)
       Unable to work (ie, disability, illness, other circumstances)4.2 (417)2.8 (86)
       In school11 (1102)10.7 (331)
       Taking care of house or family5.9 (584)5.0 (156)
       In retirement1.5 (152)0.2 (7)
       I prefer not to answer0.9 (97)0.5 (14)
       Missing0.6 (58)0.3 (8)
      Marital status, % (n)
       Married39.6 (3951)41.5 (1285)
       Divorced8.3 (831)6.8 (210)
       Widowed0.8 (82)0.4 (12)
       Separated1.9 (194)1.4 (43)
       Never married33.5 (3347)34.6 (1071)
       A member of an unmarried couple14.2 (1416)14.5 (450)
       I prefer not to answer0 (0)0 (0)
       Skip or missing1.8 (179)0.9 (28)
      Socioeconomic status, % (n)
       0–331.5 (3146)33.3 (1032)
       4–542.2 (4223)44.4 (1376)
       6–925.4 (2535)21.9 (678)
       Missing0.96 (96)0.4 (13)
      Region of the United States, % (n)
       Northeast15.3 (1528)15.6 (484)
       Midwest20.3 (2033)20.9 (649)
       South34.8 (3477)32.7 (1013)
       West24.9 (2492)25.8 (801)
       Territory0.3 (25)0.3 (8)
       Data not available4.5 (445)4.6 (144)
      Apple Watch users, % (n)72.2 (7223)82.5 (2557)
      Heart Rate SensorKit Data Opt-In Authorization, % (n)24.4 (2438)31.2 (968)
      Menstrual flow HealthKit tracking
       Tracked at least 1 menstrual cycle ever, % (n)82.7 (8266)95.1 (2948)
       Tracked at least 1 menstrual cycle within 3 mo of enrollment, % (n)70.6 (7064)89.5 (2772)
       Tracked at least 1 menstrual cycle within 6 mo of enrollment, % (n)72.4 (7236)91.4 (2833)
       Average number of calendar months tracked before baseline8.08 (25%–75%; range, 2–13)9.12 (25%–75%; range, 3–16)
       Average number of calendar months tracked within 3 mo of enrollment (among those tracking)
      Number of calendar months where any bleeding events were tracked during the 3 month follow-up period can range in value from 0 to 4 because a single menstrual cycle can span 2 calendar months. Number of calendar months tracked during the 6 month follow-up period can range from 0 to 7 months.
      2.67 (25%–75%; range, 2–3)2.94 (25%–75%; range, 3–4)
       Average number of calendar months tracked within 6 mo of enrollment (among those tracking)
      Number of calendar months where any bleeding events were tracked during the 3 month follow-up period can range in value from 0 to 4 because a single menstrual cycle can span 2 calendar months. Number of calendar months tracked during the 6 month follow-up period can range from 0 to 7 months.
      4.44 (25%–75%; range, 3–6)5.29 (25%–75%; range, 5–6)
      GED, general equivalency diploma; SD, standard deviation.
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      a Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020). First demographics entry captured for each participant
      b Age based on birth year
      c Includes all individuals identifying as Hispanic (exclusively or in addition to another race group). Detailed breakdown available in Supplemental Table 8
      d Number of calendar months where any bleeding events were tracked during the 3 month follow-up period can range in value from 0 to 4 because a single menstrual cycle can span 2 calendar months. Number of calendar months tracked during the 6 month follow-up period can range from 0 to 7 months.
      Supplemental Table 7 describes the selected characteristics obtained from ResearchKit of the 429 participants who enrolled in the study during the same time but did not respond to the demographic questionnaire. Among these participants, the mean age was 34 years. When compared with enrollees that responded to the demographics questionnaire, a greater proportion of those who did not respond were from the South (40% vs 35%), fewer were Apple Watch users (45% vs 72%), and fewer opted-in to the authorization of SensorKit heart rate access (5% vs 24%).
      On the basis of the self-reported menstrual status at the time of enrollment, 88% reported actively menstruating, 2% were lactating, 6% were menopausal, and 1% were pregnant. The baseline status and the monthly menstrual statuses across 6 months of follow-up are outlined in Table 2.
      Table 2Monthly menstrual survey status count
      Menstrual statusBaseline

      % (n)
      Survey #1

      % (n)
      Survey #2

      % (n)
      Survey #3

      % (n)
      Survey #4

      % (n)
      Survey #5

      % (n)
      Survey #6

      % (n)
      Menstruating87.6 (8763)55.4 (5540)42.7 (4274)37.9 (3791)36.6 (3659)33.6 (3355)30.2 (3021)
      Lactation1.8 (183)1.0 (102)0.8 (83)0.6 (61)0.5 (53)0.5 (45)0.4 (38)
      Menopause6.3 (634)0.3 (26)0.2 (22)0.1 (11)<0.1 (6)0.1 (10)<0.1 (5)
      Pregnant1.1 (110)0.7 (67)0.3 (32)0.4 (35)0.3 (31)0.3 (26)0.3 (32)
      Invalid response
      Invalid Responses include those that are not biologically feasible (eg, “Pregnant” & “Menopause”) and are most likely because of user error
      <0.1 (7)0 (0)0 (0)0 (0)0 (0)0 (0)0 (0)
      Prefer not to answer0.5 (54)0.1 (13)<0.1 (2)<0.1 (4)<0.1 (2)<0.1 (1)<0.1 (2)
      No response
      There is no metadata captured for individuals who do not respond to the baseline or monthly surveys. This value is derived from subtracting the “Count Completed” column from the “Count Eligible” columns in Table 2
      2.5 (249)34.9 (3490)47.3 (4732)51.9 (5189)52.9 (5293)55.7 (5571)58.7 (5873)
      Ineligible
      Individuals who reported a menstrual status of “Menopause,” “Pregnant,” or with an invalid response at baseline or in the monthly survey during a prior month are not eligible to receive the survey in subsequent months. In addition, participants who withdrew (N=11) from the study are not eligible to receive the survey. The ‘Ineligible’ group is a cumulative sum across the 6 month follow-up period.
      -7.6 (762)8.6 (855)9.1 (909)9.6 (955)9.9 (992)10.3 (1028)
      Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020).
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      a Invalid Responses include those that are not biologically feasible (eg, “Pregnant” & “Menopause”) and are most likely because of user error
      b There is no metadata captured for individuals who do not respond to the baseline or monthly surveys. This value is derived from subtracting the “Count Completed” column from the “Count Eligible” columns in Table 2
      c Individuals who reported a menstrual status of “Menopause,” “Pregnant,” or with an invalid response at baseline or in the monthly survey during a prior month are not eligible to receive the survey in subsequent months. In addition, participants who withdrew (N=11) from the study are not eligible to receive the survey. The ‘Ineligible’ group is a cumulative sum across the 6 month follow-up period.

      Retention

      Among the first 10,000 enrollees, 6519 participated in at least 1 of the MSMU data collection (65.2%). Of those eligible, 3099 participants responded to the 6-month check-in (Table 1). 5748 participants responded to the first MSMU, and 4413 and 3902 responded to the second and third, respectively, as summarized in Table 3. The demographics of those at baseline (N=10,000) and those who responded to the month 6 questionnaire (N=3099) are shown in Table 1. The participants who contributed to the sixth MSMU were broadly similar to the enrolled cohort, differing mostly in being more likely to be educated, White, and unmarried. Among the consistent responders, more were Apple Watch users (83% vs 72%) and were associated with higher levels of tracking through HealthKit than the enrolled cohort.
      Table 3Monthly menstrual survey response totals
      Menstrual survey numberCount completedCount eligible
      Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020). Monthly menstrual surveys started in January 2020. Consecutive responses to surveys not required. Individuals who reported a menstrual status of “Menopause” or “Pregnant” at baseline or in the monthly survey were not eligible to receive the survey in subsequent months. In addition, participants who withdrew from the study (N=11) are not eligible to receive the survey
      Percentage completed
      Percentage completed refers to proportion of individuals who were eligible to receive the baseline or monthly menstrual survey and completed the survey. Calculated using the ‘Count Completed’ and ‘Count Eligible’ columns.
      Baseline975110,00097.5
      15748923862.2
      24413914548.3
      33902909142.9
      43752904541.5
      53437900838.2
      63099897234.5
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      a Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020). Monthly menstrual surveys started in January 2020. Consecutive responses to surveys not required. Individuals who reported a menstrual status of “Menopause” or “Pregnant” at baseline or in the monthly survey were not eligible to receive the survey in subsequent months. In addition, participants who withdrew from the study (N=11) are not eligible to receive the survey
      b Percentage completed refers to proportion of individuals who were eligible to receive the baseline or monthly menstrual survey and completed the survey. Calculated using the ‘Count Completed’ and ‘Count Eligible’ columns.
      Of the 10,000 participants enrolled, 82.7% tracked the menstrual bleeding days via HealthKit at some point in the 2-years before study entry or in the 6 months of follow-up. 72.4% of the participants tracked at least 1 menstrual bleeding event during the 6-month follow-up period, and the participants tracked an average of 4.44 (25%–75%; range, 3–6) calendar months during the study period. Among those who completed the sixth MSMU, 95.1% contributed a tracked bleeding event, and 91.4% tracked at least 1 menstrual bleeding event during the 6-months of follow-up. Among this subset, the participants tracked an average of 5.29 (25%–75%; range, 5–6) months of cycle data (Table 1).

      Survey response time

      The participants spent a median time of 1.83 minutes to complete the demographic survey (25th–75th percentile range, 1.43–2.45 minutes) and a median time of 0.77 minutes to complete the MSMU (25th–75th percentile range, 0.55–1.10 minutes) and are noted in Supplemental Table 10.

      Discussion

      Principal findings

      This is the first app-based study of this scope with the goal of collecting longitudinal data for at least 10 years. Among the first 10,000 participants enrolled, the principle findings of this study are that (1) the racial and ethnic distribution of the enrolled cohort was similar to that of the US population, (2) Non-White participants were slightly more likely to drop out of the study than White participants over 6 months of follow-up, (3) the participant geographic distribution of the AWHS included all the US states and Puerto Rico, (4) most of the participants had graduated college or beyond, were employed for pay, and reported the use of an Apple Watch.

      Clinical implications

      The study aims to advance the understanding of menstrual cycles, the factors affecting both within-woman and between-woman variability, and the associations with various health conditions. The study will have novel opportunities to examine variations in reproductive physiology using passively collected data such as physical activity and heart rate. The possible clinical implications include understanding the associations between population-based exposures among iPhone users and the reproductive outcomes including the menstrual cycle length and irregularity, infertility, menopause, and chronic diseases such as cancer and heart disease measured via Health Records in HealthKit.

      Research implications

      Among the 10,502 participants who downloaded the app and were eligible, 96% enrolled and responded to the demographics section, which compares favorably with other longitudinal studies.
      • Wise L.A.
      • Rothman K.J.
      • Mikkelsen E.M.
      • et al.
      Design and conduct of an internet-based preconception cohort study in north America: pregnancy study online.
      • McManus D.D.
      • Trinquart L.
      • Benjamin E.J.
      • et al.
      Design and preliminary findings from a new electronic cohort embedded in the Framingham Heart Study.
      • Mahalingaiah S.
      • Cosenza C.
      • Cheng J.J.
      • Rodriguez E.
      • Aschengrau A.
      Creating a survey instrument for self-assessed menstrual cycle characteristics and androgen excess.
      The recruitment efforts were generally not targeted to specific populations but mainly comprised general media coverage and social media posts. Thirty-eight percent of the participants did not respond to the MSMU after enrollment, with a total of 35% of participants responding to the MSMU at the 6-month follow-up. At least 1 menstrual cycle was tracked via HealthKit, by 82.7% (8266/10,000) of the initial cohort and 95.1% (2948/3,099) of the participants who responded to month 6 of the MSMU. The participants contributed with an average of 4.44 (25%–75%; range, 3–6) tracked calendar months during the 6-month follow-up period. Although the race and ethnicity distribution at the baseline was more closely representative of the US population, we noted a slight increase in the proportion of White (Non-Hispanic) race and ethnicity and a higher education status for the participants responding to month 6 of the MSMU than the participants at enrollment. It is to be noted that the survey completion times were considerably shorter than expected.

      Strengths and limitations

      The AWHS overcomes several limitations of the existing studies of menstrual cycle characteristics including the following: (1) not restricting to those women attempting conception,
      • Wise L.A.
      • Rothman K.J.
      • Mikkelsen E.M.
      • et al.
      Design and conduct of an internet-based preconception cohort study in north America: pregnancy study online.
      ,
      • Buck Louis G.M.
      • Schisterman E.F.
      • Sweeney A.M.
      • et al.
      Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development--the LIFE Study.
      (2) low responses to reproductive questions surrounding menstrual cycle characteristics,
      • McManus D.D.
      • Trinquart L.
      • Benjamin E.J.
      • et al.
      Design and preliminary findings from a new electronic cohort embedded in the Framingham Heart Study.
      (3) underascertainment of the menstrual cycle characteristics for cycle-specific analysis.
      • Bao Y.
      • Bertoia M.L.
      • Lenart E.B.
      • et al.
      Origin, methods, and evolution of the three nurses’ health studies.
      Furthermore, many existing cohorts lack ascertainment on basic reproductive history and menstrual cycle characteristics, despite having well-characterized outcome data for the leading causes of mortality and morbidity.
      • Pino E.C.
      • Zuo Y.
      • Maciel De Olivera C.
      • et al.
      Cohort profile: the MULTI sTUdy Diabetes rEsearch (MULTITUDE) consortium.
      This study builds on the Tremin study
      • Treloar A.E.
      • Boynton R.E.
      • Behn B.G.
      • Brown B.W.
      Variation of the human menstrual cycle through reproductive life.
      by extending racial and ethnic diversity and obtaining expanded demographic, anthropometric, lifestyle, and behavioral data elements from HealthKit and Research Sensor and Usage Data, which allow for unique exposure and outcomes assessment. Furthermore, though the findings may have limited generalizability outside of iPhone users, the digital platform may increase access, allowing participants to engage with this digital study.
      Although the study has many strengths, several limitations must be considered. Firstly, the study is limited to Apple iPhone users, and there is a concern of generalizability to other populations using other digital platforms. Secondly, the loss to follow-up measured by the response rates for the Monthly Survey: Menstrual Updates (MSMU) is higher than other retention metrics such as tracked menstrual bleeding events in HealthKit. We have initiated the retention efforts utilizing education, communication, and engagement through a study update feature within the app and on the study website to promote monthly survey completion. To ensure continued diversity in this cohort, care must be taken to both recruit and retain the population through effective engagement strategies. Furthermore, engagement strategies may be constructed to limit the loss to follow-up of certain subpopulations. Further evaluation of the data must be conducted to understand whether nonrandom dropout may bias the longitudinal effect estimates on the basis of the monthly surveys, though the menstrual data that is tracked will be written to HealthKit, and it will limit missingness and avoid reliance on survey responses.

      Conclusion

      The AWHS captures time-varying demographic, lifestyle, and behavioral data that are built into the Research app, an app that interfaces with multiple data sources. These data streams create an opportunity for the AWHS to contribute new knowledge about long-overlooked and understudied women’s health issues.

      Acknowledgments

      The AWHS team would like to thank all the participants for signing up for the study and contributing to the advancement of women’s health research. We would like to acknowledge Kaitlyn Haughey, MS, Manasvi Marathe, MPH, and Jill MacRae, MS, for their work in supporting the study as a part of the Harvard Study Staff at study initiation; Michael Grusby, PhD, who was involved in the initial phase of this project; the Harvard Information Technology Team, including Andy Ross, BCS, Noah Hulbert, MBA; and David Waxman, MBA, from the Office of Financial Services. We would like to acknowledge Richa Gujarati, MBA, former marketing team lead at Apple, Inc, for supporting the recruitment efforts for this project.

      Supplementary Materials

      Figure thumbnail fx1
      Supplemental Figure 1Apple Women’s Health Study App steps for enrollment
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Figure thumbnail fx2
      Supplemental Figure 2Apple Women’s Health Study participants by state, first 10,000 participants
      Number of participants enrolled in each state of the total population of each state according to 2010 census. This graph represents the first 10,000 women that enrolled and responded to the demographics.
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Supplemental Table 1Survey schedule from November 2019 through June 2020
      After June 2020, the survey cadence changed, and quarterly health surveys became monthly health check-in surveys
      MonthOne-timeEvery monthEvery quarterEvery year
      At enrollment (mo)Menstrual status surveyDemographics
      2Monthly survey
      Monthly surveys include menstrual update, pregnancy update and lactation update
      3Monthly survey
      4Monthly surveyAnnual health survey
      5Monthly survey
      6Monthly surveyQuarterly health survey
      7Monthly surveyAnnual medical history
      8
      At month 8, this survey was deprecated, and a new survey version went live on the Research app.
      Monthly survey
      9Monthly surveyQuarterly health survey
      10Reproductive historyMonthly survey
      11Monthly survey
      12Monthly surveyQuarterly health survey
      13Monthly surveyDemographics
      14Monthly survey
      15Monthly surveyQuarterly health survey
      16Monthly surveyAnnual health survey
      17Monthly survey
      18Monthly surveyQuarterly health survey
      19Monthly surveyAnnual medical history
      20Monthly survey
      21Monthly surveyQuarterly health survey
      22Monthly survey
      23Monthly survey
      24Monthly surveyQuarterly health survey
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      a After June 2020, the survey cadence changed, and quarterly health surveys became monthly health check-in surveys
      b Monthly surveys include menstrual update, pregnancy update and lactation update
      c At month 8, this survey was deprecated, and a new survey version went live on the Research app.
      Supplemental Table 2Apple Women’s Health Study inclusion and exclusion criteria used in this analysis
      Inclusion criteria of the Apple Women’s Health Study
      1At least 18 y old (at least 19 y old in Alabama and Nebraska, at least 21 y old in Puerto Rico);
      2Have menstruated at least once
      3Live in the United States of America
      4Comfortable communicating in written and spoken English
      5Willing and able to provide informed consent to participate in the study
      6Have installed the Apple Research app on your iPhone (iPhone 6s with iOS version 13.2 or later)
      7Not share your iCloud account or iPhone with anyone else
      Exclusion criteria used in this analysis
      1Sex assigned at birth: male
      2Simulated devices (exclusion of devices that were used to test the Apple Women’s Health Study Research App)
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Supplemental Table 3Master table with surveys, questions, and original source of questions
      SurveyQuestionsSource
      ProfileFirst NameStudy specific
      Last Name
      Date of Birth
      Email
      Phone Number
      Country
      State
      Demographics1. Which categories describe you? Select all that apply:[STANDARDIZED QUESTION] This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      Answer ChoicesSub choices
      American Indian or Alaska NativeAmerican Indian

      Alaska Native

      Central or South American Indian

      None of these fully describe me

      I prefer not to answer
      AsianAsian Indian

      Cambodian

      Chinese

      Filipino

      Hmong

      Japanese

      Korean

      Pakistani

      Vietnamese

      None of these fully describe me

      I prefer not to answer
      Black, African American, or AfricanAfrican American

      Barbadian

      Caribbean

      Ethiopian

      Ghanaian

      Haitian

      Jamaican

      Liberian

      Nigerian

      Somali

      South African

      None of these fully describe me

      I prefer not to answer
      Hispanic, Latino, or SpanishColombian

      Cuban

      Dominican

      Ecuadorian

      Honduran

      Mexican or Mexican American

      Puerto Rican

      Salvadoran

      Spanish

      None of these fully describe me

      I prefer not to answer
      DemographicsMiddle Eastern or North AfricanAfghan

      Algerian

      Egyptian

      Iranian

      Iraqi

      Israeli

      Lebanese

      Moroccan

      Syrian

      Tunisian

      None of these fully describe me

      I prefer not to answer
      Native Hawaiian or other Pacific IslanderChamorro

      Chuukese

      Fijian

      Marshallese

      Native Hawaiian

      Palauan

      Samoan

      Tahitian

      Tongan

      None of these fully describe me

      I prefer not to answer
      WhiteDutch

      English

      European, not listed

      French

      German

      Irish

      Italian

      Norwegian

      Polish

      Scottish

      Spanish

      None of these fully describe me

      I prefer not to answer
      None of these fully describe me
      I prefer not to answer
      2. What is the highest grade or year of school you completed?[STANDARDIZED QUESTION]

      This question was adapted from the Behavioral Risk Factor Surveillance System, an annual survey conducted by the US Centers for Disease Control (CDC).
      3. Are you? Married; Divorced; Widowed; Separated; Never married; A member of an unmarried couple; I prefer not to answer[STANDARDIZED QUESTION]

      This question is from the Behavioral Risk Factor Surveillance System, an annual survey conducted by the US Centers for Disease Control (CDC).
      4. Which of the following best describes your current employment situation?[STANDARDIZED QUESTION]

      This question was adapted from the U.S. Census Current Population Survey.
      Employed for pay (part-time, full-time, self-employed)

      Unemployed

      Unable to work (ie, disability, illness, other circumstances)

      In School

      Taking care of house or family

      In retirement

      I prefer not to answer
      Branching question on unemployed:

      Unemployed for less than 1 year

      Unemployed for more than 1 year

      I prefer not to answer
      Think of this ladder as representing where people stand in the country you live in. At the top of the ladder are the people who are the best off – those who have the most money, the most education, and the most respected jobs. At the bottom are the people who are the worst off – those who have the least money, least education, the least respected jobs, or no job. The higher up you are on this ladder, the closer you are to the people at the very top; the lower you are, the closer you are to the people at the very bottom.

      1. Where would you place yourself on this ladder?

      Please select where you think you stand at this time in your life relative to other people around you. [Ladder 0 (worst off) to 10 (best off)]
      [STANDARDIZED QUESTION]

      This question is the MacArthur Scale of Subjective Social Status, which is a standardized question that research has shown is related to overall health.
      2. What is you zip code?Study specific
      3. What is your heigh?Study specific
      4. What is your current weight?Study specific
      5. What was the sex assigned on your original birth certificate?Study specific
      6. Do you identify as intersex?Study specific
      7. Which of the following best describes your gender identity? Select all that apply: [Woman; Man, Trans Woman; Trans Man; Genderqueer / Non-binary; Another gender identity; I prefer not to answer]Study specific
      Menstrual Status Survey1. Are any of these currently true for you? Select all that apply: [pregnancy; breastfeeding/pumping; menopause; none of the above; I prefer not to answer]Study specific
      2. Are the first days of your periods accurately reflected in the Health app for the last two years?Study specific
      3. Are all your period days accurately reflected in the Health app for the last two years?Study specific
      4. Were any of these true for you in the last two years? Select all that apply: [I was pregnant; I was breastfeeding or pumping; I used hormones to manage menstrual cycle or symptoms, to avoid pregnancy, to help become pregnant, for hormone replacement, or for hormone therapy; none of the above; I prefer not to answer]Study specific
      Monthly SurveyMenstrual Update1. Were any of these true for you during the previous calendar month? Select all that apply: [pregnancy; breastfeeding/pumping; menopause; none of the above; I prefer not to answer]Study specific
      2. Are all your period days during the previous calendar month accurately reflected in the Health app?Study specific
      3. Did you take hormones for any of these reasons during the previous calendar month?Study specific
      4. Did you take any of these hormones during the previous calendar month?Study specific
      5. Did any of the following happen during the previous calendar month? Select all that apply: [Significant decrease in exercise; Significant increase in exercise; Significant sleep disruptions; Significant decrease in weight; Significant increase in weight; Major stressful event; Change in medications; Significant illness; Hospitalization; Surgery; None of the above; I prefer not to answer]Study specific
      6. Are you actively trying to get pregnant this month?Study specific
      Pregnancy Update1. Are you currently pregnant?Study specific
      2. When is your due date?Study specific
      3. Would you be willing to provide some information about the outcome of your pregnancy?Study specific
      4. Did you conceive with the help of methods such as artificial insemination or in-vitro fertilization (IVF)?Study specific
      5. Was yours a single or multiple pregnancy?Study specific
      6. When did your pregnancy end?Study specific
      7. Did you have any complications related to your pregnancy?Study specific
      8. What was the outcome of your pregnancy?Study specific
      9. What was your delivery method?Study specific
      10. Are you currently breastfeeding or pumping?Study specific
      Lactation Update1. Are you still breastfeeding or pumping?Study specific
      Annual Health Survey1. How would you describe your overall physical activity level?Study specific
      2. How much exercise do you usually get per week?Study specific
      3. How often do you feel hungry?Study specific
      4. How would you rate the overall healthiness of the foods you eat?Study specific
      5. Do you follow a special diet?Study specific
      6. What time do you usually fall asleep on weekdays or workdays?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      7. What time do you usually wake up on weekdays or workdays?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      8. What time do you usually fall asleep on weekends or non-workdays?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      9. What time do you usually wake up on weekends or non-workdays?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      10. In the past 12 months, how often did you snore while you were sleeping?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      Annual Health Survey11. In the past 12 months, how often did you snort, gasp, or stop breathing while you were asleep?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      12. Have you ever told a doctor or other health professional that you have trouble sleeping?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      13. In the past month, how often did you feel excessively or overly sleepy during the day?[STANDARDIZED QUESTION]

      This question is from the National Health and Nutrition Examination Survey (NHANES), a survey developed by Centers for Disease Control and Prevention (CDC).
      14. In the last month, how often have you felt that you were unable to control the important things in your life?[STANDARDIZED QUESTION]

      This question is from the Perceived Stress Scale (PSS-4), which is a standardized survey for evaluating stress.
      15. In the last month, how often have you felt confident about your ability to handle your personal problems?[STANDARDIZED QUESTION]

      This question is from the Perceived Stress Scale (PSS-4), which is a standardized survey for evaluating stress.
      Annual Health Survey16. In the last month, how often have you felt that things were going your way?[STANDARDIZED QUESTION]

      This question is from the Perceived Stress Scale (PSS-4), which is a standardized survey for evaluating stress.
      17. In the last month, how often have you felt difficulties were piling up so high that you could not overcome them?[STANDARDIZED QUESTION]

      This question is from the Perceived Stress Scale (PSS-4), which is a standardized survey for evaluating stress.
      18. In your entire life, have you had at least 1 drink of any kind of alcohol, not counting small tastes or sips?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      19. How often did you have a drink containing alcohol in the past year?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      20. On a typical day when you drink, how many drinks do you have?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      Annual Health Survey21. Have you smoked at least 100 cigarettes in your entire life?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      22. Do you now smoke cigarettes every day, some days, or not at all?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      23. On average, how many cigarettes do you smoke per day now?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      24. If you have completely stopped smoking cigarettes, how old were you when you stopped?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      25. Have you ever used an electronic nicotine product, even one or two times?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      Annual Health Survey26. Do you now use electronic nicotine products every day, some days, or not at all?[STANDARDIZED QUESTION]

      This question is from the All of Us study, a large research program sponsored by the National Institutes of Health (NIH).
      27. Have you ever used marijuana in any form, even one or two times?Study specific
      28. How often do you currently use marijuana in any form?Study specific
      29. Does anyone regularly smoke inside your home?Study specific
      30. How would you describe your health compared to other people your age?Study specific
      Quarterly Health Survey1. Over the past month, did you wake up feeling more or less tired than you did the month before?Study specific
      2. Over the past month, were your eating habits more or less healthy than the month before?Study specific
      3. Over the past month, were you more or less physically active than the month before?Study specific
      4. Over the past month, did you feel more or less stress than the month before?Study specific
      5. How would you compare your alcohol use over the past month to the month before?Study specific
      6. How would you compare your smoking or vaping over the past month to the month before?Study specific
      Annual Medical History1. Are any of these currently true for you? Select all that apply: [Pregnancy; Breastfeeding or pumping; Menopause; None of the above; I prefer not to answer]Study specific
      2. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Endometriosis; Fibroids; Infertility; Polycystic ovarian syndrome (PCOS); Premenstrual syndrome (PMS) or Premenstrual dysphoric disorder (PMDD); None of the above; I prefer not to answer]Derived from OM Study
      3. At what age were you diagnosed with this condition?Derived from OM Study
      Annual Medical History4. How did your doctor or care provider determine you had this condition?Derived from OM Study
      5. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Hyperprolactinemia (high prolactin levels); Hyperthyroidism (high thyroid levels); Hypothyroidism (low thyroid levels); Prediabetes; Type 1 diabetes; Type 2 diabetes; None of the above; I prefer not to answer]Derived from OM Study
      6. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Arrhythmia, such as atrial fibrillation (AFib) or atrial flutter; Congenital heart disease; Congestive heart failure; Coronary artery disease (CAD); Heart attack; Heart valve disease; High cholesterol; Hypertension (high blood pressure); Stroke; Transient ischemic attack (mini-stroke); None of the above; I prefer not to answer]Study specific
      7. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Anemia (low blood count); Deep vein thrombosis (blood clots in the veins of the legs); Hemophilia (easy bleeding and bruising); Pulmonary embolism (blood clots in the veins of the lungs); Thrombophilia (frequent blood clots); None of the above; I prefer not to answer]Study specific
      8. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Acid reflux; Celiac disease; Colon polyps; Crohn's disease or ulcerative colitis; Gallbladder disease, such as gallstones; Irritable bowel syndrome (IBS); None of the above; I prefer not to answer]Study specific
      9. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Kidney disease; Kidney disease with dialysis; Kidney stones; None of the above; I prefer not to answer]Study specific
      10. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Asthma; Chronic obstructive pulmonary disease (COPD); Cystic fibrosis; Sleep apnea; None of the above; I prefer not to answer]Study specific
      11. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Arthritis; Fibromyalgia; Lupus; Osteoporosis; Sarcoidosis; None of the above; I prefer not to answer]Study specific
      12. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Blood cancer, such as leukemia or lymphoma; Breast cancer; Cervical cancer; Cervical dysplasia (pre-cancer); Colon or rectal cancer; Endometrial cancer (cancer of uterus); Endometrial hyperplasia (pre-cancer of uterus); Ovarian cancer; Thyroid cancer; None of the above; I prefer not to answer]Study specific
      Annual Medical History13. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Chronic fatigue syndrome; Epilepsy (seizures); Headaches; Insomnia; Migraine headaches; Multiple sclerosis; None of the above; I prefer not to answer]Study specific
      14. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Anxiety disorder; Attention deficit & hyperactivity disorder (ADHD); Autism spectrum disorder; Bipolar disorder; Depression; Eating disorder; Panic disorder; Post-traumatic stress disorder (PTSD); None of the above; I prefer not to answer]Study specific
      15. Have you ever been diagnosed with any of the following by a doctor or other care provider? Select all that apply: [Chlamydia; Gonorrhea; Hepatitis B or Hepatitis C; HIV/AIDS; Human Papillomavirus (HPV); Syphilis; Urinary tract infections (UTI)/bladder infections; Vaginal infections, such as yeast infections or bacterial vaginosis; Zika virus; None of the above; I prefer not to answer]Study specific
      16. Have you ever had surgery on any of the following? Select all that apply: [Appendix; Bone; Breast; Gallbladder; Heart; Stomach (including weight loss surgery); Vascular (on your arteries or veins); None of the above; I prefer not to answer]Study specific
      17. Have you ever had any of the following gynecologic surgeries? Select all that apply: [Cesarean section; Cervical surgery (removal of part or all of the cervix); Fibroid surgery (removal of fibroids); Hysterectomy (removal of uterus); Oophorectomy, unilateral (removal of only one ovary); Oophorectomy, bilateral (removal of both ovaries); Removal or ligation of fallopian tubes; None of the above; I prefer not to answer]Study specific
      18. What was the sex assigned on your original birth certificate?Study specific
      19. Do you identify as intersex?Study specific
      20. Which of the following best describes your gender identity? Select all that apply: [Woman; Man; Trans Woman; Trans Man; Genderqueer/Non-Binary; Another gender identity; I prefer not to answer]Study specific
      21. Which of the following best represents how you think of yourself? Select all that apply: [Asexual; Bisexual; Gay; Lesbian; Straight/Heterosexual; Another sexual orientation; I prefer not to answer]Study specific
      22. Have your biological mother, sister, or daughter ever been diagnosed with any of the following? Select all that apply: [Breast cancer; Cervical cancer; Cervical dysplasia (pre-cancer); Colon/rectal cancer; Endometrial cancer (cancer of uterus); Endometrial hyperplasia (pre-cancer of uterus); Endometriosis; Fibroids; High cholesterol; Hypertension (high blood pressure); Infertility; Obesity; Polycystic ovarian syndrome (PCOS); Premenstrual syndrome/Premenstrual dysphoric disorder (PMS/PMDD); Type 1 diabetes; Type 2 diabetes; None of the above; I prefer not to answer]Study specific
      23. Have your biological father, brother, or son ever been diagnosed with any of the following? Select all that apply: [Breast cancer; Colon/rectal cancer; High cholesterol; Hypertension (high blood pressure); Infertility; Obesity; Type 1 diabetes; Type 2 diabetes; None of the above; I prefer not to answer]Study specific
      24. How confident are you filling out medical forms by yourself?[STANDARDIZED QUESTION]

      This question is from the BRIEF Health Literacy Screening Tool, a survey for assessing an individual’s level of understanding about health-related topics.
      Reproductive History1. Were you born prematurely, meaning, before 37 weeks of pregnancy?Study specific
      2. How much did you weigh when you were born?Study specific
      3. At what age did you have your first menstrual cycle?Derived from OM Study
      4. After your first menstrual cycle, how long did it take for your cycle to become regular?Derived from OM Study
      5. Have you ever taken hormones for any of the following reasons? Select all that apply: [To manage menstrual cycle or symptoms (e.g. heavy bleeding, irregular periods, cramps, acne); To avoid pregnancy; To increase my likelihood of pregnancy; For hormone replacement (e.g. during menopause); For transgender hormone therapy; For cancer treatment; For other reasons; No, I have never taken hormones; I prefer not to answer]Derived from OM Study
      6. Have you ever taken any of the following hormones? Select all that apply: [Birth control pill; Hormonal IUD (intrauterine device); Hormonal implant (medication rod inserted under skin on your arm); Hormonal patch; Hormonal shot (shot every three months); Hormonal vaginal ring; None of the above; I prefer not to answer]Derived from OM Study
      7. At what age did you start using this hormone?Derived from OM Study
      8. How many years have you used this hormone for in total?Derived from OM Study
      9. How many times have you been pregnant?Derived from OM Study
      Reproductive History10. Would you be willing to provide some information about the outcome of your pregnancies?Study specific
      11. Did you conceive with the help of methods such as artificial insemination or in-vitro fertilization (IVF)?Derived from OM Study
      12. Was this a single or multiple pregnancy?Derived from OM Study
      13. What year did this pregnancy end?Study specific
      14. How many weeks did this pregnancy last?Derived from OM Study
      15. Did you have any complications related to this pregnancy? Select all that apply: [Gestational diabetes (diabetes only during pregnancy); Gestational hypertension (high blood pressure only during pregnancy); Preeclampsia or eclampsia (high blood pressure leading to other complications); Heart problems (heart failure or heart attack); Postpartum hemorrhage (very heavy bleeding during delivery); Placental abruption (separation of the placenta from uterus); Placenta previa (placenta covering the cervix); Intrauterine growth restriction (fetus was too small for weeks of pregnancy); Perinatal depression (depression during or after pregnancy); Hysterectomy (surgery to remove your uterus); Severe infection or sepsis; Seizure disorder; None of the above; I prefer not to answer]Derived from OM Study
      16. What was the outcome of this pregnancy?Derived from OM Study
      17. What was your delivery method?Derived from OM Study
      18. How many months did you breastfeed or pump?Derived from OM Study
      Adapted from Harvard University,
      Harvard University
      The ovulation and menstruation health (OM) pilot study survey instrument.
      Denny et al,
      • Denny J.C.
      • Rutter J.L.
      • et al.
      All of Us Research Program Investigators
      The “All of Us” Research Program.
      Cohen et al,
      • Cohen S.
      • Kamarck T.
      • Mermelstein R.
      A global measure of perceived stress.
      Adler et al,
      Stanford University
      MacArthur Scale of Subjective Social Status – Adult Version.
      Centers for Disease Control and Prevention,
      Centers for Disease Control and Prevention (CDC)
      Behavioral Risk Factor Surveillance System.
      Chew et al,
      • Chew L.D.
      • Bradley K.A.
      • Boyko E.J.
      Brief questions to identify patients with inadequate health literacy.
      Centers for Disease Control and Prevention.
      Centers for Disease Control and Prevention
      NHANES 2017-2018 Questionnaire Instruments.
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Supplemental Table 4Summary of sensor-based data types
      Data typeWhat is collectedWhat is not collected
      Frequently visited locations
      • Frequently visited locations but only after they are given an anonymized identifier.
      • The distance of an anonymized location from your home.
      • Arrival and departure times that are expanded to 15-min increments to make them less specific.
      GPS or specific location information: names of the places you’ve visited, addresses including home or work
      Watch on wristWhen you wear your Apple Watch and your wrist settings.How you use your Apple Watch
      Optical sensorHigh-fidelity Apple Watch optical sensor data that can be used to determine things like heart rate and blood oxygen saturation, high-fidelity accelerometer data calculated heart rate, along with reading accuracyECG data or results
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Supplemental Table 5Minimally detectable difference in mean cycle length (days) between 2-groups for an alpha=0.01 2-sided test
      Sample sizeHigh-risk group prevalence
      10%20%50%
      20,0000.90.70.5
      40,0000.60.50.4
      Assumes 12 cycles per participant and a longitudinal correlation of 0.6 among repeated cycles. Lower correlation will result in higher power.
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Supplemental Table 6Minimal detectable effect sizes for disorder outcomes
      Outcome prevalence=0.5%
      Sample sizeHigh-risk group prevalence
      10%20%50%
      20,0001.41.11.0
      50,0001.00.90.8
      100,0000.90.80.7
      Outcome prevalence=2%
      Sample sizeHigh-risk group prevalence
      10%20%50%
      20,0003.53.12.9
      50,0002.92.72.6
      100,0002.72.52.4
      Outcome prevalence=10%
      Sample sizeHigh-risk group prevalence
      10%20%50%
      20,00012.912.211.7
      50,00011.811.411.1
      100,00011.311.110.8
      Table entries correspond to minimal detectable differences in outcome proportions between 2 groups, detectable with 90% power, at the alpha=0.01 Type I error rate, for various scenarios.
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      Supplemental Table 7Selected characteristics at baseline of Apple Women’s Health Study enrollees, with no demographic data (n=429)
      Subset of participants that enrolled but did not provide demographic data over the same time span as those enrolled with demographics in Table 1; first entry captured for each participant.
      DemographicMean±SD or % (n)
      Age (y), mean±SD34.0±11.5
      Apple Watch users, n (%)45.5 (195)
      Region of the United States, % (n)
       Northeast15.4 (66)
       Midwest11.4 (49)
       South40.1 (172)
       West27.5 (118)
       Territory0.9 (4)
       Data not available4.7 (20)
      Heart Rate SensorKit Opt-In Authorization, n (%)4.7 (20)
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      a Subset of participants that enrolled but did not provide demographic data over the same time span as those enrolled with demographics in Table 1; first entry captured for each participant.
      Supplemental Table 8Hispanic ethnicity detailed breakdown of Apple Women’s Health Study participants
      EthnicityParticipants at baseline, first 10,000 Participants
      Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020); First demographics entry captured for each participant.
      Participants responding to month 6 of the “Monthly Survey: Menstrual Update” (n=3099)
      Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020); First demographics entry captured for each participant.
      Mean±SD or % (n)Mean±SD or % (n)
      Hispanic, Latino, Spanish and/or other Hispanic, % (n)12.0 (1202)10.2 (317)
      Hispanic, no other race reported7.1 (710)5.8 (181)
      Hispanic, White3.1 (312)3.2 (99)
      Hispanic, Black0.4 (38)0.3 (9)
      Hispanic, other race1.4 (142)0.9 (28)
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.
      a Subset for the first 10,000 participants enrolled and providing demographic data that met inclusion criteria (through May 20, 2020); First demographics entry captured for each participant.
      Supplemental Table 9Survey response time in seconds
      Survey type25th percentileMedian75th percentile
      Common demographics86110147
      Menstrual status survey (baseline)121940
      Monthly menstrual survey (1–6)334666
      Mahalingaiah et al. Apple Women’s Health Study cohort profile. Am J Obstet Gynecol 2022.

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